e-issn 1305 -3124 perinatal

The Official Publication ofPerinatal Medicine Foundation

Turkish Perinatology SocietyTurkish Society of Obstetrics and Gynecology

e-ISSN: 1305-3124

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Volume 23 | Issue 1 | April 2015

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Description

Perinatal Journal, the Official Publication of Perinatal MedicineFoundation, Turkish Perinatology Society and Turkish Society ofUltrasound in Obstetrics and Gynecology, is an international onlineopen access peer-reviewed scientific journal (e-ISSN: 1305-3124)published triannually in English. The manuscripts which are accept-ed for publication in the Perinatal Journal are published as a parallelpublication of Turkish version in “Perinatoloji Dergisi” (p-ISSN:1300-5251, e-ISSN:1305-3132). Translation in to Turkish language is pro-vided by the publisher as free of charge for authors. This is automat-ically accepted by the authors of manuscripts at the time of submis-sion.

The journal mainly includes original clinical and experimentalresearch articles, case reports, reviews, editorial and opinion articles,and a letters column. Perinatal Journal can be read by perinatolo-gists, obstetricians, gynecologists, radiologists, pediatricians, sonog-raphers, midwives, radiographers, and scientific members of otherrelated areas.

Aim and Scope

Perinatal Journal aims to create an interdisciplinary scientific plat-form for sharing and discussing topics on perinatal medicine and toshare its experience with international scientific community.

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Periantal Journal does not officially agree with the ideas of manu-scripts published in the journal and does not guarantee for any prod-uct or service advertisements in its content. Scientific and legal respon-sibilities of published articles belong to their authors. Materials such aspictures, figures, tables etc. sent with manuscripts should be originalor if they were published before written approval of copyright holdershould be sent with manuscript for publishing together.

All published materials will become the sole property of, and willbe copyrighted by Perinatal Journal. Therefore, "Acknowledgementof Authorship and Transfer of Copyright Agreement" presented bymanuscript submission system should be approved by the authorsduring the submission process. No payment is done for manuscripts

under the name of copyright or others approved for publishing inthe journal and no publication cost is charged.

To promote the development of global open access to scientificinformation and research, the journal provides copyrights of allonline published papers (except where otherwise noted) for free useof readers, scientists, and institutions (such as link to the content orpermission for its download, distribution, printing, copying, andreproduction in any medium, without any changing and except thecommercial purpose), under the terms of CC BY-NC-ND 3.0 License(www.creativecommons.org/licenses/by-nc-nd/3.0), provided theoriginal work is cited. To get permission for commercial purposeplease contact the publisher.

Conflicts of Interest

The authors should disclose all issues concerning financial relation-ship, conflicts of interest, and competing interest that may potential-ly influence the results of the research or scientific judgment. Allfinancial contributions or sponsorship, financial relations, and areasof conflicts of interest should be clearly explained in the relevantstep of the submission process, with full assurance that any relateddocument will be submitted to the journal when requested.

Publication Ethics and Malpractice Statement

For the details of journal's “Publication Ethics and Malpractice Statement”please visit www.perinataljournal.com.

Publication InfoOwnership: On behalf of the Perinatal Medicine Foundation,Cihat fien

Managing Editor: Murat Yayla

Administrative Office: Cumhuriyet Cad. 30/5 Elmada¤, Taksim34367 ‹stanbul

Due the Press Law of Turkish Republic dated as June 26, 2004 andnumbered as 5187, this publication is classified as a local periodi-cal. Perinatal Journal is published by Deomed Publishing (Copyright© 2015, Perinatal Medicine Foundation).

Publication Coordinator: ‹lknur Demirel

English Editor: Fikret Yeflilyurt

Graphic Design: Tolga Erbay

The Official Publication of Perinatal Medicine Foundation, Turkish Perinatology Society and Turkish Society of Ultrasound in Obstetrics and Gynecology

Deomed PublishingGür Sok., No: 7BKad›köy 34720 Istanbul, TurkeyTelefon: +90 216 414 83 43 (Pbx) Faks: +90 216 414 83 42e-posta: [email protected] • www.deomed.com

www.perinataljournal.com

Editor-in-ChiefCihat fien, Istanbul Universtiy, Istanbul, Turkey

EditorsMurat Yayla Ac›badem InternationalHospital, Istanbul, Turkey

Olufl ApiYeditepe Universtiy, Istanbul, Turkey

Advisory BoardAbdallah Adra, Beirut, LebanonArif Akflit, Eskiflehir, TurkeySaadet Arsan, Ankara, TurkeyAbdel-Latif Ashmaig, Khartoum, SudanAlev At›fl-Ayd›n, Istanbul, TurkeyManuel Carrapato, Porto, PortugalJulene Carvalho, London, UKRabih Chaoui, Berlin, GermanyFrank Chervenak, New York, NY, USABülent Çakmak, Tokat, TurkeyFiliz Çayan, Mersin, TurkeyEbru Çelik, Malatya, TurkeyVincenzo D’Addario, Bari, ItalyNur Daniflmend, Istanbul, TurkeyCansun Demir, Adana, TurkeyJan Deprest, Leuven, BelgiumEbru Dikensoy, ‹stanbul, TurkeyGian Carlo DiRenzo, Perugia, ItalyTony Duan, Shanghai, PRCJoachim Dudenhausen, Berlin, GermanyAlaa Ebrashy, Cairo, EgyptElif Gül Yapar Eyi, Ankara, TurkeyAli Gedikbafl›, Istanbul, TurkeyUlrich Gembruch, Bonn, GermanyAnne Greenough, London, UKGökhan Göynümer, Istanbul, TurkeyArif Güngören, Hatay, TurkeyMelih A. Güven, Istanbul, TurkeyJoseph Haddad, Paris, FranceDavor Jurkovic, London, UKOliver Kagan, Tübingen, GermanyBurçin Kavak, Elaz›¤, Turkey‹schiro Kawabata, Osaka, JapanSelahattin Kumru, Düzce, TurkeyMertihan Kurdo¤lu, Ankara, TurkeyAs›m Kurjak, Zagreb, CroatiaNilgün Kültürsay, Izmir, TurkeyMalcome Levene, Leeds, UK

Narendra Malhotra, Agra, IndiaGiampaolo Mandruzzato, Trieste, ItalyAlexandra Matias, Porto, PortugalRatko Matijevic, Zagreb, CroatiaIsrael Meizner, Tel Aviv, IsraelMohammed Momtaz, Cairo, EgyptGiovanni Monni, Cagliari, ItalyKypros Nicolaides, London, UKLütfü Öndero¤lu, Ankara, TurkeySoner R. Öner, Izmir, TurkeyOkan Özkaya, Isparta, TurkeyAlexander Papitashvilli, Tbilisi, Georgia‹brahim Polat, Istanbul, TurkeyRitsuko Pooh, Osaka, JapanRuben Quintero, Tampa, FL, USANebojsa Radunovic, Belgrade, SerbiaGuiseppe Rizzo, Rome, ItalyStephen Robson, Newcastle, UKRoberto Romero, Detroid, MI, USALevent Salt›k, Istanbul, TurkeyHaluk Sayman, Istanbul, TurkeyMekin Sezik, Isparta, TurkeyJiri Sonek, Dayton, OH, USAYunus Söylet, Istanbul, TurkeyMilan Stanojevic, Zagreb, CroatiaFlorin Stomatian, Cluj, RomaniaTurgay fiener, Eskiflehir, TurkeyAlper Tanr›verdi, Ayd›n, TurkeyEbru Tar›m, Adana, TurkeyNeslihan Tekin, Eskiflehir, TurkeyIlan Timor-Tritsch, New York, NY, USASeyfettn Uluda¤, Istanbul, TurkeyLiliana Voto, Buenos Aires, ArgentinaMiroslaw Wielgos, Warsaw, PolandSimcha Yagel, Tel Aviv, IsraelAhmet Yal›nkaya, Diyarbak›r, TurkeyIvica Zalud, Honolulu, HI, USA


Correspondence: Perinatal Journal, Perinatal Medicine Foundation,Cumhuriyet Cad. 30/5 Elmada¤, Taksim 34367 ‹stanbul, TurkeyPhone: (0212) 225 52 15 • Fax: (0212) 225 23 22 e-mail: [email protected]

Names are in alphabetical order.

Statistical AdvisorMurat Api, Istanbul, Turkey


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Perinatal Journalii

Coverage

The manuscripts should be prepared for one of the following article categorieswhich are peer-reviewed:

• Original Article

• Case Report

• Technical Note

• Letter to the Editor

In addition, the journal includes article categories which do not require a peerreview process but are prepared by the Editorial Board or consist of invited articles,titled as:

• Editorial• Opinion• Review• Report• Clinical Guidelines• Abstracts• Announcements• Erratum

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Following the initial review, manuscripts which have been accepted forconsideration are reviewed by at least two reviewers. The Editors of the journaldecide to accept or reject the manuscript considering the comments of thereviewers. They are authorized to reject or revise the manuscript, to suggestrequired corrections and changes upon the comments and suggestions ofreviewers, and/or to correct or condense the text by permission of the corre-sponding author. They may send the manuscript for the statistical evaluation toStatistical Advisor if necessary as well. They have also the right to reject a man-uscript after authors’ revision. Author(s) should provide additional relevant data,documents, or information upon the editorial request if necessary.

Ethical Issues

All manuscripts presenting data obtained from studies involving human subjectsmust include a statement that the written informed consent of the participantswas obtained and that the study was approved by an institutional ethics boardor an equivalent body. This institutional approval should be submitted with themanuscript. Authors of case reports must submit the written informed consentof the subject(s) of the report or of the patient’s legal representatives for thepublication of the manuscript. All studies should be carried out in accordancewith the World Medical Association Declaration of Helsinki, covering the latestrevision date. Patient confidentiality must be protected according to the univer-sally accepted guidelines and rules. Manuscripts reporting the results of experi-mental studies on animals must include a statement that the study protocol wasapproved by the animal ethics committee of the institution and that the studywas conducted in accordance with the internationally accepted guidelines,including the Universal Declaration of Animal Rights, European Convention forthe Protection of Vertebrate Animals Used for Experimental and Other ScientificPurposes, Principles of Laboratory Animal Science, and the Handbook for theCare and Utilization of Laboratory Animals. The authors are strongly requestedto send the approval of the ethics committee together with the manuscript. Inaddition, manuscripts on human and animal studies should describe proceduresindicating the steps taken to eliminate pain and suffering.

The authors should also disclose all issues concerning financial relationship,conflicts of interest, and competing interest that may potentially influence theresults of the research or scientific judgment. All financial contributions or spon-sorship, financial relations, and areas of conflicts of interest should be clearly

explained in the relevant step of the submission process, with full assurance thatany related document will be submitted to the journal when requested.

Perinatal Journal is committed to upholding the highest standards of pub-lication ethics and observes the following principles of Publication Ethics andMalpractice Statement which is based on the recommendations and guidelinesfor journal editors developed by the Committee on Publication Ethics (COPE),Council of Science Editors (CSE), World Association of Medical Editors (WAME)and International Committee of Medical Journal Editors (ICMJE). For the detailsof journal's "Publication Ethics and Malpractice Statement" please visitwww.perinataljournal.com.

Manuscript Preparation

In addition to the rules listed below, manuscripts to be published in PerinatalJournal should be in compliance with the Uniform Requirements forManuscripts Submitted to Biomedical Journals published by InternationalCommittee of Medical Journal Editors (ICMJE) of which latest version is availableat www.icmje.org.

Authors are requested to ensure that their manuscript follows the appro-priate guidelines such as CONSORT for randomized controlled trials, STROBE forobservational studies, STARD for diagnostic accuracy studies, and PRISMA forsystematic reviews and meta-analyses, for the study design and reporting ifapplicable.

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Original research articles base on clinical or experimental studies. Themain text should not exceed 2500 words (max. 16 pages), and a maximum ofsix authors is advisable.

Case reports should illustrate interesting cases including their treatmentoptions. The main text should not exceed 2000 words (max. 8 pages), and amaximum of five authors is advisable.

Opinion articles: Only by invitation and should be no more than 2000words long (max. 8 pages).

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The title of the manuscript should be carefully chosen to better reflect the con-tents of the study. No anusual abbreviations should be used in the title of themanuscript.

Abstract

Abstracts should not contain any abbreviation and references. They should beprepared under following designs.

— Abstracts of Original Research Articles should be max. 250 wordsand structured in four paragraphs using the following subtitles: Objective,

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Volume 23 | Issue 1 | April 2015 iii

Information for the Authorswww.perinataljournal.com

Methods, Results, and Conclusion. Following the abstract, each abstract shouldinclude max. 5 key words separated with comma and written in lower cases.

— Abstracts of Case Reports should be max. 125 words and structuredin three paragraphs using the following subtitles: Objective, Case, Conclusion.Following the abstract, each abstract should include max. 3 key words separat-ed with comma and written in lower cases.

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The Discussion section should mainly rely on the results derived from thestudy, with relevant citations from the most recent literature.

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— Standard journal article: Hammerman C, Bin-Nun A, Kaplan M.Managing the patent ductus arteriosus in the premature neonate: a new lookat what we thought we knew. Semin Perinatol 2012;36:130–8.

— Article published in an only electronic journal: Lee J, Romero R, XuY, Kim JS, Topping V, Yoo W, et al. A signature of maternal anti-fetal rejectionin spontaneous preterm birth: chronic chorioamnionitis, anti-human leukocyteantigen antibodies, and C4d. PLoS ONE 2011;6:e16806. doi:10.1371/journal.pone.0011846

— Book: Jones KL. Practical perinatology. New York: Springer; 1990. p.112–9.

— Chapter in a book: Sibai BM, Frangieh AY. Eclampsia. In: Gleicher N,editors. Principles and practice of medical therapy in pregnancy. 3rd ed. NewYork: Appleton&Lange; 1998. p. 1022–7.

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Perinatal Journaliv

Original ArticlesUltrasonographic evaluation of ventriculomegaly cases 1

Hakan Kalayc›, Halis Özdemir, Ça¤r› Gülümser, Ayfle Parlakgümüfl, Tayfun Çok, Ebru Tar›m, Filiz Bilgin Yan›k

Perinatal outcomes of patients diagnosed borderline gestational diabetes mellitus 6

Gök Özgül, Rauf Meleko¤lu, Sevda Yeleç, ‹pek Eskiyörük, Fatma Tuncay Özgünen

Health practices of pregnant women in Gumushane City Center 13

Handan Özcan, Nezihe K›z›lkaya Beji

The evaluation of pregnancies complicated by eclampsia: retrospective analysis of 37 cases in our clinic 20

Aytekin Tokmak, Korkut Da¤lar, Ali ‹rfan Güzel, Bergen Laleli, Salim Erkaya, Dilek Uygur

Factors affecting postpartum depression in Diyarbak›r 26

Ali Emre Tahao¤lu, Cihan To¤rul, Mehmet ‹rfan Külahç›o¤lu, Beflire Ayd›n Öztürk, Deniz Balsak,

Hanifi Bademk›ran, Erdo¤an Gül, Ümit Görkem, Tayfun Güngör

Analysis of maternal serum and urinary lipocalin-2 levels 30

Yeflim Bayo¤lu Tekin, Ülkü Mete Ural, Aynur K›rbafl, fienol fientürk, Figen K›r fiahin

Critical pulmonary stenosis with prenatal diagnosis: a case series and review of literature 34

Oya Demirci, Taner Yavuz, Resul Ar›soy, Emre Erdo¤du, P›nar Kumru, Oya Pekin

Evaluation of prenatal invasive procedures: analysis of retrospective cases 39

Aybike Tazegül Pekin, Özlem Seçilmifl Kerimo¤lu, Setenay Arzu Y›lmaz, Nadir Koçak,

Feyza Nur ‹ncesu, Ayfle Gül Kebapc›lar, Çetin Çelik

Investigation of the effects of fetal gender on umbilical artery and middle cerebral artery Doppler findings 45

Burcu Artunç Ülkümen, Halil Gürsoy Pala, Y›ld›z Uyar, Yeflim Baytur, Faik Mümtaz Koyuncu

Results of routine first trimester screening tests and following invasive procedures during pregnancy 50

Rahime Nida Ergin, Murat Yayla

Case ReportsThe association of congenital hand reduction defect and uterine anomaly 56

Bülent Kars, Önder Sakin, Yasemin Karageyim Karfl›da¤, Cenk Demir, Esra Esim Büyükbayrak

Extrauterine intrapartum treatment procedure in the unilateral advanced fetal hydrothorax case 60

Sevil Eraslan, Rauf Meleko¤lu, Ebru Çelik

Goiter in fetus without maternal thyroid disease: a case report 65

Önder Sakin, Bülent Kars, Yasemin Karageyim Karfl›da¤, Cenk Demir, Esra Esim Büyükbayrak

Letter to EditorLetter to the Editor regarding “Extrauterine intrapartum treatment procedure in the unilateral

advanced fetal hydrothorax case” 70

Baflak Kaya, Ali Gedikbafl›

ContentsVolume 23, Issue 1, April 2015


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Ultrasonographic evaluation of ventriculomegaly cases

Hakan Kalayc›, Halis Özdemir, Ça¤r› Gülümser, Ayfle Parlakgümüfl, Tayfun Çok, Ebru Tar›m, Filiz Bilgin Yan›k Department of Gynecology & Obstetrics, Medical School of Baflkent University, Ankara, Turkey

Özet: Ventrikülomegali vakalar›n›n ultrasonografikde¤erlendirilmesiAmaç: Baflkent Üniversitesi Adana ve Ankara Hastaneleri Perina-toloji bilim dal›nda tan› alm›fl veya ventrikülomegali ön tan›s› ilerefere edilmifl hastalar›n demografik verilerinin retrospektif olarakde¤erlendirilmesi. Yöntem: Bu çal›flmada May›s 2008 ve Mart 2013 tarihleri aras›n-da Baflkent Üniversitesi Ankara ve Adana Hastaneleri PerinatolojiBilim Dal›na d›flar›dan gönderilen veya klini¤imizde tespit edilenfetal ventrikülomegalisi olan 61 gebe demografik verileri, tan› ko-nulma haftalar›, efllik eden anomaliler ve gebeliklerin seyri aç›s›n-dan de¤erlendirildi. ‹statistiksel hesaplamalarda SPSS v. 16.0’danfaydalan›ld›. Bulgular: 20–41 yafl aras› 61 gebenin de¤erlendirmesinde,%45.9’unun ilk gebelikleriydi. %16.4’ü 35 yafl ve üzeriydi.%4.9’unun yard›mc› üreme teknikleri ile gebe kald›¤› izlendi. Ha-fif (10–12 mm), ›l›ml› (12.1–14.9 mm) ve ciddi ventrikülomegali(≥15 mm) oranlar› s›ras› ile %65.6, %24.7 ve %4.8 idi. Hiçbir va-kada toksoplazma, sitomegalovirüs, rubella veya Herpes virüs en-feksiyonu saptanmad›. Karyotip analizinde 3 hastada Down sen-dromu tespit edildi (%4.9). Ventrikülomegalilerin %67.2’si tek ta-rafl› idi. Ayr›nt›l› ultrasonografi haftas› olan 16–24 haftalar› aras›tespit oran› %52.5 idi. %33.3 ek anomali mevcuttu. En s›k efllikeden anomaliler s›kl›k s›ras›na göre artm›fl nukal kal›nl›k (%13.3),korpus kallozum agenezisi (%11.1) ve nazal kemik hipoplazisi(%8.9) olarak izlendi. Takiplerde %53.8 vakada bulgular›n gerile-di¤i, %19.3’ünde ilerledi¤i ve %26.9’unda de¤iflmeden kald›¤› iz-lendi.Sonuç: Ventrikülomegali tespit edildi¤inde etyoloji araflt›rmas›n-da ayr›nt›l› ultrasonografik muayene ile ek anomalilerin varl›¤›araflt›r›lmal›d›r. Selektif vakalarda ek serebral anomalileri de¤er-lendirmek için manyetik rezonans görüntüleme yönteminden fay-dalan›labilir. Karyotip analizi ve toksoplazma, rubella, sitomegalo-virüs ve Herpes virüs enfeksiyonlar›n›n araflt›r›lmas› ek anomalivarl›¤›nda ve hatta izole vakalarda ventrikülomegalinin derecesi neolursa olsun önerilmelidir. Hastalar düzenli takibe al›nmal›d›r.

Anahtar sözcükler: ‹zole ventrikülomegali, ek anomaliler, takip.

Correspondence: Hakan Kalayc›, MD. Baflkent Üniversitesi T›p Fakültesi Kad›nHastal›klar› ve Do¤um Anabilim Dal›, Ankara, Turkey. e-mail: [email protected] Received: April 15, 2014; Accepted: September 7, 2014Please cite this article as: Kalayc› H, Özdemir H, Gülümser Ç, Parlakgümüfl A, Çok T,Tar›m E, Bilgin Yan›k F. Ultrasonographic evaluation of ventriculomegaly cases.Perinatal Journal 2015;23(1):1–5.©2015 Perinatal Medicine Foundation

Available online at:www.perinataljournal.com/20150231001

doi:10.2399/prn.15.0231001QR (Quick Response) Code:

Original Article

Perinatal Journal 2015;23(1):1–5

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Abstract

Objective: To evaluate retrospectively the demographic data of thepatients diagnosed in or referred with the pre-diagnosis of ventricu-lomegaly to Perinatology Department of Adana and AnkaraHospitals of Baflkent University. Methods: In this study, 61 pregnant women with fetal ventricu-lomegaly diagnosed in our clinic or referred by other centers to thePerinatology Department of Ankara and Adana Hospitals ofBaflkent University between May 2008 and March 2013 were eval-uated in terms of their demographic data, diagnosis weeks, con-comitant anomalies and the course of their pregnancies. SPSS v.16.0 was used for statistical calculations. Results: The analysis of 61 pregnant women between 20 and 41years old showed that it was the first pregnancy of 45.9% of them.Only 16.4% of them were at or over 35 years old. It was observed that4.9% of them were conceived by assisted reproduction techniques.The rates of mild (10–12 mm), moderate (12.1–14.9 mm) and severeventriculomegaly (≥15 mm) were 65.6%, 24.7% and 4.8%, respec-tively. Toxoplasma, Cytomegalovirus, Rubella or Herpes virus infec-tions were not found in any case. Down syndrome was found in thekaryotype analysis of 3 patients (4.9%). The ventriculomegaly wasunilateral in 67.2% of the cases. The detection rate between 16 and24 weeks which were also the weeks for detailed ultrasonography was52.5%. There was an additional anomaly in 33.3% of the cases. Themost frequent concomitant anomalies were found as increased nuchalthickness (13.3%), corpus callosum agenesis (11.1%) and nasal bonehypoplasia (8.9%). In their follow-ups, it was observed that the find-ings were regressed in 53.8% of the cases, progressed in 19.3% of thecases and remained unchanged in 26.9%. Conclusion: When ventriculomegaly is detected, the presence ofadditional anomalies should be investigated by detailed ultrasono-graphic examination during etiological investigation. In the selectivecases, the physicians may utilize the method of magnetic resonanceimaging to evaluate additional cerebral anomalies. It is also necessaryto recommend karyotype analysis and investigating Toxoplasma,Rubella, Cytomegalovirus and Herpes virus infections in the pres-ence of additional anomaly and even in isolated cases regardless of thelevel of ventriculomegaly. Patients should be followed up regularly.

Keywords: Isolated ventriculomegaly, additional anomalies, follow-up.

IntroductionThe term ventriculomegaly (VM) is used for the caseswhere anterior horns of ventricle, cavum septum pellu-cidum and choroid plexus can be seen in the axial planeand lateral ventricle measurement on the plane is 10mm and above at the glomus level of choroid plexus(Fig. 1).[1,2] There are various definitions according tothe width of lateral ventricle. When lateral ventriclemeasurements are 10–12 mm and 12.1–15 mm, thedefinitions of mild and moderate VM are used.[3,4]

However, some authors deny 10-12 mm as mild VMand define mild VM as 10-15 mm.[5] In measurementswhich are 15 mm and above, severe VM term is used.[6]

While mild VM prevalence is 7.9 out of 10,000 livebirths, severe VM prevalence is reported as 3.6 out of10,000 live births.[7]

Many factors are assumed in the etiology such asinfections; cerebral atrophy induced by white matterinjury and/or cases causing absorption of cerebrospinalfluid to decrease; obstructive causes such as Dandy-Walker malformation or aqueductal stenosis; develop-mental anomalies such as encephalocele, corpus callo-sum agenesis (Figs. 2a and 2b); genetic disorders suchas trisomy 13, 18 and 21; and cases such as choroidplexus papilloma which may cause excessive cere-brospinal fluid production.[8] This expansion in ventri-cles may be accompanied by anomalies such as hydro-cephaly, gray matter migration anomalies, corpus cal-losum agenesis, trisomies and microcephaly.[5] Theincidence of associated cerebral or extracerebral anom-alies varies between 41% and 78%.[2] Many authors

believe that the presence of additional malformations isdirectly associated with the prognosis. Prognosis isobserved better in most of the isolated VM cases.[2,9]

Therefore, prenatal diagnosis becomes crucial.In this study, we aimed to analyze the demographic

data, diagnosis weeks, concomitant anomalies and thecourse of pregnancy retrospectively in patients diag-nosed with ventriculomegaly during intrauterine period.

MethodsIn this study, 61 pregnant women with fetal ventricu-lomegaly diagnosed in our clinic or referred by othercenters to the Perinatology Department of Ankara and

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Fig. 1. Moderate ventriculomegaly.

Fig. 2. (a) Corpus callosum agenesis (arrow). (b) Corpus callosum agenesis, colpocephaly, teardrop appearance (arrow).

a b



3

Adana Hospitals of Baflkent University between May2008 and March 2013 were evaluated in terms of theirdemographic data, diagnosis weeks, concomitantanomalies and the course of their pregnancies. Allfetuses were evaluated by detailed fetal biometricexamination. Statistical data were analyzed by SPSS v.16.0 (SPSS Inc., Chicago, IL, USA) software.

ResultsThe analysis of 61 pregnant women between 20 and 41years old showed that it was the first pregnancy of45.9% of them. Only 16.4% of them were at or over 35years old. It was observed that 4.9% of them were con-ceived by assisted reproduction techniques. The ratesof mild (10–12 mm), moderate (12.1–14.9 mm) andsevere ventriculomegaly (≥15 mm) were 65.6%, 24.7%and 4.8%, respectively. No Toxoplasma, Rubella,Cytomegalovirus (CMV) and Herpes virus infectionwas found in any of the pregnant women. Down syn-drome was found in the karyotype analysis of 3 fetuses(4.9%). The ventriculomegaly was unilateral in 67.2%of the cases. The detection rate between 16 and 24weeks which were also the weeks for detailed ultra-sonography was 52.5%. The most frequent concomi-tant anomalies were observed as increased nuchalthickness (13.3%), corpus callosum agenesis (11.1%),and nasal bone hypoplasia (8.9%). Additionally, obstet-ric magnetic resonance was applied to 44.3% of thepregnant women. Of pregnant women, 72.5% of themdelivered at 37 weeks or later. In their follow-ups, itwas observed that the findings were regressed in 53.8%of the cases, progressed in 19.3% of the cases andremained unchanged in 26.9%.

DiscussionIn the detailed ultrasonographic examination per-formed on 18–22 weeks of gestation, it is routinely rec-ommended to measure the width of lateral cerebralventricles.[1,10,11] In the lateral ventricle measurements,10–12 mm is defined as mild VM, 12.1–15 mm as mod-erate and 15 mm, and above as severe VM.[3,4]

Infections may also have a role in the etiology. Inthe study of Do¤an et al., severe VM was found in 5 of8 cases with CMV infection, increased periventricularechogenicity, intracranial calcification in 4 cases, thal-amic hyperechogenicity in 3 cases, and mega cisternamagna.[12] Tijana et al. found VM, which did not display

any finding on previous weeks, in patient with positivetoxoplasmosis at 25 weeks of gestation.[13] Dommergueset al. detected CMV positivity in 29% of the cases intheir study.[14] In various publications, infection positiv-ity was observed as 10–20% in severe VM cases whileit was 1–5% in mild VM cases.[9,15,16] Therefore, it is rec-ommended to evaluate all cases diagnosed with VM interms of infection.[6,15,17,18] In our study, no infection fac-tor was found; the reason is the rate of severe VM seenin our patients as low as 4.8%.

Chromosomal anomaly incidence varies in VMcases between 0% and 14%.[5,6,15] In our study, Downsyndrome was found in 4.9% (3) cases. WhileNicolaides et al. reported chromosomal anomaly inci-dence as 3% in isolated VM cases, they showed thisrate as 36% in the presence of additional anomaly.Also, aneuploidy was reported at a low rate in isolatedsevere VM cases compared to isolated mild VMcases.[19] Similarly, Melchiorre et al. reported the rate ofchromosomal anomaly in isolated cases as 2.8%.[20]

Gaglioti et al. did not find any chromosomal anomalyin severe VM cases while aneuploidy rate was 3.5% inmild and moderate VM cases.[16] Gezer et al. reportedchromosomal anomaly incidence (6.8%) in fetuses withsevere ventriculomegaly higher than the fetuses withmild ventriculomegaly (4.2%). Chromosomal anomalyincidence (8.6%) in fetuses with isolated ventricu-lomegaly was also found higher than those with addi-tional anomaly (3.8%).[21] Sezik observed Type 2triploidy case with VM accompanied by atrioventricu-lar septal defect.[22] Kara described the association ofVM and 47 XXY syndrome in a case report.[23]

In ventriculomegaly cases, it is possible to observeboth cerebral and extracerebral malformations as anadditional anomaly. They especially accompany withsevere VM. The most frequent concomitant anomaliesof severe VM cases are corpus callosum agenesis andbifid spine.[24,25] In mild and moderate VM cases, thisrate varies between 10% and 76%.[17,26] Various studiesreported additional anomaly incidence at rates reach-ing up to 50%.[6,11,15] Gaglioti et al. found additionalanomaly in 60% of severe VM cases. In 88% of thesecases, families preferred to terminate the pregnancy.[16]

Tatl› et al. found additional anomaly in 9% of caseswith 10-15 mm ventricle width.[27] In our study, themost frequent additional anomalies (33.3%) wereincreased nuchal thickness (13.3%), corpus callosumagenesis (11.1%) and nasal bone hypoplasia (8.9%).

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We observed in our study that the findings wereregressed in 53.8% of the cases, progressed in 19.3%of the cases and remained unchanged in 26.9%.Ouahba et al. reported regression in 11% of 167 mildVM cases, and they observed more regression in thesecases in terms of neurological development.[9]

Melchiorre et al. found a progression at a rate of15.7%. In those with progression, there was poorprognosis in terms of neurological development andassociation with chromosomal anomalies.[20]

During magnetic resonance imaging, Levine et al.found additional findings at a rate of 13.5% which maychange patient management in cases found to haveanomaly by ultrasonography.[28] Gezer et al. asserted thatventricle width and brain parenchyma volume rate maybe helpful to determine prognosis in magnetic reso-nance imaging. Parenchyma volumes of those with poorprognosis were found to be low.[29] We applied obstetricmagnetic resonance imaging to 44.3% of our cases. Weconfirmed the diagnosis of corpus callosum agenesis infour fetuses by ultrasonography, cortical atrophy in onecase, and encephalomalacia in one case. In line withthese findings, magnetic resonance imaging is signifi-cant to confirm the suspected diagnoses established byultrasonography. The use of magnetic resonance imag-ing is useful for pathologies such as neuronal migrationdisorders, delayed sulcation, gyrus formation and het-erotopias which can be detected at late second and thirdtrimesters and overlooked by ultrasonography.[30,31]

After the 11 years of follow-up of 101 children withisolated VM, normal psychomotor development wasobserved in 89 of them, and neurological disorder inthe spectrum reaching out from language delay up tothe severe mental retardation.[12]

Vergani et al. found neurological development retar-dation clearly lower in groups with 12 mm and lowerwidths than the group with 12 mm and above (3% vs.23%).[6] Devaseelan et al. reported neurological develop-ment retardation as 14% in children with progressedVM during intrauterine period.[32] In another study,scores below the normal levels were reported for finemotor skills and language development in children withpersisting ventricle width during prenatal period.[33]

ConclusionWhen ventriculomegaly is detected, the presence ofadditional anomalies should be investigated by detailed

ultrasonographic examination during etiological inves-tigation. In the selected cases, the physicians may uti-lize the method of magnetic resonance imaging toevaluate additional cerebral anomalies. In line with thecurrent information we have, we recommend perform-ing karyotype analysis and investigating Toxoplasma,CMV and infections such as Rubella regardless of thelevel of ventriculomegaly and even in the isolated ven-triculomegaly cases without any additional anomaly.Patients should be followed up regularly. The parentsshould be informed in detail for the neuropsychiatricconditions that may arise during postpartum period.

Conflicts of Interest: No conflicts declared.

References1. International Society of Ultrasound in Obstetrics and

Gynecology Education Committee. Sonograpic examinationof the fetal central nervous system: Guidelines for perform-ing the “basic examination” and the “fetal neurosonogram”.Ultrasound Obstet Gynecol 2007;29:109–16.

2. Cardoza JD, Goldstein RB, Filly RA. Exclusion of fetal ven-triculomegaly with a single measurement: the width of thelateral ventricle atrium. Radiology 1988;169:711–4.

3. Signorelli M, Tiberti A, Valseriati D, Molin E, Cerri V, GroliC, et al. Width of fetal lateral ventricular atrium between 10and 12 mm: a simple variation of the norm? UltrasoundObstet Gynecol 2004;23:14–18.

4. Wax JR, Bookman L, Cartin A, Pinette MG, Blackstone J.Mild fetal cerebral ventriculomegaly: diagnosis, clinical asso-ciations, and outcomes. Obstet Gynecol Surv 2003;58:407–14.

5. Bromley B, Frigoletto FD Jr, Benacerraf BR. Mild fetal lat-eral cerebral ventriculomegaly: clinical course and outcome.Am J Obstet Gynecol 1991;164:863–7.

6. Vergani P, Locatelli A, Strobelt N, Cavallone M, Ceruti P,Paterlini G, et al. Clinical outcome of mild fetal ventricu-lomegaly. Am J Obstet Gynecol 1998;178:218–22.

7. Sethna F, Tennant PWG, Rankin J, C Robson S.Prevalence, natural history, and clinical outcome of mild tomoderate ventriculomegaly. Obstet Gynecol 2011;117:867–76.

8. McKechnie L, Vasudevan C, Levene M. Neonatal outcomeof congenital ventriculomegaly. Semin Fetal Neonatal Med2012;17;301–7.

9. Ouahba J, Luton D, Vuillard E, Garel C, Gressens P, BlancN, et al. Prenatal isolated mild ventriculomegaly: outcome in167 cases. BJOG 2006;113:1072–9.

10. American College of Obstetricians and Gynecologists(ACOG). Ultrasonography in Pregnancy: ACOG TechnicalBulletin 187. Washington, DC: ACOG; 1993.

11. American Institute of Ultrasound in Medicine. AIUMPractice Guideline for the performance of an antepartumobstetric ultrasound examination. J Ultrasound Med 2003;22:1116–25.

12. Dogan Y, Yuksel A, Kalelioglu IH, Has R, Tatl› B, Yildirim A.Intracranial ultrasound abnormalities and fetal cytomegalovirus›nfection: report of 8 cases and review of the literature. FetalDiagn Ther 2011;30:141–9.

13. Zivkoviç T, Ivoviç V, Vujaniç M, Klun I, Bobiç B, Nikoliç A,et al. Adverse fetal outcome in the absence of timely prenataldiagnosis of congenital toxoplasmosis. Wien Klin Wochenschr2011;123;43–6.

14. Dommergues M, Mahieu-Caputo D, Fallet-Bianco C,Mirlesse V, Aubry MC, Delezoide AL, et al. Fetal seruminterferon-alpha suggests viral infection as the aetiology ofunexplained lateral cerebral ventriculomegaly. Prenat Diagn1996;16:883–92.

15. Pilu G, Falco P, Gabrielli S, Perolo A, Sandri F, Bovicelli L.The clinical significance of fetal isolated cerebral borderlineventriculomegaly: report of 31 cases and review of the liter-ature. Ultrasound Obstet Gynecol 1999;14:320–6.

16. Gaglioti P, Danelon D, Bontempo S, Mombrò M,Cardaropoli S, Todros T, et al. Fetal cerebral ventricu-lomegaly: outcome in 176 cases. Ultrasound Obstet Gynecol2005;25:372–7.

17. den Hollander NS, Vinkesteijn A, Schmitz-van Splunder P,Catsman-Berrevoets CE, Wladimiroff JW. Prenatally diag-nosed fetal ventriculomegaly: prognosis and outcome.Prenat Diagn 1998;18:557–66.

18. Pilu G, Hobbins JC. Sonography of fetal cerebrospinal anom-alies. Prenat Diagn 2002;22:321–30.

19. Nicolaides KH, Berry S, Snijders RJM, Thorpe-Beeston JG,Gosden C. Fetal lateral cerebral ventriculomegaly: associat-ed malformations and chromosomal defects. Fetal DiagnTher 1990;5:5–14.

20. Melchiorre K, Bhide A, Gika AD, Pilu G, PapageorghiouAT. Counseling in isolated mild fetal ventriculomegaly.Ultrasound Obstet Gynecol 2009;34:212–24.

21. Gezer C, Ekin A, Özeren M, Taner CE, Özer Ö, Koç A, etal. Fetal serebral ventikülomegalide kromozomal anomalis›kl›¤›. Perinatoloji Dergisi 2013;21 Suppl 1:S32.

22. Sezik M. Ventrikülomegali ve atriyoventriküler septal defekt:Tip 2 triploidi. Perinatoloji Dergisi 2013;21 Suppl 1:S39.

23. Kara M. Prenatal 47 XXY sendromu ve ventrikülomegalibirlikteli¤i: Vaka sunumu. Bozok T›p Dergisi 2012;1:53–6.

24. Breeze ACG, Alexander PMA, Murdoch EM, Missfelder-Lobos HH, Hackett GA, Lees CC. Obstetric and neonataloutcome in severe ventriculomegaly. Prenat Diagn 2007;27:124–9.

25. Morris JE, Rickard S, Paley MNJ, Griffiths PD, Rigby A,Whitby EH. The value of in-utero magnetic resonanceimaging in ultrasound diagnosed foetal isolated cerebral ven-ticulomegaly. Clin Radiol 2007;62:140–4.

26. Romero R, Pilu G, Jeanty P, Ghidini A, Hobbins JC. Thecentral nervous system. Prenatal Diagnosis of CongenitalAnomalies. East Norwalk, CT: Appleton & Lange; 1988. p.1–79.

27. Tatl› B, Özer I, Ekici B, Kalelio¤lu I, Has R, Eraslan E, et al.Neurodevelopmental outcome of 31 patients with borderlinefetal ventriculomegaly. Clinical Neurol Neurosurg 2012;114;969–71.

28. Levine D, Barnes PD, Robertson RR, Wong G, Mehta T.Fast MR imaging of fetal central nervous system abnormali-ties. Radiology 2003;229:51–61.

29. Gezer NS, Güleryüz H, Gezer C, Koçyi¤it A, Yeflil›rmakCD, Güçlü S, et al. Fetal manyetik rezonans görüntüleme ileyap›lan beyin hacim ölçümlerinin ventrikülomegali ileiliflkisi. Perinatoloji Dergisi 2013;21 Suppl 1:S35.

30. Benaceraf BR, Shipp TD, Bromley B, Levine D. What doesmagnetic resonance imaging add to the prenatal sonograph-ic diagnosis of ventriculomegaly? J Ultrasound Med 2007;26:1513–22.

31. Manganaro L, Savelli S, Francioso A, Di Maurizio M,Coratella F, Vilella G, et al. Role of fetal MRI in the diagno-sis of cerebral ventriculomegaly assessed by ultrasonography.Radiol Med 2009;114:1013–23.

32. Devaseelan P, Cardwell C, Bell B, Ong S. Prognosis of iso-lated mild to moderate fetal cerebral ventriculomegaly: a sys-tematic review. J Perinat Med 2010;38:401–9.

33. Lyall AE, Woolson S, Wolfe HM, Goldman BD, ReznickJS, Hamer RM, et al. Prenatal isolated mild ventricu-lomegaly is associated with persistent ventricle enlargementat ages 1 and 2. Early Hum Dev 2012;88;691–8.



5

Perinatal outcomes of patients diagnosed borderlinegestational diabetes mellitus

Gök Özgül1, Rauf Meleko¤lu2, Sevda Yeleç1, ‹pek Eskiyörük1, Fatma Tuncay Özgünen1

1Department of Gynecology & Obstetrics, Faculty of Medicine, Çukurova University, Adana, Turkey2Department of Gynecology & Obstetrics, Faculty of Medicine, Inönü University, Malatya, Turkey

Özet: Borderline gestasyonel diabetes mellitus saptanan gebelerin perinatal sonuçlar›Amaç: Çal›flman›n amac› gestasyonel diyabetin fetal ve maternalsa¤l›¤a etkileri oldukça iyi bilinmesine ra¤men, gestasyonel diya-bet kriterlerini karfl›lamayan gebelik hiperglisemisine sahip bor-derline gestasyonel diyabeti olan gebelerin maternal ve fetal duru-munu ortaya koyan az say›da çal›flma olmas›n› göz önünde bulun-durarak, hastanemizdeki borderline gestasyonel diyabeti olan has-talar›n perinatal ve neonatal sonuçlar›n› irdelemektir. Yöntem: Bu çal›flmada Ocak 2009 ve Ocak 2013 tarihleri aras›ndaÇukurova Üniversitesi T›p Fakültesi Kad›n Hastal›klar› ve Do-¤um Anabilim Dal› Gebe Poliklini¤inde antenatal izlemleri yap›-lan ve do¤umlar› klini¤imizde gerçekleflen gebeler aras›ndan 50 gOGTT sonuçlar› yüksek ancak 100 g OGTT sonuçlar› normalolan hastalar ile 50 g OGTT sonuçlar› normal olan hastalar tespitedilerek, maternal özellikleri, obstetrik ve perinatal sonuçlar› ret-rospektif olarak incelendi. Verilerin analizi için SPSS v 19.0 paketprogram› kullan›ld›. Sonuçlar aras›nda istatistiksel anlaml›l›k düze-yi için p de¤eri <0.05 olarak al›nd›. Bulgular: Çal›flmaya toplamda 239 gebe dahil edildi. 50 g OGTTsonuçlar› yüksek ancak 100 g OGTT sonuçlar› normal s›n›rlardaolan 105 gebe çal›flma grubunu, 50 g OGTT sonuçlar› normalolan 134 gebe ise kontrol grubunu oluflturdu. Çal›flma grubunda-ki gebelerin yafl ortalamalar›n›n sa¤l›kl› gebelere oranla istatistik-sel olarak anlaml› derecede yüksek oldu¤u saptand› (p=0.000). Ça-l›flma grubundaki gebelerin hastanede yat›fl sürelerinin kontrolgrubundakilere oranla istatistiksel olarak anlaml› oranda daha faz-la oldu¤u saptand› (p=0.001). Her iki grubun do¤um flekli, erkendo¤um, erken membran rüptürü, gestasyonel hipertansiyon, pre-eklampsi varl›¤›, fetal distres varl›¤› ve postpartum kanama aç›s›n-dan obstetrik sonuçlar› incelendi. Sadece postpartum kanaman›nkontrol grubuna göre çal›flma grubunda istatistiksel olarak anlam-l› derecede fazla oldu¤u saptand› (p=0.049). Yenido¤an bebeklerdeLGA, SGA, hipoglisemi, hiperbilirubinemi, yenido¤an yo¤un ba-k›m ünitesine yat›fl ve neonatal ölüm görülme oranlar› aras›nda daher iki grup aras›nda istatistiksel olarak anlaml› fark saptanmad›. Sonuç: Çal›flmam›zda borderline gestasyonel diyabeti olan hasta-lar›n postpartum kanama s›kl›¤› ve hastanede yat›fl süreleri d›fl›ndaperinatal ve neonatal sonuçlar› normoglisemik gebeler ile benzersaptanm›flt›r.

Anahtar sözcükler: Gestasyonel diyabet, glukoz tolerans testi,gebelik sonuçlar›.

Correspondence: Rauf Meleko¤lu, MD. ‹nönü Üniversitesi T›p Fakültesi Kad›nHastal›klar› ve Do¤um Anabilim Dal›, Malatya, Turkey. e-mail: [email protected] Received: November 17, 2014; Accepted: November 30, 2014Please cite this article as: Özgül G, Meleko¤lu R, Yeleç S, Eskiyörük ‹, Tuncay Özgünen F. Perinatal outcomes of patients diagnosed borderline gestational diabetes mellitus. Perinatal Journal 2015;23(1):6–12.©2015 Perinatal Medicine Foundation



Original Article


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Abstract

Objective: Although the effects of gestational diabetes mellitus tomaternal and fetal health are well known, we have few data aboutmaternal and fetal condition of borderline gestational diabetic preg-nants who have gestational hyperglycemia not meeting gestationaldiabetes criteria. Considering this, we aimed to investigate perinataland neonatal outcomes of patients who have borderline gestationaldiabetes mellitus in our hospital. Methods: In this study, we retrospectively examined maternal char-acteristics, obstetric and perinatal outcomes of pregnants whoseantenatal follow-up and birth occurred in Department of Obstetricsand Gynecology in Faculty of Medicine in Çukurova Universitybetween January 2009 and January 2013 and who have normal 50-g oral glucose tolerance test (OGTT) but abnormal 100-g OGTTand have normal 50-g OGCT test results. SPSS v. 19.0 statisticssoftware was used for data analysis. For the statistical significancelevel between results, p value was taken as <0.05. Results: A total of 239 pregnant women were included in the study.The study group consisted of 105 pregnant women whose 50-gOGTT results were abnormal but 100-g OGTT results were withinnormal limits and the control group consisted of 134 pregnantwomen whose 50-g OGTT results were within normal limits.Compared to healthy pregnant women, mean age of the women inthe study group was found to be significantly higher (p=0.000). Theduration of hospitalization in the study group was found to be statis-tically significantly higher compared to the control group (p=0.001).Mode of delivery, preterm labor, premature rupture of membranes,gestational hypertension, preeclampsia, the presence of fetal distressand postpartum hemorrhage were analyzed in both groups. Onlypostpartum hemorrhage was found to be statistically significantlyhigher in the study group compared to the control group (p=0.049).There was statistically no significant difference in neonates betweentwo groups for LGA, SGA, hypoglycemia, hyperbilirubinemia,neonatal admissions to the intensive care unit and neonatal death. Conclusion: In our study, perinatal and neonatal outcomes ofpatients who have borderline gestational diabetes mellitus and nor-moglisemic condition are same except postpartum hemorrhage andhospitalization period. To acquire perinatal and neonatal outcomesof women with borderline gestational diabetes mellitus, we need fur-ther well-designed randomized studies with larger populations.

Keywords: Gestational diabetes, glucose tolerance test, pregnancyoutcomes.


Perinatal outcomes of patients diagnosed borderline gestational diabetes

7

IntroductionGestational diabetes mellitus (GDM) is defined as the“carbohydrate intolerance occurring or found for thefirst time during pregnancy”.[1] Pregnancy is character-ized by insulin resistance and hyperinsulinemia. Thismay be predisposing for pregnant women to developdiabetes. This resistance is caused by the influence ofsome diabetogenic placental secretion hormones(growth hormone, corticotropin releasing hormone, pla-cental lactogenic hormone, progesterone etc).Decreased exercise, increased caloric intake andincreased adiposis tissue amount are also among the rea-sons of insulin resistance. Gestational diabetes is seen inwomen who have insufficient pancreatic functions anddo not have insulin release sufficient enough to toleratediabetogenic hormone change.[2]

It is recommended to all pregnant women to have50-g oral glucose tolerance test (OGTT) for gestationaldiabetic screening between 24 and 28 weeks of gesta-tion.[3] If the result is above 140 mg/dl, patient is referredto 100-g OGTT. For GDM diagnosis, at least twothreshold values of 100-g OGTT should be met orexceeded. However, there is also a major patient groupwho has positive result for 50-g OGTT but normalresult for 100-g OGTT. Although the effects of gesta-tional diabetes mellitus to maternal and fetal health arewell known, maternal and fetal conditions of borderlinegestational diabetic women who are between normalglucose values and gestational diabetic levels. Somestudies in the literature point out that the pregnantwomen with normal 100-g OGTT results despite high50-g OGTT results may have different maternal char-acteristics compared to normal pregnant women andmay have more risks in terms of adverse obstetric out-comes.[4] This group is called as “borderline GDM”.

In our study, we aimed to analyze retrospectively thepregnant women with normal 100-g OGTT resultsdespite high 50-g OGTT results and the pregnantwomen with normal 50-g OGTT results among the caseswho were followed up and delivered at the Departmentof Gynecology & Obstetrics, Faculty of Medicine,Çukurova University between January 2009 and January2013, and to investigate and compare their maternalcharacteristics and obstetric and perinatal outcomes.

MethodsThis study includes 239 pregnant women who hadtheir antenatal follow-ups and deliveries at the

Department of Gynecology & Obstetrics, Faculty ofMedicine, Çukurova University between January 2009and January 2013 in accordance with the follow-up anddelivery protocols prepared in compliance with thePrenatal Care Management Guide and Delivery andCesarean Labor Management Guide of the HealthMinistry, and their babies.

The approval of the Ethics Committee of Facultyof Medicine, Çukurova University was obtained beforethe study. Also, in compliance with the HelsinkiDeclaration Principles, all women included in thestudy were informed in written and verbally about thestudy and their informed consents were received.

The study group consisted of 105 pregnant womenwho were at 24-28 weeks of gestation, undergone GDMscreening and had normal results for 100-g OGTTdespite the high results for 50-g OGTT (those havingall values below the threshold value of 100-g OGTTand those with single high value), and the control groupconsisted of 134 pregnant women who delivered at thesame period and had normal results for 50-g glucosescreening test performed at 24-28 weeks of gestation.

Pregnant women below 18-year-old and above 35-year-old, multipara pregnant women, those with mul-tiple pregnancies, presence of major fetal anomaly infetus and of maternal chronic diseases (such as chronichypertension, diabetes mellitus, chronic renal failureasthma, pulmonary or cardiac diseases etc.), patientswith maternal thrombophilia history and pregnantwomen who undergone labor induction were excludedfrom the study.

In our clinic, we perform 50-g OGTT to pregnantwomen, who admit to follow-up clinics between 24 and28 weeks of gestation, by orally administering 50 g glu-cose dissolved in 200 ml water. One hour after patientreceives glucose solution, venous blood sample is col-lected from patient and plasma glucose levels are meas-ured spectrophotometrically via oxidase method byusing Roche diagnostic kits on Roche/Hitachi (RocheDiagnostics Corp., Indianapolis, IN, USA) device inbiochemistry laboratory.

Those with blood glucose levels:• Below 140 mg/dl are considered as normal• Above 200 mg/dL are considered as directly GDM• For those with a value between >140 mg and <200

mg, OGTT is carried out with 100 g glucose after8-14 of fasting. During this test, venous blood sam-

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Özgül G et al.

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ple is collected from patient for fasting blood glu-cose first and after 100 g glucose dissolved in 200ml is administered to patient, venous blood samplesare collected first, second, and third hours, and thesamples are analyzed in biochemistry laboratory.GDM diagnosis is established when at least twothreshold values used by National Diabetes DataGroup are met or exceeded (fasting: 105, first hour:190, second hour: 165, third hour: 145).The patients who were included in the study were

retrospectively recorded and compared in terms ofdemographical data such as age, weight, body massindex, smoking habit, gestational age, blood pressuredata during the referral for delivery; perinatal data suchas preterm labor as a perinatal outcome (delivery before37+0 weeks of gestation), pregnancy induced hyperten-sion (hypertension developed without proteinuria after20 weeks of gestation), presence of preeclampsia (hyper-tension developed with proteinuria after 20 weeks ofgestation), delivery type (vaginal delivery/cesarean),presence of cesarean, shoulder dystocia and postpartumhemorrhage due to fetal distress (≥500 ml blood lossthrough genital tract after delivery), hospitalization peri-od; and neonatal data such as APGAR score, head cir-cumference, gender, LGA rates according to gestationalage [birth weight being ≥90 p according to gestationalage], SGA rates according to gestational age [birthweight being ≤10 p according to gestational age], neona-tal hypoglycemia (blood glucose below 40 mg/dl regard-less of birth weight and gestational week), nenonatalhyperbilirubinemia (blood bilirubin levels being atpathological levels according to gestational age, weightand gender), newborn intense care need and neonatalmortality rates of babies born in both groups.

SPSS ver. 19.0 software was used for the statisticalanalysis of the data. Categorical measurements weresummarized as figures and percentages while constantmeasurements were indicated as mean and standarddeviation. The distributions were checked in the com-parison of constant measurements among groups; t-testfor two independent samples was used for variables dis-playing parametric distribution while Mann-Whitney Utest was used for variables not displaying parametric dis-tribution. Either chi-square test or Fisher’s test statisticswas used for the comparison of categorical variablessuch as smoking habit and gender. In all tests, p<0.05was considered statistically significant.

ResultsA total of 239 pregnant women were included in thestudy. While mean age of the pregnant women in thestudy group was 31.5±5.1, it was 28.9±4.4 in the con-trol group (p=0.000). It was found that the mean age ofpregnant women in the study group was statisticallyand significantly higher than the mean age of healthypregnant women. There was statistically no significantdifference between the groups in terms of gravida, par-ity, gestational week, weight, blood pressure, presenceof poor obstetric history and smoking habit.

When the groups were evaluated in terms of post-natal hospitalization period, it was seen that hospital-ization period of the pregnant women in the studygroup was 1.7±0.6 days while it was 1.5±0.5 days in thecontrol group (p=0.001). The hospitalization period ofthe pregnant women in the study group was statistical-ly and significantly higher than those in the controlgroup.

The distribution of the patients in study and con-trol groups by demographic characteristics is shown inthe Table 1.

While 54.3% of the pregnant women in the studygroup had delivered by cesarean, 45.7% of them deliv-ered vaginally. While cesarean rate in the control groupwas 44%, the rate of vaginal delivery was 56%. Therewas statistically no significant difference between thegroups in terms of delivery types (p=0.116). Pretermlabor, premature rupture of membranes, gestationalhypertension, presence of preeclampsia and fetal dis-tress, and obstetric outcomes in terms of postpartum

Table 1. Distribution of demographic characteristics according to thegroups.

Study group Control group p(Mean±SD) (Mean±SD)

Age 31.5±5.1 28.9±4.4 0.000

Weight 79.6±11.5 77.6±10.9 0.180

Gravida 2.7±1.2 2.7±1.4 0.913

Parity 1.3±0.6 1.2±0.8 0.534

Systolic blood pressure 114.3±13.6 112.1±12.2 0.188

Diastolic blood pressure 71.9±9.5 70.2±9.6 0.181

Week of gestation 38.4±1.7 38.3±1.5 0.556

Hospitalization 1.7±0.6 1.5±0.5 0.003

n (%) n (%) p

Smoking habit 4 (3.8) 1 (0.7) 0.101

Poor obstetric history 4 (3.8) 10 (7.5) 0.234



9

hemorrhage were evaluated. It was found that only post-partum bleeding was statistically and significantly high-er in the study group compared to the control group(p=0.049). The distribution of obstetric outcomes inboth groups is shown in the Table 2.

Newborn follow-up forms of 234 pregnant womenincluded in the study were analyzed and neonatal datawere collected. The newborns in both groups werecompared in terms of birth weights, head circumfer-ence measurements and gender distributions, and sta-tistically no significant difference was found (p=0.188,p=0.670, p=0.958, respectively).

While the 1-minute APGAR score of 14.2% of thenewborns in the study group was below 7, it was 12.6%in the control group. The percentage of those with 5-minute APGAR score below 7 was 2% in the studygroup while it was 2.9% in the control group. No sta-tistically significant difference was found between twogroups in terms of APGAR scores (p=0.815, p=0.599,respectively).

No statistically significant difference was seenbetween the newborns of two groups in terms of LGA,SGA, hypoglycemia, hyperbilirubinemia, hospitaliza-tion at newborn intense care unit and neonatal mortal-ity rates. The distribution of neonatal outcomes inboth groups is shown in the Table 3.

DiscussionGDM prevalence increases in the world and it affects1-14% of the pregnancies. Estimated GDM prevalenceis 1.4-2.8% in a low-risk population, 3.3-6.1% in ariskier population, and it may be more than 10% inhigh-risk population.[5]

There are less data about the gestational hyper-glycemia prevalence not meeting the criteria of gesta-tional diabetes mellitus. The data received from theAustralian studies showed that 7% of all pregnantwomen have hyperglycemia not meeting GDM criteriawhile 5.5-8.8% of them already have GDM everyyear.[6,7] There is no sufficient study in terms of bloodglucose follow-ups of this group, how to follow upthem and perinatal outcomes. Stamilio et al. confirmsthat the positivity of 50-g OGTT is an independentrisk factor in terms of perinatal complications and indi-cates that these cases may more frequently benefit fromfetal monitorization, nutritional consultation or dia-betic diet.[8]

According to the results of few studies, many obste-tricians define cases, who have positive results for 50-gOGTT but normal results for 100-g OGTT, as glu-cose intolerant or borderline gestational diabetics andrecommend more frequent follow-up.[9] Yee et al.reported advanced maternal age, multiparity and beingof Asian or Latin American ethnicity as the risk factorsfor having abnormal results of glucose tolerance test inthe absence of GDM.[10] In our study, we compared thecases in the study group who had high results in 50-gOGTT but normal results in 100-g OGTT with thecases in the control group and found that the age was

Table 2. Distribution of the obstetric outcomes according to thegroups.

Study group Control group pn (%) n (%)

Preterm labor 4 (3.8) 9 (6.7) 0.327

Premature rupture of membranes 13 (12.4) 8 (6) 0.083

Gestational HT 5 (4.8) 4 (3) 0.476

Preeclampsia 2 (1.9) 5 (3.7) 0.408

Fetal distress 4 (3.8) 2 (1.5) 0.258

Postpartum hemorrhage 3 (2.9) 0 (0) 0.049

Delivery type

Cesarean 57 (54.3) 59 (44) 0.116

Normal delivery 48 (45.7) 75 (56) 0.116

Table 3. Distribution of the neonatal outcomes according to thegroups .

Study group Control group p(Mean±SD) (Mean±SD)

Birth weight of neonatal 3224.7±446.0 3142.7±498.7 0.188

Head circumference of neonatal 34.4±1.5 34.3±1.9 0.670

n (%) n (%) p

1-minute APGAR score <7 15 (14.2) 17 (12.6) 0.815

5-minute APGAR score >7 3 (2) 4 (2.9) 0.599

Gender

Male 56 (53.3) 71 (53) 0.958

Female 49 (46.7) 63 (47) 0.958

SGA 2 (1.9) 7 (5.2) 0.182

LGA 2 (1.9) 5 (3.7) 0.408

Neonatal hypoglycemia 3 (2.9) 1 (0.7) 0.208

Hyperbilirubinemia 2 (1.9) 1 (0.7) 0.427

Hospitalization at newborn 9 (8.6) 16 (11.9) 0.400intense care unit

Neonatal death 1 (1) 1 (0.7) 0.259

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statistically and significantly high in the study groupcompared to the control group.[9,11–13]

Gestational hyperglycemia not meeting the criteriaof gestational diabetes mellitus is associated with a seriesof known health risks. It is known that the insulin resist-ance which is characteristics for the occurrence of GDMis also associated with the development of preeclamp-sia.[14] In their multi-central multi-ethnical cohort study(HAPO study), Metzger et al. evaluated 25,505 womenin terms of effects of maternal hyperglycemia on gesta-tional outcomes and reported that there was a linearassociation between preeclampsia prevalence and theresults of glucose tolerance test.[6] In our study, we foundstatistically no significant difference between the studygroup and the control group in terms of the gestationalhypertension and preeclampsia incidence.

Preterm labor is defined as the deliveries occurringbefore 37 weeks of gestation are completed. GDM andespecially pregestational DM are known risk factors forpreterm labor. Beigelman et al. found preterm laborrate as 10% in the study conducted on 3841 pregnantwomen with GDM.[15] In our study, although pretermlabor rate was found at a lower rate in the study groupthan the control group, there was no statistically signif-icant difference between the groups.

Maternal diabetes is a risk factor for cesarean deliv-ery. Cesarean delivery rate varies from 25% up to 80%in diabetic women. Many factors such as diabetic com-plications including prematurity, macrosomia andnephropathy are associated with high cesarean rates.[16] Intheir studies, Stamilio et al. observed statistically highercesarean rate in cases with high results for 5 g glucosetolerance test but normal results for 100-g OGTT com-pared to the cases with normal results for 50-g OGTT.[8]

Dudhbhai et al. found no significant difference betweenborderline diabetic pregnant women and the controlgroup in terms of the cesarean rates.[13] Hong et al. inves-tigated demographical characteristics and obstetric andneonatal outcomes of patients with borderline gestation-al diabetes, and found that the cesarean rate due to fetaldistress was higher in this group than the normo-glycemic pregnant women.[17] In our study, although wefound cesarean rates higher in the study group, there wasno statistically significant difference between twogroups. We also did not see any statistically significantdifference between two groups in terms of the cesareandelivery carried out due to fetal distress.

The conditions such as episiotomy extension dur-ing vaginal delivery, vaginal laceration and postpartum

atonia are observed more frequently in those whodeliver large baby. Jastrow et al. reported that the risksfor cephalopelvic disproportion, uterine rupture,shoulder dystocia, perineal laceration and postpartumhemorrhage due to LGA or macrosomic baby risk arehigher in mothers with maternal hyperglycemia.[18] Inour study, the postpartum hemorrhage rate was statis-tically and significantly higher in the study group thanthe control group. We found that the most frequentreasons for postpartum hemorrhage seen in the studygroup were uterine atony followed by delivery tractlacerations and rest placenta induced hemorrhage.

When we compared the groups in terms of mater-nal hospitalization periods, we found that the mothersin the study group had statistically and significantlylonger hospitalization periods than the mothers in thecontrol group. In their study, Hong et al. reported sta-tistically no significant difference between controlgroup and the study group with patients having bor-derline DM.[17] Long hospitalization periods of thepatients in our study group may be due to the highcesarean rates and postpartum hemorrhage rates.

Figueroa et al. indicated in their studies that LGAand macrosomia rates of the patients with borderlinegestational diabetes increased 2 and 1.6 times, respec-tively.[19] In the study of Bonomo et al., the authors sug-gested that even the slight changes in glucose intoler-ance may cause overgrowth in babies.[20] From 20% upto 40% of diabetic mothers are over 90th percentile inbirth weight according to the gestation. In our study,we found statistically no significant difference betweenthe groups despite the high rates of birth weight in thestudy group compared to the control group.

Birth traumas, increased preterm labor rates,obstetric conditions such as preeclampsia, and variousmetabolic disorders depending on the maternal dia-betes cause low APGAR scores and high level ofintense care needs in babies of diabetic mothers.[21]

Although Hong et al. found statistically no significantdifference between 1-minute and 5-minute APGARscores in patients with high results for 50-g OGTT butnormal results for 100-g OGTT, they reported statis-tically and significantly higher rates for newbornintense care and hospitalization periods in newborns inthis group.[17] We, on the other hand, found statistical-ly no significant difference between the groups interms of 1-minute and 5-minute APGAR scores, new-borns’ intense care needs and neonatal mortality rates.



11

Dodd et al. carried out a study by using the data of16,975 women who delivered in tertiary healthcareorganizations in Australia between 1993 and 2003, andthey found that the patients with borderline GDM hadrisks for preeclampsia and cesarean and when com-pared to the babies of mothers with normal results forglucose tolerance test, they indicated that the babies ofthese patients had increased risks for hypoglycemia andhyperbilirubinemia.[7] We did not observe statisticallyany significant difference between two groups in termsof neonatal hypoglycemia, hyperbilirubinemia, andSGA and LGA baby rates. We believe that the reasonis low numbers of patients in the study and controlgroup, and non-availability of detailed neonatal infor-mation in the patient files analyzed retrospectively.

ConclusionGestational hyperglycemia not meeting the criteria ofgestational diabetes mellitus affects a great number ofpregnant women. Hyperglycemia seen during pregnan-cy is associated with a series of negative gestational out-comes including preeclampsia, delivery trauma and typeII DM development in mother, and future obesity, typeI and type II DM development in baby. While we do nothave certain threshold values to be categorized for estab-lishing GDM diagnosis, the values for upper limit to ini-tiate the treatment in order to keep blood glucose with-in normal limits in case of gestational hyperglycemia arealso unclear. In our study, except postpartum hemor-rhage rate and hospitalization periods of the patientswith gestational diabetes, the perinatal and neonatal out-comes were similar with the outcomes of normo-glycemic pregnant women. While there are researchersrecommending to refer patients with gestational hyper-glycemia not meeting GDM and type II DM diagnosiscriteria to dieticians and to carry out blood glucose mon-itorization and follow-ups more frequently, there arealso researchers who assert that such approaches wouldincrease labor induction and cesarean rates, would raisehealthcare costs due to frequent examinations and inves-tigations but not create any significant difference inmaternal and neonatal outcomes. Our knowledge onthis issue is based on limited number of randomizedstudies. In order to make precise recommendations forthe management of such patients, we need further well-designed randomized studies with larger population.


References1. Committee opinion no. 504: Screening and diagnosis of ges-

tational diabetes mellitus. Obstet Gynecol 2011;118:751–3.2. Gabbe SG, Niebyl JR, Galan HL, Jauniaux ERM, Landon

MB, Simpson JL, Driscoll DA. Diabetes MellitusComplicating Pregnancy. Obstetrics: Normal and ProblemPregnancies. 6th ed. Philadelphia: Saunders; 2012. p: 902–4.

3. Practice Bulletin No. 137. Gestational diabetes mellitus.Obstet Gynecol 2013;122(2 Pt 1):406–16.

4. Han S, Crowther CA, Middleton P. Interventions for preg-nant women with hyperglycaemia not meeting gestationaldiabetes and type 2 diabetes diagnostic criteria. CochraneDatabase Syst Rev 2012;1:CD009037.

5. Mulla WR, Henry TQ, Homko CJ. Gestational diabetesscreening after HAPO: has anything changed? Curr DiabRep 2010;10:224–8.

6. Metzger BE, Lowe LP, Dyer AR, Trimble ER, ChaovarindrU, Coustan DR. Hyperglycemia and adverse pregnancy out-comes. N Engl J Med 2008;358:1991–2002.

7. Dodd JM, Crowther CA, Antoniou G, Baghurst P, RobinsonJS. Screening for gestational diabetes: the effect of varyingblood glucose definitions in the prediction of adverse mater-nal and infant health outcomes. Aust N Z J Obstet Gynaecol2007;47:307–12.

8. Stamilio DM, Olsen T, Ratcliffe S, Sehdev HM, MaconesGA. False-positive 1-hour glucose challenge test and adverseperinatal outcomes. Obstet Gynecol 2004;103:148–56.

9. Edelman D, Olsen MK. Diagnosis and classification of dia-betes mellitus. Diabetes Care 2010;33(Suppl 1):S62–S9.

10. Yee LM, Cheng YW, Liddell J, Block-Kurbisch IB,Caughey AB. 50-Gram glucose challenge test: is it indicativeof outcomes in women without gestational diabetes mellitus?J Matern Fetal Neonatal Med 2011;24:1102–6.

11. Gumus II, Turhan NO. Are patients with positive screeningbut negative diagnostic test for gestational diabetes underrisk for adverse pregnancy outcome? J Obstet Gynaecol Res2008;34:359–63.

12. Gezer A, Esen F, Mutlu H, Oztürk E, Ocak V. Prognosis ofpatients with positive screening but negative diagnostic testfor gestational diabetes. Arch Gynecol Obstet 2002;266:201–4.

13. Dudhbhai M, Lim L, Bombard A, Jullard K, Meenakshi B,Trachelenberg Y, et al. Characteristics of patients withabnormal glucose challenge test and normal oral glucose tol-erance test results: comparison with normal and gestationaldiabetic patients. Am J Obstet Gynecol 2006;194:e42–5.

14. Wolf M, Sandler L, Munoz K, Hsu K, Ecker JL, ThadhaniR. First trimester insulin resistance and subsequentpreeclampsia: a prospective study. J Clin Endocrinol Metab2002;87:1563–8.

15. Beigelman A, Wiznitzer A, Shoham-Vardi I, Vardi H,Holtcberg G, Mazor M. Premature delivery in diabetes: eti-ology and risk factors. Harefuah 2000;138:919–23.

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16. James DK, Steer P, Weiner C, Gonik B, Crowther C,Robson S, et al. Pregnancy and laboratory studies: a refer-ence table of clinicians. Obstet Gynecol 2010;115:868.

17. Ju H, Rumbold AR, Willson KJ, Crowther CA. Borderlinegestational diabetes mellitus and pregnancy outcomes. BMCPregnancy Childbirth 2008;8:31.

18. Jastrow N, Roberge S, Gauthier RJ, Laroche L, Duperron L,Brassard N, et al. Effect of birth weight on adverse obstetricoutcomes in vaginal birth after cesarean delivery. ObstetGynecol 2010;115(2 Pt 1):338–43.

19. Figueroa D, London MB, Mele L, Spong CY, Ramin SM,Casey B, et al. Relationship between 1-hour glucose chal-

lenge test results and perinatal outcomes. Obstet Gynecol2013;121:1241–7.

20. Bonomo M, Cetin I, Pisoni MP, Faden D, Mion E, TariccoE, et al. Flexible treatment of gestational diabetes modulat-ed on ultrasound evaluation of intrauterine growth: a con-trolled randomized clinical trial. Diabetes Metab2004;30:237–44.

21. Dabelea D, Snell-Bergeon JK, Hartsfield CL, Bischoff KJ,Hamman RF, McDuffie RS; Kaiser Permanente of ColoradoGDM Screening Program. Increasing prevalence of gesta-tional diabetes mellitus (GDM) over time and by birthcohort: Kaiser Permanente of Colorado GDM ScreeningProgram. Diabetes Care 2005;28:579–84.

Health practices of pregnant women inGumushane City Center

Handan Özcan1, Nezihe K›z›lkaya Beji2

1Vocational Health High School, Gumushane University, Gumushane, Turkey2Department of Women Health and Diseases Nursing, Florence Nightingale Faculty of Nursing, Istanbul University, Istanbul, Turkey

Özet: Gümüflhane il merkezindeki gebelerin sa¤l›kuygulamalar›Amaç: Çal›flma, Gümüflhane il merkezinde yaflayan gebelerin sa¤-l›k uygulamalar›n› araflt›rmak ve gebelerin fark›ndal›klar›n› artt›r-mak amac›yla planlanm›flt›r. Yöntem: Araflt›rma tan›mlay›c› niteliktedir. 1 Ekim – 10 Aral›k2012 tarihleri aras›nda toplam 189 gebeyle gerçeklefltirilmifltir.Veriler; say›, yüzde, aritmetik ortalama ve standart sapma ile ve-rilmifltir. Verilere normallilik analizleri uygulamas› sonras› Mann-Whitney U testi, tek yönlü varyans analizi (ANOVA) testi, farkl›-l›klar›n kayna¤›n› belirlemek amac›yla post hoc analizler yap›lm›fl-t›r. Bulgular: Gebelerin yafllar› 19–48 yafl aral›¤›nda olup, ortalama29.09±5.5’dir. Kat›l›mc›lar›n %65.1’i gelirlerinin giderlerine eflitoldu¤unu, %8.58’inin sosyal güvencesi olmad›¤›n›, %24.6’s› çal›fl-t›¤›n›, %51.3’ü il merkezinde yaflad›¤›n› söyledikleri tespit edil-mifltir. Gebelerin efllerinin e¤itim düzeylerine göre ‘GebelikteSa¤l›k Uygulamalar› Ölçek’ puan ortalamalar› aras›nda yap›lanANOVA testi analizinde istatistiksel aç›dan anlaml› fark elde edil-mifltir. ‹lkokul ve üniversite mezunlar› aras›nda farkl›l›k oldu¤usaptanm›flt›r. Büyük flehirlerde yaflayanlar›n ‘Gebelikte Sa¤l›k Uy-gumalar› Ölçek’ puan ortalamas›, köylerde yaflayanlardan dahayüksek bulunmufl ve yafl›n artmas› ile ölçek puan ortalamas› dadüflmektedir. Sonuç: Gebelikte sa¤l›k uygulamalar›nda; gebenin kendisinin veeflinin yafllar›n›n, yaflad›¤› alan›n kentsel ya da k›rsal olmas›n›nfarkl›l›klara sebep oldu¤u görülmüfltür. Gebelere ve ailelerine yö-nelik “prenatal ve postnatal e¤itim programlar›n›n” yayg›nlaflt›r›l-mas›, gebelerin efllerinin de bilgilendirilerek bu programlara kat›-l›m›n›n sa¤lanmas›, ileri yafl grubundaki gebelerin uygulamalar›n›nde¤erlendirilmesi ve düzeltilmesi ad›na ayr›nt›l› görüflmelerin ya-p›lmas› ve bu konuda fark›ndal›klar›n›n artt›r›lmas› gerekmektedir.

Anahtar sözcükler: Gebelik, sa¤l›k davran›fl›, e¤itim.

Correspondence: Handan Özcan, MD. Gümüflhane Üniversitesi Sa¤l›k HizmetleriMeslek Yüksekokulu, Gümüflhane, Turkey. e-mail: [email protected] Received: April 7, 2014; Accepted: December 1, 2014Please cite this article as: Özcan H, K›z›lkaya Beji N. Health practices of pregnantwomen in Gumushane City Center. Perinatal Journal 2015;23(1):13–19.

©2015 Perinatal Medicine Foundation



Original Article


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Abstract

Objective: The study aimed to investigate the health practices ofpregnant women living in Gumushane city center, and to increaseawareness among pregnant women. Methods: The research is of definitive characteristics. It was con-ducted with a total of 189 pregnant women between October 1stand December 10th, 2012. The data was provided as figure, per-centage, arithmetic mean and standard deviation. After normalityanalyses were applied to the data, Mann-Whitney U test, one-wayanalysis of variance (ANOVA) test and post hoc analyses to deter-mine the source of difference were carried out. Results: The ages of pregnant women are between 19- and 48-year-old, and the mean age is 29.09±5.5. Of the participants, 65.1% ofthem stated that their expenses were equal to their incomes, 8.58%of them had no social security, 24.6% of them had a job, and 51.3%of them were living in the city center. Statistically significant differ-ence was found in the ANOVA test analysis carried out among thescore averages of the “Health Practices Questionnaire” according tothe educational background of the spouses of the pregnant women.Difference was found between primary school and university gradu-ates. Score average of the “Health Practices Questionnaire” forthose living in metropolises was higher than those living in villages;it was found that the score average of the questionnaire decreased asthe age increased.Conclusion: For the health practices during pregnancy, the ages ofpregnant women and their spouses and living in whether in urban orrural areas caused differences. It is required to extend “prenatal andpostnatal training programs” among pregnant women and theirfamilies, to enable the spouses of pregnant women to join such pro-grams by informing them, to carry out detailed interviews in orderto evaluate and modify the practices of pregnant women in advancedage group, and to increase awareness on this subject matter.

Keywords: Pregnancy, health behavior, education.

IntroductionAccording to the data of TNSA-2008, a woman whoreaches at the end of her fertility age in Turkey gives2.16 births on average. Total fertility rate today is 50%lower than the rate in 1970s. In Turkey, fertility piles upin the age group 20–29. An average woman has her firstchild at 25-year-old, and two children at 30-year-old.Fertility period diminishes swiftly after 30-year-old, andreaches a negligible level at 40s.[1]

Health practices of women during pregnancy affectboth maternal and neonatal health both during pregnan-cy and postpartum period. Health practices during preg-nancy can be defined as the activities including thehealth of pregnant woman, fetus and newborn andaffecting the gestational outcome. Health practiceswhich are significant for gestational outcomes should beidentified and earned during prenatal care. These prac-tices should include various topics such as dental care,not smoking, not using alcohol or illegal substances, bal-anced nutrition and gaining appropriate amount ofweight, regular exercising, having training about preg-nancy and labor, and avoiding risky sexual acts or expo-sure to other infection factors.[2] As well as going for reg-ular health checks, proper nutrition and resting habits,factors such as knowing regular course of pregnancy andpossible gestational complications, and choosing rightinformation source also directly affect the quality of ges-tational period.[3] Dental care and checks during preg-nancy are very important in terms of fetal health. Thestudies show that more than one third of women havedental problems.[4] Risky conditions such as pretermlabor, baby with low birth weight and preeclampsia areseen in those who have periodontal problems duringpregnancy. Mothers should be encouraged for dentalchecks.[5]

Smoking during and after pregnancy causes signifi-cant health issues for fetus, newborn and child. Activesmoking is one of the major reasons for various healthrisks such as preterm labor, miscarriage, postpartumhemorrhage, ectopic pregnancy, fetus with low birthweight and placenta praevia.[6] Smoking during the firsttrimester is one of the major factors increasing the risksfor spontaneous abortion and ectopic pregnancy.[7] It wasreported that the risk for ectopic pregnancy is 1.5 – 2.5higher in smoking women.[8]

Physical activity is important for a healthy life. Theimportance of exercising during pregnancy is empha-

sized in the literature.[9] It is reported that exercising isuseful for pregnant women who have no obstetric andmedical complication, and physical activity is recom-mended minimum 30 minutes weekly in order not tohave any gestational complication.[10] Direct heavy phys-ical activities, competitive sports increasing cardiacrhythm and prolonged activities on supine position arenot recommended.[11] The recent studies in particularhave highlighted that physical activities have a signifi-cant role for a healthy pregnancy.[12,13] Problems such asfatigue particularly, physical discomfort, being unable touse time efficiently and incompetency in child care areseen more in pregnant women who do not engage inphysical activities.[14-16]

High quality care and balanced nutrition duringpregnancy is very important for the maternal health.[17]

As the education, health and nutrition condition, socio-economic life standards and provided healthcare servic-es of mother improve, the chance to have a successfulpregnancy also increases. A successful pregnancy anddelivery ensure babies to born into a healthy life.[18]

Maintaining pregnancy healthy for both mother andbaby requires medical checks from the beginning up tothe end of pregnancy. In normal pregnant women, pre-natal checks are estimated to be once a month until the28 weeks of gestation, once every 15 days between 28and 36 weeks of gestation and once a week from the 36weeks of gestation up until delivery. According to theMinistry of Health, it is aimed to follow up each preg-nant woman at least for 6 times by identifying as of thebeginning of pregnancy. Making visits regularly ensuresto decrease fetal and neonatal problems.[19]

Vaccination programs have a significant role espe-cially to decrease infant deaths. According to the WorldHealth Organization (WHO), 1/5 of the infant deaths indeveloping countries are caused by the preventable dis-eases. Thanks to the “Expanded Program onImmunization” initiated by WHO in 1974, considerabledecreases have been observed in the incidence, mortalityand morbidity rates of preventable diseases by vaccina-tion.[20] Main purposes of vaccination are to protect fetusduring pregnancy against infections such as varicella andrubella causing congenital malformation, growth retar-dation, stillbirth and neurological sequels, to protectmother against diseases such as influenza, hepatitis Bwhich progress more severely during pregnancy, and todecrease infant morbidity, mortality and infectious dis-

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Health practices of pregnant women in Gumushane City Center

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ease risk of newborn in the first 6 months.[21] There aresignificant differences in vaccination rates according tothe region, residential area and educational backgroundof mother. The percentage of fully vaccination childrenis significantly low in the Eastern Anatolia Region(64%). It is followed by Northern and Southern Regions(84% and 82%, respectively).[1]

Postpartum care is very important both for motherand baby. Considerably majority of them are beingphysicians, 82% of women had postpartum care. Fourout of five women had their first postnatal check withintwo days after the delivery. Postpartum care and its tim-ing vary according to the regions. The rate of havingcare within first 41 days is the highest among the womenin Aegean Region (92%), and the rate of women in Mid-Eastern Anatolia is only 55%.[1] The care to be providedto mother and baby is very significant for facilitating theadaptation of mother to postpartum period, early start ofand sustaining lactation, providing mother-baby interac-tion, accelerating healing process, preventing complica-tions, and for the postnatal comfort.[22]

The study aimed to investigate the health practicesof pregnant women living in Gumushane city center,and to increase awareness among pregnant women.

MethodsThe research is of definitive characteristics. A total of233 pregnant women visiting the maternity clinic forpregnancy control between October 1st and December10th 2012 were accessed and only 189 of them accept-ed to participate in the study.

During the period when the investigation wasplanned and it was started to collect the data, writtenpermission was received from Gumushane ProvincialDirectorate of Health. All participants were informedand read the purposes and methods of the investigation.The data collection tool used in the investigation hastwo parts. The first part of the form, which is intendedfor personal information, performs a literature reviewand it includes 25 questions such as age, educationalbackground, employment status, health insurance, resi-dential area, family type, pregnancy follow-up, and childnumber. The second part of the form is “HealthPractices Questionnaire” (HPQ). HPQ-II is a question-naire with 34 questions. Questions from 1 to 17 includefive-point likert scale varying between “Always” and“Never”. The answer ‘Never (a)’ is calculated as 1 point,

‘Rarely (b)’ as 2 points, ‘Sometimes (c)’ as 3 points,‘Frequently (d)’ as 4 points and ‘Always (e)’ as 5 points;each question from 18 to 34 has 5 appropriate optionswhich are scaled from 1 to 5 points. Some questionshave reverse scaling. These are the questions 6, 7, 8, 22,23, 24, 25, 26, 27, 33 and 34. The points of these ques-tions are scaled from 5 to 1, in a reverse way. A generalpoint is obtained from the total of the all questions.Getting high score represents high quality health behav-ior which has a significant benefit on pregnancy. In thestudy of Lindgreen, the lowest possible score in the scaleis 34 while the highest possible score is 170.[2] Themethod of face-to-face interview was applied in the datacollection. After the questionnaire, health practice train-ings were provided to pregnant women.

SPSS software was used for the analysis of the data.The data obtained in the study was provided as figure,percentage, arithmetic mean and standard deviation.After normality analyses were applied to the data,Mann-Whitney U test, one-way analysis of variance(ANOVA) test and post hoc analyses to determine thesource of difference were carried out. p<0.05 was con-sidered as significant.

ResultsMean age of the pregnant women is 29.09±5.5 (min:19, max: 48). Of the participants, 65.1% of them stat-ed that their expenses were equal to their incomes,8.58% of them had no social security, 24.6% of themhad a job, and 51.3% of them were living in the citycenter (Table 1).

While 66.7% of the pregnant women preferred tovisit an obstetrician at state hospital, 6.8% of them vis-ited obstetricians both at private hospital and state hos-pital. Of the pregnant women, 60.6% said that theyhad pregnancy follow-up for 5 times or more, 75.4% ofthem became pregnant voluntarily, 72.3% of them hadhealth practice training before pregnancy (from inter-net, those with pregnancy experience, TV, familyphysician, nurse), and 89.3% of them said that theywould like to be informed about health practices. Only1.7% of the participants had the history of sexuallytransmitted disease (Table 2).

Of the spouses, 10.1% were primary school gradu-ate, 14.9% were secondary school graduate, 51.1%were high school graduate, and 23.9% were universitygraduate. While 2.6% of them were unemployed,

Perinatal Journal


16

39.7% of them were civil service employees, 32.8% ofthem were worker, 18.5% of them were self-employedand 6.3% of them were engaged in other fields.

The mean score of the participants for health prac-tice questionnaire (HPQ) was 111.76±18.53.

In the analysis of ANOVA test performed betweenage groups of pregnant women and mean HPQ scores,statistically a significant difference was found.According to the post-hoc analysis to determine thesource for the difference, it was found that the differ-

ence was caused by the mean values of first group (agerange of 15-24) and third group (35-year-old andabove), and that the score average of the questionnairedecreased as the age increased (Table 3).

Statistically no significant difference was observed inthe analysis of ANOVA test carried out in the HPQscores according to the educational background of preg-nant women (p>0.05) (Table 4).

The average HPQ scores were also analyzedaccording to the employment status of pregnant

Table 2. Pregnancy history of participants.

Pregnancy history Number %

Planning the pregnancy (n=183)I got pregnant accidentally 37 20.2I got pregnant on purpose 138 75.4I got pregnant accidentally but I want to deliver 37 4.4

Health checks during pregnancy (n=188)Once 13 6.9Twice 17 9.0Three times 22 11.7Four times 22 11.7Five times or more 114 60.6

Number of pregnancyFirst pregnancy 55 30.2Second pregnancy 61 33.5Third pregnancy 43 23.6Fourth pregnancy 17 9.3Fifth pregnancy or more 6 3.3

Having training on health practices during pregnancy (n=188) Yes 136 72.3No 51 27.1

Performer of the follow-ups during pregnancy (n=168)Family physician 4 2.3Private obstetrician 41 24.4Obstetrician at state hospital 112 66.7Other 1 1.7

Table 1. Distribution of pregnant women according to definitive cha-racteristics (n=189).

Definitive characteristics Number %

Age (n=189)15–24 43 22.825–34 112 59.335 and above 34 18.0

Educational background (n=188)Primary school 48 25.5Secondary school 51 27.1High school 62 32.9University 27 14.4

Residential area (n=189)Metropolis 9 4.8City center 97 51.3County 56 29.6Village 27 14.3

Profession (n=187) Housewife 141 75.4Civil service 31 16.6Worker 6 3.2Self-employed 5 2.7Other 4 2.1

Income level (n=186)Income less than expenses 27 14.5Income equals to expenses 121 65.1Income higher than expenses 38 20.4

Table 3. Distribution of mean HPQ scores according to age groups of pregnant women.*

Mean HPQ Score

Age group N X SS F P

15–24 43 117.4884 12.56862

25–34 112 110.6786 20.691742.996 0.052

35 and above 33 107.9697 15.88924

Total 188 111.7606 18.53660

*ANOVA test was used.

women. There was no significant difference in theMann-Whitney U analysis performed between theemployment statuses and mean HPQ scores of preg-nant women (Table 5).

In the analysis of ANOVA test performed on meanHPQ scores according to the educational backgroundof the spouses of pregnant women, statistically a signif-icant difference was found. In the post-hoc analysiscarried out for determining the source of difference, itwas seen that there was difference between primaryschool graduates and university graduates.

In the analysis of ANOVA test performed on meanHPQ scores according to the most frequent residentialareas of pregnant women, statistically a significant dif-ference was found. A post-hoc analysis was performedfor the difference, and the p value was found as <0.05for the difference between the average values of thoseliving in urban and rural areas. The mean HPQ scoresof pregnant women living in the city center were foundto be higher than those living in villages.

DiscussionWhile 82.1% of the participants were in the 15–34 agerange, 47.6% of them were high school and university

graduate. According to TNSA 2008 data, about 52%of women were only primary school graduates. In thestudy, 73% of women were secondary school or high-er level graduates.

In Turkey, the lowest employment rate amongwomen was in Central and Eastern Regions.[1] Ourstudy, we observed that the rates of unemployedwomen in Gumushane, which is a province in the BlackSea Region, were high similar to the women living inCentral and Eastern Regions.

While 51.3% of the women participated in thestudy were living in the large city, 29.6% of them wereliving in counties, 14.3% of them in villages, and 4.8%of them in the city. The most of the pregnant womenbeing living in the city and the metropolis is importantin terms of having follow-up, care and training duringpregnancy. In our study, we found statistically a signif-icant difference in the analysis of ANOVA test per-formed on mean HPQ scores according to the mostfrequent residential area of pregnant women. Themean scores of those living in the city were higher thanthose living in the villages.

It is known that carrying out the delivery in healthyconditions and getting postpartum follow-ups regular-



17

Table 5. Distribution of mean HPQ scores according to employment statuses of pregnant women.*

Mean HPQ Score

Employment status N X SS U P

Unemployed 140 83.24

Employed 31 98.47 18.536 1783.50 0.121

Total 171

*Mann-Whitney U test was used.

Table 4. Distribution of mean HPQ scores according to educational background of pregnant women.*

Mean HPQ Score

Educational background N X SS F P

Primary school 47 109.8298 15.94190

Secondary school 51 111.6667 21.24116

High school 63 112.6190 17.50615 0.274 0.844

University 27 113.2963 20.30312

Total 188 111.7606 18.53660

*ANOVA test was used.

ly decrease maternal and perinatal newborn deaths.[23]

Total visits before the delivery is a significant indica-tion for evaluating the sufficiency of prenatal care.While pregnant women need to have follow-ups for 6times during the pregnancy, insufficient number of vis-its shows that this service is not carried out actively.[24]

Although the mean HPQ scores in the study are low,the rate of participants to visit a health institution dur-ing pregnancy for five or more times is 60.6%.

In the analysis of ANOVA test performed on meanHPQ scores according to the educational backgroundof the spouses of pregnant women, statistically a signif-icant difference was found. As the educational back-ground increases, HPQ score also increases. Similarly,as in the study of Çakmakç› and Eser, there was statis-tically a significant difference between the pregnantwomen whose spouses were university/college gradu-ate and those whose spouses were high school or lowerlevel graduates.[25]

In the analysis of ANOVA test performed on themean HPQ scores according to the age groups of preg-nant women, statistically a significant difference wasfound. Mean HPQ score of young pregnant womenwas 117.48 while it was 107.96 for pregnant womenwith advanced ages. The reason for difference based onage may be that young group tries to learn by search-ing studies as a source of information, and that theadvanced age group utilizes their experience.

The results of our study are similar to the studiesperformed to analyze the effects of age and education-al background of women on gestational health. Themajor factors increasing the possibility to carry out adelivery in a healthcare institution are the young agesof women, early in the rank of birth order, mother hav-ing high number of prenatal care and high level of edu-cation. It has been reported that the possibility todeliver a baby in a healthcare institution in an urbanarea is 1.2 times higher than rural areas, and the rate ofhome birth is higher in Eastern Regions than CentralAnatolian Regions (27%).[1,19]

ConclusionFor the health practices during pregnancy, the ages ofpregnant women and their spouses and living inwhether in urban or rural areas caused differences.Therefore, it is required to extend “prenatal and post-natal training programs” among pregnant women and

their families, to enable the spouses of pregnantwomen to join such programs by informing them, tocarry out detailed interviews in order to determine themistakes and to modify the practices of pregnantwomen in advanced age group, and to increase aware-ness on this subject matter.


References1. Türkiye Nüfus ve Sa¤l›k Araflt›rmas› TNSA. Ankara:

Hacettepe Üniversitesi Nüfüs Etütleri Enstitüsü; 2008.2. Lindgreen K. Testing the health practices in pregnancy

questionnaire- II. JOGNN 2005;34:465–72.3. Sözeri C, Cevahir R, fiahin S, Semiz O. Gebelerin gebelik

süreci ile ilgili bilgi ve davran›fllar›. F›rat Sa¤l›k HizmetleriDergisi 2006;1:93–104.

4. Ovenbacher S, Boggess KA, Murtha AP, Jared HL, Lieff S,McKaig RG, et al. Progressive periodontal disease and risk of very preterm delivery. Obstet Gynecol 2006;107:29–36.

5. Hullah E, Turok Y, Nauta M, Yoong W. Self-reported oralhygiene habits, dental attendance and attitudes to dentistryduring pregnancy in a sample of immigrant women in northlondon. Arch Gynecol Obstet 2008;277:405–9.

6. Marako¤lu K, Erdem D. Türkiye’de, Orta Anadolu’daki birevde gebe kad›nlarda sigara kullan›m›n›n de¤erlendirilmesi.Turkiye Klinikleri J Med Sci 2011;31:928–34.

7. Getahun D, Amre D, Rhoads G, Demissie K. Maternal andobstetric risk factors for sudden infant death syndrome in theUnited States. Obstet Gynecol 2004;103:646–52.

8. Goel P, Radotra A, Singh I, Aggarwal A, Dua D. Effects ofpasssive smoking on outcome in pregnancy. J Postgrad Med2003;154:316–24.

9. Gharaibeh M, Al-Ma’atiah R, Al Jada N. Lifestyle practicesof Jordanian pregnant women. Int Nurs Rev 2005;52:92–100.

10. Ezmerli NM. Exercise in pregnancy. Prim Care Update ObGyns 2000;7:260–5.

11. Committee on Obstetric Practice. ACOG committee opinion.Exercise during pregnancy and the postpartum period.Number 267, January 2002. American College ofObstetricians and Gynecologists. Int J Gynaecol Obstet 2002;77:79–81.

12. American College of Sports Medicine. Impact of physicalactivity during pregnancy and postpartum on chronic diseaserisk. Med Sci Sports Exerc 2006;38:989–1006.

13. Hedegaard M, Damm P, Ottesen B, Petersson K, HenriksenTB. Leisure time physical activity is associated with areduced risk of preterm delivery. Am J Obstet Gynecol2008;198:180.e1–5.

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14. Evenson KR, Moos MK, Carrier K, Siega-Riz AM.Perceived barriers to physical activity among pregnantwomen. matern. Child Health J 2009;13:364–75.

15. Pereira MA, Rifas-Shiman SL, Kleinman KP, Rich-EdwardsJW, Peterson KE, Gillman MW. Predictors of change inphysical activity during and after pregnancy: Project Viva.Am J Prev Med 2007;32:312–9.

16. Mudd L, Nechuta S, Pivarnik J, Paneth N; N; MichiganAlliance for National Children's Study. Factors associatedwith women’s perceptions of physical activity safety duringpregnancy. Prev Med 2009;49:194–9.

17. Lundberg P, Trieu TN. Vietnamese women’s culturalbeliefs and practices related to the postpartum period.Midwifery 2011;27:731–6.

18. Duran Ö, Ceyhan O. Tokat Karfl›yaka Do¤um ve ÇocukBak›mevinde do¤an bebeklerin gebelik haftas›, do¤um flekli,do¤um a¤›rl›¤›, boy uzunlu¤u ve anomali durumu ile anne vebabaya ait özellikler aras›ndaki iliflki. Erciyes ÜniversitesiSa¤l›k Bilimleri Dergisi (E. Ü. Journal of Health Sciences)2004;13:26–34.

19. Turan T, Ceylan S, Teyikçi S. Annelerin düzenli prenetalbak›m alma durumlar› ve etkileyen faktörler. F›rat Sa¤l›kHizmetleri Dergisi 2008;3:157–73.

20. Kurçer M, fiimflek Z, Solmaz A, Dedeo¤lu Y, Gülel R.fianl›urfa Harrankap› Sa¤l›k Oca¤› bölgesinde 0–2 yafl çocukve gebelerde afl›lanma oranlar› ve afl›lamada sorunlar. HarranÜniversitesi T›p Fakültesi Dergisi 2005;2:10–5.

21. Yenicesu C, Demirel Y. Gebelerde afl›lar. Turkiye KlinikleriJournal of Family Medicine - Special Topics 2011;2:75–81.

22. P›nar G, Do¤an L, Alg›er N, Kaya N, Çakmak F. Annelerindo¤um sonu konforunu etkileyen faktörler. Dicle T›pDergisi 2009;36:184–90.

23. Ergin F, Baflar P, Karahasano¤lu B, Befler E. Güvenliolmayan do¤umlar ve do¤um sonras› evde bak›m hizmet-lerinin de¤erlendirilmesi. Türk Silahl› Kuvvetleri KoruyucuHekimlik Bülteni 2005;4:78–92.

24. Taflk›n L. Kad›n Sa¤l›¤› ve Hastal›klar› Hemflireli¤i. XI.bask›. Ankara: Sistem Ofset Matbaac›l›k; 2012. p: 67–80.

25. Çakmakç› A, Eser E. Gebelikte olumlu davran›fl envanteri:bir metodolojik çal›flma. Hemflirelik Forumu 2003;6:8–18.



19

The evaluation of pregnancies complicated byeclampsia: retrospective analysis of

37 cases in our clinicAytekin Tokmak, Korkut Da¤lar, Ali ‹rfan Güzel, Bergen Laleli, Salim Erkaya, Dilek Uygur

Gynecology & Obstetrics Clinic, Zekai Tahir Burak Maternal Health Training and Research Hospital, Ankara, Turkey

Özet: Eklampsi ile komplike olan gebeliklerinde¤erlendirilmesi: Klini¤imizdeki 37 olgunun retrospektif analiziAmaç: Eklampsi ile komplike olan gebeliklerin klinik özellikleri-nin ve maternal ve perinatal sonuçlar›n›n de¤erlendirilmesi. Yöntem: Zekai Tahir Burak Kad›n Sa¤l›¤› E¤itim ve Araflt›rmaHastanesinde Ocak 2009 ve Aral›k 2013 tarihleri aras›nda eklamp-si tan›s› konulan ve tedavi edilen toplam 37 hasta tan›mland›. Has-tane kay›tlar›ndan saptanan ve dosyalar› incelenen bu hastalar kli-nik özellikleri, laboratuvar parametreleri ve maternal ve perinatalsonuçlar›na göre retrospektif olarak de¤erlendirildi. Bulgular: Çal›flma süresince hastanemizde toplam 89.908 do¤u-mun gerçekleflti¤i saptand›. Eklampsi insidans› 0.4/1000 do¤umolarak hesapland›. Çal›flmam›zda yer alan olgular›n yafl ortalamas›27.2±6.6 y›l ve ortalama gebelik yafl› 33.2±4.5 haftayd›. Olgular›n%78.4’ü nullipar idi. Eklamptik nöbetlerin ço¤unlu¤unun antena-tal dönemde (%59.6) ve 28. gebelik haftas›ndan sonra (%89.2)gerçekleflti¤i anlafl›ld›. Neonatal morbidite oran› %61.1 ve perina-tal mortalite oran› %12.5 olarak bulundu. Majör morbidite oran›%43.2 ve morbiditeye neden olan önde gelen sebep HELLP sen-dromuydu (%37.8). Otuz yafl›nda multipar (G2P1) bir kad›n›n,do¤umdan sonra 10. günde intrakranial kanama nedeniyle kaybe-dildi¤i saptand›. Sonuç: Eklampsi, maternal ve perinatal morbidite ve mortaliteninen önemli nedenlerinden biridir. Her zaman önlenemese de, ek-lampsi geliflme riski yüksek olan hastalar›n düzenli antenatal bak›malmalar›n›n sa¤lanmas›, uygun koflullara sahip üçüncü basamakmerkezlerde hospitalize edilerek, konvülziyonlar›n önlenmesi, kanbas›nc›n›n kontrol alt›na al›nmas› ve uygun zamanda do¤umungerçeklefltirilmesi ile en iyi yaklafl›m sa¤lanabilir.

Anahtar sözcükler: Eklampsi, klinik özellikler, maternal ve peri-natal sonuçlar.

Correspondence: Aytekin Tokmak, MD. ZTB Kad›n Sa¤l›¤› E¤itim ve Arafl. Hast.Kad›n Hastal›klar› ve Do¤um Klini¤i, Ankara, Turkey. e-mail: [email protected] Received: November 2, 2014; Accepted: January 5, 2015Please cite this article as: Tokmak A, Da¤lar K, Güzel, A‹, Laleli B, Erkaya S, Uygur D. The evaluation of pregnancies complicated by eclampsia: retrospective analysis of 37 cases in our clinic. Perinatal Journal 2015;23(1):20–25.©2015 Perinatal Medicine Foundation



Original Article


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Abstract

Objective: We aimed to evaluate the clinical characteristics andmaternal and perinatal outcomes of pregnancies complicated byeclampsia. Methods: A total of 37 patients were identified who were diagnosedand treated in Zekai Tahir Burak Maternal Health Training andResearch Hospital between January 2009 and December 2013.These patients found in and reviewed by their hospital records wereevaluated retrospectively in terms of their clinical characteristics,laboratory parameters, and maternal and perinatal outcomes. Results: It was found that a total of 89,908 deliveries were per-formed in our hospital during the study. Eclampsia incidence wascalculated as 0.4/1000 deliveries. Mean age of the cases in our studywas 27.2±6.6 years and mean gestational age was 33.2±4.5 weeks.The rate of the cases who were nullipara was 78.4%. It was under-stood that the most of the eclamptic seizures occurred during theantenatal period (59.6%) after 28 weeks of gestation (89.2%).Neonatal morbidity rate was 61.1% and perinatal mortality rate was12.5%. While major morbidity rate was 43.2%, the leading cause ofthe morbidity was HELLP syndrome (37.8%). It was found that athirty-year-old woman who was multipara (G2P1) died on the post-partum 10th day due to intracranial hemorrhage.Conclusion: Eclampsia is one of the most significant reasons ofmaternal and perinatal morbidity and mortality. Even though it is notalways possible to prevent it, the best approach can be provided byensuring patients with highest risk for eclampsia to have regular ante-natal care, preventing convulsions through hospitalization in tertiaryhealthcare centers with proper conditions, bringing blood pressureunder control and carrying out delivery at the most convenient time.

Keywords: Eclampsia, clinical characteristics, maternal and perina-tal outcomes.


The evaluation of pregnancies complicated by eclampsia

21

IntroductionHypertensive disorders are the most frequent medicalcomplication of pregnancy, and it has been reportedthat they affect 5-10% of pregnancies in the USA.[1]

Despite its higher incidence and wider incidence rangein developing countries, its incidence rate (0.16–1/1000 delivery) is stable in developed countries.[2]

Eclampsia is a specific neurological complication ofpregnancy, it is characterized by hypertension andtonic clonic convulsions, and its pathophysiology is stillunclear. It has been found that the cerebral anomaliesdeveloping in eclampsia are similar to the changes inhypertensive encephalopathy.[3] Early marriage, nulli-parity, insufficient prenatal care, low socio-economicalcondition and malnutrition are the risk factors foreclampsia as in preeclampsia. While eclamptic seizuremay develop after severe preeclampsia, it also maydevelop unexpectedly without hypertension and pro-teinuria.[4] A mild hypertension can be seen only in 30-60% of the women developing eclampsia.[3] Headache,blurring of vision, photophobia and mental changesmay be early diagnoses of an approaching eclampsia;however, the eclampsia may develop even withoutthese findings.

Eclampsia is a life-threatening complication ofpregnancy. Its most frequently reported reason isHELLP syndrome.[3] Maternal mortality rate ofeclampsia was reported was as high as 15%.[5]

Intracranial hemorrhage, pulmonary edema, renal,hepatic and respiratory failures are the leading mortal-ity reasons. Increased perinatal mortality is a result ofeclampsia, and perinatal mortality rate was reported as10% in a multicentric study carried out in Brazil.[6]

Chronic placental insufficiency, preterm labor andablatio placentae are among perinatal mortality rea-sons.[7] It is easy to establish eclampsia diagnosis; how-ever, it should be remembered that conditions such asepilepsy, encephalitis, meningitis, brain tumors, cys-ticercosis and ruptured brain aneurysm may triggereclampsia during advanced weeks of gestation andpuerperium. All pregnants having convulsion shouldbe considered as eclamptic until all other reasons areruled out.[8] Eclampsia requires immediate treatment inorder to minimize maternal and fetal morbidity andmortality. In this study, we aimed to analyze eclampsiacases in our hospital which is a tertiary healthcare cen-ter in Central Anatolia.

MethodsThirty-seven cases who were established eclampsiadiagnosis and treated in high-risk pregnancy and deliv-ery room departments of Zekai Tahir Burak MaternalHealth Training and Research Hospital betweenJanuary 2009 and December 2013 were evaluated ret-rospectively. Patient data were obtained from patientfiles. Demographic characteristics, laboratory findingsand obstetric outcomes were recorded. For eachwomen, age, gravida, parity, abortion, gestational bodymass index (BMI), blood pressure measurements, weekof gestation at diagnosis, additional disease, smokinghabit, initial symptoms, educational level, the phasethat delivery occurs, laboratory findings, hospitaliza-tion period, magnesium application, delivery type,birth weight, Apgar score, and finally maternal - fetalmorbidity and mortality were investigated. It was seenthat the weeks of gestation were calculated accordingto last menstrual periods, and that the gestational agewas noted according to ultrasound screenings carriedout on the first trimester in those who did not knowtheir last menstrual period. Full urinalysis, full bloodcounts, liver and kidney function tests and LDH valuesof all cases were recorded. It was found that fetal bio-metry and Doppler examination by ultrasonographyand continuous external fetal monitorization by car-diotocography were carried out for each patient. With12-hour dosing interval, 12 mg betamethasone wasadministered to all pregnant women at or below 34weeks of gestation for fetal lung maturation.

Eclampsia was identified according to the presenceof following criteria: the presence of at least two amonghypertension, proteinuria, thrombocytopenia, andincreased serum AST level within 24 hours after convul-sions developed during pregnancy or within 10 daysduring following delivery. The diagnosis of HELLPsyndrome was established according to hemolysis (LDH>600 U/L), thrombocytopenia (<100×103/µL) andincreased liver enzyme (AST>70U/L). It was found that10-minute intravenous loading dose of 4.5 g magnesiumsulphate (MgSO4) was administered to all women havingeclamptic seizure and then convulsion prophylaxis wasinitiated so as to progress as 2 g/h intravenous infusion,and nifedipine and alpha-methyldopa were used in theanti-hypertensive treatment in order to keep diastolicblood pressure between 90 and 100 mmHg and severehypertension under control.

Perinatal Journal

Tokmak A et al.

22

Statistical Package for the Social Sciences (SPSS)version 15.0 (SPSS Inc., Chicago, IL, USA) was usedfor statistical analysis. Definitive data and frequencieswere calculated by the computer. Conformity of thedata to normal distribution was evaluated byKolmogorov-Smirnov test. The data with constant andnormal distribution were provided as mean±standarddeviation, and the data without constant and normaldistribution were provided as median (minimum-max-imum). Categorical variables were given as figure (per-centage).

ResultsDuring the 5-year period of the study, a total of 89,908deliveries occurred in our hospital. It was found that 37of these pregnancies were complicated with eclampsia.Eclampsia incidence was calculated as 0.4/1000 deliv-eries. Eclampsia was more common in nullipara cases(78.4% vs. 21.6%). Mean age and weeks of gestation ofthe patients were 27.2±6.6 (range: 16 to 42) years and33.2±4.5 (range: 25 to 39) weeks, respectively. Whilemean systolic blood pressure value was 155.7±26.9mmHg, it was 101.6±17.5 mmHg for diastolic bloodpressure. The clinical and laboratory findings of thepatients are shown in the Table 1. Eclamptic seizureoccurred during antepartum period in 22 patients, dur-ing postpartum period in 10 patients and during intra-partum period in 5 patients. Eclamptic seizure devel-oped without hypertension in 5 patients, and headachewas the most frequent initial symptom (Table 2). Therates of cesarean and vaginal delivery were 89.2% and10.8%, respectively. Two out of 4 patients who hadvaginal delivery developed postpartum eclampsia, onepatient had intrauterine fetal death and one multiparapatient developed intrapartum eclampsia on the secondphase of the delivery. The educational level of morethan half of the patients was primary school or below.One patient had gestational diabetes while one patienthad smoking history. Multiple pregnancy was found intwo patients (one twin, and one triplet). It was seen intwo patients that eclampsia developed without protein-uria. While maternal morbidity developed in 16patients, the diagnosis of HELLP syndrome was estab-lished in 14 of them, disseminated intravascular coagu-lation (DIC) in one patient, sudden temporary loss ofvision in one patient and renal failure followingdetachment in one patient. It was found that one

patient was referred to the Intense Care Unit ofAnesthesiology and Reanimation Department ofAnkara Training and Research Hospital due tointracranial hemorrhage, but died on the way.Maternal mortality was found as 2.7% due to this case.Prematurity and intrauterine growth retardation(IUGR) were the most frequent reasons for perinatalmorbidity (Table 3). Perinatal mortality rate wasfound as 12.5% (5/40).

Table 1. Clinical and laboratory characteristics of cases.

Variable Result

Age (year)* 27.2±6.6

Nullipara† 29 (78.4)

Gravida‡ 2 (1–6)

Parity‡ 0 (0–3)

Abortion‡ 1 (0–6)

BMI (kg/m2)* 29.8±4.8

Smoking† 1 (2.7)

Educational level†

Illiterate 2 (5.4)

Primary school 17 (45.9)

Secondary school 8 (21.6)

High school 10 (27)

SBP (mmHg)* 155.7±26.9

DBP (mmHg)* 101.6±17.5

Hospitalization period (day)* 8.6±3.3

AST (U/L)* 236.2±458.9

ALT (U/L)* 176.8±305.1

Creatinine (mg/dL)* 0.7±0.2

Platelet (x103/µL)* 179.4±108.6

LDH (U/L)* 1008.4±705.9

Proteinuria in spot urine (mg/dL)†

0 2 (5.4)

0< and ≤30 3 (8.1)

>30 and ≤300 22 (59.5)

>300 10 (27)

BMI: Body mass index; DBP: Diastolic blood pressure; SBP: Systolic blood pres-sure. Data *: 9±SD; †: n(%); ‡: median (minimum–maximum).

Table 2. Initial symptom.

Symptom n (%)

Headache 10 (27)

Blurring of vision 8 (21.6)

Epigastric pain 2 (5.4)

Recurring seizure 5 (13.5)



23

DiscussionEclampsia is a life-threatening gestational complica-tion developing acutely. It has a high risk of morbidityand mortality for mother and fetus. When eclampsiausually occurs following severe preeclampsia, it mayappear without any preeclamptic symptoms. Munro[9]

reported that 38% of eclamptic seizures occurred with-out any symptom and finding previously. Its incidencereported in developed countries is 1/2000–1/3000;however, this rate is much more in developing coun-tries.[4] The eclampsia rates reported in Turkey vary. Intheir study, Y›ld›r›m et al.[10] investigated 113 eclampsiacases and found eclampsia rate as 1.2/1000 delivery,which was reported as 1.7/1000 in another study car-ried in the western region of Turkey.[11] The study per-formed in Southeastern Anatolia found the incidencerate as 19/1000[12] while it was reported as 1.2/1000 inNortheastern Anatolia.[13] In our study, we found alower rate which was 0.4/1000 (1/2430). The reasonmay be that especially the eclampsia cases developingduring the postpartum period referred to other multi-disciplinary hospitals in the region.

Liu et al.[14] found that eclampsia incidence gradual-ly decreased and nulliparity, anemia and the presenceof cardiac disease in singleton deliveries increased therisk of eclampsia for 2.3–4.8 times. In another study, itwas argued that being younger than 20-year-old andolder than 35-year-old, long intervals between deliver-ies, low socio-economic level, gestational diabetes, ges-tational obesity and gaining weight during pregnancyless or more than recommended were found to be therisk factors associated with eclampsia, and that multi-parity and smoking decreased the eclampsia.[15] Y›ld›r›met al. showed in their studies that 63.7% of eclampticseizures developed in nullipara cases.[10] Similarly, wefound in our study that nulliparity was more commonamong eclamptic cases (78.4%).

Lopez-Llera[16] categorized eclampsia according tothe onset time of the seizure and defined as antepartumif it develops before delivery, as intrapartum if it occursduring delivery and as postpartum if it develops within7 days after delivery. It was reported that 38–53% ofthe eclamptic seizures developed during antepartumperiod while 11–44% of them developed during post-partum period.[3] However, it can be difficult to distin-guish them since antepartum and intrapartum periodsintertwine. Also, in higher than 90% of the eclamptic

cases, it develops after 28 weeks of gestation.[4] In linewith the literature, we observed eclamptic seizure inmost of our cases during antepartum period (59.4%)and after 28 weeks of gestation (89.2%).

The first step of eclampsia management is to preventmaternal injuries and to provide cardiopulmonary sup-port. Afterwards, it is to prevent the recurrence of con-vulsions and to decrease blood pressure to the safe lev-els. There are strong evidences for using routine magne-sium sulphate (MgSO4) for the prophylaxis of seizures inthe literature, and a full consensus has been reached.[17,18]

The recommendation for patient with eclamptic seizureis to administer 1–2 g/h maintenance dose for at least 24hours after 4–6 g intravenous loading dose.[1] However,in 9.4% of the cases, it was reported that eclampticseizures may recur despite MgSO4 prophylaxis.[17] Weinitiate MgSO4 prophylaxis for all our severe preeclamp-tic and eclamptic patients. We monitor our patients bytheir urination, respiratory rate, patellar reflex and inter-mittent serum magnesium levels. In our study, similar tothe literature, the seizure recurred under MgSO4 pro-

Table 3. Obstetric and maternal-perinatal outcomes.

Variable Result

Week of gestation* 33.2±4.5

≤28 week of gestation† 4 (10.8)

Birth weight* 1988.9±973.6

Apgar score‡ 6 (0–9)

Multiple pregnancy†

Twin 1 (2.7)

Triple 1 (2.7)

Perinatal morbidity†

Prematurity 22 (61.1)

IUGR 12 (32.4)

Perinatal mortality† 5 (12.5)

Maternal complication† 16 (43.2)

HELLP 14 (37.5)

Maternal mortality† 1 (2.7)

Delivery type†

Vaginal delivery 4 (10.8)

Cesarean section 33 (89.2)

Period that seizure occurred†

Antepartum 22 (59.5)Postpartum 10 (27)Intrapartum 5 (13.5)

IUGR: Intrauterine growth retardation. Data *: 9±SD; ‡: n(%); ‡: median (mini-mum–maximum).

Perinatal Journal

Tokmak A et al.

24

phylaxis in 5 (13.5%) patients, and we kept the seizureunder control in all these patients by single dosediazepam (10 mg).

In women developing eclampsia, detachment, DIC,HELLP, cerebral hemorrhage and maternal mortalityrisk increased.[4] The risk of HELLP syndrome isreported about 10–15% in eclamptic cases.[3] However,in recent publications in our country, the rate ofeclamptic patients developing HELLP syndromereached up to 40% and the eclampsia was grouped intwo categories as developing HELLP and not develop-ing HELLP.[10,11,19] In line with the literature, HELLPsyndrome was the most common complication in ourpatients while one patient had DIC, one patient hadrenal failure following detachment and one patient hadsudden temporary loss of vision. Also, our patientdeveloping HELLP died after intracranial hemorrhageon postpartum 10th day in the intense care unit of amultidisciplinary hospital.

In the study investigating maternal death of 174cases, Akar et al. found maternal mortality rate as40/100,000 and preeclampsia- and eclampsia-inducedcomplications as the most common direct maternaldeath.[20] It is reported in the world that eclampsia-induced maternal mortality rates has increased up to15%.[5] Eclamptic cases are more common in develop-ing countries and it is explained by the multiple num-bers of convulsions occurring out of hospital and non-presence of antenatal follow-ups of these cases. In ourcountry, maternal mortality rate in eclamptic cases isreported between 0 and 14.6%.[21] In our study, wefound eclampsia-induced maternal mortality rate as2.7% (1 case).

Perinatal morbidity and mortality rates are high inthe babies of eclamptic mothers. Preeclampsia andeclampsia are responsible for 2.7% of perinatal mortali-ty independent from prematurity and IUGR,preeclampsia rate is 12% in newborns with IUGR and19% in preterm newborns.[22] In a multinational studysupported by WHO and involved 29 countries, perina-tal mortality rates were found as 2.6%, 9.2% and 22.6%in non-preeclamptic/non-eclamptic, preeclamptic andeclamptic pregnant women, respectively.[23] These com-plications are most likely prematurity-induced RDS,apnea, jaundice, kernicterus, malnutrition, hypo-glycemia, seizure, periventricular leukomalacia and pro-longed hospitalization periods.[24,25] While most of our

cases (61.1%) were born as premature, 12 (32.4%) caseshad IUGR. One case died during perinatal period and 4cases during neonatal period. We found perinatal mor-tality rate as 12.5%.

ConclusionIn conclusion, severe preeclampsia and eclampsia aresignificant reasons for maternal and perinatal morbidi-ty and mortality in the world. Understanding thepathophysiology better, close antenatal follow-ups andappropriate treatment by hospitalizing risky cases intertiary healthcare centers with proper conditions maydecrease eclampsia incidence and associated secondarymaternal and perinatal morbidity and mortality rates.


References1. Moussa HN, Arian SE, Sibai BM. Management of hyperten-

sive disorders in pregnancy. Women’s Health 2014;10:385–404.

2. Norwitz ER. Eclampsia; incidence and epidemiology. In:Lockwood CJ (ed) UpTodate. Last updated in Jul 14, 2014.Retrieved from http://www.uptodate.com/contents/eclampsia.

3. Sibai BM. Diagnosis, prevention, and management ofeclampsia. Obstet Gynecol 2005;105:402–10.

4. Mattar F, Sibai BM. Eclampsia. VIII. Risk factors for mater-nal morbidity. Am J Obstet Gynecol 1999;182:307–12.

5. Ghulmiyyah L, Sibai B. Maternal mortality from preeclamp-sia/eclampsia. Semin Perinatol 2012;36:56–9.

6. Giordano JC, Parpinelli MA, Cecatti JG, Haddad SM, CostaML, Surita FG, et al. The burden of eclampsia: results froma multicenter study on surveillance of severe maternal mor-bidity in Brazil. PLoS One 2014;9:e97401.e1–10.

7. Sibai BM. Eclampsia. VI. Maternal-perinatal outcome in 254consecutive cases. Am J Obstet Gynecol 1990;163:1049–54.

8. Cunningham FG, Leveno KJ,Bloom SL, Hauth JC, GilstrapLC, Wenstrom KD. Hypertensive Disorders in Pregnancy.Williams Obstetrics. 22nd ed. Columbus, OH: McGraw-HillCompanies; 2005; p: 787.

9. Munro PT. Management of eclampsia in the accident andemergency department. J Accid Emerg Med 2000;17:7–11.

10. Y›ld›r›m G, Aslan H, Gül A, Aktafl FN, Çakmak D, Güngör-dük K, et al. Eklampside maternal ve perinatal sonuçlar: 113olgunun de¤erlendirilmesi. Perinatoloji Dergisi 2007;15:61–7.

11. As›c›oglu O, Güngördük K, Yildirim G, Aslan H, Günay T.Maternal and perinatal outcomes of eclampsia with andwithout HELLP syndrome in a teaching hospital in westernTurkey. J Obstet Gynaecol 2014;34:326–31.



25

12. Sumnulu I, ‹ldeniz M, Özel N. The incidence of pregnancyinduced hypertension in southeast Turkey. Int J GynaecolObstet 1989;28:211–5.

13. ‹ngec M, Kumtepe Y, Borekci B, Bebek Z, Kadanal› S.2001–2003 y›llar›ndaki 81 eklampsi olgusunun maternal veperinatal sonuclar›. Jinekoloji ve Obstetik Dergisi 2005;19:135–41.

14. Liu S, Joseph KS, Liston RM, Bartholomew S, Walker M,León JA, et al.; Maternal Health Study Group of CanadianPerinatal Surveillance System (Public Health Agency ofCanada). Incidence, risk factors, and associated complica-tions of eclampsia. Obstet Gynecol 2011;118:987–94.

15. Coghill AE, Hansen S, Littman AJ. Risk factors for eclamp-sia: a population-based study in Washington State, 1987-2007. Am J Obstet Gynecol 2011;205:553.e1–7.

16. Lopez-Llera M. Main clinical subtypes of eclampsia. Am JObstet Gynecol 1992;166:4–9.

17. Witlin AG, Sibai BM. Magnesium sulfate therapy inpreeclampsia and eclampsia. Obstet Gyencol 1998;92:883–9.

18. Hall DR, Odendaal HJ, Smith M. Is the prophylactic admin-istration of magnesium sulphate in women with pre-eclamp-sia indicated prior to labor? BJOG 2000;107:903–8.

19. Kumtepe Y, Dündar O, Cetinkaya K, Ingeç M. Preeclampsiaand eclampsia incidence in the eastern anatolia region of

Turkey: the effects of high altitude. J Turk Ger Gynecol Assoc2011;12:26–30.

20. Akar ME, Eyi EG, Yilmaz ES, Yuksel B, Yilmaz Z. Maternaldeaths and their causes in Ankara, Turkey, 1982–2001. JHealth Popul Nutr 2004;22:420–8.

21. Erden AC, Yayla M. Preeklampsi ve eklampside maternal vefetal morbidite-mortalite. Perinatoloji Dergisi 1993;1:24–30.

22. Dodd JM, O’Brien C, Grivell RM. Preventing pre-eclamp-sia – are dietary factors the key? BMC Med 2014;12:176.

23. Abalos E, Cuesta C, Carroli G, Qureshi Z, Widmer M, VogelJP, et al.; WHO Multicountry Survey on Maternal andNewborn Health Research Network. Pre-eclampsia, eclamp-sia and adverse maternal and perinatal outcomes: a secondaryanalysis of the World Health Organization MulticountrySurvey on Maternal and Newborn Health. BJOG 2014;121Suppl 1:14–24.

24. Goldenberg RL, Culhane JF, Iams JD, Romero R.Epidemiology and causes of preterm birth. Lancet2008;371:75–84.

25. Saigal S, Doyle LW. An overview of mortality and sequelaeof preterm birth from infancy to adulthood. Lancet2008;371:261–9.

Factors affecting postpartum depression in Diyarbak›r

Ali Emre Tahao¤lu1, Cihan To¤rul1, Mehmet ‹rfan Külahç›o¤lu1, Beflire Ayd›n Öztürk1, Deniz Balsak1, Hanifi Bademk›ran1, Erdo¤an Gül1, Ümit Görkem2, Tayfun Güngör2

1Gynecology & Obstetrics Clinic, Diyarbak›r Maternity and Pediatrics Hospital, Diyarbak›r, Turkey2Department of Gynecology & Obstetrics, Hitit University, Çorum, Turkey

IntroductionGestation is a period when a woman has her physiolog-ical, psychological and social changes. Prenatal and post-

natal changes, newborn care, breast feeding problems,new environment, and changes in social status may causethe health of pregnant woman to deteriorate. A peak in

Özet: Diyarbak›r'da postpartum depresyonu etkileyen faktörlerAmaç: Bu çal›flman›n amac› Türkiye’nin güneydo¤usunda yer alanDiyarbak›r ilinde postpartum depresyonu (PPD) etkileyen faktör-leri yafl gruplar›na göre incelemektir. Yöntem: Klini¤imize baflvuran 495 postpartum dönemdeki kad›-na Edinburgh postpartum depresyon skoru (EPDS) anket sorular›soruldu. Elli bir adölesan (18 yafl alt›) ve 35 yafl üstü olan 72 lohu-sa için ayr› istatistiksel inceleme yap›ld›. EPDS skor sonucuna gö-re 13 puan cut-off de¤er olarak belirlendi. Bulgular: Toplam 495 hastan›n 101’inde (%20.4) EPDS skoru 13ve üzerinde idi. Adölesan lohusalarda bu oran %27.4, 35 yafl üstülohusalarda ise %19.4 idi. Geçirilmifl depresyon öyküsünün post-partum depresyonu etkileyen anlaml› bir de¤iflken oldu¤u bulun-du (p<0.005). Sonuç: Postpartum depresyon anne ve çocuk sa¤l›¤›n› etkileyenönemli ve gözden kaç›r›lmas› olas› bir hastal›kt›r. Bu durum özel-likle adölesan ça¤da risklidir. Geçirilmifl depresyon hikayesi post-partum depresyon etyolojisinde en önemli de¤iflkendir. Postpar-tum depresyon için bu dönemde tarama yap›labilir. Türkiye’nin enyüksek üreme h›z›na sahip olan Güneydo¤u Anadolu bölgesindepostpartum depresyonu s›n›rlayan en büyük etken akraba ve arka-dafl çevresinin puerperal dönemde lohusalara verdi¤i destek olabi-lir.

Anahtar sözcükler: Postpartum dönem, postpartum depresyon.

Correspondence: Ali Emre Tahao¤lu, MD. Diyarbak›r Kad›n Do¤um ve Çocuk Hastal›klar›Hastanesi Kad›n Hast. ve Do¤um Klini¤i, Diyarbak›r, Turkey. e-mail: [email protected] Received: April 23, 2014; Accepted: January 5, 2015Please cite this article as: Tahao¤lu AE, To¤rul C, Külahç›o¤lu M‹, Ayd›n Öztürk B,Balsak D, Bademk›ran H, Gül E, Görkem Ü, Güngör T. Factors affecting postpartumdepression in Diyarbak›r. Perinatal Journal 2015;23(1):26–29.©2015 Perinatal Medicine Foundation



Original Article


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Abstract

Objective: The aim of this study is to investigate the factors affect-ing postpartum depression (PPD) according to age groups inDiyarbak›r city located on the southeastern part of Turkey. Methods: The questions of Edinburgh postpartum depression scale(EPDS) were asked to 495 women who referred to our clinic at theirpostpartum periods. A separate statistical analysis was carried out for51 adolescent women (below 18-year-old) and 72 puerperantwomen over 35-year-old. Score 13 according to EPDS score resultwas determined as cut-off value. Results: In 101 out of 495 (20.4%) patients, EPDS score was 13 andabove. This rate was 27.4% in adolescent puerperant women, and19.4% in puerperant women over 35-year-old. It was found thatdepression history was a significant variable affecting postpartumdepression (p<0.005).Conclusion: Postpartum depression is a significant disease possibleto overlook which affects the health of mother and baby. This isrisky especially during adolescent period. Depression history is animportant variable in the etiology of postpartum depression. Thisperiod can be screened for postpartum depression. The greatest fac-tor limiting postpartum depression in Southeastern Anatolia Regionwhich has the highest reproduction rate in Turkey can be the sup-port provided to the puerperant women by relatives and friends dur-ing puerperal period.

Keywords: Postpartum period, postpartum depression.



27

the depression rate was reported at postpartum fourthand eighth weeks.[1] In a meta-analysis, it was reportedthat postpartum depression rate in the first three post-partum months was 14.5%, and major depression crite-ria were satisfactorily met in 6.5% of postpartumwomen, and this was at higher levels especially in nulli-para population.[1] Changes during pregnancy may bringalong many problems and cause stress.[2] The periodafter pregnancy is 3–4 times more risky in terms of men-tal illnesses than gestational period.[3] Therefore, possi-ble postpartum depression may constitute a significanthealth problem.

According to Diagnostic and Statistical Manual ofMental Disorders (DSM), having 5 or more of the crite-ria for at least two weeks is defined as postpartumdepression (PPD). These are insomnia-hypersomnia,psychomotor agitation or retardation, fatigue, unhappi-ness or sense of guilt, decreased concentration, changesin appetite and suicide ideation. These episodes beginwithin postpartum four weeks and ends within 1 year.According to DSM, PPD is described as non-psychoticmajor depression.[4]

Identifying and preventing postpartum depression inadvance is significant in terms of the health of baby andmother. Edinburgh Postpartum Depression Scale(EPDS) can be used to investigate postpartum depres-sion.[5] Although this scale is not diagnostic, sensitivity ofPPD is 61.5% and specificity of PPD is 77.4% for thosescoring 13 and above.[6]

MethodsOur study was carried out on 495 puerperant womenwho referred to Diyarbak›r Maternity and PediatricsHospital between September 2012 and May 2013. Theapproval of the Ethics Committee of Okmeydan›Training and Research Hospital was obtained. Patientconsent forms were received from all participants.Women who delivered term babies (at 37 weeks andabove) were included in the study. The exclusion crite-ria included multiple pregnancy, pregnancy by assistedreproductive techniques, history of mental diseasediagnosis, antenatal fetal anomaly and mother or babybeing in the intense care unit.

All puerperant women included in the study onpostpartum 8 weeks were asked EPDS questions andfactors that may affect postpartum depression. EPDS isa questionnaire with 10 items, each having 4 options

where each option is scored between 0 and 3 and max-imum total score is 30.[6]

The study was separated into 3 groups according tothe age groups which are adolescents, puerperantwomen who are over 35-year-old and all puerperantwomen. Statistical analysis was performed by SPSS15.0 (SPSS Inc., Chicago, IL, USA) and definitive sta-tistics and chi-square test were used.

ResultsThe factors affecting postpartum depression were inves-tigated by categorizing 495 puerperant women in thestudy according to their age groups, which were adoles-cent puerperant women and puerperant women over 35-year-old. As risk factors, their ages, number of their liv-ing children, financial status, educational status, deliverytype, if they had any emesis problem, gender of baby,depression history and if the pregnancy was intendedwere asked. Among all the age groups, it was found thatonly depression history affected PPD (p<0.001).

In 101 out of 495 (20.4%) patients, EPDS score was13 and above. In the factors investigated, it was foundthat only the depression history was a significant factoraffecting postpartum depression in puerperant women(Table 1).

Table 1. Statistical analysis of 495 patients.

No depression Depression exists p(n=394) (n=101) value

AgeMean: 26.7±6.6 (14–52) 26.7±6.5 26.5±7.1 0.7540

Number of living children 2.2 (0–10) 3.8 (0–11) 0.115

Financial status600 TL and below 78.4 72.3 0.162600–1500 TL 19.3 22.81500–5000 TL 2.3 5

Educational levelIlliterate 36.3 35.6 0.718Literate 23.4 23.8Primary school 23.9 19.8Secondary school 7.1 9.9High school 6.6 5.9University 2.8 5

Delivery type (C/S) 207 54 0.602

Emesis (present) 64 17 0.887

Depression history (exists) 6 16 <0.001

Gender of baby (male) 198 55 0.452

Planned pregnancy (exists) 41 14 0.325

Perinatal Journal

Tahao¤lu AE et al.

28

It was seen in 495 patients who were analyzed thatage, number of living children, educational status,financial status, delivery type, emesis problem, if thepregnancy was intended or not and gender of babywere not significant factors in terms of postpartumdepression.

Postpartum depression was identified in 51patients, of which 14 cases (27.4%) were adolescentpuerperant women below 18-year-old (Table 2). Noneof the factors analyzed had a significant effect on post-partum depression.

Postpartum depression was identified in 14 (19.4%)out of 72 patients who were puerperant women above35-year-old (Table 3). None of the factors had anyeffect on postpartum depression.

DiscussionEven though the pregnancy and delivery are physio-logical, they may affect the health of mother and babyin a negative way. While most of the women can adapt-ed to physiological, psychological and social changesoccurring during pregnancy and delivery, some womenmay suffer mental illnesses at different levels.[7] It hasbeen shown that PPD constitutes a risk in mother-infant relationship, and affects cognitive and emotion-al development of baby.[8] Verbal and visual communi-cation problems of baby and disorders in emotional,cognitive, verbal and social abilities are the negativeeffects of PPD.[9]

In our study, we found that number of living chil-dren, financial status, educational level, delivery type,presence of emesis during pregnancy, whether preg-nancy being intended or not and gender of baby didnot affect postpartum depression. It was observed thatonly depression history affected postpartum depres-sion. It has been already shown in many studies thatdepression history is a significant factor affecting post-partum depression.[10,11]

In our study, we found that the rate of postpartumdepression at postpartum 8 weeks in Diyarbak›r cityand nearby regions was 20.4% (according to EPDS,cut-off was 13 and above). The study carried out inTrabzon found PPD rate as 28.1%.[12] However, otherstudies performed in Turkey found PPD rate as14.0%, 16.8% and 14.0%, respectively.[11,13,14] We foundPPD rate during adolescent period as 27.4% which wasthe highest result among the age groups. There are

contradictory results among age groups for PPD.Some studies found that being below 25-year-old is asignificant factor for PPD.[15,16] Some other studiesshowed that postpartum depression presented no dif-ference among age groups.[17]

The prevalence of postpartum depression duringthe test period may differ according to population size,

Table 3. Statistical analysis of puerperant women above 35-year-old.


Number of living children 5 (0–10) 5 (0–11) 0.835

Financial status600 TL and below 77.6 78.6 0.969600–1500 TL 17.2 14.31500–5000 TL 5.2 7.1

Educational levelIlliterate 44.8 50 0.460Literate 10.3 14.3Primary school 20.7 28.6Secondary school 12.1 -High school 5.2 -University 6.9 7.1



Depression history (exists) 2 2 0.168



Table 2. Statistical analysis of puerperant women below 18-year-old.


Number of living children 1 1 0.079

Financial status600 TL and below 64.9 50 0.337600–1500 TL 35.1 501500–5000 TL - -

Educational levelIlliterate 35.1 28.6 0.871Literate 16.2 28.6Primary school 16.2 14.3Secondary school 16.2 21.4High school 13.5 7.1University 2.2 -



Depression history (exists) 1 0 1.000





29

study design, test type and cut-off value. Mostly, thenegative results of this situation which cannot bedetected by healthcare professionals on health ofmother and baby should be known and it should be onthe alert against this mood disorder in puerperantwomen especially with depression history.

Routine screening is performed for postpartumdepression diagnosis in some countries such asAustralia and the USA.[18] Such screening proceduresmay also be helpful in Turkey to detect such a compli-cated condition for baby and mother.

The depression rate is correlated with other regionsin Anatolia region which has the highest fertility rate inTurkey, and in Diyarbak›r which on the 10th rank forfertility rate.[19] The reason for this situation can beexplained with the support from relatives and friendsduring postpartum period.

ConclusionAlthough postpartum depression is usually overlooked,it is a significant mood disorder, which should be diag-nosed and treated, and it affects maternal health anddevelopment of baby.


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3. Deveci, A. Postpartum psikiyatrik bozukluklar. BirinciBasamak için Psikiyatri 2003;2:42–6.

4. American Psychological Association. Diagnostic and StatisticalManual of Mental Disorders. DSM-IV-tr. 4th ed. WashingtonDC: American Psychiatric Association; 2000.

5. Cox JL, Holden JM, Sagovsky R. Detection of postnataldepression. Development of the 10-item Edinburgh PostnatalDepression Scale. Br J Psychiatry 1987;150:782–6.

6. Aydin N, Inandi T, Yigit A, Hodoglugil NN. Validation ofthe Turkish version of the Edinburgh Postnatal DepressionScale among women within their first postpartum year. SocPsychiatry Psychiatr Epidemiol 2004;39:483–6.

7. Gülseren L. Do¤um sonras› depresyon: Bir gözden geçirme.Turk Psikiyatri Derg 1999;10:58–67.

8. Murray L, Cooper PJ. Effects of postnatal depression oninfant development. Arch Dis Child 1997;77:99–101.

9. Brand SR, Brennan PA. Impact of antenatal and postpartummaternal mental illness: how are the children? Clin ObstetGynecol 2009;52:441–55.

10. Gonidakis F, Rabavilas AD, Varsou E, Kreatsas G,Christodoulou GN. A 6-month study of postpartum depres-sion and related factors in Athens Greece. Compr Psychiatry2008;49:275–82.

11. Kirpinar I, Gözüm S, Pasinlio¤lu T. Prospective study ofpostpartum depression in eastern Turkey prevalence, socio-demographic and obstetric correlates, prenatal anxiety andearly awareness. J Clin Nurs 2010;19:422–31.

12. Ayvaz S, Hocao¤lu C, Tiryaki A, Ak I. Incidence of postpar-tum depression in Trabzon province and risk factors at ges-tation. [Article in Turkish] Turk Psikiyatri Derg 2006;17:243–51.

13. Danaci EA, Dinç G, Deveci A, Sen FS, Içelli I. Postnataldepression in Turkey: epidemiological and cultural aspects.Soc Psychiatry Psychiatr Epidemiol 2002;37:125–9.

14. Gulseren L, Erol A, Gulseren S, Kuey L, Kilic B, Ergor G.From antepartum to postpartum: a prospective study on theprevalence of peripartum depression in a semiurban Turkishcommunity. J Reprod Med 2006;51:955–60.

15. Lanes A, Kuk JL, Tamim H. Prevalence and characteristicsof postpartum depression symptomatology among Canadianwomen: a cross-sectional study. BMC Public Health2011;11:302.

16. Inandi T, Elci OC, Ozturk A, Egri M, Polat A, Sahin TK.Risk factors for depression in postnatal first year, in easternTurkey. Inter J Epidemiol 2002;31:1201–7.

17. Goker A, Yan›kkerem E, Demet MM, Dikayak S, YildirimY, Koyuncu FM. Postpartum depression: is mode of deliverya risk factor? ISRN Obstet Gynecol 2012;2012:616759.

18. Hübner-Liebermann B, Hausner H, Wittmann M.Recognizing and treating peripartum depression. DtschArztebl Int 2012;109:419–24.

19. Türkiye ‹statistik Kurumu (TÜ‹K). Do¤um ‹statistikleri,2012. Ankara: TÜ‹K; 2013; Nr. 13618.

Analysis of maternal serum and urinary lipocalin-2 levels

Yeflim Bayo¤lu Tekin1, Ülkü Mete Ural1, Aynur K›rbafl2, fienol fientürk1, Figen K›r fiahin1

1Department of Obstetrics & Gyneceology, Faculty of Medicine, Recep Tayyip Erdo¤an University, Rize, Turkey2Department of Biochemistry, Faculty of Medicine, Recep Tayyip Erdo¤an University, Rize, Turkey

Introduction

Lipocalin-2 is a glycoprotein weighing 25 kDa fromlipocalin family. It was first defined as a matrix protein ingranules within human neutronphiles.[1] In different celltypes, it has a role as a growth and differentiation factor.

Its expression was found in many organs such as liver,kidney and adipose tissue. It was shown that it is alsosecreted at higher rates in also inflammatory reactions.[2]

It has been determined that lipocalin-2 is an inflam-matory marker closely associated with insulin resistanceand hyperglycemia, and has a role to create insulin resist-

Özet: Maternal serum ve üriner lipokalin-2 düzeylerinin de¤erlendirilmesiAmaç: Lipokalin-2 lökositlerden salg›lanan bir glikoproteindir.Preeklampsinin indükledi¤i endotel hasar›na ve gestasyonel diya-betin oluflturdu¤u hiperglisemiye ba¤l› olarak maternal kanda veidrarda lipokalin-2 düzeylerinin etkilendi¤i bilinmektedir. Ancaksa¤l›kl› gebelerdeki düzeylerini araflt›ran yeterli say›da çal›flma bu-lunmamaktad›r. Bu çal›flmada sa¤l›kl› gebelerde lipokalin-2 düzey-lerindeki de¤iflikliklerin belirlenmesi amaçlanm›flt›r. Yöntem: Bu çal›flma kesitsel ve vaka kontrollü olarak yürütülmüfl-tür. Ayn› hasta grubundan ilk ve üçüncü trimesterde kan ve idrar-da lipokalin-2 düzeyleri belirlenerek karfl›laflt›r›lm›flt›r. Ayr›ca ol-gular›n tam kan parametreleri, biyokimyasal ve üriner verileri dede¤erlendirilmifltir. Bulgular: Lipokalin-2 düzeyleri hem maternal kanda hem de id-rarda üçüncü trimesterde istatistiksel olarak anlaml› düzeyde düfl-mektedir (p<0.05). Ancak di¤er hematolojik, biyokimyasal ve üri-ner parametrelerde anlaml› de¤ifliklik saptanmam›flt›r (p>0.05). Sonuç: Lipokalin-2 preeklampsi ve gestasyonel diyabet gibi gebe-lik komplikasyonlar›n›n erken tan›s›nda kullan›lan yeni bir mar-kerdir. Sa¤l›kl› gebeliklerde lipokalin-2 seviyelerinin ilk trimeste-re göre 3. trimesterde daha düflük seviyelere indi¤i görülmektedir.Ancak daha genifl olgu serileri ile longitudinal olarak maternal se-rum ve idrar düzeylerinin belirlendi¤i çal›flmalara ihtiyaç vard›r.

Anahtar sözcükler: Gebelik, lipokalin-2, biyokimyasal marker.

Correspondence: Yeflim Bayo¤lu Tekin, MD. Recep Tayyip Erdo¤an Üniversitesi T›p Fakültesi, Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, Rize, Turkey. e-mail: [email protected] Received: October 4, 2014; Accepted: January 12, 2015Please cite this article as: Bayo¤lu Tekin Y, Mete Ural Ü, K›rbafl A, fientürk fi, K›r fiahin F.Analysis of maternal serum and urinary lipocalin-2 levels. Perinatal Journal 2015;23(1):30–33.©2015 Perinatal Medicine Foundation



Original Article


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Abstract

Objective: Lipocalin-2 is a glicoprotein secreted by leukocytes. It isknown that lipocalin-2 levels are affected in maternal blood andurine depending on the endothelial damage induced by preeclamp-sia, and hyperglycemia created by gestational diabetes. However,there are not sufficient studies investigating the levels in healthypregnants. In our study, we aimed to determine the changes inlipocalin-2 levels of healthy pregnant women. Methods: This study was carried out as cross-sectional and case-controlled. Lipocalin-2 levels were determined in blood and urineat first and third trimesters in the same patient group and they werecompared. Also, full blood parameters, biochemical and urinarydata of the cases were also evaluated. Results: Lipocalin-2 levels decrease at a statistically significant levelin both maternal blood and urine at the third trimester (p<0.05).However, no significant change was found in other hematologic,biochemical and urinary parameters (p>0.05).Conclusion: Lipocalin-2 is a new marker used in the early diagnosisof gestational complications such as preeclampsia and gestational dia-betes. It is seen that lipocalin-2 levels in healthy pregnant womendecrease to lower levels in third trimester compared to first trimester.However, further studies are required with more populations wherematernal serum and urine levels are determined longitudinally.

Keywords: Pregnancy, lipocalin-2, biochemical marker.



31

ance for gestational diabetes.[3] It was shown that it issecreted from mature renal epithelium, and it is useful toidentify renal damage at early period. Also, it was foundthat maternal lipocalin-2 levels increased at the earlyperiod depending on the preeclampsia.[4]

Although lipocalin-2 levels were found to be high ingestational complications such as preeclampsia and ges-tational diabetes in the literature, there are no sufficientstudies evaluating lipocalin-2 levels in normal pregnan-cies and changes during pregnancy. Our aim in thisstudy is to evaluate lipocalin-2 levels in healthy pregnantwomen and to determine changes during pregnancy. Inthis way, it would be more significant to understand ifthe changes found in gestational complications are phys-iological responses or the results of the disease patho-genesis. In our study, we aimed to determine and com-pare lipocalin-2 values at first and third trimesters inhealthy pregnant women not complicated by any preg-nancy-induced diseases, and to identify the changes inlipocalin-2 levels during pregnancy.

MethodsThis is a cross-sectional case-controlled study. Thestudy was carried out for a year in antenatal polyclinic ofa university hospital. The study was approved by thelocal ethics committee of the university, and the con-sents of the participants were received by informingthem about the study.

Pregnant women between 18- and 35-year-oldreferred to the hospital for their first antenatal visit wereincluded in the study. Patients with chronic hyperten-sion, preeclampsia, pregestational diabetes history orthose diagnosed with gestational diabetes in their previ-ous pregnancies were excluded from the study. Also thepatients with the history of renal, cardiovascular,autoimmune and hepatobiliary system diseases wereexcluded from the study.

First venous blood and urine samples were collectedfrom the patients who referred within their firsttrimester during their 9–12 weeks of gestation and foundto have single alive fetus. Second blood and urine sam-ples were collected at the visit carried out between 34and 36 weeks of gestation. Blood and urine samples werefirst centrifuged and then separated as supernatant, andkept at -20°C. Full blood parameters and routine bio-chemical and urinary analyses of the participants weredone concurrently in order to determine possible addi-tional pathologies and hematologic, biochemical andurinary anomalies which may be induced by pregnancy.

Lipocalin-2 serum and urine levels were studied byELISA method and according to the recommendationsof Biovender (Research and Diagnostic Products,Heidelberg, Germany). Intra-assay and inter-assay coef-ficients of variation (CV) were found as 7.5% and 9.7%.Sensitivity was calculated as 0.02 ng/ml.

Statistical analysis was carried out by SPPS statisticalsoftware (SPSS Inc., Chicago, IL, USA) version 17.0.Normal distribution of the data was tested byKolmogorov-Smirnov test and Lilliefor’s correction test.The data displaying normal distribution were provided asmean±standard deviation. Paired-sample test was used tocompare first and second blood and urine samples. Thevalue p<0.05 was considered statistically significant.

ResultsForty healthy pregnant women who referred in their firsttrimester were included in the study. Five of the cases didnot come for their visits. Two cases were excluded fromthe study due to gestational diabetes and one case due topreeclampsia. The study was completed with a total of 32cases. Mean age of the participants was 28.9±5.6 and thegravida was 2.0±1.1. Maternal hematologic, biochemicaland urinary parameters of first and third trimesters werecompared. In both visits, no significant difference wasfound in hemoglobin, hematocrit and platelet valuesfrom full blood parameters and in glucose, BUN, creati-nine, ALT, AST and urinary pH and density values frombiochemical parameters (Table 1). It was seen that both

Table 1. Comparison of maternal serum and urinary parameters according to the trimesters.

First trimester Last trimester P value

s-lipocalin-2 (ng/ml) 78.79±20.4 60.48±20.69 0.001u-lipocalin-2 (ng/ml) 76.84±62.50 36.34±29.79 0.022Glucose (mg/dL) 90.84±13.29 92.15±13.07 0.837Creatinine (mg/dL) 0.57±0.07 0.57±0.06 0.705BUN (mg/dL) 14.36±4.02 14.8±3.4 0.530ALT (U/L) 11.45±4.86 11.33±3.96 0.893AST (U/L) 14.62±3.15 14.70±2.86 0.711WBC (K/uL) 10.93±1.68 9.94±1.48 0.053Hb (g/dL) 11.3±1.08 11.58±1.33 0.083Hct (%) 33.20±2.48 33.96±2.43 0.172PLT (K/uL) 236.91±61.74 233.47±60.25 0.431u-pH 6.37±0.76 6.14±0.56 0.217Density 1.012±0.004 1013±0.005 0.507

ALT: alanine transaminase; AST: aspartate transaminase; BUN: blood urea nitrogen;Hb: hemoglobin; Hct: hematocrit; PLT: platelet; s-: serum; u-: urinary; WBC: whiteblood cell.

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urinary and serum lipocalin-2 levels were significantlylow in the third trimester compared to the first trimester(Table 1).

DiscussionIn our study, we evaluated maternal serum and urinarylipocalin-2 levels in the first and third trimesters ofnon-complicated pregnant women, and we found thatlipocalin levels of both in urine and serum were signif-icantly lower in the third trimester. In their study,Edelstam et al. evaluated lipocalin-2 levels on healthypregnant women during the third trimester at 33, 36and 39 weeks of gestation and postpartum period.They reported that lipocalin-2 levels increaseddepending on the week of gestation; however, theselevels reached their highest values at postpartum peri-od.[5] They stated that increasing lipocalin-2 levels maybe associated with postpartum infection.

Lipocalin-2 levels are usually the discussion topic ofthe studies carried out on complicated pregnancies. Asbeing a marker to determine endothelial damage, theyare used in studies on preeclampsia.[6] The lipocalin-2values in pregnant women complicated withpreeclampsia were reported at higher levels. It waseven shown that this increase induced by endothelialdamage began in the second trimester and continuedto increase on the third trimester. In these studieswhere healthy pregnant women were included as con-trol group, it was stated that lipocalin-2 levels were sta-ble in healthy cases.[6] Similarly, Karampas et al. foundin their longitudinal studies where healthy pregnantwomen were compared with pregnant women compli-cated with preeclampsia and growth retardation thatlipocalin-2 levels were similar to normal pregnantwomen in all three trimesters.[7] Ödum et al. reportedthat lipocalin-2 in the urine were at high levels in nor-mal pregnant women unlike preeclampsia.[8] However,we observed in our study that lipocalin-2 levels werenot stable in normal pregnant women, and they weresignificantly low both in urine and serum in the thirdtrimester compared to the first trimester.

In a study performed on 130 healthy individualswhere lipocalin-2 was used to determine renal functionand glomerular filtration, serum lipocalin-2 levels ofnon-pregnant women were compared with the valuesat all three trimesters of gestation. However, this wasnot a case-controlled study, and the values at the sec-ond trimester were high significantly.[9]

The strength of our study is to be a case-controlledstudy. Analysis of lipocalin-2 levels of the same patientgroup in urine and serum at both first and thirdtrimesters, and significantly low results obtained inboth analyses show the reliability of the study.However, small number of population, cases beingpreconceptional, and non-availability of secondtrimester and postpartum values are among the limita-tions of the study.

ConclusionLipocalin-2 is a promising marker as the early identifi-er of endothelial damage, and for the early diagnosis ofpreeclampsia as well as glucose intolerance and hyper-glycemia. However, in the light of existing studies, itraises concern that lipocalin-2 levels in healthy preg-nant women do not have clear standard ranges, andthere are contradictory results about the progress ofblood and urine levels during pregnancy. The resultsof our study contribute to the determination of thenormal progress of lipocalin-2 in healthy pregnantwomen as a candidate marker to predict severe gesta-tional complications. On the other hand, further stud-ies with wider populations where reference ranges aredetermined well according to the trimesters in healthypregnant women will help to enhance the diagnosticcapabilities of lipocalin-2.


References1. Kjeldsen L, Bainton DF, Sengelov H, Borregaard N.

Identification of neutrophil gelatinase-associated lipocalin asa novel matrix protein of specific granules in human neu-trophils. Blood 1994;83:799–807.

2. Cowland JB, Sorensen OE, Sehested M, Borregaard N.Neutrophil gelatinase-associated lipocalin is up-regulated inhuman epithelial cells by IL-1 beta, but not by TNF-alpha.J Immunol 2003;171:6630–9.

3. Lou Y, Wu C, Wu M, Xie C, Ren L. The changes of neu-trophil gelatinase-associated lipocalin in plasma and itsexpression in adipose tissue in pregnant women with gesta-tional diabetes. Diabetes Res Clin Pract 2014;104:136–42.

4. D’Anna R, Baviera G, Giordano D, Todarello G, Corrado F,Buemi M. Second trimester neutrophil gelatinase-associatedlipocalin as a potential prediagnostic marker of preeclampsia.Acta Obstet Gynecol Scand 2008;87:1370–3.



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5. Edelstam G, Löwbeer C, Kral G, Gustafsson SA, Venge P.New reference values for routine blood samples and humanneutrophilic lipocalin during third-trimester pregnancy.Scand J Clin Lab Invest 2001;61:583–92.

6. D’Anna R, Baviera G, Giordano D, Todarello G, Russo S,Recupero S, et al. Neutrophil gelatinase-associated lipocalinserum evaluation through normal pregnancy and in preg-nancies complicated by preeclampsia. Acta Obstet GynecolScand 2010;89:275–8.

7. Karampas G, Eleftheriades M, Panoulis K, Rizou M,Haliassos A, Hassiakos D, et al. Maternal serum levels ofneutrophil gelatinase-associated lipocalin (NGAL), matrix

metalloproteinase-9 (MMP-9) and their complex MMP-9/NGAL in pregnancies with preeclampsia and those with asmall for gestational age neonate: a longitudinal study.Prenat Diagn 2014;34:726–33.

8. Ødum L, Andersen AS, Hviid TV. Urinary neutrophilgelatinase-associated lipocalin (NGAL) excretion increasesin normal pregnancy but not in preeclampsia. Clin ChemLab Med 2014;52:221–5.

9. Ma∏yszko JS, Rams L, Drozdowska-Rams L, Ma∏yszko J.Serum neutrophil gelatinase-associated lipocalin as a markerof kidney function in pregnancy – useful or doubtful? ArchMed Sci 2010;6:744–7.

Critical pulmonary stenosis with prenatal diagnosis: a case series and review of literature

Oya Demirci1, Taner Yavuz2, Resul Ar›soy1, Emre Erdo¤du1, P›nar Kumru1, Oya Pekin1

1Perinatology Clinic, Zeynep Kamil Maternity and Pediatrics Training and Research Hospital, Istanbul, Turkey2Pediatric Cardiology Unit, Zeynep Kamil Maternity and Pediatrics Training and Research Hospital, Istanbul, Turkey

Özet: Prenatal tan›l› kritik pulmoner stenoz: Olgu serisi ve literatür derlemesiAmaç: Ventriküler septumu intakt olan kritik pulmoner stenozlu(PS) olgularda sa¤ ventrikül kavitesinin morfolojisi, triküspit kapakboyutu ve postnatal uygulanan tedavilerin de¤erlendirilmesi amaç-lanm›flt›r. Yöntem: Çal›flmaya ikinci ve üçüncü trimestrede fetal ekokardi-yografide kritik PS düflünülen 7 olgu al›nd›. Sa¤ ventrikülde hiper-trofi ve hipoplazinin yan› s›ra pulmoner kapak seviyesinde ileriyönde jet ak›m ve duktus arteriozusta ters ak›m saptanan fetüslerkritik PS olarak de¤erlendirildi. Sa¤ ventrikül kavitesinin morfolo-jisine göre olgular bipartit veya tripartit olarak ayr›ld›. Gestasyonhaftas›na göre triküspit kapak Z-skoru hesapland›. Bulgular: ‹kinci trimesterde tan› konulan olgularda bipartit,üçüncü trimesterde tan› konulan olgularda tripartit sa¤ ventrikülkavitesi belirlendi. Bipartit sa¤ ventrikül morfolojili olgular›n tri-küspit kapak Z-skoru, tripartit olanlardan daha düflük olarak he-sapland›. Yedi olgunun ikisi monokoryonik diamniyotik ikiz gebe-likti. Bipartit olan 3 olguda prostaglandin E1 (PGE1) infüzyonunara¤men postnatal 2. günde balon valvüloplasti yap›ld› ve 3 olgudada Blalock-Taussing flant gereksinimi oldu. Tripartit dört olgudaise PGE1 infüzyonu ile siyanoz kontrolü daha iyi sa¤lanm›fl, üç ol-guda postnatal 2. haftada, dördüncü olguda ise postnatal 55. gün-de balon valvüloplasti uyguland›. Blalock-Taussing flant gereksini-mi olmad›. Sonuç: Kritik PS olgular›nda sa¤ ventrikülün iki ya da üç parçal›olma durumuna, triküspit kapa¤›n darl›k derecesine ba¤l› olarakpostnatal dönemdeki uygulanacak tedavi yöntemleri de¤iflebil-mektedir.

Anahtar sözcükler: Kritik pulmoner stenoz, triküspit darl›k, tri-küspit yetmezlik, postnatal tedavi.

Correspondence: Oya Demirci, MD. Zeynep Kamil Kad›n ve Çocuk Hastal›klar› E¤itim veAraflt›rma Hastanesi, Perinatoloji Klini¤i, ‹stanbul, Turkey. e-mail: [email protected] Received: October 27, 2014; Accepted: January 24, 2015Please cite this article as: Demirci O, Yavuz T, Ar›soy R, Erdo¤du E, Kumru P, Pekin O. Critical pulmonary stenosis with prenatal diagnosis: a case series and review of literature. Perinatal Journal 2015;23(1):34–38.©2015 Perinatal Medicine Foundation



Original Article


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Abstract

Objective: The aim of the study is to investigate the morphology ofright ventricular cavity, the tricuspid valve size and the treatmentsapplied at postnatal period in cases with critical pulmonary stenosis(PS) having intact ventricular septum. Methods: Seven cases included in the study who were considered tohave critical PS in fetal echocardiography at second and thirdtrimesters. The fetuses found to have antegrade jet stream at pul-monary valve level and reverse flow at ductus arteriosus as well ashyperthrophy and hypoplasia on the right ventricle were determinedas critical PS. The cases were categorized as bipartite or tripartiteaccording to the morphology of right ventricular cavity. Z-score oftricuspid valve was calculated according to the week of gestation. Results: Bipartite right ventricle cavity was found in cases diag-nosed at second trimester, and tripartite right ventricle cavity incases diagnosed at third trimester. Tricuspid valve Z-score of thecases with bipartite right ventricle morphology was less than thosewith tripartite. Two out of seven cases were monochorionic diamni-otic twin pregnancies. Balloon valvuloplasty was performed on post-natal second day despite the prostaglandin E1 (PGE1) infusion in 3cases with bipartite, and 3 cases required Blalock-Taussing shunt. Infour tripartite cases, cyanosis control was better by PGE1 infusion,and balloon valvuloplasty was performed on postnatal second day in3 cases and on postnatal 55th day in 4 cases. No Blalock-Taussingshunt was required.Conclusion: In critical PS cases, the treatment methods to beapplied during postnatal period may vary according to the right ven-tricle being of two or three parts and the stenosis level of tricuspidvalve.

Keywords: Critical pulmonary stenosis, tricuspid stenosis, tricuspiddeficiency, postnatal treatment.


Critical pulmonary stenosis with prenatal diagnosis

35

IntroductionCritical pulmonary stenosis (PS) causes reverse flow inthe ductus arteriosus of fetus and severe right ventricularhypertrophy. Secondary to hypertrophy, the right ven-tricular cavity gets narrow especially at apex. Duringneonatal period, it causes shunt and cyanosis at interatri-al level from right to left. Critical PS can also be evaluat-ed within pulmonary atresia with intact ventricular sep-tum (PAIVS) due to the fact that it may progress to pul-monary atresia (PA) as week of gestation advances.[1] Themost distinguishing characteristic of the fetus with criti-cal pulmonary stenosis from mild and medium PS is thereverse flow of ductus arteriosus seen in ultrasonograph-ic examination.[1,2] There is no concomitant genetic dis-ease or extra cardiac anomaly in most of the PAIVS andcritical PS cases.[1] The abnormal appearance inquadrilocular during cardiac examination between 18and 22 weeks of gestation at second trimester is usuallythe most striking characteristics and it initiates theprocess toward the diagnosis. However, although somecases have PS at critical levels, the sizes of right ventriclemay seem normal and it may cause late diagnosis. Insome other cases, PAIVS and critical PS diagnosis maybe established even at the first trimester.[1]

Right ventricular cavity morphologically consists ofthree parts which are inlet, apex and outlet. Ventricularhyperthropy occurs at various levels depending on thesize of narrowing of the right ventricular outlet and theweek of gestation that pulmonary atresia occurs, stenosison tricuspid valve and the level of failure.[1] As a result ofthe overgrowth of intracavity muscular layer, apex ofright ventricle (bipartite) or both apex and outlet (unipar-tite) may not develop. In critical PS, right ventricle usu-ally has all three parts (tripartite). Sometimes, apicalregion may not develop well and may have bipartite mor-phology as in PAIVS.[1,2] Z-score is used when evaluatingtricuspid valve size.[1–3] In cases which developed rightventricular hypoplasia with bipartite and unipartite mor-phology, severe tricuspid valve stenosis (low Z-score) isalso observed.[1,2]

For newborns with critical pulmonary stenosis, vari-ous treatment options are offered according to right ven-tricular morphology usually at postnatal early periodsuch as balloon valvuloplasty, ductal stent, Blalock-Taussing (BT) shunt operation, biventricular repair atadvanced periods, and Glenn or Fontan procedures. Inour study, we aimed to investigate the morphology of

right ventricular cavity, tricuspid valve Z-scores andtreatments applied in cases with critical pulmonarystenosis (PS) having intact ventricular septum.

MethodsSeven cases considered having critical PS in fetalechocardiography at second and third trimesters at thePerinatology Clinic of Zeynep Kamil Maternity andPediatrics Training and Research Hospital between2013 and 2014 were included in the study. The fetusesfound to have antegrade jet stream at pulmonary valvelevel and reverse flow at ductus arteriosus as well ashyperthrophy and hypoplasia on the right ventricle weresuspected to be critical PS. The cases with postnatalclinical progress and echocardiography findings com-patible with critical PS were included in the study. Thecases were categorized as bipartite or tripartite accord-ing to the morphology of right ventricular cavity. Z-score of tricuspid valve was calculated according to theweek of gestation.[3] Tricuspid valve insufficiency wascategorized as mild, medium and severe.[4,5]

Ultrasonographic examinations were performed withthe use of Voluson 730 Pro (GE Healthcare,Milwaukee, WI, USA). Transthoracic echocardiogra-phy was carried out on the first day after the delivery.Prenatal and postnatal echocardiography measurementswere evaluated by pediatric cardiology and perinatologydepartments. Statistical analysis was done by SPSS v.11.5 (SPSS, Inc., Chicago, IL, USA). Constant datawere provided as median.

ResultsMedian week of gestation for the cases was 32 (range:24 to 34) weeks when prenatal diagnosis was estab-lished. In the fetal ultrasonography during secondtrimester for the cases which were diagnosed at thirdtrimester, the size of right ventricle was normal, and noabnormality was observed at the right ventricle outlet.Bipartite right ventricle cavity was found in cases diag-nosed at second trimester, and tripartite right ventriclecavity in cases diagnosed at third trimester. No casedeveloped pulmonary atresia. Median delivery weekwas 37 (range: 37 to 39 weeks) and median birth weightwas 2950 (2570–3060) g. Two of the seven cases weremonochorionic diamniotic twin pregnancy, and twin-to-twin transfusion syndrome was not developed ineither case. One of the twin pregnancies delivered at 37

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weeks of gestation while the other one at 34 weeks ofgestation. Development of fetuses was normal in thetwin pregnancy which delivered at 37 weeks of gesta-tion; however, selective intrauterine growth retardation(IUGR) developed in the other twin pregnancy deliv-ered at 34 weeks of gestation. While critical PS wasobserved in the elder fetus, there was perimembranousventricular septal defect in the donor fetus.Chromosome examinations of all cases were normal;one case had anal atresia. Tricuspid valve Z-score of thecases with bipartite right ventricle morphology was lessthan those with tripartite. Also, in 5 cases with negativetricuspid valve Z-score, medium tricuspid failure wasdetected. Prostaglandin E1 (PGE1) infusion was initiat-ed in all cases as soon as they were born. In 3 bipartitecases, cyanosis developed at early period despite thePGE1 infusion, and all had balloon valvuloplasty onpostnatal second day. In one case, BT shunt was per-formed since cyanosis continued on 5th day after bal-loon valvuloplasty, no problem observed during 3-month follow-up. Another case had operation due toanal atresia after valvuloplasty; when cyanosis increasedafter the operation, the case was referred for BT shuntbut passed away when 15-day-old before shunt wasapplied. The other 37-week-old twin with bipartitemorphology was applied BT shunt at the same day sincesufficient clinical response was not received after bal-loon valvuloplasty. Clinical findings were stable during3-month clinic follow-up. In four tripartite cases,cyanosis was kept under control better with PGE1 infu-

sion; balloon valvuloplasty was applied in 3 cases onpostnatal 2nd week (9th, 11th and 12th day, respective-ly); also ductal stent was placed to one case (case nr. 6).Fourth case was monitored in the newborn intense careunit for 54 days by PGE1 treatment on receptor babydeveloping selective IUGR; and balloon valvuloplastywas applied on 55th day (Table 1).

DiscussionCritical PS is a cardiac anomaly which is present at post-natal early period together with right ventricularhypoplasia and where pulmonary circulation depends onductus. It requires postnatal emergency medical andinvasive/surgical treatment. Therefore, diagnosing atprenatal period and delivering at a tertiary center arevery significant in terms of applying prostoglandin E1treatment at postnatal period without any delay and tomake preparations for required procedures afterwards.

In our study, we aimed to discuss treatment methodsapplied at postnatal period according to the right ven-tricular morphologies of 7 cases which were diagnosedas critical PS during prenatal period. In cases whereright ventricular outlet of fetal is congested or closed, itis the tricuspid valve size which determines the develop-ment level of right ventricle.[1] The postnatal treatmentplanning of critical PS and PAIVS cases is determinedaccording to tricuspid valve Z-scores.[6] In compliancewith the literature, we found that tricuspid valve Z-scores of those with bipartite right ventricular morphol-

Table 1. Summary of the prenatal and postnatal data of 7 cases with critical pulmonary stenosis.

Case Week of Chromosomal/ Week of gestation Cardiac Right Tricuspid Postnatal gestation- extra-cardiac and weight insufficiency, ventricle/ insufficiency– treatmentdiagnosis anomaly (percentile) hydrops component stenosis/Z-score

1 25 n/a 39-2950 g (10–50p) n/a Two Exists–medium /-2.02 Balloon valvuloplasty on 2nd dayBT shunt on 5th day - ALIVE

2 24 Anal atresia 37-2650 g (10–50p) n/a Two Exists–medium /-2.05 Balloon valvuloplasty on 2nd dayExitus on 15th day before BT shunt

3 22 MCDA n/a 37-2570 g (10–50p) n/a Two Exists – medium/-2.65 Balloon valvuloplasty on 2nd daytwin BT shunt on 2nd day - ALIVE

4 36 n/a 37-3000 g (10–50p) n/a Three n/a/0.17 Balloon valvuloplasty on 9th day – ALIVE

5 34 n/a 39-3060 g (10–50p) n/a Three n/a/0.14 Balloon valvuloplasty on 11th day – ALIVE

6 32 n/a 38-2450 g (10–50p) n/a Three Exists–mild /-0.49 Balloon valvuloplasty on 12th day+ductal stent – ALIVE

7 34 MCDA n/a 34-3150 g (50–95p) n/a Three Exists–mild /-0.65 Balloon valvuloplasty on 55th day – ALIVEtwin


Critical pulmonary stenosis with prenatal diagnosis

37

ogy were less than those with tripartite.[2,7-9] Given thetreatments applied during postnatal period, those withbipartite were required to have balloon valvuloplastydespite the prostaglandin treatment and also BT shuntwas required since there was no sufficient recovery.Similar to our study, Cho et al. reported that BT shuntrequirement was higher in those with bipartite rightventricular cavity among critical PS and PAIVS cases.[10]

Many studies highlighted that prenatal tricuspid valvesizes are significant to predict prognosis during postna-tal period.[2,7-9] The narrowing of tricuspid valve affectsright ventricular development negatively while tricuspidvalve deficiency affects right ventricular developmentpositively. Therefore, in cases with high level of narrow-ing on tricuspid valve, the tricuspid valve deficiency issignificant for the development of right ventricle.[1] Inour study, we found distinctive tricuspid valve deficien-cy in our 3 bipartite cases which had distinctive narrow-ing of tricuspid valve (Z-score <-2). It is considered thatthe tricuspid valve deficiency increases the volume loadon right ventricle and supports the development of rightventricle.[1] In cases having only narrowing on the tricus-pid valve without any deficiency, it is possible to observemuscular pulmonary atresia as a result of the overgrowthof muscle layer on infundibular area.[11] Similarly,Lowenthal et al. reported that postnatal prognosis wasbetter in PAIVS and critical PS cases with mid- andsevere deficiency on tricuspid valve.[7]

In monochorionic twin pregnancies, especially intwin-to-twin transfusion syndrome, the narrowing oratresia on the right ventricular outlet of the receptorfetus was higher than the normal population.[12–14] Inour two cases with monochorionic twin pregnancies,twin-to-twin transfusion syndrome did not develop.On the other hand, one case had selective IUGR andcritical pulmonary stenosis was found in elder fetus.Similarly, Gardiner et al. reported in their series of 21cases that there were 2 cases with monochorionic twinpregnancy which did not develop twin-to-twin transfu-sion syndrome.[2] While we diagnosed one of our twinpregnancy cases at second trimester, we diagnosedother one at third trimester, and we did not found anycardiac pathology in second trimester ultrasonography.In the ultrasonographic screening at 18-22 weeks, rightventricle can be seen at relatively normal size, andtherefore it can be overlooked. At the same time, thenarrowing on right ventricular outlets displays pro-gression and we are able to detect such patients at third

trimester since hyperthrophy on right ventricleincreases gradually.[15,16]

In cases with critical PS, chromosomal anomaly andextra cardiac anomaly are quite rare. Similarly, we foundin our study no chromosomal anomaly, but anal atresiaas extra cardiac anomaly only in one case. Generally,cardiac failure and intrauterine growth retardation arenot observed during intrauterine period in cases withPAIVS and critical pulmonary stenosis.[1] Correlatively,our cases did not develop any cardiac failure finding.Except the twin pregnancy with selective intrauterinegrowth retardation, we did not find intrauterine growthretardation in any of our cases.

ConclusionConsequently, in critical PS cases, the treatment meth-ods to be applied during postnatal period may varyaccording to the right ventricle being of two or threeparts and the stenosis level of tricuspid valve.Therefore, diagnosing at prenatal period and catego-rizing cases will facilitate to maintain postnatal hemo-dynamic stability and to plan required invasive and/orsurgical treatment options by initiating prostaglandintreatment.


References1. Yagel S, Silverman NH, Gembruch U. Fetal Cardiology:

Embryology, Genetics, Physiology, EchocardiographicEvaluation, Diagnosis and Perinatal Management of CardiacDiseases (Series in Maternal Fetal Medicine). 2nd ed.London: Informa Helatcare; 2008; p: 267–80.

2. Gardiner HM, Belmar C, Tulzer G, Barlow A, Pasquini L,Carvalho JS, et al. Morphologic and functional predictors ofeventual circulation in the fetus with pulmonary atresia orcritical pulmonary stenosis with intact septum. J Am CollCardiol 2008;51:1299–308.

3. Schneider C, McCrindle BW, Carvalho JS, Hornberger LK,McCarthy KP, Daubeney PE. Development of Z-scores forfetal cardiac dimensions from echocardiography. UltrasoundObstet Gynecol 2005;26:599–605.

4. Bolger AF, Eigler NL, Maurer G. Quantifying valvularregurgitation. Limitations and inherent assumptions ofDoppler techniques. Circulation 1988;78:1316–8.

5. Rivera JM, Vandervoort PM, Vazquez de Prada JA, Mele D,Karson TH, Morehead A, et al. Which physical factorsdetermine tricuspid regurgitation jet area in the clinical set-ting? Am J Cardiol 1993;72:1305–9.

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6. Hanley FL, Sade RM, Blackstone EH, Kirklin JW, FreedomRM, Nanda NC. Outcomes in neonatal pulmonary atresiawith intact ventricular septum. A multiinstitutional study. JThorac Cardiovasc Surg 1993;105:406–23.

7. Lowenthal A, Lemley B, Kipps AK, Brook MM, Moon-Grady AJ. Prenatal tricuspid valve size as a predictor of post-natal outcome in patients with severe pulmonary stenosis orpulmonary atresia with intact ventricular septum. FetalDiagn Ther 2014;35:101–7.

8. Peterson RE, Levi DS, Williams RJ, Lai WW, Sklansky MS,Drant S. Echocardiographic predictors of outcome in fetus-es with pulmonary atresia with intact ventricular septum. JAm Soc Echocardiogr 2006;19:1393–400.

9. Salvin JW1, McElhinney DB, Colan SD, Gauvreau K, delNido PJ, Jenkins KJ, et al. Fetal tricuspid valve size andgrowth as predictors of outcome in pulmonary atresia withintact ventricular septum. Pediatrics 2006;118:e415–20.

10. Cho MJ, Ban KH, Kim MJ, Park JA, Lee HD. Catheter-based treatment in patients with critical pulmonary stenosisor pulmonary atresia with intact ventricular septum: a singleinstitute experience with comparison between patients withand without additional procedure for pulmonary flow.Congenit Heart Dis 2013;8:440–9.

11. Davignon AL, Greenwold WE, Dushane JW, Edwards JE.Congenital pulmonary atresia with intact ventricular sep-tum. Clinicopathologic correlation of two anatomic types.Am Heart J 1961;62:591–602.

12. Zosmer N, Bajoria R, Weiner E, Rigby M, Vaughan J, FiskNM. Clinical and echographic features of in utero cardiacdysfunction in the recipient twin in twin-twin transfusionsyndrome. Br Heart J 1994;72:74–9.

13. Lougheed J, Sinclair BG, Fung Kee Fung K, Bigras JL, RyanG, Smallhorn JF, et al. Acquired right ventricular outflowtract obstruction in the recipient twin in twin-twin transfu-sion syndrome. J Am Coll Cardiol 2001;38:1533–8.

14. Herberg U, Gross W, Bartmann P, Banek CS, Hecher K,Breuer J. Long term cardiac follow up of severe twin to twintransfusion syndrome after intrauterine laser coagulation.Heart 2006;92:95–100.

15. Todros T, Paladini D, Chiappa E, Russo MG, Gaglioti P,Pacileo G, et al. Pulmonary stenosis and atresia with intactventricular septum during prenatal life. Ultrasound ObstetGynecol 2003;21:228–33.

16. Paladini D, Volpe P. Ultrasound of Congenital FetalAnomalies: Differential Diagnosis and Prognostic ‹ndica-tors. 2nd ed. Boca Raton, FL: CRC Press; 2014; p: 184–6.

Evaluation of prenatal invasive procedures: analysis of retrospective cases

Aybike Tazegül Pekin1, Özlem Seçilmifl Kerimo¤lu1, Setenay Arzu Y›lmaz1,Nadir Koçak2, Feyza Nur ‹ncesu1, Ayfle Gül Kebapc›lar1, Çetin Çelik1

1Department of Gynecology & Obstetrics, Faculty of Medicine, Selçuk University, Konya, Turkey2Department of Medical Genetics, Faculty of Medicine, Selçuk University, Konya, Turkey

Özet: Prenatal invaziv giriflimlerin de¤erlendirilmesi:Retrospektif olgular›n analiziAmaç: Bu çal›flmam›zda amaç, klini¤imizde uygulanan prenatalinvaziv giriflimlerin sonuçlar›n› sunmakt›r. Yöntem: Nisan 2011–2014 tarihleri aras›nda uygulanan prenatalinvaziv giriflimlerin kay›tlar› retrospektif olarak tarand›, invaziv gi-riflimlerin endikasyonlar›, komplikasyonlar› ve karyotip sonuçlar›de¤erlendirildi. Bulgular: Ultrasonografide tespit edilen sadece minör ve/veyamajör anomalisi olan 72 (%23.4) gebeye, tarama testlerinde artm›flrisk nedeniyle baflvuran 226 (%73.3) hastaya, aile öyküsü olan 5(%1.6) hastaya ve ileri anne yafl› nedeniyle 5 (%1.6) hastaya prena-tal invaziv giriflim uyguland›. Bu hastalar›n %81.8’ine (n=252) am-niyosentez, %11.7’sine (n=36) koryon villus biyopsisi, %6.5’ine(n=20) ileri gebelik haftas› nedeniyle kordosentez uyguland›. Kar-yotip analizi sonuçlar› 278 (%90.2) hastada normal, 11 (%3.5) has-tada sitogenetik sonuç al›namad› ve 19 (%6.2) hastada anöploidi,(%2.9 trizomi ve %3.3 di¤er genetik anormallikler/ varyasyonlar)olarak bildirildi. Karyotip sonucu, 46XX+22p ve 46XY,9qh olan 2hasta takip edildi. Ultrasonografi de¤erlendirmesinde minör belir-teç veya majör anomali saptanmayan hastalar›n sonuçlar› normalvaryant olarak kabul edildi. Bu gebelikler sa¤l›kl› canl› do¤um ilesonuçland›. Ultrasonografi bulgular› da olan karyotip anomalileritermine edildi. Sonuç: Prenatal tarama testleri halen prenatal invaziv giriflimlerinilk s›radaki endikasyonlar›n› oluflturmaktad›r. Ancak minör ve/ve-ya majör anomaliler anöploidik fetüslerin büyük k›sm›nda görün-tülenebilmektedir, bu nedenle prenatal tan› endikasyonu konulanfetüsler dikkatle de¤erlendirilmelidir.

Anahtar sözcükler: Prenatal tan›, amniyosentez, koryon villus bi-yopsisi.

Correspondence: Aybike Tazegül Pekin, MD. Selçuk Üniversitesi T›p Fakültesi Kad›nHastal›klar› ve Do¤um Anabilim Dal›, Konya, Turkey. e-mail: [email protected] Received: October 18, 2014; Accepted: February 1, 2015Please cite this article as: Tazegül Pekin A, Seçilmifl Kerimo¤lu Ö, Y›lmaz SA, Koçak N,‹ncesu FN, Kebapc›lar AG, Çelik Ç. Evaluation of prenatal invasive procedures: analysis of retrospective cases. Perinatal Journal 2015;23(1):39–44.©2015 Perinatal Medicine Foundation



Original Article


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Abstract

Objective: In this study, we aimed to present the results of prena-tal invasive procedures carried out in our clinic. Methods: The records of the prenatal invasive procedures carriedout between April 2011 and 2014 were analyzed retrospectively, andthe indications, complications and karyotype results of invasive pro-cedures were evaluated. Results: Prenatal invasive procedure was applied to 72 (23.4%)pregnant women who had only minor and/or major anomaliesaccording to ultrasonography, 226 (73.3%) patients who referred forincreased risk at screening tests, 5 (1.6%) patients with family histo-ry and 5 (1.6%) patients with advanced maternal age. Amniocentesiswas carried out for 81.8% (n=252) of these patients, chorionic villussampling for 11.7% (n=36) of them, and cordocentesis due toadvanced week of gestation for 6.5% (n=20) of them. Karyotypeanalysis results were normal in 278 (90.2%) patients but no cytoge-netic result was obtained in 11 (3.5%) patient, and aneuploidy wasreported in 19 (6.2%) patients (trisomy in 2.9% and other geneticanomalies / variations in 3.3%). Two patients with karyotype resultsas 46XX+22p and 46XY,9qh were followed up. The results of thepatients whose ultrasonography examination did not show anyminor marker or major anomaly were considered as normal variants.Such pregnancies resulted in healthy live births. Karyotype anom-alies also having ultrasonography findings were terminated. Conclusion: Prenatal screening tests are still the major indicationsfor prenatal invasive procedures. However, minor and/or majoranomalies can be displayed in most of the aneuploidic fetuses; there-fore, fetuses established with prenatal diagnosis indication should beevaluated carefully.

Keywords: Prenatal diagnosis, amniocentesis, chorionic villus sam-pling.

IntroductionIn pregnancies with the risk of fetal chromosomalanomaly, chorionic villus sampling (CVS) at the firsttrimester, amniocentesis at the second trimester andinvasive prenatal diagnosis methods such as cordocen-tesis at further weeks may be carried out for diagnosticpurposes. While all these prenatal invasive methodscan be done mainly for fetal karyotype analysis, theyalso can be carried out to identify single gene diseasessuch as sickle cell anaemia or thalassemia major, and toinvestigate fetal infections, fetal blood type, hematocritvalue, enzymes associated with metabolic diseases andlung maturation.[1] Fetal blood transfusion, amniore-duction, amnioinfusion, fetal shunt and laser practicescan be can be listed as the other invasive procedures forfetal treatment purposes.[1] During a few decades, inva-sive procedure indications have become based onnuchal translucency and maternal serum biochemistryparameters rather than being based on advancedmaternal age.[2,3] In this way, with the use of firsttrimester screening tests, CVS practices have becomeprevalent and they have enabled earlier diagnosis. Also,using maternal serum markers has increased the detec-tion rates and decreased false positivity rates, thusdecreased invasive procedure rates. With the tests ana-lyzing cell-free fetal DNA (cfDNA) becoming popularrecently, the decrease of false positivity and invasiveprocedure rates is expected.[4,5] Karyotype analysis canbe done in case of advanced maternal age, trisomy inprevious pregnancy or history of fetus with sex chro-mosome anomaly, presence of translocation, inversionor chromosomal anomaly in spouses, markers indicat-ing aneuploidy or presence of major anomaly in theultrasonography, positive prenatal test results,increased nuchal translucency and maternal anxiety.[6,1]

Amniocentesis is considered to be the easiest methodwith the least risk for maternal and fetal morbidityamong prenatal invasive diagnosis methods.[7]

American College of Obstetricians and Gynaecologists(ACOG) reports the risk of pregnancy loss associatedwith the procedure during amniocentesis performedafter 15 weeks of gestation as 1/300–500.[6] Also, it isreported in experienced centers that the risk of preg-nancy loss with CVS is similar with amniocentesis.[6]

Fetal loss risk after cordocentesis is shown as 1.4%.[8] Inour study, we aimed to present the results of prenatalinvasive procedures that we carried out with variousindications in our clinic.

MethodsA total of 308 pregnant women were included in thestudy who were applied prenatal invasive procedures forthe purpose of karyotype analysis between 2011 and2014 in our clinic. The approval of Ethics Committee ofthe Selçuk University Hospital was obtained for thestudy. The consent forms were received from thepatients in our clinic by informing them that their ultra-sound images and genetic results can be used in the studybefore the examination and the procedure. The caseswere evaluated retrospectively in terms of invasive pro-cedure indications, cell culture success, genetic resultsand fetal prognosis. The pregnant women with risk rateover 1/250 according to the first trimester combined testresult, the pregnant women with risk rate over 1/300according to second trimester screening tests, pregnantwomen having major anomaly or ultrasonographicmarkers which may be associated with fetal karyotypeanomaly, pregnant women who are above 40-year-oldbut did not have any prenatal screening test and preg-nant women with karyotype anomaly risk in their obstet-ric history were recommended invasive proceduresappropriate for their weeks of gestation. The patientsand their spouses were informed about the indicationrelated with the procedure, the technique to be applied,complications and the rates to accomplish result andtheir written consents were received. Before the proce-dure, blood type and HIV and hepatitis B serology ofpregnant women were evaluated. CVS was carried outtransabdominally between 11 and 14 weeks of gestationunder sterile conditions with 18-Gauge (G) needle.Classical amniocentesis procedure at appropriate weekof gestation was preferred in cases with retroverteduterus or posterior located placenta which were techni-cally not suitable for transabdominal CVS procedure.Amniocentesis procedure was carried out between 15and 20 weeks of gestation with 21-G needle under ster-ile conditions by entering through a distant zone fromplacenta and aspiring 1–2 ml fluid for each week of ges-tation. First 2 ml amniotic fluid was not examined inorder to avoid maternal contamination. Cordocentesisprocedure was carried out by using 22-G needle in preg-nancies older than 21 weeks. By entering through theplacental insertion zone or free floating area of umbilicalcord, 2–3 ml fetal blood was collected from umbilicalvein with an injector washed with heparin. Voluson 730Expert (General Electric Healthcare, Milwaukee, WI,USA) and 3.5 MHz convex probe were used during theprocedures. The procedure was carried out after fetus

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and placenta were examined systematically. After theprocedure, a single dose of 300 microgram anti-Dimmunoglobulin was administered intramuscularly tothe pregnant women with Rh alloimmunization risk.Routine antibiotic prophylaxis was not applied. Thepatients were discharged in the same day. Fetal loss with-in three weeks following the procedure was consideredas the complication of the procedure.

The samples collected for genetic analysis were cul-tured for 1 week for CVS, for 3 days for cordocentesisand for approximately 15–20 days for amniocentesisthrough the methods suitable for the samples, and cul-ture extractions were done. Metaphase preparationsobtained after the culture were stained by using TrypsinGiemsa banding method (GTG). In all cases, 25metaphase plates were evaluated for structural irregular-ities and 50 metaphase plates were evaluated for numer-ical irregularities. Computerized analysis system wasused in karyotyping analysis. Chromosomal anomalieswere defined according to International System forHuman Cytogenetic Nomenclature (ISCN) 2009.[9]

The statistical analysis of data was done by usingSPSS software, version 16.0 (SPSS, Inc., Chicago, IL,USA). The data in parametric tests were provided asmean±standard deviation. Percentage values were usedin groups.

ResultsOf 308 pregnant women who undergone invasive proce-dures, mean age was 31.3±6.4 (range: 16 to 46) years,gravida was 2.4±1.1 (range: 1 to 7) and parity was 1.2±1.0(range: 0 to 6). Prenatal invasive test was applied to 72(23.4%) pregnant women who had only minor and/ormajor anomalies according to ultrasonography, 226(73.3%) patients who referred for increased risk atscreening tests, 5 (1.6%) patients with family history and5 (1.6%) patients with advanced maternal age. The mostfrequent invasive procedure indications were increasedrisk at triple test (46%), major and/or minor anomalies(23.4%), increased risk at first trimester combined test(17%) and increased risk at quad test (10.3%) (Fig. 1).Increased nuchal thickness (2.9%) and increased nuchaltranslucency (2.3%) where the most frequent ultrasono-graphic findings among karyotype analysis indications(Table 1). Amniocentesis was carried out for 81.8%(252) of these patients, CVS for 11.7% (36) of them, andcordocentesis due to advanced week of gestation for6.5% (20) of them. Karyotype analysis results were nor-

mal in 278 (90.2%) patients but no cytogenetic resultwas obtained in 11 (3.5%) patient, and aneuploidy wasreported in 19 (6.2%) patients (trisomy in 2.9% andother genetic anomalies/variations in 3.3%) (Table 2).Cordocentesis was applied to one (0.3%) of the caseswithout cytogenetic result, CVS was applied to two(0.6%) of them and amniocentesis was applied to eight(2.5%) of them. There was ultrasonographic marker in16 (84.2) of 19 fetuses found to have aneuploidy. Theresults of two patients, whose karyotype results were46XX+22p and 46XY,9qh but there was no ultrasono-graphic finding, were considered as normal variant andfollowed up. Such pregnancies resulted in healthy livebirths. The follow-ups of two patients whose chromoso-mal analysis results were found as 46XX/47XX+ mar(live healthy delivery) and 46XY,inv(9) (intrauterine fetaldeath at 33 weeks) were discontinued. Gestational prog-noses of these patients were learnt by contacting thepatients. There was major anomaly (omphalocele) in thefetus whose chromosome structure was reported as46XY,inv(9). Fifteen pregnancies which were found tohave karyotype anomalies with ultrasonographic find-ings were terminated upon the requests of patients andfamilies. Four of the terminated fetuses had minor mark-ers and 11 fetuses had major anomalies. In this way, theresults of three patients were considered as variation andthe aneuploidy rate was calculated as 5.2% (16/308). Thepregnancy of a patient, who undergone cordocentesisdue to the diagnosis of non-immune hydrops fetalis at 20weeks, was terminated due to the onset of the pains.Also, another pregnancy undergone CVS due toincreased nuchal translucency at 11 weeks of gestation


Evaluation of prenatal invasive procedures

41

Fig. 1. The rates of invasive procedure indications.

was terminated at 13 weeks of gestation. The karyotypeanalysis of this fetus was 46,XY,inv(Y)(p11;q11).Procedure-related fetal loss rate was 0.6%.

DiscussionIn our study, we found the most frequent invasive pro-cedure indications as increased risk at triple test (46%)and major and/or minor anomalies detected by ultra-sonography (23.4%) while various amniocentesis seriespublished in Turkey reported advanced maternal age asthe most frequent invasive procedure indication.[10,11] Wefound the invasive procedure rate due to advancedmaternal age as 1.6%, and invasive procedures were rec-ommended due to the advanced maternal age risk onlyto the patients who were over 40-year-old and did notundergo prenatal screening tests. Tongsong et al.reported advanced maternal age as the most frequentamniocentesis indication (86.3%), and found invasiveprocedure rate associated with anomalies found by ultra-sonographically as 0.6%.[12] Tabor et al. also reportedadvanced maternal age as the most frequent indication

and they reported invasive procedure rate with ultra-sonography indication as 9%.[13] While previously theliterature was reporting advanced maternal age as the50–60% of amniocentesis indications,[13–15] it is not con-sidered as an amniocentesis indication by itself today. In

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Table 1. Invasive procedure indications according to ultrasonographic findings.

Ultrasonographic findings n=308 %

Normal 236 76.6Bilateral cleft palate/lip 1 0.3Hypoplastic left heart + hydrops fetalis 1 0.3AVSD 3 1Hydrops fetalis 6 1.9Cystic hygroma 5 1.6Cystic hygroma + omphalocele 3 1Omphalocele 2 0.6Choroid plexus cyst >10 mm + SUA 2 0.6Fallot’s tetralogy 2 0.6Dandy-Walker syndrome 2 0.6Echogenic intestine grade 3 + ECF 2 0.6Echogenic intestine grade3 + pyelectasis + increased nuchal thickness 1 0.3Echogenic intestine grade 3 + pyelectasis + hypoplasic nasal bone 1 0.3Holoprosencephaly + corpus callosum agenesis 2 0.6ECF + pyelectasis 8 2.6Ventriculomegaly/hydrocephaly 8 2.6Ventriculomegaly + cleft palate-lip + hydrocephaly 1 0.3VSD+ARSA 1 0.3Ventriculomegaly + SUA 1 0.3Absence/hypoplasia of nasal bone 3 1Increased nuchal thickness 9 2.9Increased nuchal translucency 7 2.3Corpus callosum agenesis + ventriculomegaly + Fallot’s tetralogy 1 0.3

AVSD: atrioventricular septal defect; ARSA: aberrant right sub-clavian artery; ECF: echogenic cardiac focus; SUA: sin-gle umbilical artery; VSD: ventricular septal defect.

Table 2. Karyotype analysis results.

Cytogenetic results N=308 %

Normal 278 90.2

No cytogenetic result 11 3.5

46XY,t(16;22)(p13;q13) 1 0.32

46XY,inv(Y)(p11,q11) 1 0.32

Trisomy 13 1 0.32

46XY+15p 1 0.32

Trisomy 21 6 1.94

Trisomy 18 2 0.64

Triploidy 69 XXX 1 0.32

46XX/47XX+mar 1 0.32

46XX+22p 2 0.64

46XY,inv(9) 1 0.32

46XY,9qh 2 0.64

recent years, invasive procedure rates have decreasedrecommended due to only advanced maternal age risk[16]

by the prevalent use of prenatal screening tests andextracellular DNA determination in maternal blood. Byour study, we believe that the reason of the high rates ofinvasive procedure rates associated with major and/orminor anomalies detected by ultrasonography resultsfrom the high number of pregnant women with fetalanomalies and minor markers referred to our clinic sinceour clinic is a reference hospital.

In our study, increased nuchal thickness (2.9%),increased nuchal translucency (2.3%) were among theultrasonographic findings of invasive procedure indica-tions and there were ultrasonographic markers in 16(84.2%) of 19 fetuses who had aneuploidy. Nyber andSouter analyzed 7 studies in their meta-analysis wheregenetic sonograms were evaluated, and they reported thatnuchal thickness increase was the most frequent markerfollowed by choroid plexus cyst, echogenic cardiac focus,pyelectasis and humerus shortness.[17] On the other hand,choroid plexus cysts are not considered as a marker fortrisomy 21 today. It has been shown that many ultrasono-graphic markers do not clearly increase previous trisomy21 risk of pregnant women; however, it increases 3–4times in the presence of ventriculomegaly, nuchal thick-ness increase and aberrant right sub-clavian artery, and6–7 times in case of hypoplasia of nasal bone.[18]

In our study, we found the rate of detecting chromo-somal anomaly in invasive procedures as 5.2%. Due tothe non-existence of concomitant ultrasonographic find-ings in three patients, presence of similar chromosomalstructure in paternal/maternal chromosomal analysis,completion of pregnancies with healthy live births andnon-existence of anomaly in postnatal evaluations, cyto-genetic changes were considered as variant. Our rate todetect chromosomal anomaly was higher than the ratesreported in other regions of Turkey[19,20] and the rate ofchromosomal anomalies found as 2.4% in risky group.[21]

We believe that the reason results from the association ofour invasive procedures with the indications and the wideuse of screening tests. First trimester combined test isapplied to all pregnant women in our clinic, and integrat-ed test is carried out on patients if they have mid-levelrisk accordingly; however, we recommend secondtrimester quad screening test if the patient is considerednot to be at appropriate week. Also, ultrasonography isperformed for all pregnant women in order to evaluatefetal anomaly between 18 and 23 weeks of gestation.

In 11 (3.5%) of our cases which undergone amnio-centesis, there was no reproduction in the culture. Weattributed the reason to the laboratory errors associatedwith the period when the genetic laboratory of our hos-pital was established. In 7 of the patients without repro-duction in the culture, analyses were run for 13, 18, 21and X,Y chromosomes with fluorescence in situ hybridi-sation (FISH) method. The results evaluated as normalwere confirmed by quantitative fluorescence polymerasechain reaction (QF-PCR). Four patients recommendedcordocentesis refused the procedure. The literaturereports the rate not obtaining reproduction in the cul-ture after amniocentesis between 15 and 20 weeks as0.6–1%.[22] However, these rates are reported higher inthe studies performed in Turkey.[19,23]

In our study, we found procedure-related fetal lossrate as 0.6%. The pregnancy of a patient who under-gone cordocentesis with the diagnosis of non-immunehydrops fetalis was lost at 21 weeks of gestation, andanother pregnancy which undergone CVS due toincreased nuchal translucency at 11 weeks was terminat-ed at 13 weeks of gestation. The karyotype analysis ofthis fetus was 46,XY,inv(Y)(p11;q11). Also, we foundthat another fetus, which was found to have omphalo-cele with chromosome structure as 46XY,inv(9), was inutero ex at 33 weeks of gestation. However, this preg-nancy was not deemed as procedure-related loss. In astudy where pregnancy loss rates were compared inpatients who undergone amniocentesis but no invasiveprocedure, it was reported that pregnancy loss riskincreased 1% (95% CI, 0.3–1.5%) by amniocentesis.[7]

Although differences were found among studies in ameta-analysis systematically evaluating complicationsassociated with amniocentesis and CVS procedures,pregnancy loss rate before 24 weeks of gestation wasreported as 0.9% after amniocentesis and as 1.3% afterCVS.[24] Second trimester amniocentesis is considered asa safer method than early amniocentesis and transcervi-cal CVS; however, transabdominal CVS for prenataldiagnosis purpose before 15 weeks of gestation is recom-mended as the first option.[25] In our study, we observedamniotic fluid leakage in 1 patient after amniocentesis at16 weeks of gestation. The pregnancy of the patientwhose fluid leakage stopped within 48 hours by strictbed rest resulted with healthy live birth at term.Amniotic fluid leakage is seen in 1–2% of the patientsafter amniocentesis and stops usually by itself; however,infection, oligohydramnios and fetal loss rate increase incase of persistent fluid leakage.[26]


Evaluation of prenatal invasive procedures

43

ConclusionAmniocentesis is the most easy-to-use invasive prenataldiagnosis method with the lowest complication rate, andalso the procedure used most frequently in our study forprenatal diagnostic purposes. However, when firsttrimester combined test is preferred most frequently inscreenings, the rate of CVS procedure with similar com-plication rates will increase and this method will offerearlier diagnosis opportunity. Also, together with thenuchal translucency measured according to the stan-dards, wide use of first trimester combined tests whichhas lower false positivity rates will decrease unnecessaryinvasive procedure rates. Today, the indication of“advanced maternal age” which comes first in prenatalinvasive procedures has been superseded by the indica-tion of “increased risk at prenatal screening tests.”Besides, together with the active use of ultrasonographydevices with higher resolution beginning from the earlyweeks of gestation, viewable minor and/or major anom-alies also become indications for invasive proceduresmore frequently. Despite all these practices, the rates ofinvasive procedures for fetal karyotyping purposes willdecrease significantly as the tests evaluating extracellularfree fetal DNA in maternal blood are used widely.


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4. Chiu RW, Akolekar R, Zheng YW, Leung TY, Sun H, ChanKC, et al. Noninvasive prenatal assessment of trisomy 21 bymultiplexed maternal plasma DNA sequencing: large scalevalidity study. BMJ 2011;342:c7401.

5. Gil MM, Akolekar R, Quezada MS, Bregant B, NicolaidesKH. Analysis of cell-free DNA in maternal blood in screen-ing for aneuploidies: meta-analysis. Fetal Diagn Ther 2014;35:156–73.

6. American College of Obstetricians and Gynecologists.ACOG Practice Bulletin No. 88, December 2007. Invasiveprenatal testing for aneuploidy. Obstet Gynecol 2007;110:1459–67.

7. Tabor A, Philip J, Madsen M, Bang J, Obel EB, Norgaard-Petersen B. Randomized controlled trial of genetic amnio-centesis in 4606 low-risk women. Lancet 1986;1(8493):1287–93.

8. AU Ghidini A, Sepulveda W, Lockwood CJ, Romero R.Complications of fetal blood sampling. Am J Obstet Gynecol1993;5:1339–44.

9. Shaffer LG, Slovak ML, Campbell LJ, editors. ISCN 2009:An international system for human cytogenetic nomencla-ture (2009) Basel: S. Karger; 2009.

10. Saatçi Ç, Özkul Y, Tafldemir fi, Kiraz A, Müderris ‹, Taflc›o¤luN ve ark. Retrospective analysis of 2295 cases with ›nvasiveprenatal diagnosis. Perinatal Journal 2007;15:120–6.

11. Kaplan Ö, Güney M, Yüksel M. 2. Trimester genetik taramaamniyosentez: 1586 olgunun de¤erlendirilmesi. SüleymanDemirel Üniversitesi T›p Fakültesi Dergisi 2012;19:144–7.

12. Tongsong T, Wanapirak C, Sirivatanapa P, PiyamongkolW, Sirichotiyakul S, Yampochai A. Amniocentesis-relatedfetal loss: a cohort study. Obstet Gynecol 1998;92:64–7.

13. Tabor A, Vestergaard CHF, Lidegaard Ø. Fetal loss rateafter chorionic villus sampling and amniocentesis: an 11-yearnational registry study. Ultrasound Obstet Gynecol 2009;34:19–24.

14. Sjögren B, Uddenberg N. Decision making during the prena-tal diagnostic procedure. A questionnaire and interview studyof 211 women participating in prenatal diagnosis. PrenatDiagn 1989;9:263–73.

15. Lindemann CH, Theile U. Prenatal karyotyping in secondtrimester pregnancies. Prenat Diagn 1989;9:594–8.

16. American College of Obstetricians and GynecologistsCommittee on Genetics, Committee opinion no. 545: nonin-vasive prenatal testing for fetal aneuploidy. Obstet Gynecol2012;120:1532–4.

17. Nyberg DA, Souter VL. Use of genetic sonography foradjusting the risk of fetal Down syndrome. Semin Perinatol2003;27:130–44.

18. Agathokleous M, Chaveeva P, Poon LCY, Kosinski P,Nicolaides KH. Meta-analysis of second trimester markers fortrisomy 21. Ultrasound Obstet Gynecol 2013;41:247–61

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20. Yayla M, Bayhan G, Yal›nkaya A, Alp N. Yüksek riskli gebe-liklerde 2. trimester genetik amniyosentez: 165 olgununklinik de¤erlendirilmesi Perinatoloji Dergisi 1999;7:40–6.

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22. Golbus MS, Loughman WD, Epstein CJ, Halbasch G,Stephens JD, Hall BD. Prenatal genetic diagnosis in 3000amniocentesis. N Engl J Med 1979;300:157–63.

23. Pala HG, Artunç Ülkümen B, Eskicio¤lu F, Uluçay S, ÇamS, Bülbül Baytur Y, et al. Amniocentesis results of Manisatertiary care in 2012. Perinatal Journal 2014;22:23–7

24. Mujezinovic F, Alfirevic Z. Procedure-related complicationsof amniocentesis and chorionic villus sampling. A systematicreview. Obstet Gynecol 2007;110:687–94.

25. Alfirevic Z, Sundberg K, Brigham S. Amniocentesis andchorionic villus sampling for prenatal diagnosis. CochraneDatabase Syst Rev 2003;(3):CD003252.

26. Crane JP, Rohland BM. Clinical significance of persistantamniotic fluid leakage after genetic amniocentesis. PrenatDiagn 1986;6:6–25.

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Investigation of the effects of fetal gender on umbilicalartery and middle cerebral artery Doppler findingsBurcu Artunç Ülkümen, Halil Gürsoy Pala, Y›ld›z Uyar, Yeflim Baytur, Faik Mümtaz Koyuncu

1Department of Gynecology & Obstetrics, Faculty of Medicine, Celal Bayar University, Manisa, Turkey

Özet: Fetal cinsiyetin umbilikal arter ve orta serebral arter Doppler bulgular›na etkisinin araflt›r›lmas›Amaç: Bu çal›flmada fetal cinsiyetin, umbilikal arter ve orta sereb-ral arter Doppler ölçümlerine etkisini araflt›rmay› amaçlad›k. Yöntem: 2013-2014 y›llar›nda Celal Bayar Üniversitesi Perinato-loji Poliklini¤ine baflvuran üçüncü trimesterde olan 60 sa¤l›kl› te-kil gebelikte yap›lm›fl olan umbilikal arter (UA) ve orta serebral ar-ter (MCA) Doppler ultrasonografik ölçümleri retrospektif olarakgörüntü ve dosya kay›tlar›ndan tarand›. Umbilikal arter ve MCADoppler endeksleri en az ard›fl›k 3 dalga formu elde edilerek he-sapland›. Gebelikler fetal cinsiyete göre iki ayr› grupta de¤erlendi-rildi (k›z fetüsler 31 ve erkek fetüsler 29 olgu) ve karfl›laflt›r›ld›.Her iki grup aras›ndaki fark SPSS v.20 ile de¤erlendirildi. Bulgular: Çal›flmaya dahil edilen 60 gebeli¤in 31 tanesinde k›z fe-tüs (%51.67) ve 29 tanesinde erkek fetüs (%48.33) tespit edildi.K›z ve erkek fetüslerde s›ras› ile ortalama maternal yafl 29.14±6.21ve 31.88±5.16 (p=0.162), ortalama gestasyonel hafta 31.71±3.77 ve33.88±4.41 (p=0.111) olarak tespit edildi. Umbilikal arter PI k›z veerkek fetüslerde s›ras› ile 1.00±0.24 ve 1.03±0.21 olarak tespit edil-di (p=0.761). Orta serebral arter PI k›z ve erkek fetüslerde s›ras› ile2.16±0.67 ve 1.84±0.85 olarak tespit edildi (p=0.197). Serebro-um-bilikal oran MCA PI/UA PI olarak hesapland›. Serebro-plasentaloran, istatistiksel olarak anlaml› olmamakla birlikte k›z fetuslardadaha yüksek olarak bulundu; erkek fetüslerde ortalama 1.86±0.92iken k›z fetüslerde ortalama 2.23±0.78 idi (p=0.172). Sonuç: Günümüzdeki yeni yaklafl›m intrauterin dönemde bebe¤incinsiyetinin göz ard› edilmemesi yönündedir. Erkek fetüslerdeMCA rezistans›nda azalma daha büyük çal›flmalarda de¤erlendiril-melidir.

Anahtar sözcükler: Fetal cinsiyet, Doppler, orta serebral arter(MCA), umbilikal arter (UA).

Correspondence: Halil Gürsoy Pala, MD. Celal Bayar Üniversitesi T›p Fakültesi Kad›nHastal›klar› ve Do¤um Anabilim Dal›, Manisa, Turkey. e-mail: [email protected] Received: July 10, 2014; Accepted: February 6, 2015Please cite this article as: Artunç Ülkümen B, Pala HG, Uyar Y, Baytur Y, Koyuncu FM.Investigation of the effects of fetal gender on umbilical artery and middle cerebral arteryDoppler findings. Perinatal Journal 2015;23(1):45–49.©2015 Perinatal Medicine Foundation



Original Article


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Abstract

Objective: In this study, we aimed to investigate the effects of fetalgender on umbilical artery and middle cerebral artery Dopplermeasurements. Methods: Umbilical artery (UA) and middle cerebral artery (MCA)Doppler ultrasonographic measurements were screened retrospec-tively from image and file records of 60 healthy singleton pregnantwomen who were on their third trimesters and referred to thePerinatology Clinic of Celal Bayar University between 2013 and2014. Umbilical artery and MCA Doppler indexes were calculatedby obtaining at least 3 consecutive waveforms. The pregnancieswere evaluated in two different groups according to fetal gender (31female fetuses and 29 male fetuses) and compared. The differencebetween two groups was analyzed by SPSS v.20. Results: Female fetuses were identified in 31 (51.67%) out of 60pregnancies and male fetuses were identified in 29 (48.33%) casesincluded in the study. Mean maternal ages of female and male fetus-es were 29.14±6.21 and 31.88±5.16 (p=0.162), and mean gestationalweeks were 31.71±3.77 and 33.88±4.41 (p=0.111), respectively.Umbilical artery PI in female and male fetuses was found as1.00±0.24 and 1.03±0.21, respectively (p=0.761). Middle artery PI infemale and male fetuses was found as 2.16±0.67 and 1.84±0.85,respectively (p=0.197). Cerebral-umbilical rate was calculated asMCA PI/UA PI. Although cerebral-placental rate was not statistical-ly significant, it was higher in female fetuses; while it was 1.86±0.92in male fetuses, it was 2.23±0.78 in female fetuses (p=0.172). Conclusion: Today, the new approach is not to ignore the gender ofbaby during intrauterine period. The decrease in MCA resistance ofmale fetuses should be evaluated in greater studies.

Keywords: Fetal gender, Doppler, middle cerebral artery (MCA),umbilical artery (UA).

IntroductionUltrasonographic examination is one of the mostimportant tools of modern obstetric practice. In partic-ular, Doppler ultrasonography provides valuable dataabout fetal circulation and fetal hemodynamic condi-tion.[1] The vessels most frequently used for the evalu-ation of the fetal well-being are umbilical artery (UA),middle cerebral artery (MCA), and ductus venosus(DV).[2] In case of placental failure and associated fetalstress, the increases in umbilical artery resistanceindexes are the leading hemodynamic changes infetus.[3] Following these changes, MCA resistanceindexes decrease as a result of cerebral redistribution,which helps to maintain blood flow towards fetal brainby this adaptation mechanism.[4]

In the studies of Askling et al. and James, theincreases of placental dysfunction in male fetuses andof associated gestational complications such aspreeclampsia and ablatio placentae were shown.[5,6]

Also, an increase in preterm labor and postterm preg-nancy frequency was found in male fetuses.[7-10]

Intrapartum fetal distress and increased cesarean ratesare also observed more frequently in male fetuses.[11]

Besides, hyperemesis gravidarum and placental inva-sion anomalies are more frequent in female fetuses.[6]

Based on fetal gender being effective on placenta-tion, we considered that fetal gender might cause achange in Doppler indexes that we use for placentalperfusion evaluation, and we aimed in this study toinvestigate the effect of fetal gender on umbilical arteryand fetal middle cerebral artery flow measurements.

MethodsSixty healthy singleton pregnant women who were ontheir third trimesters between 28 and 36 weeks of ges-tation and had their Doppler ultrasound examinationin the perinatology clinic of our hospital betweenJanuary 2013 and June 2014 were included in thestudy. The study group was separated into two groupsby pairing according to week of gestation and maternalage, and fetuses being male and female. While 29 caseswere identified as male fetuses, 31 cases were femalefetuses. Approval of Local Ethics Committee wasobtained for the study planned retrospectively.

Week of gestation was calculated according to thelast menstrual period (LMP) and it was confirmed by

first trimester ultrasound findings. Multiple pregnan-cies, pregnant women with chronic systemic diseases(such as diabetes, liver and kidney diseases, connectivetissue disease etc.) and pregnancies with preeclampsiaand intrauterine growth retardation were excluded fromthe study. Also, the pregnancies found to have fetalchromosomal or structural anomalies were excludedfrom the study.

Ultrasound measurements were done by usingVoluson 730, RAB 3.5-MHz probe (GE MedicalSystems, Milwaukee, WI, USA). All measurements weredone by a single operator (H.G.P.). Umbilical arteryDoppler measurements were done through freeregion.[12,13] MCA Doppler measurement was done on theaxial section where thalamic nuclei are seen on the dis-play. Willis polygon was distinguished by color flow.The measurements were done through the proximal 1/3part close to the internal carotid artery with origin.Doppler indexes were calculated by obtaining 3 consec-utive waveforms. Amniotic fluid index (AFI) was consid-ered as the total of amniotic fluid depths measured on 4quadrants.

The statistical analysis was done by SPSS v.20(SPSS Inc., Chicago, IL, USA). The results were pro-vided as mean±standard deviation (SD). The p valueless than 0.05 was considered as statistically significant.The difference between the groups was calculated byusing t-test.

ResultsFemale fetuses were identified in 31 (51.67%) out of 60pregnancies and male fetuses were identified in 29(48.33%) cases included in the study. Mean maternalages of female and male fetuses were 29.14±6.21 and31.88±5.16 (p=0.162), and mean gestational weeks were31.71±3.77 and 33.88±4.41 (p=0.111), respectively.Umbilical artery PI in female and male fetuses was foundas 1.00±0.24 and 1.03±0.21, respectively (p=0.761) (Fig.1). Middle umbilical artery PI in female and male fetus-es was found as 2.16±0.67 and 1.84±0.85, respectively(p=0.197) (Fig. 2). Cerebral-placental rate was calculat-ed as MCA PI/UA PI. Although cerebral-placental ratewas not statistically significant, it was higher in femalefetuses; while it was 1.86±0.92 in male fetuses, it was2.23±0.78 in female fetuses (p=0.172). The clinical dataabout the study group are shown in the Table 1. No sig-

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Artunç Ülkümen B et al.

46

nificant relation was found between UA PI & MCA PIand maternal age & parity (Table 2). AFI was found as14.86±4.28 in male fetuses and 13.99±5.42 in femalefetuses (p=0.594). There was no significant relationshipbetween AFI and estimated fetal weight (r=0.131; p=0.368) and the week of gestation (r=0.008; p=0.958).

DiscussionIn our study, although we did not observe any statistical-ly significant level in male fetuses, we identifieddecreased MCA resistance and slightly increased umbil-ical artery resistance. Although different placentationprocesses and implantation and angiogenesis pathwaysare defined depending on the fetal gender, Doppler dif-ference associated with fetal gender in terms of evaluat-

ing placental perfusion has been analyzed only in onestudy so far.[14] A total of 388 term pregnant women wereincluded in this study carried out by Prior et al., and 212(54.6%) male and 176 (45.4%) female fetuses were iden-tified in these pregnancies. In this study, no differencewas observed between fetal genders in terms of UA PI.MCA PI was higher among female fetuses (mean femalefetus value: 1.42; mean male fetus value: 1.34) (p=0.004).MCA PSV (peak systolic velocity) was higher in femalefetuses (p<0.001). Mean cerebral-umbilical rate was 1.74in male fetuses and 1.81 in female fetuses (p=0.10).Umbilical venous velocity was higher in female fetuses(p=0.009).

It was shown in previous studies that male fetuses aremore associated with placental insufficiency and there-fore the gestational complications related with placenta-


Investigation of the effects of fetal gender on umbilical artery and middle cerebral artery Doppler findings

47

Fig. 1. UA PI values in female and male fetuses. Fig. 2. MCA PI values in female and male fetuses.

Table 1. Clinical characteristics of the pregnant women included in the study.

Pregnancies with Pregnancies with pmale fetuses female fetuses

n=29 n=31

Maternal age (mean±SD 31.88±5.16 29.14±6.21 0.162

Parity (mean±SD) 1.06±1.03 0.71±1.10 0.330

Week of gestation (mean±SD) 33.88±4.41 31.71±3.77 0.111

Birth weight (g) (mean±SD) 3160.0±709.67 3021.43±972.09 0.613

UA PI (mean±SD) 1.03±0.21 1.00±0.24 0.761

MCA PI (mean±SD) 1.84±0.85 2.16±0.67 0.197

Cerebral-umbilical rate (mean±SD) 1.86±0.92 2.23±0.78 0.172

AFI (cm) (mean±SD) 14.86±4.28 13.99±5.42 0.594

tion failure (such as miscarriage, intrauterine loss,preeclampsia, IUGR etc.) are observed more frequentlyin male fetuses.[5,6] In a study evaluating pregnancies withloss of end diastolic flow, it was shown that 63.2% of thecases were male fetuses, and 83% of the pregnancies withreverse end diastolic flow were male fetuses.[15] Prior et al.reported that decreased resistance in MCA flow even inthe male fetuses considered to have uterine artery flowand umbilical artery flow within normal ranges and tohave fetal growth compatible with the week of gestationand normal placental functions compared to femalefetuses depends on a physiological adaptation to the var-ious levels of placentation in male fetuses.[14] Also,Ghidini and Salafia, and Clifton showed in their studiesthat the progress of angiogenesis is weaker in male fetus-es and it is more difficult for male fetuses to adapt poormaternal environmental conditions.[16,17] By the change ofmaternal conditions during intrauterine period, theresponses of male and female fetuses towards these poorconditions and the steroidogenesis pathways in thisprocess and protein and gene expressions vary.[17] Malefetuses may adapt better to the poor intrauterine micro-environment molecularly and metabolically.[17] So, malefetus differ molecularly even in the implantation and pla-centation phases of pregnancy. Presence of decreasedresistance in MCA flow even in male fetuses displayingnormal clinical development may show that male fetuseshave a physiological adaptation to the differences in pla-centation.

Cerebral-umbilical rate is the most reliable measure-ment showing brain sparing effect in babies withIUGR.[18] In our study, we did not find any differencebetween female and male fetuses in terms of cerebral-umbilical rate. However, we also did not expect a signif-icant difference in terms of cerebral redistribution sinceour study group consisted of healthy pregnant women attheir third trimesters. In the study of Yücel et al. where

Doppler findings of term pregnancies were comparedaccording to fetus genders, there was no significant dif-ference between female and male fetuses in terms of UAand MCA pulsatility indexes.[19]

In our study, we did not observe any significant dif-ference in female and male fetuses in terms of AFI. Intheir study, Perni et al. reported a positive correlationbetween AFI and fetal weight in female fetuses before 38weeks of gestation.[20] In our study, there was no associa-tion between AFI and estimated fetal weight and theweek of gestation.

The weakest aspect of our study was the populationsize. Our study was limited with 60 patients since weplanned the study retrospectively and excluded thebabies with chronic disease, placental insufficiency find-ings or fetal anomaly from the study. By this size, thepower of the study was 0.6 (α-error= 0.05; d=0.5). Theadvantage of our study was that it was paired by thematernal age, parity and the week of gestation when thecases were separated as female and male fetuses. Also,measuring values by a single operator minimized theinter-observer difference.

ConclusionConsequently, placentation perfusion may varydepending on the fetal gender. Our preliminary resultswe provided here should be confirmed by further com-prehensive studies.


References1. Alfirevic Z, Stampalija T, Gyte GML. Fetal and umbilical

Doppler ultrasound in high-risk pregnancies. CochraneDatabase Syst Rev 2010;(1):CD007529.

2. Mari G, Abuhamad A, Cosmi E, Segata M, Altaye M,Akiyama M. Middle cerebral artery peak systolic velocity:technique and variability. J Ultrasound Med 2005;24:425–30.

3. Piazze J, Padula F, Cerekja A, Cosmi EV, Anceschi MM.Prognostic value of umbilical-middle cerebral artery pul-satility index ratio in fetuses with growth restriction. Int JGynaecol Obstet 2005;91:233–7.

4. Vyas S, Nicolaides KH, Bower S, Campbell S. Middle cere-bral artery flow velocity waveforms in fetal hypoxaemia. Br JObstet Gynaecol 1990;97:797–803.

5. Askling J, Erlandsson G, Kaijser M, Akre O, Ekbom A.Sickness in pregnancy and sex of child. Lancet 1999;354:2053.

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Table 2. Relationship between UA & MCA PI and maternal age andparity*.

Maternal age Parity

UA PI r 0.014 -0.261p 0.922 0.089

MCA PI r 0.101 0.041p 0.489 0.779

*Spearman’s correlation analysis; r=Spearman’s correlation coefficient

6. James WH. Sex ratios of offspring and the causes of placen-tal pathology. Hum Reprod 1995;10:1403–6.

7. James WH. Why are boys more likely to be preterm thangirls? Plus other related conundrums in human reproduc-tion. Hum Reprod 2000;15:2108–11.

8. McGregor JA, Leff M, Orleans M, Baron A. Fetal genderdifferences in preterm birth: findings in a North Americancohort. Am J Perinatol 1992;9:43–8.

9. Cooperstock M, Campbell J. Excess males in preterm birth:interactions with gestational age, race and multiple birth.Obstet Gynecol 1996;88:189–93.

10. Divon MY, Ferber A, Nisell H, Westgren M. Male genderpredisposes to prolongation of pregnancy. Am J ObstetGynecol 2002;187:1081–3.

11. Bekedam DJ, Engelsbel S, Mol BWJ, Buitendijk SE, van derPal-de Bruin KM. Male predominance in fetal distress dur-ing labor. Am J Obstet Gynecol 2002;187:1605–7.

12. Burrel SJ, Kingdom JC. The use of umbilical artery Dopplerultrasonography in modern obstetrics. Curr Opin ObstetGynecol 1997;9:370–4.

13. ISUOG Practice Guidelines. Use of Doppler ultrasonographyin obstetrics. Ultrasound Obstet Gynecol 2013;41: 233–9.

14. Prior T, Wild M, Mullins E, Bennett P, Kumar S. Sex spe-cific differences in fetal mid cerebral artery and umbilicalvenous doppler. PLoS One 2013;8(2):e56933.

15. Edwards A, Megens A, Peek M, Wallace EM. Sexual originsof placental dysfunction. Lancet 2000; 355:203–4.

16. Ghidini A, Salafia CM. Gender differences of placental dys-function in severe prematurity. BJOG 2005;112:140–4.

17. Clifton VL. Review: Sex and the human placenta: mediatingdifferential strategies of fetal growth and survival. Placenta2010;31 Suppl:S33–9.

18. Gramellini D, Folli MC, Raboni S, Vadora E, Merialdi A.Cerebral-umbilical Doppler ratio as a predictor of adverseperinatal outcome. Obstet Gynecol 1992;79:416–20.

19. Yücel A, Y›lmazer M, Acar M, De¤irmenci B, Köse S,Haktan›r A, Fenkçi V, Cevrioglu S. Termde normal gebelerde,Doppler indeksleri ve non-stres test de¤erlerinin fetus cin-siyetine göre karfl›laflt›r›lmas›. Kocatepe T›p Dergisi 2005;6:19–24.

20. Perni SC, Predanic M, Cho JE, Kalish RB, Chasen ST.Association of amniotic fluid ›ndex with estimated fetalweight. J Ultrasound Med 2004;23:1449–52.


Investigation of the effects of fetal gender on umbilical artery and middle cerebral artery Doppler findings

49

Results of routine first trimester screening tests andfollowing invasive procedures during pregnancy

Rahime Nida Ergin1, Murat Yayla2

1Department of Obstetrics & Gyneceology, Faculty of Medicine, Bahçeflehir University, Istanbul, Turkey2Obstetrics & Gyneceology Clinic, International Hospital, Istanbul, Turkey

Özet: Gebelikte rutin ilk üç ay taramas›n›n sonuçlar› ve sonras›nda yap›lan tan›sal giriflimlerAmaç: Bu çal›flmada gebeli¤in ilk üç ay›nda kombine test yap›langebelerde risk da¤›l›m›n›n gösterilmesi, tarama sonras› yap›lan di-¤er ifllem ve giriflimler ile tan›sal test uygulanan hastalar›n geneldemografik ve klinik özelliklerinin incelenmesi amaçlanm›flt›r. Yöntem: 2008–2011 y›llar› aras›nda ilk üç ay gebelik taramas›naait kombine test verileri retrospektif-kesitsel olarak de¤erlendiril-di. Ense kal›nl›¤› (NT) ölçümü sonras›nda ayn› gün içinde kombi-ne testi tamamlamak için ikili test uyguland›. Taramalar›n sonra-s›nda uygulanan tan›sal giriflimler oran, endikasyonlar›, karyotip vepostnatal sonuçlar aç›s›ndan karfl›laflt›r›ld›. Bulgular: Toplam 1109 gebe de¤erlendirmeye al›nd›. Takiptekigebelerin ortalama yafl› 31.07±3.73 y›ld›. Serbest βhCG ölçümü1.26±0.94 MoM ve PAPP-A ölçümü 1.16±0.65 MoM saptand›. Bi-rinci üç ayda ortalama NT de¤eri 1.60±0.67 mm bulundu. Eflikde¤eri 1/250 al›nd›¤›nda olgular›n %3,1’inde tarama testi pozitifsaptand›. ‹lk üç ay taramas› sonunda 22 olguya ve ikinci üç ay ta-ramalar› sonras›nda 19 olguya daha tan›sal giriflim yap›ld›¤› göz-lendi (toplamda %6.4). Giriflim yap›lan hastalar›n %11.3’ündekaryotip anomalisi saptand›. Kombine test sonucu pozitif olangrupta anne yafl›na ba¤l› anksiyete gibi di¤er nedenlerle giriflim ya-p›lanlara göre karyotip anomalisi daha fazla (%20) gözlendi. Sonuç: Çal›flmam›zdaki gebelik takiplerinde ilk üç ay taramas›ndakombine testte yanl›fl pozitiflik oran› %3.1 olmas›na ra¤men toplamgiriflim oran› iki kat›ndan fazlad›r (%6.4). Tan›sal ifllem say›s› yafl s›-n›r›ndan kaynaklanan anne anksiyetesine ve hekimlerin sadece NTveya ikili test sonucunu dikkate almalar› nedeni ile artmaktad›r. Ta-n›sal giriflimlerde %11’lere ulaflan kromozom anomalisi ile %10’la-ra ulaflan sonland›rma gereksinimi ile karfl›lafl›lm›flt›r. Anne veya he-kim anksiyetesine ba¤l› uygulanan giriflimlerin hiçbirinde sonland›r-ma gerektiren bir kromozom anomalisine rastlanmam›flt›r.

Anahtar sözcükler: Kombine test, koryon villüs biyopsisi, amni-yosentez, anksiyete.

Correspondence: Rahime Nida Ergin, MD. Bahçeflehir Üniversitesi T›p Fakültesi Kad›nHastal›klar› ve Do¤um Ana Bilim Dal›, ‹stanbul, Turkey. e-mail: [email protected] Received: January 12, 2014; Accepted: February 17, 2015Please cite this article as: Ergin RN, Yayla M. Results of routine first trimester screening tests and following invasive procedures during pregnancy. Perinatal Journal2015;23(1):50–55.©2015 Perinatal Medicine Foundation



Original Article


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Abstract

Objective: The purpose of this study is to show distribution ofrisk in pregnancies which underwent first trimester combinedtests, and investigate general demographic and clinical character-istics of patients, underwent invasive diagnostic tests after screen-ing tests. Methods: Combined test data of first trimester screening in 2008-2011 were evaluated retrospectively and cross-sectional. After themeasurement of nuchal translucency (NT), double test wasapplied to complete combined test within the same day. Invasivediagnostic procedures were compared in terms of rate, indications,karyotype and postnatal outcomes. Results: A total of 1109 pregnant women were included. Theirmean age was 31.07±3.73 years. Free-βhCG was 1.26±0.94 MoMand PAPPA was 1.16±0.65 MoM. Mean NT value was 1.60±0.67mm. With threshold of 1/250, screening test was positive in 3.1%of the cases. Additional 22 cases due to first trimester screeningand 19 cases due to second trimester screening had invasive pro-cedures (6.4% in total). Invasive procedures revealed karyotypeanomaly in 11.3%. Karyotype anomalies were more frequent ingroup (20%) with positive combined test compared to ones per-formed for other reasons like maternal anxiety.Conclusion: Although false positive rate is 3.1% in first trimestercombined test, rate of total invasive procedures is more than dou-ble (6.4%). Number of invasive diagnostic procedures increaseddue to maternal anxiety of age and physicians evaluating only NTor double tests. With diagnostic procedures, chromosome anom-alies reaches 11% and termination need reaches 10%. Invasiveprocedures performed due to anxiety of mother or physicianrevealed no chromosomal anomaly requiring termination.

Keywords: Combined test, chorionic villus sampling, amniocen-tesis, anxiety.


Results of routine first trimester screening tests and following invasive procedures during pregnancy

51

IntroductionBy the development of ultrasonographic fetal biometrymeasurements and early and effective screening pro-grams based on biochemical methods in the early diag-nosis of chromosomal anomalies, maternal preferenceshave increased actively.[1-3] Combined test, as one of theefficient screening programs, includes fetal nuchalscreening and double screening test from maternalblood consecutively between 11 and 14 weeks of gesta-tion, and chromosome anomaly is used for the riskdetermination of trisomy 21 in particular. In this study,we aimed to show the distribution of combined testresults in pregnant women who underwent combinedscreening test between 11 and 14 weeks of gestationand to investigate general demographic, laboratory andclinical characteristics of patients who underwent inva-sive procedures and diagnostic tests according to theresults of screening tests.

MethodsThe data of patients for first trimester screeningsbetween 2008 and 2011 were evaluated retrospectivelyand as cross-sectional. Before the screening tests, allpregnant women were informed and their consentswere obtained for the efficiency of ultrasonographyand biochemical procedure to be carried out. First, theweek and day of gestation were determined. In fetuseswhich had 45–84 mm ultrasonographic crown-rumplength (CRL), nuchal translucency (NT) was measuredaccording to current rules.[1] In addition to this meas-urement, fetal anatomy was evaluated. Then, in thesame day, 4–6 ml peripheral venous blood was collect-ed for double test (free beta human chorionicgonadotropin [f-βhCG] and pregnancy-associatedplasma protein A [PAPP-A]) calculation, and it wasstudied in the same laboratory with same method in 24hours.

The risk distribution of f-βhCG and PAPP-AMoM values reached during screening program andcombined test results were obtained. The patientswhose combined test risk scores were 1/250 and abovewere considered as positive and they were informedabout other screening methods and diagnostic meth-ods again. For karyotype analysis, chorionic villus sam-pling (CVS) at 12–14 weeks of gestation or amniocen-tesis at 16–20 weeks of gestation was carried out.Chromosome analyses were performed in the genetic

laboratory of the same institution. In the risk groupswhich had and did not have invasive procedures, gesta-tional follow-ups were continued to determine gesta-tional prognosis. The distribution of the numbers andreasons of CVS and amniocentesis carried out afterscreening tests and karyotype results, and perinatalprognosis of the group which had invasive procedurewere re-investigated after the delivery, and amniocen-tesis and CVS groups were compared. T-test andMann-Whitney U tests were performed for statisticaldata, and the value p<0.05 was considered statisticallysignificant.

ResultsIn a period of four years, 1109 pregnant women wereincluded in the study in total. Mean age of the caseswas 31.07±3.73 years. Mean f-βhCG value was1.26±0.94 MoM and PAPP-A value was 1.16±0.65MoM in the first trimester. Mean NT value in the firsttrimester was 1.60±0.67 mm. When threshold value ofthe combined test result was considered as 1/250,screening test result was positive in 3.15% (35/1109) ofthe cases. It was observed that 30 (85.7%) of these 35cases accepted diagnostic procedure. After firsttrimester briefing and screening, additional 22 casesalso requested diagnostic procedures and had invasiveprocedures. Given the additional screenings during thesecond trimester, additional 19 cases also had diagnos-tic procedures.

Among pregnant women found to be positive in thefirst trimester screening test, 5 (14%) out of 35 casesdid not accept invasive diagnostic method recommend-ed and preferred to decrease their risks by consecutivescreenings, and no chromosomal anomaly finding wasfound neither during follow-up nor postnatal period.Chromosome anomaly was found in 20% (6/30) ofthose who underwent CVS or amniocentesis after pos-itive screening finding, and pregnancy was terminatedin all cases. Although combined test result was withinlow risk range, both physicians and pregnant womenconsidering maternal age as too advanced, and separateinterpretation of increased nuchal translucency andbiochemical risk level in consecutive screening testscaused anxiety and uncertainty in some cases. This anx-iety caused pregnant women to prefer CVS or amnio-centesis directly or to have second trimester screeningtests. Non-directing consultancy was provided again by

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the physicians who carried out the screening in thisgroup which had negative screening test results andrequested procedures, and therefore invasive proce-dures were carried out since they did not change theirminds. No karyotype anomaly was observed in these 22pregnant women within low risk range. In the lastgroup consisting of 19 cases, which were examinedduring second trimester and found to have positiveresults for biochemical test or genetic marker, had 4structural fetal anomalies and all underwent invasiveprocedures. Among them, there were 2 karyotypeanomalies not requiring termination and 2 structuralanomalies which were required to terminate.

In terms of the reasons of the procedures (n=71),combined test was effective in 30 cases, advanced mater-nal age in 15 cases, positive genetic sonography in 13cases, maternal anxiety in 7 cases, and positive result forsecond trimester screening test in 6 cases. The reasonsof diagnostic procedures were observed in the firsttrimester screening tests in 52/71 cases and in the sec-ond trimester screening tests in 19/71 cases. In total,6.4% of the screened cases (CVS in 1% and amniocen-tesis in 5.4%) underwent diagnostic procedures.

In 11.27% of the patients which underwent the inva-sive procedure had karyotype anomaly (three fetuses hadtrisomy 21, two fetuses had trisomy 18, two fetuses hadmosaic XXY and one fetus had triploidy). It was deter-mined that karyotype anomalies were more frequent inthe group (6/30: 20%) with positive result for combined,and less frequent in the group (1/19: 5.3%) with nega-tive result for combined test but positive result for sec-ond trimester biochemistry or genetic ultrasonographyscreening test and in the group (1/22: 4.5%) with anxi-

ety. In the last two groups, the karyotype anomalydetected was 47, XXY.

The distribution of screened pregnant womenaccording to combined test risk results and the distri-bution of diagnostic procedures performed are shownin Table 1; karyotype anomalies found are shown inTable 2, and the comparison of the groups which hadand did not have procedures is shown in Table 3. Asexpected, mean maternal age and mean fetal NT werestatistically significant in the group which underwentprocedures. When cases which underwent amniocen-tesis or CVS were compared, it was seen that mean agewas low but mean fetal NT and risk score were higherin those underwent CVS (Table 4).

Among the cases which had no karyotype anomalyafter procedure and followed up until delivery deliv-ered, 87.3% of them delivered at term, 9.5% of themdelivered preterm or IUGR but healthy babies, and3.2% of them had fetal loss at prenatal period. Also, in3.2% of this group, there was minor anomaly. In none

Table 1. Results of combined test risk and the distribution of diag-nostic procedures.

Risk rate Number of Number pregnant Number of screened women underwent karyotype pregnant diagnostic anomaly women procedure detected

>1/250 35 30 6

1/251-1/1000 70 12 -

1/1001-1/10,000 444 22 1

1/10,001-1/100,000 560 7 1

Total 1109 71 8

Table 2. Laboratory and clinical characteristics of karyotype anomalies.

Case Maternal Week of NT f-ββhCG PAPP-A Combined Diagnostic Karyotypeage gestation (mm) (MoM) (MoM) test risk procedure

1 40 12 9 - - 1/6 CVS Trisomy 21

2 27 12 2.9 1.5 0.5 1/2 CVS Trisomy 21

3 40 13 3.2 2.1 1.0 1/6 Amniocentesis Trisomy 21

4 35 12 4.5 0.4 0.1 1/2 CVS Trisomy 18

5 30 12 1.5 0.3 0.4 1/21,836 CVS Trisomy 18

6 36 13 1.7 0.7 0.6 1/3850 Amniocentesis Mozaic XXY

7 29 13 1.2 0.9 0.8 1/50,000 Amniocentesis Mozaic XXY

8 31 13 3.0 0.1 0.06 1/2 CVS Triploidy

CVS: Chorionic villus sampling



53

of the procedures applied due to the anxiety of motheror physician, no chromosomal anomaly requiring ter-mination was observed. False negative major chromo-some anomaly was not observed in any of the cases fol-lowed-up, and no such findings were reported to us inthe following 3 years.

DiscussionUsing biochemical parameters as trisomy 21 screeningtest efficiently has increased the rates of maternal pref-erences in gestational follow-up practices.[2] However,in the perinatology, one of the cornerstones (or even ofthe milestones) in screening and determined karyotypeanomalies is to add ultrasonographic nuchal translu-cency measurement into biochemical analyses as tri-somy 21 screening test during relatively early period ofpregnancy such as first trimester.[3] Ultrasonographicnuchal translucency measurement together withmaternal age and f-βhCG and PAPP-A measurementsfrom maternal serum between 11 and 14 weeks of ges-tation are defined as “combined test”. Also, in pregnantwomen recommended first trimester combined screen-ing test by adding combined test into the clinical use, itis seen that the rate of pregnant women accepting pro-cedure increases significantly.[4]

In the studies carried out in Turkey,[5,6] mean f-βhCG values were reported between 0.82 and 1.07MoM and mean PAPP-A values were reportedbetween 1.06 and 1.61 MoM. In our study group, wefound these values as 1.25 and 1.16 MoM, respective-ly. f-βhCG value in our study was slightly higher thanthe values in other studies. We believe that the differ-ence may result from various laboratory methods. Inthe same studies, NT values were found between 1.16and 1.58 mm. Mean NT value of normal cases wefound in our study was 1.53 mm and it is similar to theresults of other studies.

Including combined test into clinical practice causedconflicts to determine fetal chromosome anomaly risk inthe use of second trimester tests, increase in false posi-tivity rates and unnecessary invasive procedures.[7]

Applying these tests of two different periods in clinicalpractice with various combinations has been improvedby SURUSS (Serum, Urine and Ultrasound ScreeningStudy) study and it was reported that “Integrated Test”practice (NT death + PAPP-A in 11 weeks of gestationand carrying out quad test – αFP, uE3, hCG and inhib-

in A – in the early second trimester) was effective.[7,8] Inthis prospective study carried out in multiple centerwhere over 47,000 pregnancies were followed up, it wasstated that it is the best method with 85% early detec-tion rate and 0.9% false positivity rate.[7,8] In our study,we found false positivity rate as 4.3% for combinedtest.[7,8] However, in following modeling and clinicalstudies, “Contingent sequential” (recommending inva-sive diagnostic procedures for those evaluated to havehigh risk in first trimester test and carrying out quad testat second trimester in pregnancies with threshold riskvalues) method was shown as the effective method withthe high early detection rate of anomaly and high rate offalse positivity rate which are 1, 3, and 5%.[9,10] Althoughit is stated in some publications that contingent sequen-tial screening method has a complex structure and lowdetection rate in the comparison of sequential and con-tingent prenatal Down syndrome screening test,[11] it wasreported in FASTER (First and Second Trimester

Table 3. The mean and standard deviation distribution of age, NT andbiochemical markers in cases.

Procedure Age* NT* ββhCG PAPP-A MoM MoM

Yok Mean 30.84 1.53 1.25 1.16Standard deviation 3.473 0.34 0.93 0.64

CVS / AS Mean 34.43 2.60 1.30 1.04Standard deviation 5.38 2.14 1.08 0.75

Total Mean 31.07 1.60 1.25 1.15Standard deviation 3.73 0.67 0.94 0.65

*: Statistically significant; p<0.05. AS: Amniocentesis, CVS: Chorionic villus sam-pling

Table 4. The mean and standard deviation distribution of age, NT andbiochemical markers in procedures.

Procedure Age* NT* ββhCG PAPP-A MoM MoM

CVS Mean 30.64 4.92 1.16 0.66N 11 11 10 10Standard deviation 10.38 2.89 0.79 0.0

AS Mean 35.11 2.14 1.33 1.11N 60 56 56 56Standard deviation 3.64 1.64 1.13 0.77

Total Mean 34.43 2.60 1.30 1.04N 71 67 66 66Standard deviation 5.38 2.14 1.08 0.75

*: Significant difference with Mann-Whitney U test; p<0.05. AS: Amniocentesis,CVS: Chorionic villus sampling

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Evaluation of Risk) study that the results of firsttrimester combined screening test at 11 weeks of gesta-tion are better than the results of quad test at secondtrimester and similar to the results at 13 weeks of gesta-tion.[12] It was shown that both sequential consecutivescreening test and full-integrated screening test havelow false positivity rates and high detection rates forDown syndrome.[12] However, considering the costs andtime loss to be brought by carrying out these tests rou-tinely and consecutively in general screening proce-dures, the efficiency and practicality of a well-combinedtest should not be overlooked. The results of our studyhaving 4-year clinical experience show that high anom-aly detection rate and low false positivity rates are simi-lar to the rates reported in the literature.[12-14]

Ultrasonographic nasal bone measurement, ductusvenosus, hepatic artery and tricuspid valve flows andmany other parameters have been offered to increase thedetection rates of these tests until recently.[15] In fact, itwas reported that maternal serum sampling before orsimultaneously with NT measurement increased testperformance.[16]

By including combined test into clinical practice inEngland, the number of positive Down syndromescreening test in 2003–2004 decreased in 2008-2009.[17]

This also provided a 72% decrease in the requests tocytogenetics laboratory and the total screening positivi-ty rate from 9% to 3.1% in 9 years.[17] In our study, falsepositivity rate was 3.1% in first trimester screening com-bined test in the gestational follow-ups, and it is consis-tent with the results of that study. However, total proce-dure rate was more than double (6.4%) compared to testpositivity in our study. The reason is the high rate ofinvasive procedures due to the anxiety of mother and/orphysician. However, there was no chromosome anomalyin such cases.

Today, parallel to the technical developments ofmolecular biology, detection rates were 98% for trisomy21, 96% for trisomy 18 and 13, and invasive test rate was0.7% by including extracellular free fetal DNA inmaternal blood into the combined test.[18,19]

Perhaps, by including molecular tests into routinepractices after their efficiencies are proven by wideseries, anxiety indications of mothers and/or physicians,which are the major reason for high rate of invasive pro-cedures, may be decreased substantially. It has beenshown that the most significant preference criteria ofmothers among invasive test versus non-invasive follow-

up methods is to diagnose Down syndrome with at least95% accuracy with related test.[20] Therefore, investigat-ing extracellular free DNA in maternal blood and com-bined tests have high potential for patient admission.

ConclusionAlthough false positivity rate is 3.1% in first trimestercombined test during pregnancy follow-ups in ourstudy, the rate of total invasive procedures is more thandouble (6.4%). In some pregnant women, the requestfor invasive procedure due to anxiety caused by “agelimit”, which is especially an old habit, increases thenumber of diagnostic procedures. In addition, physi-cians taking only nuchal translucency or double testresult into consideration also increase the number ofprocedures as well as general anxiety. As a result of theboth first and consecutive second trimester screeningtests, 15.5% of the diagnostic procedures are CVS and84.5% are amniocentesis. While 73% of these proce-dures are caused by first trimester screening tests andbriefing, and 27% of them are caused by secondtrimester screening tests. At the end of diagnostic pro-cedures, chromosome anomalies reach up to 11% andtermination need reaches up to 10%. No anomalyrequiring termination has been found in any of theprocedures caused by the anxiety of mother or physi-cian.

Proper screening and briefing during pregnancymay decrease the number of procedures associatedwith false positivity, and therefore financial losses andpossible fetal losses. The basic rule to prevent anxietyis to issue reports which do not include age and doubletest results or to interpret such reports accordingly.Considering the costs and efficiency of trisomy 21screening tests, “combined test” examination to be car-ried out by proper individuals and laboratories seemsto continue until other screening tests to be done onmaternal blood become cheaper and are widely used.


References1. Nicolaides KH. Screening for chromosomal defects.

Ultrasound Obstet Gynecol 2003;21:313–21.2. Salonen R, Turpeinen U, Kurki L, Lappalainen M, Ammälä

P, Hiilesmaa V, et al. Maternal serum screening for Down’ssyndrome on population basis. Acta Obstet Gynecol Scand1997;76:817–21.



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3. Wald NJ, Hackshaw AK. Combining ultrasound and bio-chemistry in first-trimester screening for Down’s syndrome.Prenat Diagn 1997;17:821–9.

4. Tringham GM, Nawaz TS, Holding S, Mcfarlane J, LindowSW. Introduction of first trimester combined test increasesuptake of Down’s syndrome screening. Eur J ObstetGynecol Reprod Biol 2011;159:95–8.

5. fianl› DB, Kartkaya K. Determination of the median levels offirst trimester screening test parameters in our region.[Article in Turkish] Perinatal Journal 2012;20:6–11.

6. Özer Ö, Say›n CN, Varol FG. The assessment of nuchaltranslucency and serum markers for down syndrome screen-ing with ductus venosus Doppler measurements in the firsttrimester. J Turk Ger Gynecol Assoc 2010;11:194–8.

7. Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L,Mackinson AM. First and second trimester antenatal screen-ing for Down’s syndrome: the results of the Serum, Urineand Ultrasound Screening Study (SURUSS). J Med Screen2003;10:56–104.

8. Wald NJ, Rodeck C, Hackshaw AK, Rudnicka A. SURUSSin perspective. BJOG 2004;111:521–31.

9. Wright D, Bradbury I, Benn P, Cuckle H, Ritchie K.Contingent screening for Down syndrome is an efficientalternative to non-disclosure sequential screening. PrenatDiagn 2004;24:762–6.

10. Cuckle H, Benn P, Wright D. Down syndrome screening inthe first and/or second trimester: model predicted perform-ance using meta-analysis parameters. Semin Perinatol2005;29:252–7.

11. Wald NJ, Rudnicka AR, Bestwick JP. Sequential and contin-gent prenatal screening for Down syndrome. Prenat Diagn2006;26:769–77.

12. Malone FD, Canick JA, Ball RH, Nyberg DA, ComstockCH, Bukowski R, et al; First- and Second-TrimesterEvaluation of Risk (FASTER) Research Consortium. First-

trimester or second-trimester screening, or both, for Down’ssyndrome. N Engl J Med 2005;353:2001–11.

13. Kagan KO, Wright D, Baker A, Sahota D, Nicolaides KH.Screening for trisomy 21 by maternal age, fetal nuchaltranslucency thickness, free beta-human chorionicgonadotropin and pregnancy-associated plasma protein-A.Ultrasound Obstet Gynecol 2008;31:618–24.

14. Borrell A, Casals E, Fortuny A, Farre MT, Gonce A,Sanchez A, et al. First-trimester screening for trisomy 21combining biochemistry and ultrasound at individually opti-mal gestational ages. An interventional study. Prenat Diagn2004;24:541–5.

15. Nicolaides KH. Screening for fetal aneuploidies at 11 to 13weeks. Prenat Diagn 2011;31:7–15.

16. Ekelund C, Wright D, Ball S, Kirkegaard I, Nørgaard P,Sørensen S, et al. Prospective study evaluating performanceof first-trimester combined screening for trisomy 21 usingrepeat sampling of maternal serum markers PAPP-A andfree β-hCG. Ultrasound Obstet Gynecol 2012;40:276–81.

17. Morgan S, Delbarre A, Ward P. Impact of introducing anational policy for prenatal Down syndrome screening onthe diagnostic invasive procedure rate in England.Ultrasound Obstet Gynecol 2013;41:526–9.

18. Nicolaides KH, Syngelaki A, Poon LC, Gil MM, Wright D.First-trimester contingent screening for trisomies 21, 18 and13 by biomarkers and maternal blood cell-free DNA testing.Fetal Diagn Ther 2014;35:185–92.

19. Fairbrother G, Johnson S, Musci TJ, Song K. Clinical expe-rience of noninvasive prenatal testing with cell-free DNA forfetal trisomies 21, 18, and 13, in a general screening popula-tion. Prenat Diagn 2013;33:580–3.

20. Chan YM, Leung TY, Chan OK, Cheng YK, Sahota DS.Patient’s choice between a non-invasive prenatal test andinvasive prenatal diagnosis based on test accuracy. FetalDiagn Ther 2014;35:193–8.

The association of congenital hand reduction defectand uterine anomaly

Bülent Kars1, Önder Sakin2, Yasemin Karageyim Karfl›da¤3, Cenk Demir1, Esra Esim Büyükbayrak2

1Department of Gynecology & Obstetrics, Private Dragos Gülen Medical Center, Istanbul, Turkey2Department of Gynecology & Obstetrics, Dr. Lütfi K›rdar Kartal Training and Research Hospital, Istanbul, Turkey

3Health High School, K›rklareli University, K›rklareli, Turkey

IntroductionCongenital hand reduction defect is the stump end orfull or partial absence of an extremity at the distal of apoint. Transverse forming defect is also known astransverse reduction defect, transverse melia or trans-verse arrest.[1]

Congenital anomaly is seen about 1% of newborns,and 10% of such cases are upper extremity anomalies.Congenital hand reduction defect is seen one in every20,000 births. In 50% of these cases, there is simpletransverse reduction defect on forearm or hand, and noother concomitant anomaly. In other 50% of the cases,

Özet: Konjenital el redüksiyon defekti ile uterusanomalisinin birlikteli¤iAmaç: Fetal el anomalileri prenatal ultrasonografik incelemelerdegözden kaçabilmektedir. Bu yaz›m›zda uterus anomalisi olan birolguda; 2 boyutlu ve 3 boyutlu ultrason ile antenatal takipte tan›-s›n› koydu¤umuz bir el redüksiyon defekti olgusunu sunmay›amaçlad›k.Olgu: ‹kili test taramas›nda ultrasonda fark edilmeyen ancak üçlütest amac›yla yap›lan ultrason kontrolünde bir ekstremitesinde elyoklu¤u tespit edilen hastaya genetik dan›flmanl›k verildi. Hastayaamniosentez yap›ld›ktan sonra fetüsün karyotipi normal (46 --) ola-rak geldi. Perinatoloji konsültasyonu, anomali taramas› ve fetal eko-kardiyografide efllik eden baflka bir anomali tespit edilmedi. Hasta-n›n geri kalan gebelik süreci sorunsuz geçti ve 3300 g, tekiz canl›makat ile prezante olan fetüs sezaryen operasyonu ile do¤urtuldu veailenin izni ile elin foto¤raflar› çekildi. Sonuç: Konjenital el redüksiyon defektleri uterus anomalileri ilebirliktelik gösterebilen durumlard›r. Bu anomalilerin tan›s› erkengebelik haftalar›nda yap›lan ultrason incelemesinde rahatl›kla kona-bilir ve bu nedenle erken anomali taramalar›n›n bir parças› olmal›-d›r.

Anahtar sözcükler: Konjenital tan›, do¤umsal el deformiteleri.

Correspondence: Bülent Kars, MD. Özel Dragos Gülen T›p Merkezi Kad›n Hastal›klar›ve Do¤um Klini¤i, ‹stanbul, Turkey. e-mail: ‹[email protected]: November 27, 2014; Accepted: February 16, 2015Please cite this article as: Kars B, Sakin Ö, Karageyim Karfl›da¤ Y, Demir C, Esim Büyükbayrak E. The association of congenital hand reduction defect and uterine anomaly. Perinatal Journal 2015;23(1):56–59.©2015 Perinatal Medicine Foundation



Case Report


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Abstract

Objective: Fetal hand anomalies can be overlooked in ultrasono-graphic examinations. In our report, we aim to present the case ofhand reduction defect in a patient with uterine anomaly that wediagnosed during antenatal follow-up with the use of 2D and 3Dultrasound examinations.Case: Genetic consultation was provided to a patient who hadabsence of hand in one extremity during the ultrasound control per-formed for triple test while nothing was detected in the ultrasoundfor double test screening. After the amniocentesis, the karyotype offetus was found as normal (46 --). No other anomaly was observed inperinatology consultation, anomaly screening and fetal echocardiog-raphy. Remaining gestational period of the patient was free of prob-lem and a single 3300 g fetus was delivered by cesarean sectionthrough breech presentation and the pictures of the hand were takenwith the permission of the family. Conclusion: Congenital hand reduction defects may occur togetherwith uterine anomalies. Such anomalies can be diagnosed easily dur-ing ultrasonographic examinations in early weeks of gestation, andtherefore they should be a part of early anomaly screening procedures.

Keywords: Congenital diagnosis, congenital hand deformities.


The association of congenital hand reduction defect and uterine anomaly

57

there is more than one reduction and 25% of suchcases also have anomalies in other organs or in cranio-facial structures.[2] Congenital hand reduction defect ofupper extremity is usually an isolated anomaly.

Congenital hand anomalies may occur togetherwith uterine anomalies. In our case, we aimed to dis-cuss hand reduction defect that we diagnosed duringantenatal follow-up with the use of 2D and 3D ultra-sound examinations.

Case ReportIn the obstetric examination of a 27-year-old patient whoreferred to our clinic for the complaint of delayed men-struation, gestation was observed through fetal cardiacactivity which was intrauterine but located on cornualregion close to right uterine. The patient who was preg-nant for the first time had no kin marriage and specificfinding in her family history. The patient was prescribedfolic acid support and called for follow-up two weekslater in terms of cornual pregnancy. In her follow-ups,the localization of gestational sac was normal. Doublescreening test of the patient between 11 and 14 weeksof gestation were within normal ranges. The patientwho started to take iron support visited the clinic forAFP screening at 17 weeks of gestation. In the USGexamination, absence of hand in the extremity wasfound and genetic consultation was provided to thepatient (Figs. 1 and 2). After the genetic amniocente-sis, the karyotype of fetus was found as normal (46 --).No other anomaly was observed in perinatology con-

sultation, anomaly screening and fetal echocardiogra-phy. Remaining gestational period of the patient wasfree of problem and a single 3300 g fetus was deliveredby cesarean section through breech presentation andthe pictures of the hand were taken with the permis-sion of the family (Fig. 3). It was found during the oper-ation that uterus was unicornuate, and the presence ofnon-communicating horn was detected on the left. Bothtubes and ovaries were normal.

DiscussionThe best time to evaluate fetal hands with ultrasound isbetween the end of first trimester and mid-period of sec-

Fig. 1. 2D USG image for the absence of hand.

Fig. 2. 3D USG image for the absence of hand. Fig. 3. Postnatal image for the absence of hand.

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ond trimester. During this period, fetus moves frequent-ly and hands are on open position more frequently thannext periods. 3D USG is not necessary; however, it maybe useful to define the morphology better.[3] We detect-ed our case who referred for AFP test at 17 weeks of ges-tation when we observed the absence of the hand in theextremity. We applied 3D USG to the patient at thesame session and confirmed the diagnosis.

Hand anomalies may be isolated and also mayaccompany to other skeletal and organ anomalies, aneu-ploidies, syndromes and bone dysplasias.[4,5] Therefore, ifa hand anomaly is detected, the patient should bereferred to a center where all fetal and cardiac anomaliescan be investigated. We therefore carried out geneticscreening by amniocentesis, and investigated otheranomalies at further weeks by perinatology consultationand anomaly screening. We found no additional con-comitant pathology.

Congenital transverse arrest, amniotic band syn-drome and Adams-Oliver syndrome (an autosomaldominant inherited syndrome with aplasia cutis andasymmetric transverse extremity defects) are amongthe distinctive diagnosis of congenital distal handreduction defect which is also a complication of earlyperiod chorion villus sampling.

Amniotic band syndrome is usually sporadic andgenerally causes asymmetric anomaly.[6] Amnioticband, which develops after embryologic developmentis completed, may cause many hand defects from handreduction up to syndactyly.

Congenital transverse arrest is seen rarely althoughthere are great differences among societies and coun-tries in terms of its incidence rate. Genetics, environ-mental factors and teratogenic agents are shown as thereason in the etiology; however, actual reasons havenot been clearly identified. Ninety-eight percent ofcongenital transverse arrest is unilateral.[7] It wasreported that transverse arrest may be seen togetherwith some congenital anomalies; and transverse arrestwas found together with congenital band syndrome inone case.[1] Unicornuate uterine anomaly was found inthe patient. However, before identifying this uterineanomaly, it was seen in the ultrasound during the firstreferral of the patient that gestational sac was locatedin a region close to cornual area. Uterine anomaly wasconfirmed by the cesarean section carried out due tobreech presentation in the case. In the literature, it has

been stated that there is a relationship between uterineanomalies and extremity defects. It has been reportedthat it may cause reduction defects and problems inextremity development associated with compression inuterine anomalies.[8]

Extremity processes can be seen with ultrasound at8 weeks of gestation at the earliest. Femur andhumerus can be seen as of 9 weeks of gestation,tibia/fibula and radius/ulna as of 10 weeks of gestation,fingers and toes as of 11 weeks of gestation, and alllong bones can be seen fully as of 11 weeks of gesta-tion.[9,10]

The aim in early anomaly screening is to diagnoseminor or major anomalies before it is too late and to beable to get early management chance. Therefore, care-fully checking the extremities of fetuses in the ultra-sound examination to be performed for double test willhelp to identify this anomaly at early weeks.

ConclusionCongenital hand reduction defects may occur togetherwith uterine anomalies. Such anomalies can be diag-nosed easily by carrying out ultrasonographic examina-tions in early weeks of gestation, and therefore theyshould be a part of early anomaly screening procedures.


References1. Jain S, Lakhtakia PK. Profile of congenital transverse defi-

ciencies among cases of congenital orthopaedic anomalies. JOrthop Surg (Hong Kong) 2002;10:45–52.

2. Pilu G, Nicolaides KH. Fetal Anomalilerin Prenatal Tan›s› /18–23 Gebelik Haftas› Ultrasonu. Çeviri: Hayri Ermifl.Nashville, TN: Panthenon 2000; p: 94.

3. Reiss RE, Foy PM, Mendiratte V, Kelly M, Gabbe SG. Easeand accuracy of evaluation of fetal hands during obstetricalulrasonography: a prospective study. J Ultrasound Med 1995;14:813–20.

4. Budorick NE. The fetal musculoskeletal system. In: CallenPW, ed. Ultrasonography in Obstetrics and Gynecology. 4thed. Philadelphia: Saunders; 2000; p: 331–77.

5. Ploeckinger-Ulm B, Ulm MR, Lee A, Kratochwil A,Bernaschek G. Antenatal depiction of fetal digits with threedimentional ultrasonography. Am J Obstet Gynecol 1996;175:571–4.

6. Rypens F, Ziereisen F, Avni F. Perinatal diagnosis of muscu-loskeletal anomalies. In: Avni FE, ed. Perinatal Imaging:


The association of congenital hand reduction defect and uterine anomaly

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From Ultrasound to MR Imaging. New York: Springer;2002; p: 197-226.

7. Ogino T, Saitou Y. Congenital constriction band syndromeand transverse deficiency. J Hand Surg Br 1987;12:343–8.

8. Graham JM, Miller ME, Stephan MJ, Smith DW. Limbreduction anomalies and early in utero limb compression. JPediatr 1980;96:1052–6.

9. Van Zalen-Sprock RM, Brons JT, van Vugt JM, van derHarten HJ, van Geijn HP. Ultrasonographic and radiologicvisualization of the developing embryonic skeleton. UltrasoundObstet Gynecol 1997;9:392–7.

10. Timor-Tritsch IE, Farine D, Rosen MG. A close look atearly embryonic development with the high-frequencytransvaginal transducer. Am J Obstet Gynecol 1988;159:676–81.

Extrauterine intrapartum treatment procedure in theunilateral advanced fetal hydrothorax case

Sevil Eraslan, Rauf Meleko¤lu, Ebru Çelik Department of Gynecology & Obstetrics, Faculty of Medicine, Inönü University, Malatya, Turkey

Introduction

Congenital hydrothorax is the fluid accumulation inpleural cavity seen in one per 10,000–15,000 pregnan-cies and it has many reasons such Noonan syndrome,chromosomal anomalies, immune system disease, car-

diac failure etc.[1,2] Primary congenital pleural effusionmay be unilateral or bilateral; it is usually on the rightside and in cheilosis form.[3] While it may regress spon-taneously, it has a variable prognosis reaching up tofetal or neonatal death.[4,5] Particularly, some of thebilateral severe congenital hydrothorax cases may

Özet: Tek tarafl› ileri derecede fetal hidrotoraksolgusunda ekstrauterin intrapartum tedaviprosedürüAmaç: Konjenital hidrotoraks, 10.000–15.000 gebelikte bir görü-len nadir bir anomalidir. Prenatal tan›n›n ilerlemesi, fetal hidroto-raks yönetiminde ekstrauterin intrapartum tedavi (EXIT) prose-dürünün uygulanmas›na olanak sa¤lam›flt›r. Bu makalede 3. tri-mesterde ultrasonografide saptanm›fl, do¤umda EXIT ifllemininuyguland›¤›, tek tarafl› ileri derecede fetal hidrotoraks olgusu su-nulmufltur.Olgu: Otuz befl yafl›nda primigravid, t›bbi ve obstetrik öyküsündeherhangi bir özellik saptanmayan, rutin obstetrik takibi s›ras›nda ilkkez gebeli¤in 36. haftas›nda fetüste plevral efüzyon ve polihidram-niyos saptanmas› üzerine klini¤imize yönlendirilen hastada yap›lanobstetrik ultrasonografide sa¤da tek tarafl› plevral efüzyon ve poli-hidramniyos d›fl›nda ek anomali izlenmedi. Sezaryen s›ras›nda peri-natolog, neonatalog ve çocuk cerrah›n›n steril bir flekilde haz›r ola-rak bulundu¤u vakada EXIT prosedürü uyguland›. Sonuç: EXIT prosedürü, fetal hidrotoraks olgular›nda, do¤umdayenido¤andan büyük miktarda plevral efüzyonun boflalt›mas› s›ra-s›nda plasentofetal sirkülasyona izin verdi¤i için güvenli bir tedaviseçene¤idir.

Anahtar sözcükler: EXIT prosedürü, hidrotoraks, obstetrik cer-rahi giriflimler.

Correspondence: Rauf Meleko¤lu, MD. ‹nönü Üniversitesi T›p Fakültesi Kad›nHastal›klar› ve Do¤um Anabilim Dal›, Malatya, Turkey. e-mail: [email protected]: November 12, 2014; Accepted: February 24, 2015Please cite this article as: Eraslan S, Meleko¤lu R, Çelik E. Extrauterine intrapartumtreatment procedure in the unilateral advanced fetal hydrothorax case. Perinatal Journal2015;23(1):60–64.©2015 Perinatal Medicine Foundation



Case Report


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Abstract

Objective: Congenital hydrothorax is a rare anomaly seen in oneper 10,000–15,000 pregnancies. Progress of the prenatal diagnosishas enabled the practice of extrauterine intrapartum treatment(EXIT) procedure in the fetal hydrothorax management. In thisreport, we presented a unilateral advanced fetal hydrothorax casefound on ultrasonography at third trimester and underwent EXITprocedure during delivery. Case: No additional anomaly was observed except unilateral pleuraleffusion and polyhydramnios on the right in the obstetric ultra-sonography of the thirty-five-year-old primigravida patient with nospecific finding in medical and obstetric histories who was referred toour clinic when pleural effusion and polyhydramnios were found infetus at 36 weeks of gestation for the first time during routine obstet-ric follow-up. EXIT procedure was carried out in the case whereperinatologists, neonatologist and pediatric surgeon were present ina sterile way during the cesarean operation. Conclusion: EXIT procedure is a safe treatment option in fetalhydrothorax cases since it allows placentofetal circulation during largeamount of pleural effusion discharge from newborn at birth.

Keywords: EXIT procedure, hydrothorax, obstetric surgical proce-dures.


Extrauterine intrapartum treatment procedure in the unilateral advanced fetal hydrothorax case

61

progress rapidly and may result in intrauterine deathdue to pulmonary hypoplasia developing as a result oflong-term pressure. Antepartum treatment optionshave been developed depending on the increase ofultrasonography use in prenatal diagnosis. Prenataltreatment varies depending on the pleural effusionamount and the diagnosis week of gestation.[6] If isolat-ed pleural effusion is detected before 32 weeks of ges-tation, it usually has a poor prognosis and it is fatal in55% of the cases. Mortality rate is 30% in pleural effu-sion cases diagnosed after 32 weeks of gestation.[7] Ifhydrops fetalis accompanies pleural effusion cases,mortality rate is almost 100%.[6] When prenatal diag-nosis is accurate and other fatal anomalies are ruledout, prenatal invasive procedure is useful, even life-sav-ing in some bilateral cases with poor prognosis. In thepresence of pleural effusion especially diagnosed atfirst and second trimesters, thoracic needling is notcurative and thoracoamniotic shunt is preferred in suchcases since recurrence rate is high.[8]

Thoracoamniotic shunt placed by using intrauter-ine thoracentesis or double pigtail catheter in fetalhydrothorax management is not always efficient sinceit depends on fetal and placental position.

If drainage and ventilation are insufficient for rapidlung expansion and alveolar gas exchange when thora-centesis is carried out after postnatal emergency intu-bation in pleural effusion management, permanenthypoxemic cerebral damage may occur.

Progress of the prenatal diagnosis has enabled thepractice of extrauterine intrapartum treatment (EXIT)procedure in the fetal hydrothorax management.[9]

EXIT is the procedure representing the operationscarried out on newborn before cord flow is cut whenfetal-placental unit is functional during the delivery. Itis applied first in congenital diaphragmatic hernia.[10]

While the most frequent indication is external andinternal airway obstructions, there are also other indi-cations. These indications are the removal of obstruc-tive apparatus (gripper, balloon) in the temporary tra-cheal obstruction, great neck masses (cervical ter-atoma, lymphangioma), congenital high airwayobstruction syndrome (CHAOS), extracorporeal mem-brane oxygenization (ECMO).[11]

EXIT procedure helps to gain time for safe adapta-tion of newborn.[12]

In this report, we presented an unilateral advancedfetal hydrothorax case found on ultrasonography atthird trimester and underwent EXIT procedure.

Case ReportThirty-five-year-old primigravida patient with no spe-cific finding in medical and obstetric histories wasreferred to our clinic when pleural effusion and polyhy-dramnios were found in fetus at 36 weeks of gestationfor the first time during routine obstetric follow-up. Inthe obstetric ultrasonography of the patient whose preg-nancy developed spontaneously, it was found that fetalbiometric measurements were consistent with the weekof gestation, there was no additional anomaly exceptunilateral pleural effusion and polyhydramnios on theright (Fig. 1). In the examinations to understand the rea-sons of fetal pleural effusion of patient whose blood typewas 0 Rh (+), maternal TORCH panel was negative andfetal echocardiography (ECO) result was normal.Biochemical examinations, gram staining, culture andkaryotype analyses were done on thoracentesis fluid col-lected during intrauterine fetal thoracentesis. There wasno reproduction in the culture analysis made on pleuralfluid found to be in chylothorax characteristics accord-ing to biochemical parameter. The result of karyotypeanalysis was normal. The patient was provided newborn,pediatric surgery and anesthesia consultations byPerinatology Department, and cesarean operation

Fig. 1. The image of pleural effusion on the right side of fetusfound at the 36 week of gestation via gray-scale ultrasono-graphy.

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under elective conditions at 38 weeks of gestation andEXIT procedure were planned.

Spinal anesthesia was applied in the case where intra-operative perinatologist, neonatologist and pediatricsurgeon were present in a sterile way. No drug wasadministered for the relaxation of uterine. By perform-ing hysterectomy through lower segment transverseincision, 2840 g male baby was delivered. The newbornwas placed on a sterile and flat surface on the legs ofmother as maintaining uteroplacental and placentofetalcirculation, not stretching the cord and on the placentalevel without clamping. While obstetrician was provid-ing maternal hemostasis, the pulse of the umbilical cordwas checked during the procedure. Underwaterdrainage was performed by inserting tube thoracostomyinto right pleural cavity via 16G intravenous catheterthrough 4th intercostal space (Fig. 2). Newborn evaluat-ed by neonatologist during tube thoracostomy anddrainage did not require intubation. During this period,about 400 cc pleural fluid in cheilosis form was dis-charged. The baby, whose cord was clamped on thefourth minute of labor and who was stabilized after tubethoracostomy, was transferred to newborn intense careunit for examination, treatment and follow-up.

In the direct chest radiography during the follow-ups in newborn intense care unit, pneumothorax wasobserved in the left lung and therefore thorax tube wasalso placed on the left side. No pathological finding wasfound in the examinations carried out for pleural effu-sion etiology. Newborn received respiratory support bynasal continuous positive airway pressure (nCPAP), andbilateral thorax tubes were removed when pleural effu-sion on the right and pneumothorax on the leftregressed on the third day in newborn intense care unit.On the 14th day in newborn intense care unit, the babywas discharged in a healthy condition with completelyregressed pleural effusion by recommending newbornclinical follow-up.

DiscussionFetal hydrothorax may occur due to idiopathic and sec-ondary reasons. Among the secondary reasons, there arecardiac, pulmonary and gastrointestinal malformations,infectious, hematologic and chromosomal diseases andimmune hydrops.[13]

Fetal hydrothorax is a rare anomaly and its patho-genesis is not known clearly although its incidence rates

increase depending on the increase of early diagnosistogether with the wide use of antenatal ultrasonography.Pleural effusion case was first found by Carrol in a preg-nant woman at 27 weeks of gestation.[14] Generally, 75%of the cases are diagnosed at third trimester. In the liter-ature, the earliest diagnosis of pleural effusion case wasreported in the 13 week of gestation.[15] Pleural effusionis usually detected by ultrasonography at third trimesterand it frequently accompanies to polyhydramnios devel-oping secondarily as a result of the external pressure ofadvanced pleural effusion to esophagus.[16]

The prognosis of pleural varies. Perinatal mortalityrate associated with pleural effusion is about 50%.Considering the clinical progress of such patients, it isseen that 22% of them regress spontaneously, 43% ofthem recover by treatment, and 35% of them result infetal or neonatal death. In the absence of polyhydram-nios, unilateral pleural effusion cases generally regress

Fig. 2. EXIT procedure (a). Underwater drainage procedure by in-serting thorax tube into the right pleural cavity (b).

a

b



63

spontaneously. In pleural effusion cases caused byhydrops, the prognosis is poor independent from thegestational age and the presence of bilateral effusion.[15]

The initial treatment of fetal pleural effusion is thedrainage with aspiration needle in company with ultra-sonography. In the meantime, amniocentesis can be per-formed or the etiology can be investigated by collectingfetal blood sample. Reasons such as anemia and cardiacarrhythmia, which are among the causes of pleural effu-sion but can be treated, should be investigated. In case ofthe re-accumulation of pleural fluid in the follow-upsafter drainage, pleuro-amniotic shunt can be consid-ered.[15]

It was reported in the literature that EXIT proce-dure was first used when removing tracheal clip placedto prevent tracheal obstruction caused by severe con-genital diaphragmatic hernia.[17]

EXIT is a procedure generally used in the manage-ment of extrinsic (teratomas, lymphangiomas) or intrin-sic (laryngeal atresia, congenital upper airway obstruc-tion syndrome) obstructive malformations of upper air-ways diagnosed during prenatal period.[18] The widestseries in the literature was reported by Bouchard et al. in2002. Thirty-one cases applied EXIT were detailed. Intheir series, they did not report any case applied forpleural effusion, but they stated that they applied EXITprocedure due to mass in the neck in 13 cases and thatthey lost only one case during the EXIT procedure.[19]

First application of EXIT procedure in the severeadvanced fetal bilateral pleural effusion case detectedduring prenatal period was reported by Prontera et al. inthe literature.[20]

In the case reported by Prontera et al., which hadpregestational diabetes and normal follow-up resultsuntil 32 weeks of gestation, severe isolated bilateral pleu-ral effusion was found at 38 weeks of gestation, the casewas applied EXIT supported bilateral thoracentesis pro-cedure; the newborn was extubated on the 5th day of itslife, and was discharged on 25th day in a healthy condi-tion. They emphasized that the close and efficient coop-eration among anesthetist, obstetrician, neonatologistand pediatric surgeon to maintain fetoplacental circula-tion during EXIT procedure, and pointed out the neces-sity to plan the procedure in detail.[20] In our case, weworked with the teams of anesthesia, newborn and pedi-atric surgery in our clinic with continuous communica-

tion and cooperation both when deciding to apply EXITprocedure and planning the procedure, and we preparedplans for interventions against possible complications.

There are two significant complications which mayaffect EXIT procedure. First, intraoperative uterinehemorrhage may require delivering placenta swiftly; andsecondly, since uterine contractions may disorder utero-placental circulation right after the delivery, halothaneadministration may be required to prevent such disorderand to help the relaxation of uterine. We ensured intra-operative uterine hemostasis rapidly in our case of whichwe planned perinatal management and we did not needany medication reducing uterine contractions.[20]

ConclusionAlthough intrapartum thoracentesis is a preferredmethod in fetuses with severe pleural effusion in thelast period of gestation, thoracentesis together withultrasound may cause fetal lung injury and fetal distressinduced by excessive amount of pleural fluid collection,and this procedure cannot be applied in some cases dueto inappropriate fetal position. EXIT is a procedureappropriate to use in cases where intrauterine drainageis technically difficult or impossible and postpartumdrainage may cause deep and extended hypoxia untilpleural fluid drainage is done sufficient enough toallow lung expansion in the newborn. It is a safe treat-ment options as it allows placentofetal circulation dur-ing the discharge of pleural effusion in large amounts.More experience and further studies are required inorder to reveal maternal and neonatal effects of apply-ing EXIT procedure in fetal hydrothorax cases, andthis procedure should be limited with viable newbornsappearing only at late gestational periods today.


References1. John E. Pleural effusion in the newborn. Med J Aust 1974;1:

102–3.2. Longaker MT, Laberge JM, Dansereau J, Langer JC,

Crombleholme TM, Callen PW et al. Primary fetal hydrotho-rax: natural history and management. J Pediatr Surg 1989;24:573–6.

3. Agrawal R, Aggarwal R, Kriplani A, Bhatla N. Primary FetalHydrothorax. Indian Pediatr 2002;39:92–5.

4. Eddleman KA, Levine AB, Chitkara U, Berkowitz RL.Reliability of pleural fluid lymphocyte counts in the antena-

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tal diagnosis of congenital chylothorax. Obstet Gynecol1991;78(3 Pt 2):530–2.

5. Aubard Y, Derouineau I, Aubard V, Chalifour V, Preux PM.Primary fetal hydrothorax: a literature review and proposedantenatal clinical strategy. Fetal Diagn Ther 1998;13:325–33.

6. Pijpers L, Reuss A, Stewart PA, Wladimiroff JW. Noninvasivemanagement of isolated bilateral fetal hydrothorax. Am JObstet Gynecol 1989;161:330–2.

7. Hagay Z, Reece A, Roberts A, Hobbins JC. Isolated fetalpleural effusion: a prenatal management dilemma. ObstetGynecol 1993;81:147–52

8. Gonen R, Degani S, Shapiro I, Samberg I, Sharf M. Theeffect of drainage of fetal chylothorax on cardiac and bloodvessel hemodynamics. J Clin Ultrasound 1993;21:265–8.

9. Kern C, Ange M, Morales, Peiry B, Pfister RE. Ex utero intra-partum treatment (EXIT), a resuscitation option for intra-thoracic foetal pathologies. Swiss Med Wkly 2007;137:279–85.

10. Mychaliska GB, Bealer JF, Graf JL, Rosen MA, Adzick NS,Harrison MR. Operating on placental support: the ex uterointrapartum treatment procedure. J Pediatr Surg 1997;32:230–1.

11. MacKenzie TC, Crombleholme TM, Flake AW. The ex-utero intrapartum treatment. Curr Opin Pediatr 2002;14:453–8.

12. Henry PY, Aravindan CS, Sivakumar K, Krishna HR.Extrauterine ›ntrapartum treatment (EXIT) in bilateral pri-mary fetal hydrothorax. Indian J Pediatr 2009;76:99–101.

13. Lange IR, Manning FA. Antenatal diagnosis of congenitalpleural effusions. Am J Obstet Gynecol 1981;140:839–40.

14. Carrol B. Pulmonary hypoplasia and pleural effusions associ-ated with fetal death in utero: ultrasonic findings. AJR Am JRoentgenol 1977;129:749–50.

15. National Institute for Health and Clinical Excellence.Insertion of pleuro-amniotic shunt to drain fetal pleural effu-sion (Interventional Procedure Consultation Document)[Internet]. 2006 [cited 2014 Sept 2]. Available from:www.nice.org.uk/ip333 overview

16. Mandelbrot L, Dommergues M, Aubry MC, Mussat P,Dumez Y. Reversal of fetal distress by emergency in uterodecompression of hydrothorax. Am J Obstet Gynecol 1992;167:1278–83.

17. Mychaliska GB, Bealer JF, Graf JL, Rosen MA, Adzick NS,Harrison MR. Operating on placental support: the ex uterointrapartum treatment procedure. J Pediatr Surg 1997;32:227–31.

18. Hirose S, Farmer DL, Lee H, Nobuhara KK, Harrison MR.The ex utero intrapartum treatment procedure: looking backat the EXIT. J Pediatr Surg 2004;39:375–80

19. Bouchard S, Johnson MP, Flake AW, Howell LJ, Myers LB,Adzick NS, et al. The EXIT procedure: experience and out-come in 31 cases. J Pediatr Surg 2002;37:418–26.

20. Prontera W, Jaeggi ET, Pfizenmaier M, Tassaux D, PfisterRE. Ex utero intrapartum treatment (EXIT) of severe fetalhydrothorax. Arch Dis Child Fetal Neonatal Ed 2002;86:F58–60.

Goiter in fetus without maternal thyroid disease: a case report

Önder Sakin1, Bülent Kars2, Yasemin Karageyim Karfl›da¤3, Cenk Demir2, Esra Esim Büyükbayrak1

1Department of Gynecology & Obstetrics, Dr. Lütfi K›rdar Kartal Training and Research Hospital, Istanbul, Turkey2Private Dragos Gülen Medical Center, Istanbul, Turkey

3Health High School, K›rklareli University, K›rklareli, Turkey

Introduction

Thyroid disorders are the common endocrine disor-ders seen during perinatal period. While maternal thy-roid anomalies can be diagnosed easily by maternalserum tests, it is considerably difficult to determine anddiagnose fetal goiter.[1] Different biochemical disordersin the thyroid hormone synthesis or maternal autoim-mune thyroid diseases may cause fetal goiter.[2]

Goiter may be related with fetal hypothyroidism orhyperthyroidism. Many authors believe the necessityto determine fetal thyroid function in order to initiateearly treatment process for this condition.[3]

Weiner et al. reported in 1980 for the first time thatthey diagnosed fetal goiter by prenatal sonographymethod.[4]

Presence of a large thyroid gland on fetal neck regionmay cause a difficult delivery due to polyhydramnios by

Özet: Maternal tiroid hastal›¤› olmayan fetüsteguatr: Olgu sunumuAmaç: Amaç, etkilenen fetüslerde fiziksel ve zihinsel geliflme geri-liklerine yol açabildi¤i için prenatal tan› ve tedavisinin önemli ol-du¤unu düflündü¤ümüz fetal hipotiroidizmi güncel bilgiler ›fl›¤›n-da tart›flmakt›r.Olgu: Otuz haftal›k gebe iken rutin ultrasonografi incelemesindetespit edilmifl bir fetal guatr olgusu sunuldu. Gebenin özgeçmiflin-de tiroid hastal›¤› öyküsü mevcut de¤ildi ve laboratuvar testlerin-de tiroid otoantikorlar› da dahil tüm tiroid fonksiyon testleri nor-maldi. Doppler ultrasonografide fetüste diffüz olarak büyümüfl vekanlanmas› artm›fl tiroid bezi izlendi. Bu bulgularla fetal guatr›nfetal hipotiroidizme ba¤l› olabilece¤i düflünüldü. Kesin tan› içinamniyosentez veya kordosentez önerilen hasta invazif giriflimlerikabul etmedi. Sonuç: Fetal guatr tan› ve izleminde ultrasonografi ve Dopplerbulgular› önemlidir.

Anahtar sözcükler: Fetal guatr, ultrasonografi, prenatal tan›.

Correspondence: Önder Sakin, MD. ‹stanbul Dr. Lütfi K›rdar Kartal E¤it. ve Arafl. Hast.,Kad›n Hastal›klar› ve Do¤um Klini¤i, ‹stanbul, Turkey. e-mail: [email protected]: October 29, 2014; Accepted: December 20, 2014Please cite this article as: Sakin Ö, Kars B, Karageyim Karfl›da¤ Y, Demir C, Esim Büyükbayrak E. Goiter in fetus without maternal thyroid disease: a case report.Perinatal Journal 2015;23(1):65–69.©2015 Perinatal Medicine Foundation



Case Report


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Abstract

Objective: The aim is to discuss fetal hypothyroidism which weconsider that its prenatal diagnosis and treatment is significant sinceit may cause physical and mental growth retardation in affectedfetuses.Case: A fetal goiter case was presented which was found during rou-tine ultrasonographic examination at 30 weeks of gestation. Thepregnant women had no thyroid history and all thyroid functiontests were normal including thyroid auto-antibodies in laboratorytests. In the Doppler ultrasonography, a thyroid gland grown dif-fusely with increased bloodshot was observed in the fetus. By thesefindings, it was considered that fetal goiter would be caused by fetalhypothyroidism. Amniocentesis or cordocentesis was recommendedas final diagnosis, but the patient refused invasive procedures. Conclusion: Doppler and ultrasonographic findings are importantfor fetal goiter diagnosis and follow-up.

Keywords: Fetal goiter, ultrasonography, prenatal diagnosis.

esophageal and tracheal pressure and also hyperexten-sion on neck by mass effect.[5]

Fetal hypothyroidism generally depends on anti-thyroid treatments or endemic iodine deficiency.Their incidence rate is very low without maternal dis-ease.[6]

As in the world, hypothyroidism screening is car-ried out successfully during newborn period in Turkeyand successful treatments are performed as of the earlyperiod.

However, hypothyroidism developing in fetal peri-od is very significant for the life. The possibility ofcongenital hypothyroidism which causes mental retar-dation but mostly possible to treat is 1 out of each 4000live birth.[7] Fetal goiter hypothyroidism forming only10–15% of all congenital hypothyroidism cases israrely seen (one out of 4000).[8] Thanks to the develop-ment in ultrasonography technology, even though it isa rare case, the number of reports prepared for fetalgoiter investigations increases day by day.[9]

Case ReportThe 28-year-old patient having her first pregnancyadmitted to our hospital for examination on her 30weeks of gestation. A great homogeneous mass wasdetected on the anterior side of fetal neck during ultra-sonographic examination. The mother was married toher second cousin. There was no thyroid disease in thehistory or family history of the mother. She had no

iodine or thyroid drug history. In the maternal exami-nation, no examination finding related with thyroiddisease was found. There was also no anomaly in rou-tine gestational analyses.

In the ultrasonographic examination, a wide, sym-metric and bilobulated mass pressuring trachea on theanterior side of the fetal neck (47.4x32.2x26.6 mm) (Fig.1) and mild polyhydramnios were found. Due to itspressure on esophagus and trachea, angle changes madeby growing thyroid tissue on the background, deteriora-tion in normal traces and concomitant polyhydramnios,we suspected of the presence of goiter. The mass was invery vascularized appearance in the Doppler examina-tion (Fig. 2). Fetal heart rate was 220 bpm. It was seenas a tachycardia in sinusoidal type. No other anomalywas observed in the fetus. Fetal growth and movementswere normal. Maternal serum thyroid function tests andthyroid ultrasound results were normal. The mother waseuthyroid, free T3 was 3.34 pg/ml, free T4 was 2.30ng/dl and TSH was 3.86 IU /ml. Anti-thyroid antibod-ies were negative. The family was informed about fetalcondition and prognosis. The family refused to have anyinvasive procedure such as amniocentesis, cordocentesisand/or intraamniotic thyroxine treatment. Fetal condi-tion, cardiac activity, fetal development, thyroid dimen-sions and fetal thyroid bleeding were followed up bycolor Doppler. No pathology was seen to explain fetaltachycardia. In the follow-ups during further weeks,fetal heart rate was observed within normal ranges.Since newborn cardiac evaluation was not characterized,

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66

Fig. 1. 2D ultrasound image of fetal goiter. Fig. 2. Doppler ultrasound image of fetal goiter.


Goiter in fetus without maternal thyroid disease

67

no further evaluation and diagnosis method wasrequired.

The patient delivered a male baby (2600 g) bycesarean since the delivery began on 36 weeks of gesta-tion and due to pelvic contraction. One-minuteAPGAR score was 6, and five-minute score was 7.There was bilobulated goiter; however, it caused noobstruction in the airway of newborn and resuscitationwas not required. The baby had no problem with post-natal respiratory adaptation. Postnatal color Dopplerexamination confirmed enlarged thyroid gland.

Iodothyronines in cord blood and TSH measure-ments confirmed the diagnosis of hypothyroidism. As ofthe first neonatal day, oral 50 mcg/day thyroxine hor-mone treatment was initiated. Fetal tachycardia was notobserved after the delivery. Weight, height and psy-chomotor developments of child were normal in the first6 months, and the follow-ups have been maintained.

DiscussionA great goiter may cause fetal neck hyperextensionresulting with malpresentation and complicated deliveryprocess. The trachea may be obstructed after birth dueto goiter, and this may cause asphyxia and death. Duringthe delivery, pediatric anesthesia and pediatric ENTexperts should be present in the delivery room with theirintubation and bronchoscopy devices. Neonatal screen-ing programs are successfully used in the diagnosis ofcongenital hypothyroidism just after the delivery andnormal development is remedied significantly by earlypostnatal treatment. On the other hand, some babiesexposed to congenital hypothyroidism have difficultiesand delays in neuromotor, perception and language abil-ities despite the postnatal early treatment. Therefore, itis important to place emphasis on prenatal treatment ofcongenital hypothyroidism.[10]

The enlargement of thyroid gland can be seen byultrasonography on the anterior side of the fetal neck ashomogenous straight masses with high echogenicity anddistinct edges. The mass can be bilobulated and its sizecan enlarge up to 30–35 mm.[11] There are also nomo-grams for thyroid dimensions appropriate to relatedfetal weeks of gestation.

It can be considered that the treatment of fetalhypothyroidism during intrauterine period is controver-sial; however, it has been reported that the treatment offetuses with large goiter is indicated. The reason is that

it may cause obstruction due to trachea, and the mechan-ic problems during delivery may cause morbidity.[12]

One of the prenatal examinations is Doppler ultra-sound. It can be seen in the Doppler ultrasound that neckvessels spread around soft tissue mass. If it is hypervascu-lar, the increase in the diameters of carotid and jugularveins can be seen. In case of hyperthyroidism, the diffuseincreased flow in the gland can be seen. In case ofhypothyroidism, peripheral flow around the gland can beobserved.[6]

However, in another source, it was reported that thedetection of the increase in blood flow towards fetal thy-roid is an unreliable finding of hyperthyroid, and evensurprisingly, that increased blood flow was found by usingpower Doppler for hypothyroidism.[13] Consequently, it isnot possible to make clear interpretation about thyroidfunctions just based on Doppler findings.

Amniotic fluid concentrations of TSH reflect fetalserum levels properly. However, Bruner and Dellingerasserted that fetal cord blood measurements are morereliable, and the evaluation made by amniocentesis is sus-picious.[14] Fetal thyroid functions can be evaluated prop-erly by fetal blood sampling method; however, thismethod is more risky since it has a 1% risk of fetaldeath.[15] However, the publications stating that thedetermination of thyroid hormone levels found throughamniotic fluid is not reliable for the diagnosis are pre-dominant.[16]

The association of fetal goiter with chromosomalanomalies was analyzed, and it was found that it has noassociation with aneuploidy. However, in the Pendredsyndrome, hearing loss in sensorineural type and goitercan be seen. It is an autosomal recessive condition andthyroid hormone synthesis is insufficient.[6]

Different approaches may be applied in fetal treat-ment. If fetal goiter is detected in pregnant womenreceiving treatment for maternal hyperthyroidism,decreasing the drug dose by considering the placentaltransition of drugs and following up fetal thyroid glandmeasurements have been recommended. If fetal goitersizes decrease as a result of this treatment, it is recom-mended to perform no procedure. However, if goitercontinues to enlarge or no respond is received, thefetus may have hyperthyroid and it is suggested to ana-lyze direct fetal thyroid hormones by doing cordocen-tesis. If fetal hyperthyroidism is found as a result,maternal treatment dose is increased until a fetal

Perinatal Journal

Sakin Ö et al.

68

respond is received. Propylthiouracil is recommendedas the drug.[6]

Intra-amniotic levothyroxine injection as the leastinvasive approach in fetal treatment referred byAbuhamad et al. is a treatment method accepted widelyso far.[17] In this sense, Medeiros-Neto et al. foundincreased TSH and decreased sT4 in the cordocentesisanalysis of the fetus with 29×34 mm fetal goiter at 23weeks of gestation, and they performed intrauterinelevothyroxine treatment. As a result of 400 mcg levothy-roxine single-dose injection, the size of thyroid wasfound as 4.8×12.5 cm at the end of 4 weeks and the treat-ment was considered as sufficient.[18]

The treatment dose estimation recommended byAbuhamad et al. is to do intraamniotic levothyroxineinjection with the dose of 10 mcg/kg according to thebirth weight.[17]

However, as a result of different treatments andcase reports later, Ribault et al. evaluated the treat-ments of 18 compiled cases. For 1–4 weeks, they made1–7 injections and found that there was 70–800 mcgdose difference in each application and 3–23 mc/kg dif-ference in each protocol. Also, fetal hormonal analysiswas performed through amniotic fluid in some caseswhile it was done through cord blood in some othercases. In the conclusion section of that study, theauthors reported that there has been no certain con-sensus on the treatment of fetal hypothyroidism.[16]

In their recent case report, Khamisi et al. foundmaternal hormones within normal ranges and fetal TSHas >100 mU/l in pregnant women with fetal goiter at 18weeks of gestation, and they administered intraamnioticthyroxine for 9 times at intervals of 7–10 days between 24and 33 weeks of gestation. They administered 10 mcg/kgin the first 6 applications, and 5 mcg/kg in the last 3 appli-cations. Fetal development was normal; however, thedelivery was made by cesarean at 34 weeks of gestationdue to the suspicion of chorioamnionitis. Since TSH washigher than 596 mU/L (reference values: 8.0±5.12) in thecord blood during delivery, thyroxine treatment was ini-tiated just after the delivery. In the conclusion section ofthe investigation, it was indicated that new investigationsare required for intraamniotic thyroxine treatment.[2]

ConclusionAs a conclusion, ultrasound and Doppler examinations,diagnosing and following up fetal goiter are of vital

importance. Fetal hypothyroidism is a negative patholo-gy for the development of central nervous system andphysical and mental development. Fetal goiter which isnot present in the ultrasound during the early periodsbut becomes evident in the advanced weeks of gestationshould not be overlooked. Mental retardation and otherdevelopment disorders can be prevented by early diag-nosis and treatment. Therefore, we believe that it will beuseful to remember fetal goiter in the ultrasonographicscreenings even during advanced weeks of gestation.


References1. Singh PK, Parwin CA, Gronowski AM. Establishment of

reference intervals for markers of fetal thyroid status inamniotic fluid. J Clin Endocrinol Metab 2003;88:4175–9.

2. Khamisi S, Lindgren P, Karlssson FA. A rare case ofdyshormonogenetic fetal goiter responding to intra-amniot-ic thyroxine injections. Eur Thyroid J 2014;3:51–6.

3. Perrotin F, Sembely-Taveau C, Haddad G, Lyonnais C,Lansac J, Body G. Prenatal diagnosis and early in utero man-agement of fetal dyshormonogenetic goiter. Eur J ObstetGynecol Reprod Biol 2001;94:309–14.

4. Weiner S, Scharf JI, Bolognese RJ, Librizzi RJ. Antenataldiagnosis and treatment of a fetal goiter. J Reprod Med 1980;24:39–42.

5. Davidson KM, Richards DS, Schatz DA, Fisher DA.Successful in utero treatment of fetal goiter and hypothy-roidism. N Engl J Med 1991;324:543–6.

6. Paula JW, Anne K, Roya S, Janice LB, Karen YO, MichaelDP. Face and neck anomalies – Goiter. Diagnostic imagingobstetrics. 2nd edition. Utah Amirsys 2013. p: 4/54–5.

7. Delange F. Neonatal screening for congenital hypothy-roidism: results and perspectives. Horm Res 1997;48:51–61.

8. Fisher DA. Fetal thyroid function: diagnosis and manage-ment of fetal thyroid disorders. Clin Obstet Gynecol 1997;40:16–31.

9. Meideros-Neto GA, Stanbury JB. Inherited Disorders of theThyroid System. Boca Raton: CRC Pres; 1994; p: 1–218.

10. Morine M, Takeda T, Minekawa R, Sugiyama T, Wasada K,Mizutani T, et al. Antenatal diagnosis and treatment of a caseof fetal goitrous hypothyroidism associated with high-outputcardiac failure. Ultrasound Obstet Gynecol 2002;19:506–9.

11. Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, RouseDJ, Spong CY. Tiroid ve di¤er endokrin bozukluklar.Williams Obstetrik. 23. bask›. Istanbul: Nobel T›p Kitapevi;2010. p. 1128–35.

12. Mestman JR. Tyroid and parathyroid diseases in pregnancy.In: Gabbe SG, Niebly JR, Simpson JL, editors. Obstetrics:normal and problem pregnancies. 5th edition. London:Churchill Livingstone; 2007. p.1023–9.

13. Merz E. Obstetrik ve jinekolojide ultrason. Çeviri: Özden S.2. bask›. Cilt 1. ‹stanbul: Do¤an T›p Kitapevi; 2002. p.247–52.

14. Bruner JP, Dellinger EH. Antenatal diagnosis and treatmentof fetal hypothyroidism. A report of two cases. Fetal DiagnTher 1997;12:200–4.

15. Simsek M, Mendilcioglu I, Mihci E, Karagüzel G, Taskin O.Prenatal diagnosis and early treatment of fetal goitroushypothyroidism and treatment results with two-year follow-up. J Matern Fetal Neonatal Med 2007;20:263–5.

16. Ribault V, Castanet M, Bertrand AM, Guibourdenche J,Vuillard E, Luton D, et al.; French Fetal Goiter StudyGroup. Experience with intraamniotic thyroxine treatment

in nonimmune fetal goitrous hypothyroidism in 12 cases. JClin Endocrinol Metab 2009;94:3731–9.

17. Abuhamad AZ, Fisher DA, Warsof SL, Slotnick RN, PylePG, Wu SY, et al. Antenatal diagnosis and treatment of fetalgoitrous hypothyroidism: case report and review of the liter-ature. Ultrasound Obstet Gynecol 1995;6:368–71.

18. Medeiros-Neto G, Bunduki V, Tomimori E, Gomes S,Knobel M, Martin RT, et al. Prenatal diagnosis and treatmentof dyshormonogenetic fetal goiter due to defective thyroglob-ulin synthesis. J Clin Endocrinol Metab 1997;82:4239–42.


Goiter in fetus without maternal thyroid disease

69

Letter to the Editor regarding “Extrauterine intrapartum treatment procedure inthe unilateral advanced fetal hydrothorax case”

Baflak Kaya, Ali Gedikbafl› Perinatology Unit, Gynecology & Obstetrics Clinic, Kanuni Sultan Süleyman Training and Research Hospital, Istanbul, Turkey

This letter has been written for the aspects to critici-ze for the EXIT procedure in the case report of unilate-ral advanced fetal hydrothorax case published in Perina-tal Journal.[1] Although various treatment and manage-ment recommendations and studies have been providedfor fetal hydrothorax in the literature, better results areobtained by using improved fetal treatment methods.

If hydrothorax develops before 27 weeks of gestati-on, pulmonary development is affected and cardiac failu-re and intrauterine loss may occur associated with cardi-ac and central vein pressure.[2] Besides, isolated fetalhydrothorax developing at late second trimester andthird trimester may not cause hypoplasia.[3] Poor prog-nostic factors are bilateral effusion development, non-regression of effusion spontaneously, hydrops and pre-maturity.[4]

The type of treatment during prenatal period is de-termined primarily according yo the severity of effusionand diagnosis week of gestation. Conservative manage-ment may be preferred since spontaneous regressionmay develop in the presence of mild-mid unilateralpleural effusion not causing mediastinal shift andhydrops and not accompanied by polyhydramnios.[5,6] Ifrapid increase in effusion, hydrops or polyhydramniosdevelopment is observed during the follow-up, invasivefetal treatment should be performed by using thoraco-amniotic shunt. When thoracoamniotic shunt procedu-re is significant especially before 36 weeks of gestation,thoracentesis or thoracoamniotic shunt can be preferred

in further weeks of gestation. Thoracoamniotic shuntshould be preferred primarily in the presence of severepleural effusion where mediastinal shift is accompaniedby hydrops or polyhydramnios.[5,7,8] Direct shunt appli-cation should also be considered in hydropic fetuses withbilateral effusion.[9] Nicolaides and Azar reached 50%survival rate in hydrothorax cases with non-immunehydrops by applying thoracoamniotic shunt.[10]

Decompression of effusion fluid by thoracentesis al-lows normal pulmonary development to continue, alsomay fix hydrops and polyhydramnios.[11] It also helps todiagnose for the etiology of hyrops and pleural effusi-on.[6,12] However, since fluid is accumulated rapidly in24–48 hours in the most of the cases, thoracoamnioticshunt should be preferred especially in the cases detectedin the early second trimester.[8,13] On the other hand, whi-le some authors prefer thoracentesis in the initial treat-ment, they apply thoracoamniotic shunt in case of reac-cumulation of pleural effusion.[13] It may not be alwayspossible to apply thoracoamniotic shunt due to the inap-propriate fetal position and increased fetal skin edema.Transplacental application during the procedure is notpreferred for thoracoamniotic shunt.[6] In such caseswhere thoracoamniotic shunt cannot be applied, multip-le thoracentesis, conservative follow-up of hydropic fetusor early labor of fetus are other possible treatment opti-ons.[13]

Since prematurity is a poor prognostic factor affec-ting survival, it is recommended to carry out the delivery

Correspondence: Ali Gedikbafl›, MD. Kanuni Sultan Süleyman E¤itim ve Araflt›rma Hast.,Kad›n Hastal›klar› ve Do¤um Klini¤i, ‹stanbul, Turkey. e-mail: [email protected] Received: February 24, 2015; Accepted: February 24, 2015Please cite this article as: Kaya B, Gedikbafl› A. Letter to the Editor regarding“Extrauterine intrapartum treatment procedure in the unilateral advanced fetal hydrothorax case”. Perinatal Journal 2015;23(1):70–71.©2015 Perinatal Medicine Foundation



Letter to the Editor


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71

in tertiary centers at 37-38 weeks of gestation.[5] It is re-ported that draining mid-severe pleural effusion just be-fore the delivery helps neonatal resuscitation and venti-lation support.[5,6] However, Klam et al. found no diffe-rence between those applied thoracentesis just beforethe delivery and postpartum practices in terms of Apgarscore, entubation and ventilation requirements and sur-vival rates.[8]

In the case presented, it is seen that thoracentesis wasapplied to investigate the etiology of pleural effusion at36 weeks of gestation and to treat the case. In this case,in the presence of appropriate fetal position, thoracoam-niotic shunt treatment could be planned if transplacen-tal transition was not required technically.

Extrauterine intrapartum treatment (EXIT) can beuseful in cases which are near term or at term with seve-re pleural effusion where intrauterine drainage failed.Prontera et al. who defined EXIT procedure for the firsttime due to fetal hydrothorax carried out this procedurein a case which had bilateral severe pleural effusion, in-creased central venous pressure findings, cardiac diasto-lic function disorder and with lungs completely collap-sed and echogenic. Fetal thoracentesis could not be app-lied due to polyhydramnios and fetal position, and post-natal drainage was not preferred due to the presence ofbilateral and severe pleural effusion and the concern ofpostnatal long and severe hypoxia. Therefore, thoracen-tesis and EXIT procedure were preferred as the leastcomplicated methods.[2]

When patients who were applied EXIT procedureand other cases delivered by cesarean section were com-pared in terms of maternal complications, wound sitecomplications and estimated blood loss were more in ca-ses who were applied EXIT procedure.[14]

As congenital fetal hydrothorax is a rare clinical con-dition with limited number of case reports in the litera-ture, there are disputes about the treatment options andmost suitable delivery time. First of all, it is required torefer such cases to tertiary centers and to plan treatmentand delivery in such centers. The treatment should beplanned according to the characteristics and clinicalcondition of current case, the experience of the teamwhich will carry out invasive procedure, and the suitabi-lity of technical conditions.


References1. Eraslan S, Meleko¤lu R, Çelik E. Tek tarafl› ileri derecede

fetal hidrotoraks olgusunda ekstrauterin intrapartum tedaviprosedürü. Perinatoloji Dergisi 2015;23:60–4.

2. Prontera W, Jaeggi ET, Pfizenmaier M, Tassaux D, PfisterRE. Ex utero intrapartum treatment (EXIT) of severe fetalhydrothorax. Arch Dis Child Fetal Neonatal Ed 2002;86:F58–60.

3. Gül A, Aslan H, Cebeci A, Polat ‹, Agral› G, Ceylan Y.Primary fetal hydrothorax: successful perinatal outcomeswith single thoracentesis just prior to delivery. J Turk GerGynecol Assoc 2004;5:143–6.

4. Aubard Y, Derouineau I, Aubard V, Chalifour V, Preux PM.Primary fetal hydrothorax: a literature review and proposedantenatal clinical strategy. Fetal Diagn Ther 1998;13:325–33.

5. Yinon Y, Kelly E, Ryan G. Fetal pleural effusions. Best PractRes Clin Obstet Gynaecol 2008;22:77–96.

6. Petersen S, Kaur R, Thomas JT, Cincotta R, Gardener G.The outcome of isolated primary fetal hydrothorax: a 10-year review from a tertiary center. Fetal Diagn Ther2013;34:69–76.

7. Pellegrinelli JM, Kohler A, Kohler M, Weingertner AS,Favre R. Prenatal management and thoracoamniotic shunt-ing in primary fetal pleural effusions: a single centre experi-ence. Prenat Diagn 2012;32:467–71.

8. Klam S, Bigras JL, Hudon L. Predicting outcome in primaryfetal hydrothorax. Fetal Diagn Ther 2005;20:366–70.

9. Derderian SC, Trivedi S, Farrrell J, Keller RL, Rand L,Goldstein R, et al. Outcomes of fetal intervention for pri-mary hydrothorax. J Pediatr Surg 2014;49:900–3.

10. Nicolaides KH, Azar GB. Thoraco-amniotic shunting. FetalDiagn Ther 1990;5:153–64.

11. Cardwell MS. Aspiration of fetal pleural effusions or ascitesmay improve neonatal resuscitation. South Med J 1996;89:177–8.

12. Smith RP, Illanes S, Denbow ML, Soothill PW. Outcome offetal pleural effusions treated by thoracoamniotic shunting.Ultrasound Obstet Gynecol 2005;26:63–6.

13. Deurloo KL, Devlieger R, Lopriore E, Klumper FJ, OepkesD. Isolated fetal hydrothorax with hydrops: a systematicreview of prenatal treatment options. Prenat Diagn 2007;27:893–9.

14. Noah MM, Norton ME, Sandberg P, Esakoff T, Farrell J,Albanese CT. Short-term maternal outcomes that are asso-ciated with the EXIT procedure, as compared with cesareandelivery. Am J Obstet Gynecol 2002;186:773–7.

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Publication Ethics and Malpractice Statement

Perinatal Journal is committed to upholding the highest standards ofpublication ethics and observes the following principles ofPublication Ethics and Malpractice Statement which is based on therecommendations and guidelines for journal editors developed bythe Committee on Publication Ethics (COPE), Council of ScienceEditors (CSE), World Association of Medical Editors (WAME) andInternational Committee of Medical Journal Editors (ICMJE).

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PERINATALJOURNAL

Contents

Original Article 1

6

13

26

30

39

45

56

60

50

65

20

70

Case Reports

Letter to Editor

Ultrasonographic evaluation of ventriculomegaly cases Hakan Kalayc›, Halis Özdemir, Ça¤r› Gülümser, Ayfle Parlakgümüfl, Tayfun Çok,Ebru Tar›m, Filiz Bilgin Yan›k

Perinatal outcomes of patients diagnosed borderline gestational diabetes mellitusGök Özgül, Rauf Meleko¤lu, Sevda Yeleç, ‹pek Eskiyörük, Fatma Tuncay Özgünen

Health practices of pregnant women in Gumushane City Center Handan Özcan, Nezihe K›z›lkaya Beji

The evaluation of pregnancies complicated by eclampsia:retrospective analysis of 37 cases in our clinic

Aytekin Tokmak, Korkut Da¤lar, Ali ‹rfan Güzel, Bergen Laleli, Salim Erkaya, Dilek Uygur

Factors affecting postpartum depression in Diyarbak›rAli Emre Tahao¤lu, Cihan To¤rul, Mehmet ‹rfan Külahç›o¤lu, Beflire Ayd›n Öztürk,Deniz Balsak, Hanifi Bademk›ran, Erdo¤an Gül, Ümit Görkem, Tayfun Güngör

Analysis of maternal serum and urinary lipocalin-2 levelsYeflim Bayo¤lu Tekin, Ülkü Mete Ural, Aynur K›rbafl, fienol fientürk, Figen K›r fiahin

Critical pulmonary stenosis with prenatal diagnosis: a case series and review of literatureOya Demirci, Taner Yavuz, Resul Ar›soy, Emre Erdo¤du, P›nar Kumru, Oya Pekin

Evaluation of prenatal invasive procedures: analysis of retrospective casesAybike Tazegül Pekin, Özlem Seçilmifl Kerimo¤lu, Setenay Arzu Y›lmaz, Nadir Koçak,Feyza Nur ‹ncesu, Ayfle Gül Kebapc›lar, Çetin Çelik

Investigation of the effects of fetal gender on umbilical artery andmiddle cerebral artery Doppler findings

Burcu Artunç Ülkümen, Halil Gürsoy Pala, Y›ld›z Uyar, Yeflim Baytur, Faik Mümtaz Koyuncu

Results of routine first trimester screening tests and following invasive proceduresduring pregnancy

Rahime Nida Ergin, Murat Yayla

The association of congenital hand reduction defect and uterine anomaly Bülent Kars, Önder Sakin, Yasemin Karageyim Karfl›da¤, Cenk Demir, Esra Esim Büyükbayrak

Extrauterine intrapartum treatment procedure in the unilateral advancedfetal hydrothorax case

Sevil Eraslan, Rauf Meleko¤lu, Ebru Çelik

Goiter in fetus without maternal thyroid disease: a case reportÖnder Sakin, Bülent Kars, Yasemin Karageyim Karfl›da¤, Cenk Demir, Esra Esim Büyükbayrak

Letter to the Editor regarding “Extrauterine intrapartum treatment procedure in theunilateral advanced fetal hydrothorax case”

Baflak Kaya, Ali Gedikbafl›

34

e-issn 1305 -3124 perinatal

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