Analysis of diagnostic consistency rate and pregnancy outcomes in pregnant women with high-risk NIPT undergoing transabdominal amniocentesis.

OBJECTIVE

To explore the diagnostic performance and positive predictive value (PPV) of non-invasive prenatal testing (NIPT) for different high-risk subtypes confirmed by amniocentesis, to analyze pregnancy outcomes, and to identify factors influencing true-positive results, thereby providing evidence for clinical genetic counseling and prenatal decision-making.

METHODS

A total of 342 pregnant women with high-risk NIPT findings and receiving subsequent amniocentesis were retrospectively included. Confirmatory diagnosis rates and PPVs were compared among different NIPT subtypes, and pregnancy outcomes were analyzed across groups. Stratified analyses were conducted according to maternal age, gestational age at amniocentesis and clinical indications. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of true-positive NIPT results.

RESULTS

Chromosomal abnormalities were confirmed in 218 of 342 enrolled cases (63.7%). PPV varied substantially among NIPT subtypes. Trisomy 21 (T21) had the highest PPV of 68.5%, followed by sex chromosome anomalies and trisomy 18 (T18), while trisomy 13 (T13) and pathogenic copy number variation (CNV) presented lower PPV. Variants of uncertain significance (VUS) accounted for 70.7% of all pathogenic CNV cases. Pregnancy outcomes differed significantly among high-risk NIPT subgroups. The sex chromosome anomaly group had the highest continued pregnancy rate, whereas trisomy 21 cases showed the highest pregnancy termination rate. All subtypes had higher PPV in women aged 35 years and above than in younger counterparts; statistical comparison was not conducted due to small sample size. No significant PPV difference was found among groups with different gestational age groups (P>0.05). Univariate analysis demonstrated that advanced maternal age was correlated with increased PPV. Multivariate logistic regression indicated that NIPT subtype and concurrent abnormal ultrasound soft markers were independent risk factors for true-positive results, while gestational age exerted no independent impact on diagnostic efficiency. The established regression prediction model had moderate discriminative power for true-positive prediction, with an area under the curve (AUC) of 0.695 (P<0.001).

CONCLUSION

PPV varies considerably among high-risk NIPT subtypes, and NIPT cannot replace invasive prenatal diagnosis. NIPT subtype classification and abnormal ultrasound soft markers independently affect true-positive results, and advanced maternal age elevates the detection risk of chromosomal anomalies. Stratified genetic counseling should integrate NIPT subtype, maternal age, and ultrasound findings. Early amniocentesis is recommended for high-risk pregnancies with autosomal trisomy, advanced maternal age, or abnormal ultrasound soft markers to facilitate standardized prenatal diagnosis and informed pregnancy decision-making.