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Volume 188, Number 4 Letters 1119 Am J Obstet Gynecol REFERENCES 1. Bustard MA, Farley A, Smith GN. The maternal and fetal phar- macokinetics of glyceryl trinitrate (GTN) in the near-term sheep [abstract]. Placenta 2001;22:A46. 2. Bustard MA, Ryan G, Seaward G, Seleniak M-E, Smith GN. Human maternal and fetal steady-state pharmacokinetics of transdermal glyceryl trinitrate (GTN)[abstract 465]. J Soc Gy- necol Investig 2002;9(1 Suppl):216A. doi:10.1067/mob.2003.226 Placental types and twin-twin transfusion syndrome To the Editors: Bermudez et al, 1 in proposing a classifica- tion system for monochorionic (MC) placental anatomy, report that 79% (19/24) of pregnancies with mixed su- perficial and deep anastomoses have twin-twin transfu- sion syndrome (TTTS) and that 81% (21/26) of MC pregnancies without TTTS have no deep arteriovenous (AV) anastomoses. Because these extraordinary findings contradict previous studies, 2,3 their methods used for their ex vivo placental injection study warrant critical ex- amination. First, surely laser treatment invalidates postnatal injec- tion studies because not only are the anastomoses de- stroyed months earlier in vivo but also their respective cotyledons. We note that no pictures were provided of any postablation anastomoses. Second, the injection of air rather than the more modern colored dye technique renders detection problematic because only by demon- strating mixing of dyes within a shared cotyledon can the presence of deep AV anastomoses be confirmed. 3 Third, fewer than one fifth of placentas studied were from preg- nancies without TTTS, suggesting huge referral bias. Fourth, 45 of 176 (26%) of placentas were excluded from their study, which may have biased their findings if these were from more advanced-stage TTTS with single or dou- ble intrauterine death, possibly as a result of laser treat- ment of the wrong vessels. Fifth, parametric statistics are inappropriate for nonnormally distributed data (ie, mean number of anastomoses without TTTS = 1.77, SD 1.27), and the authors need to represent their entire data either nonparametrically or categorically. These methodologic flaws undermine the authors’ principal conclusion that superficial anastomoses are not protective against TTTS. In any case, reanalysis of their own data prompts the opposite conclusion. Thus, 85 of 89 (96%) of those without, and 20 of 42 (48%) of those with, superficial anastomoses had TTTS (χ 2 , P < .0001). Indeed, only 20 of 105 (19%) patients with TTTS had su- perficial anastomoses, in keeping with our studies and those of others. 2,3 Based on their erroneous findings, the authors sug- gest that ultrasound scanning for superficial anastomoses in MC twins is unwarranted. However, in vivo studies of arterioarterial anastomoses (AAAs) have confirmed that AAAs not only protect against the development of TTTS but also improve outcome in established disease in the minority who have TTTS with an AAA. Thus, in our study of 105 consecutive MC pregnancies, to which the authors fail to refer, the chance for development of TTTS was re- duced 9-fold when an AAA was identified by color Doppler imaging. 4 Furthermore, in a smaller study of TTTS, also not acknowledged, outcome was significantly improved in those in whom an AAA was identified at di- agnosis. 5 Review of our more recent experience shows that, overall, fetal and neonatal survival is twice as high when AAAs are detected compared with when they are not (35/42 [83%] vs 41/102 [40%], χ 2 P < .0001). Myles J. O. Taylor, MD, Ling Wee, MD, and Nicholas M. Fisk, MD Centre for Fetal Care, Department of Maternal and Fetal Medicine, Im- perial College School of Medicine, Queen Charlotte’s and Chelsea Hospi- tal, Du Cane Road, London W12 OHS, United Kingdom; e-mail: [email protected] REFERENCES 1. Bermudez C, Becerra CH, Bornick PW, Allen MH, Arroyo J, Quintero RA. Placental types and twin-twin transfusion syn- drome. Am J Obstet Gynecol 2002;187:489-94. 2. Machin G, Still K, Lalani T. Correlations of placental vascular anatomy and clinical outcomes in 69 monochorionic twin preg- nancies. Am J Med Genet 1996;61:229-36. 3. Denbow ML, Cox P, Taylor M, Hammal DM, Fisk NM. Placental angioarchitecture in monochorionic twin pregnancies: relation- ship to fetal growth, fetofetal transfusion syndrome, and preg- nancy outcome. Am J Obstet Gynecol 2000;182:417-26. 4. Taylor MJ, Denbow ML, Tanawattanacharoen S, Gannon C, Cox PM, Fisk NM. Doppler detection of arterio-arterial anastomoses in monochorionic twins: feasibility and clinical application. Hum Reprod 2000;15:1632-6. 5. Taylor MJ, Denbow ML, Duncan KR, Overton TG, Fisk NM. An- tenatal factors at diagnosis that predict outcome in twin-twin transfusion syndrome. Am J Obstet Gynecol 2000;183:1023-8. doi:10.1067/mob.2003.259 Reply To the Editors: We would like to thank Drs Taylor, Wee, and Fisk for their interest in our article. Our paper de- scribes a practical classification of monochorionic pla- centas and its relationship to twin-twin transfusion syndrome (TTTS), based on the types of anastomoses present: type A, no anastomoses; type B, only deep anas- tomoses; type C, only superficial; and type D, superficial and deep anastomoses. Because there are no other pos- sible types of anastomoses, this classification should be unquestioned. The type, size, number, and direction of flow of all vascular anastomoses are documented endoscopically in each of our laser surgeries for TTTS and recorded on videotape and color prints. This evidence is available for review. The alternative, not ablating the anastomoses to preserve the evidence histologically, would seem prepos- terous. Air injection of vessels of lasered placentas was used to check for patency of the ablated anastomoses and to disclose any potential communications not de- tected during surgery. The suggestion that air injection is less accurate than dye injection for the assessment of deep and superficial anastomoses is unsubstantiated. Al- though our study reflects the referral nature of our cen- ter, this does not affect the relative frequencies of the different placental types in patients with TTTS. The in- sinuation that placentas in our series were excluded be-

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Page 1: Reply

Volume 188, Number 4 Letters 1119Am J Obstet Gynecol

REFERENCES

1. Bustard MA, Farley A, Smith GN. The maternal and fetal phar-macokinetics of glyceryl trinitrate (GTN) in the near-term sheep[abstract]. Placenta 2001;22:A46.

2. Bustard MA, Ryan G, Seaward G, Seleniak M-E, Smith GN.Human maternal and fetal steady-state pharmacokinetics oftransdermal glyceryl trinitrate (GTN)[abstract 465]. J Soc Gy-necol Investig 2002;9(1 Suppl):216A.

doi:10.1067/mob.2003.226

Placental types and twin-twin transfusion syndromeTo the Editors: Bermudez et al,1 in proposing a classifica-tion system for monochorionic (MC) placental anatomy,report that 79% (19/24) of pregnancies with mixed su-perficial and deep anastomoses have twin-twin transfu-sion syndrome (TTTS) and that 81% (21/26) of MCpregnancies without TTTS have no deep arteriovenous(AV) anastomoses. Because these extraordinary findingscontradict previous studies,2,3 their methods used fortheir ex vivo placental injection study warrant critical ex-amination.

First, surely laser treatment invalidates postnatal injec-tion studies because not only are the anastomoses de-stroyed months earlier in vivo but also their respectivecotyledons. We note that no pictures were provided ofany postablation anastomoses. Second, the injection ofair rather than the more modern colored dye techniquerenders detection problematic because only by demon-strating mixing of dyes within a shared cotyledon can thepresence of deep AV anastomoses be confirmed.3 Third,fewer than one fifth of placentas studied were from preg-nancies without TTTS, suggesting huge referral bias.Fourth, 45 of 176 (26%) of placentas were excluded fromtheir study, which may have biased their findings if thesewere from more advanced-stage TTTS with single or dou-ble intrauterine death, possibly as a result of laser treat-ment of the wrong vessels. Fifth, parametric statistics areinappropriate for nonnormally distributed data (ie,mean number of anastomoses without TTTS = 1.77, SD1.27), and the authors need to represent their entire dataeither nonparametrically or categorically.

These methodologic flaws undermine the authors’principal conclusion that superficial anastomoses are notprotective against TTTS. In any case, reanalysis of theirown data prompts the opposite conclusion. Thus, 85 of89 (96%) of those without, and 20 of 42 (48%) of thosewith, superficial anastomoses had TTTS (χ2, P < .0001).Indeed, only 20 of 105 (19%) patients with TTTS had su-perficial anastomoses, in keeping with our studies andthose of others.2,3

Based on their erroneous findings, the authors sug-gest that ultrasound scanning for superficial anastomosesin MC twins is unwarranted. However, in vivo studies ofarterioarterial anastomoses (AAAs) have confirmed thatAAAs not only protect against the development of TTTSbut also improve outcome in established disease in theminority who have TTTS with an AAA. Thus, in our studyof 105 consecutive MC pregnancies, to which the authorsfail to refer, the chance for development of TTTS was re-duced 9-fold when an AAA was identified by color

Doppler imaging.4 Furthermore, in a smaller study ofTTTS, also not acknowledged, outcome was significantlyimproved in those in whom an AAA was identified at di-agnosis.5 Review of our more recent experience showsthat, overall, fetal and neonatal survival is twice as highwhen AAAs are detected compared with when they arenot (35/42 [83%] vs 41/102 [40%], χ2 P < .0001).

Myles J. O. Taylor, MD, Ling Wee, MD, and Nicholas M. Fisk, MD

Centre for Fetal Care, Department of Maternal and Fetal Medicine, Im-perial College School of Medicine, Queen Charlotte’s and Chelsea Hospi-tal, Du Cane Road, London W12 OHS, United Kingdom; e-mail:[email protected]

REFERENCES

1. Bermudez C, Becerra CH, Bornick PW, Allen MH, Arroyo J,Quintero RA. Placental types and twin-twin transfusion syn-drome. Am J Obstet Gynecol 2002;187:489-94.

2. Machin G, Still K, Lalani T. Correlations of placental vascularanatomy and clinical outcomes in 69 monochorionic twin preg-nancies. Am J Med Genet 1996;61:229-36.

3. Denbow ML, Cox P, Taylor M, Hammal DM, Fisk NM. Placentalangioarchitecture in monochorionic twin pregnancies: relation-ship to fetal growth, fetofetal transfusion syndrome, and preg-nancy outcome. Am J Obstet Gynecol 2000;182:417-26.

4. Taylor MJ, Denbow ML, Tanawattanacharoen S, Gannon C, CoxPM, Fisk NM. Doppler detection of arterio-arterial anastomosesin monochorionic twins: feasibility and clinical application.Hum Reprod 2000;15:1632-6.

5. Taylor MJ, Denbow ML, Duncan KR, Overton TG, Fisk NM. An-tenatal factors at diagnosis that predict outcome in twin-twintransfusion syndrome. Am J Obstet Gynecol 2000;183:1023-8.

doi:10.1067/mob.2003.259

ReplyTo the Editors: We would like to thank Drs Taylor, Wee,and Fisk for their interest in our article. Our paper de-scribes a practical classification of monochorionic pla-centas and its relationship to twin-twin transfusionsyndrome (TTTS), based on the types of anastomosespresent: type A, no anastomoses; type B, only deep anas-tomoses; type C, only superficial; and type D, superficialand deep anastomoses. Because there are no other pos-sible types of anastomoses, this classification should beunquestioned.

The type, size, number, and direction of flow of allvascular anastomoses are documented endoscopically ineach of our laser surgeries for TTTS and recorded onvideotape and color prints. This evidence is available forreview. The alternative, not ablating the anastomoses topreserve the evidence histologically, would seem prepos-terous. Air injection of vessels of lasered placentas wasused to check for patency of the ablated anastomosesand to disclose any potential communications not de-tected during surgery. The suggestion that air injection isless accurate than dye injection for the assessment ofdeep and superficial anastomoses is unsubstantiated. Al-though our study reflects the referral nature of our cen-ter, this does not affect the relative frequencies of thedifferent placental types in patients with TTTS. The in-sinuation that placentas in our series were excluded be-

Page 2: Reply

1120 Letters April 2003Am J Obstet Gynecol

cause of increased mortality, stage, or wrong surgery inpatients undergoing the laser procedure has no basisand is simply unfair. In fact, most of the excluded pla-centas were from control patients. Analysis of the datausing nonparametric tests, while more appropriate, doesnot change the results: median number of anastomoses(4, range 1-11, vs 1, range 0-4, P < .001), deep anasto-moses (types B and D) (4, range 1-11, vs 1, range 1-2, P <.001), and superficial anastomoses (types C and D) (2,range 1-3, vs 1, range 1-4, P < .94) for TTTS and controlplacentas, respectively.

Our article suggests for the first time that superficialanastomoses may prevent, cause, or be indifferent to thedevelopment of TTTS, depending on the location of thehemodynamic equator and the nearest branch of the su-perficial vessel. Blanket statements about the protectiverole of superficial anastomoses are therefore inaccurateand outdated. Moreover, sparing of superficial anasto-moses during laser surgery may result in persistent or re-verse TTTS or be catastrophic in cases with anintrauterine death.1

Our placental classification relies on the ability to detectsuperficial and deep anastomoses endoscopically or at pla-cental pathologic examination. However, the diagnosisneed not be made with ultrasound in non-TTTS or in es-tablished TTTS patients. In the article cited by Taylor et al,detection of superficial anastomoses (arterioarterial only)was used to predict TTTS in patients who, in fact, alreadyhad the syndrome.1 In some instances, detection did notoccur until after five ultrasound examinations, 1 month

into the disease and at gestational ages of up to 34 weeks,mostly in anterior placentas and in vessels >2 mm. Review oftheir article claiming improved outcomes in three patientswith arterioarterial anastomoses from a population of 23patients with TTTS treated with amniocentesis, septostomy,and feticide, actually shows no difference in at least one sur-vivor relative to patients without these anastomoses (3/3 vs11/20, P = .253, Fisher exact test, and not .026 as re-ported).2 Finally, we deplore the poor survival outcomes ofTTTS patients treated in Dr Taylor’s laboratory (76/144,52.7%), particularly those without arterioarterial anasto-moses (40%). These outcomes are in sharp contrast withsurvival rates of >80% in all experienced laser centers, re-gardless of the types of anastomoses present.

Carlos Bermúdez, MD, Josep M. Martinez, MD, and RubénA. Quintero, MD

St Joseph’s Women’s Hospital, Florida Institute for Fetal Diagnosis andTherapy, 13601 Bruce B Downs Blvd, Suite 160, Tampa, FL 33613; e-mail: [email protected]

REFERENCES

1. Taylor MJ, Denbow ML, Tanawattanacharoen S, Gannon C, CoxPM, Fisk NM. Doppler detection of arterio-arterial anastomosesin monochorionic twins: feasibility and clinical application.Hum Reprod 2000;15:1632-6.

2. Taylor, MJ, Denbow ML, Duncan KR, Overton TG, Fisk NM. An-tenatal factors at diagnosis that predict outcome in twin-twintransfusion syndrome. Am J Obstet Gynecol 2000;183:1023-8.

doi:10.1067/mob.2003.259