The recurrence of sonographic ‘soft markers’: ominous sign or ‘just’ genetics?

Ginsberg, Yuval; Khatib, Nizar; Weiner, Zeev; Beloosesky, Ron; Bronshtein, Moshe

doi:10.1002/pd.5034

Cited by 6 publications

(5 citation statements)

References 15 publications

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“…USMs are detected during fetal sonographic anatomical screening in approximately 10% of normal fetuses in the USA 17 . Ginsberg showed that there is a high recurrence rate of solitary USMs, which supports the hypothesis that genetic factors form the basis for the reappearance of USMs 18 . Therefore, there were different incidences of USMs among fetuses of different races.…”

Section: Discussionsupporting

confidence: 56%

Identification of copy number variations among fetuses with ultrasound soft markers using next-generation sequencing

Wang

Chen

Zhou

et al. 2018

Sci Rep

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A prospective analysis investigating the associations between pathogenic copy number variations (pCNVs) and ultrasound soft markers (USMs) in fetuses and evaluating the clinical value of copy number variation sequencing (CNV-seq) in such pregnancy studies was carried out. 3,398 unrelated Chinese women with singleton pregnancies and undergone amniocentesis at 18–36 weeks of gestation for fetal CNV-seq were included. According to the prenatal fetal ultrasound screening results, the samples were divided into 3 groups: normal ultrasound (n = 2616), solitary USM (n = 663), and two or more USMs (n = 119). CNV-seq was performed successfully using all samples. The prevalence of pCNVs in fetuses with normal ultrasound and USMs was 3.03% (79/2616) and 2.94% (23/782), respectively. The risk of segmental aneuploidies was significantly higher in the two or more USMs group (5/119, 4.20%) than in the normal ultrasound (27/2616, 1.04%) or solitary USM (9/663, 1.36%) groups (p = 0.002 and p = 0.031, respectively). Assuming that the resolution of karyotyping is ~5 Mb, a cytogenetic analysis would miss 33 of 102 (32.35%) pCNVs in these samples. Our results suggest an association between pCNVs and fetal USMs; multiple USMs indicate an increased risk of fetal segmental aneuploidies. In prenatal diagnostic testing, CNV-Seq identified additional, clinically significant cytogenetic information.

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Section: Discussionsupporting

confidence: 56%

Identification of copy number variations among fetuses with ultrasound soft markers using next-generation sequencing

Wang

Chen

Zhou

et al. 2018

Sci Rep

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“…However, the detection of USMs cause stress in pregnant women, and the depressive symptoms may persist until delivery ( Ahman et al, 2010 ; Nevay et al, 2016 ). Previous studies have shown that USMs, such as EICF, thickened nuchal fold, and mild pyelectasis were commonly repeated in subsequent pregnancies, providing deeper insights into the genetic predisposition and recurrence of USMs ( Ginsberg et al, 2017 ). In particular, the interpretation of abnormal results and clinical genetic consultation in pregnant women who have had USMs and undergone NIPS may also cause confusion for them and the clinicians.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Prenatal Screening Based on Second-Trimester Ultrasonographic Soft Markers in Low-Risk Pregnant Women

et al. 2021

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Background: We aimed to assess the clinical application of noninvasive prenatal screening (NIPS) based on second-trimester ultrasonographic soft markers (USMs) in low-risk pregnant women.Methods: Data of pregnant women between April 2015 and December 2019 were retrospectively analyzed. Pregnant women [age at expected date of confinement (EDC) of <35 years; low risks for trisomy 21 (T21) and trisomy 18 (T18) based on maternal serum screening; presenting second-trimester USMs (7 types)] who successfully underwent NIPS and had available follow-up information were included in our study. Cases with positive NIPS results were prenatally diagnosed. All patients were followed up for 6 months to 2 years after NIPS, and their clinical outcomes were obtained. Subgroup analyses were performed according to the different USMs.Results: NIPS suggested that among a total of 10,023 cases, 37 (0.37%) were at high risk of aneuploidy, including 4 T21, 6 trisomy 13 (T13), and 27 sex chromosome abnormalities (SCA). Ten cases with aneuploidy (0.10%) were confirmed by prenatal diagnosis, consisting of two T21 and eight SCA. The eight fetuses with SCA consisted of one monosomy X, two XXY, one XXXY, one XXX, one XYY, and two mosaicisms. T21 was detected in one fetus with absent or hypoplastic nasal bone and one fetus with echogenic intracardiac focus (EICF). SCA was detected in five fetuses with EICF, two fetuses with multiple soft markers, and one fetus with echogenic bowel. The positive rate of chromosomal aneuploidy was significantly higher in fetuses with absent or hypoplastic nasal bone (6.25 vs. 0.10%, p = 0.017), echogenic bowel (3.7 vs. 0.10%, p = 0.029), and multiple soft markers (0.678 vs. 0.10%, p = 0.045) than in the total fetuses. The positive predictive values (PPVs) of NIPS in these three groups were 100%, 50%, and 100%, respectively. EICF accounted for 93.25% (9,346/10,023) of the study population, whereas the PPV of NIPS was only 20%.Conclusion: NIPS is an advanced screening test for low-risk pregnant women. In the 10,023 pregnant women sampled, SCA were more common than autosomal trisomy, and EICF was the most frequent USM but the least predictive aneuploidy. Further aneuploidy evaluation is suggested for low-risk pregnant women whose ultrasound indicates absent or hypoplastic nasal bone, echogenic bowel, or multiple soft markers. NIPS can serve as a second-line complementary screening for these women.

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“…Cordocentesis is associated with a risk of complication; the foetal loss rate within 2 weeks in the study was 0.47%, lower than that reported in other studies, in which cordocentesis was performed in pregnancies with a gestational age of < 24 weeks (early cordocentesis is more difficult and has a tendency to increase the rates of adverse outcomes) [7]. Ultrasound soft markers are defined as minor nonspecific findings on ultrasound scans, which are often transient and have little or no pathological significance, such as an echogenic intracardiac focus, a thickened nuchal fold and an echogenic bowel; although not pathological per se, ultrasound soft markers have been found to be linked to foetal aneuploidies such as Down syndrome [8]. In this study, the most common indication for diagnostic genetic testing was ultrasound soft markers, which accounted for 73.16% of the indications, and the rate of foetal chromosome abnormality was 2.02% (50/ 2478).…”

Section: Discussionmentioning

confidence: 99%

Cytogenetic analysis of 3387 umbilical cord blood in pregnant women at high risk for chromosomal abnormalities

Sun

Zhang

et al. 2020

Mol Cytogenet

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Background: Cordocentesis in our practice is most commonly indicated for rapid karyotyping in the second or third trimester and is regarded as the gold standard for foetal chromosomal aberration diagnosis in pregnancies at high risk for chromosomal abnormalities. In this study, we investigated 3387 umbilical cord blood samples for karyotyping from pregnant women who underwent cordocentesis and explored the pregnancy outcomes of foetal sex chromosome mosaicism and chromosomal polymorphism. Results: Out of the 3387 samples, 182 abnormal karyotypes were detected. Ultrasound soft markers were the most common prenatal diagnostic indication, but the detection rate of abnormal karyotypes was 2.02%, while it was 46.97% in the genome-wide NIPT-positive group. The rate of aneuploidy was lower in the soft marker group than in the other groups. Out of 16 cases with sex chromosome mosaicism, three pregnant women with foetuses with a lower proportion of sex chromosome mosaicism delivered healthy foetuses; the foetus with karyotype 46,X,i(Y)(q10)[20]/45, X[6] showed unclear genitals. Three foetuses with chromosomal polymorphisms had postnatal disorders. Conclusions: NIPT should not be recommended as the first-tier screening for chromosomal aberration for pregnancies with ultrasound soft markers or pathological ultrasound findings, but NIPT can be considered an acceptable alternative for pregnancies with contraindications to cordocentesis or the fear of procedure-related foetal loss. Mosaicism found in amniotic fluid cell culture requires further cordocentesis for karyotype confirmation, and the continuation of pregnancy is safe when a normal karyotype is identified in foetal blood culture. Further genetic testing and parental karyotype analysis are needed for foetal chromosomal polymorphisms.

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The recurrence of sonographic ‘soft markers’: ominous sign or ‘just’ genetics?

Cited by 6 publications

References 15 publications

Identification of copy number variations among fetuses with ultrasound soft markers using next-generation sequencing

Identification of copy number variations among fetuses with ultrasound soft markers using next-generation sequencing

Noninvasive Prenatal Screening Based on Second-Trimester Ultrasonographic Soft Markers in Low-Risk Pregnant Women

Cytogenetic analysis of 3387 umbilical cord blood in pregnant women at high risk for chromosomal abnormalities

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