Copy number variants in fetuses with non-structural ultrasound abnormalities among pregnant women without adverse pregnancy history

Objective To analyze fetal copy number variants (CNVs) in pregnant women without adverse pregnancy history whose fetuses presented non-structural ultrasound abnormalities, and explore the correlations between CNVs status, ultrasonic phenotypes and maternal age. Methods A total of 426 pregnant women without adverse pregnancy history were consecutively recruited prospectively, followed by retrospective data analysis. Participants were divided into <35 years (n = 368) and ≥35 years (n = 58) groups. All fetuses were classified by types of non-structural ultrasound abnormalities. Chromosomal microarray analysis (CMA) was used to detect pathogenic/likely pathogenic CNVs (P/LP CNVs) and variants of uncertain significance (VUS). Subgroup comparisons of CNV detection rates were performed. Results Abnormal ultrasound soft markers were the most common manifestation (83.1%), followed by fetal growth restriction (12.2%) and abnormal amniotic fluid volume (4.2%). The overall detection rates of P/LP CNVs and VUS were 4.5% and 9.2%, respectively. The detection rates of P/LP CNVs and VUS in fetuses with abnormal ultrasound soft-markers were 3.4% and 9.6%, respectively. Both the detection rates of P/LP CNVs and VUS reached 9.6% in fetal growth restriction fetuses. The detection rate of P/LP CNVs was 5.6% in fetuses with abnormal amniotic fluid volume, whereas no VUS was detected. CNVs detection rates varied greatly among different soft markers: the detection rate was highest in fetuses with renal pelvic dilatation (33.3%, 5/15), followed by short long bones (17.9%, 5/28) and increased NT thickness (14.3%, 17/119). There were no significant differences in P/LP CNVs ( p = 0.090) and VUS ( p = 0.631) rates between pregnant women aged <35 years and ≥35 years. Conclusion Fetal CNVs vary substantially across different non-structural ultrasound abnormalities in low-risk pregnancies. Fetal growth restriction and several ultrasound soft markers are associated with elevated CNVs risks. Maternal age has no significant impact on fetal CNVs detection. Stratified risk assessment and individualized management are recommended for this population.