Should second‐trimester hypoplastic nasal bone be sole indication for diagnostic testing with chromosomal microarray analysis?

Lostchuck, Emily; Hui, Lisa

doi:10.1002/uog.20141

Cited by 12 publications

(17 citation statements)

References 6 publications

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“…Duchovny et al studied a cohort of 57 fetuses with absent NB, diagnosed either in first-trimester (n = 37, 65%) or at the secondtrimester scan (n = 20, 35%), and reported that pathogenic CNVs were found only in the group with associated multiple defects 7. In line with these results, Lostchuck et al found that in 80 fetuses with isolated hypoplastic NB at the second-trimester scan, the most frequent chromosomal abnormality at karyotype analysis was trisomy 21 (10%); in the remaining cases, no abnormal CNVs were detected if the finding was isolated, while abnormal CNVs reached 30% in nonisolated forms 9. Following these results, both authors suggest that an absent NB in the first or second trimester represents an indication for a detailed anatomical examination, and that CMA should be performed only if associated fetal abnormalities are detected.…”

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confidence: 81%

“…[4][5][6] In the second trimester, the diagnosis of an absent NB is an indication for a detailed anomaly scan, and, if additional anomalies are detected, a chromosomal microarray analysis (CMA) should be offered as the risk of microdeletion/microduplication syndromes is increased. [7][8][9] However, a recent study reported that CMA provides a diagnostic yield of 5.8% even in those cases with an apparently isolated absent NB at the second-trimester scan and with low risk at screening tests for major aneuploidies. 10 The accuracy of the first-trimester scan in assessing fetal congenital anomalies is around 28%, and some of the defects cannot be diagnosed at this stage reducing the likelihood of classifying an absent NB as truly isolated.…”

Section: Introductionmentioning

confidence: 99%

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First‐trimester absent nasal bone: is it a predictive factor for pathogenic CNVs in the low‐risk population?

et al. 2020

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Objective: To evaluate the association of first-trimester absent nasal bone (NB) and genetic abnormalities at G-banding karyotype and chromosomal microarray analysis (CMA) according to the nuchal translucency (NT) thickness. Methods: This is a retrospective cohort study of fetuses that underwent the firsttrimester scan for the combined test at 11 +0 to 13 +6 weeks' gestation. Invasive test with G-banding karyotype and/or CMA was performed based on the result of the combined test or if fetal defects were detected or for patient's choice, after genetic counseling. All cases with absent NB in the first and second trimester underwent a detailed anomaly scan with echocardiography in the second trimester, had a longitudinal ultrasound, and postnatal follow-up up to at least 1 year. Results: Between 2013 and 2018, 7228 women underwent the first-trimester scan at 11 +0 to 13 +6 weeks. Overall prevalence of absent NB was 1.3% (96/7228). Of those, in 86 pregnancies (1.2%), the absence of NB was confirmed also in the second trimester: 0.58% (40/6909) in the group with NT <95th centile; 6%(14/233) in the group with NT between 95 and 99th centile; and 37.2% (32/86) in the group with NT >99th centile, respectively. CMA pathogenic variants were found only in the group with NT >99th centile with a diagnostic yield of 9.4%. Fetuses with absent NB and NT between 95 and 99th centile had in 57% (8/14) a major chromosomal anomaly, while in the NT <95 centile group, there were 5% (2/40) of chromosomal abnormalities (one inherited from the father). Conclusion: In the first trimester, the risk for genetic syndromes detectable by CMA is related mainly to the NT thickness rather than to the absence of NB per se. In fetuses with absent NB and NT >99th centile, CMA should be performed after karyotype analysis, while for NT between 95 and 99th centile, a karyotype should be proposed as first-line procedure. Data provided by our study may be helpful in counseling women/couples when an absent NB is identified in the first trimester.

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confidence: 81%

Section: Introductionmentioning

confidence: 99%

First‐trimester absent nasal bone: is it a predictive factor for pathogenic CNVs in the low‐risk population?

et al. 2020

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“…The diagnostic yields of CMA over NIPT and karyotyping varied greatly between the reviewed studies, from 0 in three of these studies involving fetuses with other USMs rather than MVM 19,20,26 to 9.64% in fetuses with MVM in our prospective cohort study (Table 4). These discrepancies could be partially explained by the small sample sizes involved, by differences in cohort selection, and especially by the involvement of fetuses with different USMs.…”

Section: Results Of Meta-analysismentioning

confidence: 94%

“…The search revealed 799 studies, of which 9 studies in addition to our own study met the final inclusion criteria and were included in the meta-analysis (Figure 1). [18][19][20][21][22][23][24][25][26] Quality assessment of the included studies using QUADAS-2 was shown in Figure S1 of Supporting Information. Overall, 1817 fetuses were involved in this meta-analysis, including 405 fetuses with MVM and 1412 fetuses with other USMs (Table S3 of Supporting Information).…”

Section: Results Of Meta-analysismentioning

confidence: 99%

Should chromosomal microarray be offered to fetuses with ultrasonographic soft markers in second trimester: A prospective cohort study and meta‐analysis

Han

et al. 2020

Prenatal Diagnosis

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Objective: To evaluate whether chromosomal microarray (CMA) should be offered to fetuses with ultrasonographic soft markers (USMs) in the second trimester. Methods: A prospective cohort study and meta-analysis were conducted. In the prospective cohort study, 564 fetuses with USMs were enrolled. In the meta-analysis, eligible articles describing copy number variations in fetuses with USMs were included. Results: In the prospective cohort study, the diagnostic yields of CMA over noninvasive prenatal testing (NIPT) and karyotyping were significantly higher in fetuses with mild ventriculomegaly (MVM) than those in local control cohorts with normal ultrasound. However, the yields of CMA over NIPT and karyotyping in fetuses with other USMs were similar to controls. About ten studies, involving 405 fetuses with MVM and 1412 fetuses with other USMs, were included in the meta-analysis. The pooled diagnostic yields of CMA over NIPT and karyotyping in fetuses with MVM were 4.9% and 3.2%, respectively. In fetuses with other USMs, the yields of CMA over NIPT and karyotyping were 1.2% and 0.4%, respectively. Conclusion: It is reasonable to offer CMA as a first-tier test to fetuses with MVM. However, for fetuses with other USMs, the considerations to perform CMA should not differ from pregnancies with normal ultrasound. 1 | INTRODUCTION Ultrasound has become a crucial tool for the prenatal evaluation of growth and anatomy worldwide. 1 In China, a routine prenatal ultrasound is performed at 18 to 24 weeks gestational age for the detection of fetal anomalies and pregnancy complications and the majority of women choose to participate. 2 In addition to fetal structural abnormalities or abnormal fetal development, many other nonspecific, often transient anatomic findings, also known as "soft markers," can also be detected. 3,4 Although these soft markers are not anatomic abnormalities, there is evidence that they convey a statistically increased risk for fetal aneuploidy. 3,5 When ultrasonographic soft markers (USMs) are detected in second trimester, the finding can raise questions about prenatal diagnostic testing procedures. As technologies evolve, various methods are currently implemented in prenatal genetic testing, including noninvasive prenatal testing (NIPT) and invasive testing using karyotyping or chromosomal microarray (CMA). As compared to invasive testing, NIPT using cell-free fetal DNA (cffDNA) from maternal plasma is noninvasive and more acceptable by women. In contrast, invasive prenatal testing is performed by chorionic villi sampling, amniocentesis, or cord blood sampling, which is associated with an increased risk of miscarriage and other side-effects. 6 Karyotyping using the cells obtained from invasive testing is the conventional cytogenetic test with a

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“…We read with interest the Letter to the Editor by Lostchuck and Hui reporting on a population‐based series of prenatal diagnostic procedures performed from 18 weeks' gestation following the diagnosis of hypoplastic nasal bone (NB) on ultrasound. Of the 127 amniocenteses performed for an indication including hypoplastic NB, 80 were performed for isolated hypoplastic NB.…”

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confidence: 99%

Diagnostic value of chromosomal microarray in fetuses with isolated hypoplastic nasal bone

Nisbet

Reidy

et al. 2019

Ultrasound in Obstet & Gyne

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We read with interest the Letter to the Editor by Lostchuck and Hui 1 reporting on a population-based series of prenatal diagnostic procedures performed from 18 weeks' gestation following the diagnosis of hypoplastic nasal bone (NB) on ultrasound. Of the 127 amniocenteses performed for an indication including hypoplastic NB, 80 were performed for isolated hypoplastic NB. There were no cases of pathogenic copy-number variant (CNV) in the 47/80 cases that were analyzed by chromosomal microarray (0%; 95% CI, 0-7.1%). We note that the upper limit of this CI for the yield of chromosomal microarray analysis (CMA) is similar to the overall CMA yield for a fetus with any ultrasound abnormality 2 .We reported recently our tertiary-center experience with isolated hypoplastic NB, including newborn followup and postnatal microarray results 3 . We found a nontrisomy-21 abnormality in two of the 39 fetuses, resulting in a frequency of pathogenic CNV in isolated hypoplastic NB of 5.1%. The first fetus had Wolf-Hirschhorn syndrome presenting as isolated hypoplastic NB on ultrasound at 19 weeks; amniocentesis was performed at 24 weeks due to subsequent early-onset fetal growth restriction. The second case underwent chorionic villus sampling for advanced maternal age which detected de-novo microdeletions (1p31.3 (1.2 Mb) and 6p21q22.1 (2.2 Mb)); however, fetal anatomy was normal on first-trimester ultrasound. Subsequent ultrasound examinations showed isolated hypoplastic NB at 20 weeks and then mild ventriculomegaly and fetal growth restriction in the third trimester; the newborn had minor dysmorphisms, a hypoplastic corpus callosum and paraventricular cysts on postnatal magnetic resonance imaging 3 .Our findings are not dissimilar to those of Lostchuck and Hui, with the frequency of pathogenic results in our cohort being within their reported CI. However, our results highlight the limitations of conclusions based only on a cross-sectional prenatal dataset. It is important to keep in mind that the timing of invasive testing may not necessarily align with the exact time of the initial detection of hypoplastic NB. Invasive testing could be undertaken after additional ultrasound findings arise. The data captured by Lostchuck and Hui included only amniocenteses from 18 weeks and would not have included those cases returning at 16 weeks for review of uncertain findings, such as a NB that could not be confidently assessed at 12-13 weeks.Until larger population-based series, providing prenatal and postnatal data, are available, we caution against considering hypoplastic NB as a marker for trisomy 21 only. Fetuses with isolated hypoplastic NB and a low-risk cell-free DNA result should undergo detailed tertiary-level follow-up ultrasound and genetic counseling, including consideration of the risks of atypical chromosomal abnormalities detectable by CMA. References 1. Lostchuck E, Hui L. Should second-trimester hypoplastic nasal bone be sole indication for diagnostic testing with chromosomal microarray analysis? Ultrasound Obstet Gynecol 20...

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Should second‐trimester hypoplastic nasal bone be sole indication for diagnostic testing with chromosomal microarray analysis?

Cited by 12 publications

References 6 publications

First‐trimester absent nasal bone: is it a predictive factor for pathogenic CNVs in the low‐risk population?

First‐trimester absent nasal bone: is it a predictive factor for pathogenic CNVs in the low‐risk population?

Should chromosomal microarray be offered to fetuses with ultrasonographic soft markers in second trimester: A prospective cohort study and meta‐analysis

Diagnostic value of chromosomal microarray in fetuses with isolated hypoplastic nasal bone

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