Application of noninvasive prenatal testing-plus in fetal ultrasound cardiovascular abnormalities: An observational study

Congenital heart disease (CHD), the most common birth defect in China with high neonatal mortality, is frequently associated with chromosomal abnormalities including copy number variations (CNVs), yet conventional ultrasound screening has limitations in detecting these genetic underpinnings; noninvasive prenatal testing plus (NIPT Plus) may address this gap, but its clinical efficacy in diagnosing fetal CHD remains unclear. To explore the clinical efficacy of NIPT Plus in the diagnosis of fetal CHD. Pregnant women whose fetuses were identified with congenital structural heart defects or abnormal cardiac soft markers via ultrasound between August 2019 and September 2023 were enrolled. All participants underwent NIPT-Plus and invasive prenatal diagnostic procedures, including chromosome karyotyping and/or chromosomal microarray analysis (CMA). The concordance between CNVs detected by NIPT-Plus and results from invasive prenatal diagnosis was analyzed. Among fetuses with congenital structural cardiac malformations or abnormal cardiac soft markers identified by prenatal ultrasound, 39 cases underwent NIPT-Plus testing, with a positive rate of 30.77% (12/39). Seven cases withdrew from the study for personal reasons after NIPT-Plus showed no abnormalities, and the remaining 32 cases received further confirmation via invasive prenatal diagnosis. Of these 32 cases, 12 were positive for NIPT-Plus, 11 of which were consistent with CMA validation results, yielding a positive predictive value of 91.67%. Additionally, 10 cases had CNVs > 4 Mb, 9 of which matched CMA results, with a positive predictive value of 90%. No significant difference was observed between NIPT-Plus and CMA results. NIPT-Plus exhibits favorable detection performance and clinical utility in the auxiliary diagnosis of fetal cardiovascular developmental abnormalities. However, in clinical practice, its results should be validated in combination with ultrasound findings and invasive tests such as amniocentesis to minimize the risks of false positives and missed diagnoses.