False Positives and Negatives in NIPT: A Meta-Analytical Approach to Understanding Limitations

Abstract

Background:Non-invasive prenatal testing (NIPT) revolutionizes aneuploidy screening using cell-free fetal DNA, yet diagnostic inaccuracies, including false positives and negatives, pose challenges to clinical applications.
Objective:To evaluate the prevalence, contributing factors, and clinical implications of false-positive and false-negative results in NIPT to improve diagnostic accuracy and patient outcomes.
Method:A one-year meta-analysis was conducted at Barasat Government Medical College, Kolkata, with 100 pregnant patients. Diagnostic accuracy metrics, including false-positive and false-negative rates, were calculated using statistical models. Clinical parameters like fetal fraction, maternal conditions, and assay methodologies were analyzed for their impact on test outcomes.
Results:Of the 100 patients, 5 tested positive for chromosomal abnormalities; however, 3 were confirmed as false positives (60%). Among 95 negative results, 3 were identified as false negatives (3.2%). The false-positive rate for trisomy 21 was 2.5%, while for trisomies 18 and 13, it was 0.5% each. False negatives were linked to low fetal fraction (<4%) in 67% of cases and assay limitations in 33%. Whole-genome sequencing achieved a sensitivity of 99.5% and specificity of 98.9%, outperforming targeted sequencing (sensitivity 94.2%, specificity 96.5%). Counseling reduced post-test anxiety in 70% of false-positive cases. Overall, NIPT demonstrated a positive predictive value (PPV) of 86% and a negative predictive value (NPV) of 96%.
Conclusions:NIPT demonstrates high diagnostic accuracy but is limited by specific biological and methodological factors. Integrating advanced methodologies and robust counseling can minimize errors, improving patient outcomes and healthcare efficiency.