Is there still a role for nuchal translucency measurement in the changing paradigm of first trimester screening?

Bardi, Francesca; Bosschieter, Pien F. N.; Verheij, Joanne; Go, Attie T.J.I.; Haak, Monique; Bekker, Mireille N.; Sikkel, Esther; Coumans, A.; Pajkrt, Eva; Bilardo, C. M.

doi:10.1002/pd.5590

Cited by 61 publications

(82 citation statements)

References 40 publications

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“…To be able to compare the current data with the literature cohort tested with karyotyping, we took only microscopically visible aberrations into account. Strong association between chromosomal aberrations and fetal NT >3 mm was already suggested by Pandya et al 29 When karyotypically visible aberrations are taken into account, our pooled cohort showed 11% of abnormal cases, whereas the clinical data of Kagan et al 7 showed chromosomal aberrations in 7.1% of fetuses (p95 ‐> 3.4 mm, 507/7109), Äyräs et al 30 in 9.6% (p95 ‐> 3.4 mm, 65/679), Nicolaides et al 31 in 13% (NT = 3 mm 7/52) and Bardi et al 32 in 14% (p95‐p99, 124/894). Although the incidence of chromosome aberrations presented in this paper is within the previously published range (7%‐14%), one has to be aware that the incidence based on fetal invasive testing, such as in our study, might represent the upper bound risk estimate, but on the other hand, in population‐based studies the bias could be caused by missing pediatric cases with less pronounced symptoms caused by a chromosomal aberration that is not always evident at birth or even within the first 3 years.…”

Section: Discussionmentioning

confidence: 53%

Nuchal translucency of 3.0‐3.4 mm an indication for NIPT or microarray? Cohort analysis and literature review

Petersen

Smith²,

Opstal

et al. 2020

Acta Obstet Gynecol Scand

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Introduction:Currently fetal nuchal translucency (NT) ≥3.5 mm is an indication for invasive testing often followed by chromosomal microarray. The aim of this study was to assess the risks for chromosomal aberrations in fetuses with an NT 3.0-3.4 mm, to determine whether invasive prenatal testing would be relevant in these cases and to assess the residual risks in fetuses with normal non-invasive prenatal test (NIPT) results. Material and methods:A retrospective study and meta-analysis of literature cases with NT between 3.0 and 3.4 mm and 2 cohorts of pregnant women referred for invasive testing and chromosomal microarray was performed: Rotterdam region (with a risk >1:200 and NT between 3.0 and 3.4 mm) tested in the period Results: A total of 522 fetuses were referred for invasive testing and chromosomal microarray. Meta-analysis indicated that in 1:7.4 (13.5% [95% CI 8.2%-21.5%]) fetuses a chromosomal aberration was diagnosed. Of these aberrant cases, 47/68 (69%) involved trisomy 21, 18, and 13 and would potentially be detected by all NIPT approaches. The residual risk for missing a (sub)microscopic chromosome aberration depends on the NIPT approach and is highest if NIPT was performed only for common trisomies-1:21 (4.8% [95% CI 3.2%-7.3%]). However, it may be substantially lowered if a genome-wide 10-Mb resolution NIPT test was offered (~1:464). Conclusions:Based on these data, we suggest that the NT cut-off for invasive testing could be 3.0 mm (instead of 3.5 mm) because of the high risk of 1:7.4 for a chromosomal aberration. If women were offered NIPT first, there would be a significant diagnostic delay because all abnormal NIPT results need to be confirmed by diagnostic testing. If the woman had already received a normal NIPT result, the residual risk of

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Section: Discussionmentioning

confidence: 53%

Nuchal translucency of 3.0‐3.4 mm an indication for NIPT or microarray? Cohort analysis and literature review

Petersen

Smith²,

Opstal

et al. 2020

Acta Obstet Gynecol Scand

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“…The possibility of a differential diagnosis, such as Noonan syndrome, is only introduced when there are structural abnormalities, and PND has shown the NIPT result to be a false positive. This occurred in only two (1%) of our cases and further highlights the importance of 11‐ to 14‐week ultrasound which may indicate other chromosomal or congenital abnormalities not assessed by NIPT 34 …”

Section: Discussionmentioning

confidence: 55%

Increasing maternal age is not a significant cause of false‐positive results for monosomy X in non‐invasive prenatal testing

et al. 2020

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Objective: The accuracy of cell-free DNA aneuploidy screening varies by the chromosome assessed. The positive predictive value is consistently low for monosomy X (MX), at less than 30%. This study aims to investigate maternal age and other possible predictors of false-positive MX screening results in order to guide pre-test and posttest counselling. Methods: A total of 52 499 NIPT samples were tested over 69 months, across three specialist obstetric services. Outcome data were available for 96 out of 107 cases high risk for MX. Cytogenetic outcomes were compared to clinical and demographic data to look for trends that may indicate higher likelihood of a false-positive NIPT result. Results: The likelihood of a false-positive MX result significantly increased with the absence of ultrasound features suggestive of MX and with lower PAPP-A levels. Non-significant trends towards false-positive results were identified with increased maternal age, increased body mass index and Caucasian ethnicity. Conclusion: Maternal age is not a reliable predictor of a false-positive result. Assessment of ultrasound findings and placental serology in the first trimester is important for appropriate post-test counselling and should continue to be a part of screening even when NIPT is used as a first-tier screening test.

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“…Implementation of two ultrasound scans in the first trimester if NIPT is performed early has to be discussed. Offering NIPT at 11+0-13+6 weeks in order to look for increased nuchal translucency and structural fetal anomalies, following the ISUOG guidelines, seems to be the more comprehensive approach [ 12 , 13 , 14 ]. A recent study showed that management would be changed in almost 10% of cases, when ultrasound was done before blood for NIPT was drawn [ 15 ].…”

Section: Introduction and Overviewmentioning

confidence: 99%

Chances and Challenges of New Genetic Screening Technologies (NIPT) in Prenatal Medicine from a Clinical Perspective: A Narrative Review

Bedei

Wolter

Weber

et al. 2021

Genes

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In 1959, 63 years after the death of John Langdon Down, Jérôme Lejeune discovered trisomy 21 as the genetic reason for Down syndrome. Screening for Down syndrome has been applied since the 1960s by using maternal age as the risk parameter. Since then, several advances have been made. First trimester screening, combining maternal age, maternal serum parameters and ultrasound findings, emerged in the 1990s with a detection rate (DR) of around 90–95% and a false positive rate (FPR) of around 5%, also looking for trisomy 13 and 18. With the development of high-resolution ultrasound, around 50% of fetal anomalies are now detected in the first trimester. Non-invasive prenatal testing (NIPT) for trisomy 21, 13 and 18 is a highly efficient screening method and has been applied as a first-line or a contingent screening approach all over the world since 2012, in some countries without a systematic screening program. Concomitant with the rise in technology, the possibility of screening for other genetic conditions by analysis of cfDNA, such as sex chromosome anomalies (SCAs), rare autosomal anomalies (RATs) and microdeletions and duplications, is offered by different providers to an often not preselected population of pregnant women. Most of the research in the field is done by commercial providers, and some of the tests are on the market without validated data on test performance. This raises difficulties in the counseling process and makes it nearly impossible to obtain informed consent. In parallel with the advent of new screening technologies, an expansion of diagnostic methods has begun to be applied after invasive procedures. The karyotype has been the gold standard for decades. Chromosomal microarrays (CMAs) able to detect deletions and duplications on a submicroscopic level have replaced the conventional karyotyping in many countries. Sequencing methods such as whole exome sequencing (WES) and whole genome sequencing (WGS) tremendously amplify the diagnostic yield in fetuses with ultrasound anomalies.

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Is there still a role for nuchal translucency measurement in the changing paradigm of first trimester screening?

Cited by 61 publications

References 40 publications

Nuchal translucency of 3.0‐3.4 mm an indication for NIPT or microarray? Cohort analysis and literature review

Nuchal translucency of 3.0‐3.4 mm an indication for NIPT or microarray? Cohort analysis and literature review

Increasing maternal age is not a significant cause of false‐positive results for monosomy X in non‐invasive prenatal testing

Chances and Challenges of New Genetic Screening Technologies (NIPT) in Prenatal Medicine from a Clinical Perspective: A Narrative Review

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