Study on copy number variant detection results of 472 fetuses with non-structural ultrasound abnormalities in non-advanced age pregnant women and the correlation with adverse obstetric history

Objective To investigate copy number variant (CNV) results in 472 fetuses with non-structural ultrasound abnormalities among pregnant women under 35 years, and analyze the association between adverse obstetric history and pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS). Methods A total of 472 pregnant women aged <35 years with fetal non-structural ultrasound abnormalities were retrospectively enrolled. All participants were divided into groups with or without adverse obstetric history. We summarized the distribution of non-structural ultrasound abnormalities, calculated the overall and stratified detection rates of P/LP CNVs and VUS, and compared differences between groups. Results The mean maternal age was 28.73 ± 3.59 years; 22.0% had a positive history. Abnormal ultrasound soft markers accounted for 82.6% of cases, followed by fetal growth restriction (12.3%) and abnormal amniotic fluid volume (4.0%). The overall detection rates were 5.7% for P/LP CNVs and 9.1% for VUS. The highest detection rate of P/LP CNVs was observed in fetuses with abnormal amniotic fluid volume (10.5%), while the highest detection rate of VUS was seen in abnormal ultrasound soft markers (9.2%). The combined detection rate of P/LP and VUS differed among different types of isolated abnormal ultrasound soft markers, with tricuspid regurgitation, persistent right umbilical vein and persistent left superior vena cava showing higher detection rates. No significant differences in overall P/LP CNV and VUS rates were found between women with and without adverse pregnancy history ( p > 0.05). Conclusion Non-advanced age pregnant women with fetal non-structural ultrasound abnormalities carry a non-negligible risk of P/LP CNVs and VUS. Different ultrasound soft markers present distinct CNV detection rates. Adverse obstetric history does not alter the P/LP CNVs and VUS detection rate.