isuog consensus statement on the impact of non-invasive prenatal testing (nipt) on prenatal...

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Ultrasound Obstet Gynecol 2014; 44: 122–123 Published online 3 June 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.13393 isuog.org CONSENSUS STATEMENT ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT) on prenatal ultrasound practice The emergence of effective cell-free fetal DNA-based tech- niques to screen for trisomy 21 and other aneuploidies has greatly expanded the range of prenatal tests avail- able over the last few years. Non-invasive prenatal testing (NIPT) is rapidly being incorporated into prenatal care, thus changing the traditional approach to prenatal screen- ing and diagnosis. However, although NIPT techniques are highly efficient, their role and performance must be considered alongside and combined with other screening modalities. The role of prenatal ultrasound in particular needs to be reassessed as NIPT becomes more widely available. It is important to emphasize that the main goal of prenatal screening is to provide accurate information that will facilitate the delivery of optimized antenatal care, with the best possible outcome for both mother and fetus. Women should be informed about prenatal screening performance by appropriately trained health professionals, allowing them to make an informed decision. It is the parent’s choice to undergo such procedures, and their wishes should be determined and respected. The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) has compiled the following Consensus Statement, which will be updated on a regular basis. All women should first be offered a first-trimester ultrasound scan according to ISUOG guidelines 1 , regardless of their intention to undergo NIPT. Pre-test counseling is essential. Various options should be explained clearly to women, discussing the pros and cons of each, including the expected test performance and potential adverse effects. Following a normal early pregnancy scan, as defined by ISUOG guidelines 1 , three options should be considered for women who wish to have a further risk assessment for trisomy 21 and, to a lesser extent, trisomies 13 and 18: (1) Screening strategies based on individual risk cal- culated from maternal age and nuchal translu- cency measurement and/or maternal serum markers and/or other ultrasound markers in the first trimester (defined by the conventional crown– rump length range of 45 – 84 mm). At the moment, ISUOG endorses this strategy. Following such screening, women can be offered a choice, according to their calculated individual risk, of having no further testing, undergoing NIPT, or undergoing invasive testing. Cut-offs should be defined on a local/national basis and will be affected by public health priorities and available resources. (2) Invasive testing based on background risk (includ- ing, for example, maternal age and history of aneu- ploidy), with no other individual risk calculation. (3) NIPT as a first-line screening test. Most current guidelines endorse NIPT only for high-risk populations for which adequate data exist. Using NIPT on intermediate- or low-risk patients might be endorsed as a widely available option only when new data emerge and NIPT costs decrease. NIPT is not a diagnostic test and confirmatory invasive testing is required in the presence of any abnormal results. NIPT has not been evaluated extensively in low-risk populations, in which its positive predictive value is lower than in high-risk populations. First-trimester risk estimates for trisomies 21, 18 and 13 based on nuchal translucency measurements and maternal biochemistry should not be computed in a woman who has already received a normal NIPT result for these trisomies. NIPT may be discussed as an alternative to invasive testing following an abnormal result on combined screening or offered to patients who are not sufficiently reassured by an ‘intermediate risk’ result. The role of NIPT as an alternative to standard invasive testing in women considered to be at very high risk (>1:10) after combined screening but with no Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. CONSENSUS STATEMENT

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Page 1: ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT) on prenatal ultrasound practice

Ultrasound Obstet Gynecol 2014; 44: 122–123Published online 3 June 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.13393

isuog.orgCONSENSUS STATEMENT

ISUOG consensus statement on the impact of non-invasiveprenatal testing (NIPT) on prenatal ultrasound practice

The emergence of effective cell-free fetal DNA-based tech-niques to screen for trisomy 21 and other aneuploidieshas greatly expanded the range of prenatal tests avail-able over the last few years. Non-invasive prenatal testing(NIPT) is rapidly being incorporated into prenatal care,thus changing the traditional approach to prenatal screen-ing and diagnosis. However, although NIPT techniquesare highly efficient, their role and performance must beconsidered alongside and combined with other screeningmodalities. The role of prenatal ultrasound in particularneeds to be reassessed as NIPT becomes more widelyavailable.

It is important to emphasize that the main goal ofprenatal screening is to provide accurate informationthat will facilitate the delivery of optimized antenatalcare, with the best possible outcome for both motherand fetus. Women should be informed about prenatalscreening performance by appropriately trained healthprofessionals, allowing them to make an informeddecision. It is the parent’s choice to undergo suchprocedures, and their wishes should be determined andrespected.

The International Society of Ultrasound in Obstetricsand Gynecology (ISUOG) has compiled the followingConsensus Statement, which will be updated on a regularbasis.

• All women should first be offered a first-trimesterultrasound scan according to ISUOG guidelines1,regardless of their intention to undergo NIPT.

• Pre-test counseling is essential. Various options shouldbe explained clearly to women, discussing the pros andcons of each, including the expected test performanceand potential adverse effects.

• Following a normal early pregnancy scan, as defined byISUOG guidelines1, three options should be consideredfor women who wish to have a further risk assessmentfor trisomy 21 and, to a lesser extent, trisomies13 and 18:

(1) Screening strategies based on individual risk cal-culated from maternal age and nuchal translu-

cency measurement and/or maternal serum markersand/or other ultrasound markers in the firsttrimester (defined by the conventional crown–rump length range of 45–84 mm).

At the moment, ISUOG endorses this strategy.Following such screening, women can be offereda choice, according to their calculated individualrisk, of having no further testing, undergoingNIPT, or undergoing invasive testing. Cut-offsshould be defined on a local/national basis and willbe affected by public health priorities and availableresources.

(2) Invasive testing based on background risk (includ-ing, for example, maternal age and history of aneu-ploidy), with no other individual risk calculation.

(3) NIPT as a first-line screening test.

Most current guidelines endorse NIPT only forhigh-risk populations for which adequate dataexist. Using NIPT on intermediate- or low-riskpatients might be endorsed as a widely availableoption only when new data emerge and NIPT costsdecrease.

• NIPT is not a diagnostic test and confirmatory invasivetesting is required in the presence of any abnormalresults.

• NIPT has not been evaluated extensively in low-riskpopulations, in which its positive predictive value islower than in high-risk populations.

• First-trimester risk estimates for trisomies 21, 18 and13 based on nuchal translucency measurements andmaternal biochemistry should not be computed in awoman who has already received a normal NIPT resultfor these trisomies.

• NIPT may be discussed as an alternative to invasivetesting following an abnormal result on combinedscreening or offered to patients who are not sufficientlyreassured by an ‘intermediate risk’ result.

• The role of NIPT as an alternative to standard invasivetesting in women considered to be at very highrisk (>1:10) after combined screening but with no

Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. CONSENSUS STATEMENT

Page 2: ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT) on prenatal ultrasound practice

Consensus Statement 123

ultrasound anomaly should be evaluated in prospectivestudies. Expert opinion currently suggests that NIPTshould not replace invasive testing in this group. Thisis based on the fact that only 70% of chromosomalabnormalities in this population are trisomy 21, 18 or13. Furthermore, emerging microarray techniques mayprovide additional, clinically relevant information insome cases.

• In the presence of a fetal structural anomaly, theindications for fetal karyotyping and/or microarraytesting should not be modified by a normal NIPT resultobtained previously.

• Accuracy of NIPT in twin pregnancies should beinvestigated further.

• Variations in NIPT performance by different providersshould be investigated further.

• The so-called ‘genetic sonogram’, which includeslooking for soft markers of trisomy 21, should notbe performed in women with a normal NIPT resultdue to its high false-positive rate and poor positivepredictive value.

• It is becoming technically feasible to test non-invasively,not only for trisomies but also for other geneticsyndromes. Both healthcare providers and womenshould therefore be clearly aware of the tests beingperformed and of their performance, as having multipletests may increase the false-positive rate.

• Prospective, publicly-funded studies assessing thecost-effectiveness of various screening strategies shouldbe performed as a matter of urgency.

Writing group

L.J. Salomon*, Z. Alfirevic†, F. Audibert‡, K. O. Kagan§,D. Paladini¶, G. Yeo** and N. Raine-Fenning††, onbehalf of the ISUOG Clinical Standards Committee.*Department of Obstetrics and Fetal Medicine, HopitalNecker-Enfants Malades, Assistance Publique-Hopitauxde Paris, Paris Descartes University, Paris, France andSFAPE (Societe Francaise d’Amelioration des PratiquesEchographique); †Department for Women’s and Chil-dren’s Health, University of Liverpool, Liverpool, UK;‡Department of Obstetrics and Gynaecology, CHUSainte Justine, University of Montreal, Montreal, QC,Canada; §Department of Obstetrics and Gynecology,University of Tuebingen, Tuebingen, Germany; ¶FetalMedicine and Surgery Unit, Giannina Gaslini Institute,Genoa, Italy; **Department of Maternal Fetal Medicine,Obstetric Ultrasound and Prenatal Diagnostic Unit, KKWomen’s and Children’s Hospital, Singapore; ††Divisionof Obstetrics & Gynaecology, School of Clinical Sciences,University of Nottingham, Nottingham, UK

[Correction added on 5 September 2014, after first onlinepublication: author Dario Paladini was added].

Reference

1. Salomon LJ, Alfirevic Z, Bilardo CM, Chalouhi GE, Ghi T,Kagan KO, Lau TK, Papageorghiou AT, Raine-Fenning NJ,Stirnemann J, Suresh S, Tabor A, Timor-Tritsch IE, Toi A, Yeo G.ISUOG practice guidelines: performance of first-trimester fetal ul-trasound scan. Ultrasound Obstet Gynecol 2013; 41: 102–113.

Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. Ultrasound Obstet Gynecol 2014; 44: 122–123.