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

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.

Foetal Nasal Bone Length Measurement and Evolving Normogram in Southern Indian Population in Normal Pregnancies: A Cross-sectional Study

Introduction: Assessment of the foetus to detect aneuploidies between 12 to 24 weeks of gestation is an integral part of the ultrasound scanning. Absence or hypoplastic nasal bone is a very important marker of foetal aneuploidy. Thus, identifying the range of foetal Nasal Bone Length (NBL) in normal gestation is very important to screen for aneuploidies. Aim: This study aimed at ascertaining the reference range of foetal NBL between 11 to 24 weeks of pregnancy. Materials and Methods: A multicentre, cross-sectional study was conducted from 2018 to 2020. After obtaining Ethical approvals from each centre, NBL was measured in 826 patients between 11-24 weeks of pregnancy. Transabdominal scans were performed and the data was used to construct the NBL normogram for this Gestational Age (GA). Linear regression analysis was used to analyse the relationship between NBL and Gestational Age. Scatter plots for NBL as function of GA was constructed. The 5th and 50th percentile values were calculated for each gestational week. Results: With one unit increase in GA (weeks), NBL increased by 0.402 times (r=0.897, p<0.001). Mean NBL was 4.05 mm. The medians NBL for 12-14 weeks were 2.1-2.5 mm, 15-18 weeks was 3.0-4.6 mm, 19-21 weeks was 5.3-5.8 mm, 22-24 weeks was 6.0-6.6 mm. Conclusion: This study highlights the importance of nasal bone evaluation in the second trimester of pregnancy to detect foetuses with Down syndrome. Since NBL increases linearly with GA, it aids detecting the hypoplastic nasal bone at different GA.

Fetal absent/hypoplastic nasal bone: a single center follow up study from a tertiary referral hospital in India

Background: This study was undertaken to determine perinatal outcomes in fetuses with absent/hypoplastic nasal bone (AHNB) when considered as a broad entity irrespective of time at which it is identified and identify subgroups with the highest risk of abnormal outcome based on screening status and associated findings.Methods: This was an observational study involving a total of 142 pregnant women whose fetuses were identified with AHNB by ultrasongraphy (USG) during a three year period from January 2016 to December 2018. These women were offered aneuploidy screening/non-invasive prenatal testing (NIPT) or direct invasive testing either alone or in combination. Outcome data was collected and a sub-group analysis was done by dividing them into 8 subgroups based on screening status and associated findings.Results: Out of 12758 scans done during the study period, 142 fetuses (1.11%) were identified with AHNB. 80 (56%) opted the biochemical screening test, 5 (3.5%) opted NIPT while 60 (42.9%) opted for invasive testing. 21 (14.8%) had an abnormal karyotype. In sub-group analysis, the best outcome was seen in group 1, where the biochemical screening was negative and no other aneuploidy markers or anomalies were seen.Conclusions: The present study confirms the association of AHNB with chromosomal disease. However, isolated AHNB with low risk in biochemical screening is rarely associated with aneuploidy. In contrast, a significant no of fetuses yielded abnormal chromosome results when AHNB was associated with high risk in biochemical screening, additional aneuploidy markers or associated anomalies.

Prenatal diagnosis of cri-du-chat syndrome by SNP array: report of twelve cases and review of the literature

Background Cri-du-chat syndrome (CdCS; OMIM#123450) is a classic contiguous gene syndrome caused by chromosome 5p terminal deletion (5p-), which characterized by a high-pitched cat-like cry, developmental delay, severe psychomotor, mental retardation, and dysmorphic features in infancy. Prenatal diagnosis of CdCS is difficult due to the non-specific ultrasound features. And reports using array analysis are rare. This study presented the first retrospective analysis of prenatal series of CdCS fetuses diagnosed by single nucleotide polymorphism (SNP) array in China. Case presentation A total of 35,233 pregnant women were enrolled from Jan 2014 to April 2019 in our center, there are twelve 5p- cases with abnormal sonographic signs revealed by SNP array, giving an incidence of 0.034% (12/35,233). Clinical information and molecular basis included: maternal demographics, indications for invasive testing, sonographic findings and SNP array results. Among all the 5p- cases revealed, nine cases were diagnosed by both karyotyping and SNP array, three cases were detected only by SNP array. Half of our cases (6/12) had an isolated 5p terminal deletion, which sizes ranged from 9.0 Mb to 30 Mb. The other half of cases (6/12) characterized by unbalanced translocation, with sex ratio 7:5 (female: male), when combine the clinical features observed from this study and available literature, the most frequent anomaly observed in prenatal ultrasound examination of CdCS was cerebral abnormalities, accounted for 44.4% (16/36) of the existing cases. Features that are less consistent included: choroid plexus cyst (13.8%, 5/36), single umbilical artery (13.3%, 4/30), ventricular septal defect (11.1%, 4/36), hydrops fetalis (8.3%, 3/36), ascites (8.3%, 3/36), increased NT/NF (8.3%, 3/36), absent/severely hypoplastic nasal bone (5.5%, 2/36), in order. Conclusion Prenatal findings such as cerebral abnormalities, absent/hypoplastic nasal bone, hydrops fetalis, ascites or encephalocele may act as suggestive signs of CdCS or other microdeletion/duplication syndromes. Combining typical karyotyping with chromosomal microarray analysis (CMA) is a definitive method for a precise diagnosis of CdCS and provides more accurate results in order to offer genetic counseling to families which need to deal with cryptic aberrations.

Prenatal Sonographic Detection of Multiple Congenital Anomalies: A Case of Severe Arthrogryposis Multiplex Congenita (AMC)

This case study describes an obstetrical patient who presented for a routine second-trimester morphology sonogram in which the fetus was found to have arthrogryposis multiplex congenita. Other abnormalities visualized included a single umbilical artery, hypoplastic nasal bone, polyhydramnios, and poorly visualized lateral ventricles. Amniocentesis demonstrated a normal microarray with a negative result for cytomegalovirus and toxoplasmosis. This case study highlights the utility of prenatal sonography to identify functional abnormalities of the fetal musculoskeletal system.