Systematic Review of Accuracy Differences in NIPT Methods for Common Aneuploidy Screening.

Area of Science:

• Genetics and Genomics
• Prenatal Diagnostics
• Maternal-Fetal Medicine

Background:

• Non-invasive prenatal testing (NIPT) is a widely adopted screening method for fetal aneuploidies, offering higher accuracy than traditional approaches.
• Various NIPT technologies exist, including whole-genome sequencing (WGS), single nucleotide polymorphisms (SNPs), microarray, and rolling circle amplification (RCA).
• Comprehensive comparative evaluations of NIPT method performance, particularly predictive values for trisomy detection, are limited.

Purpose of the Study:

• To systematically review and compare the accuracy of different NIPT methods used for common aneuploidy screening.
• To evaluate the performance metrics, including sensitivity, specificity, and predictive values, across various NIPT technologies.

Main Methods:

• A systematic review of clinical studies published between 2003 and 2023, encompassing WGS, SNPs, microarray, and RCA NIPT methods.
• Data extraction from major databases (PubMed, Embase, Web of Science, Scopus, clinicaltrials.gov, Cochrane Library) without restrictions.
• Calculation of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) from extracted true/false positive/negative data for trisomy 21 (T21), 18 (T18), and 13 (T13).

Main Results:

• Twenty articles with 21 studies, involving 92,164 pregnant women, were included in the review.
• All NIPT methods demonstrated high sensitivity (>97%) for T21 detection, surpassing traditional screening.
• SNP and RCA methods showed lower PPVs compared to other NIPT methods; microarray had lower sensitivity for T18; WGS and RCA generally had lower PPVs for T13.

Conclusions:

• Different NIPT methods exhibit similar clinical sensitivity, specificity, and NPV for common fetal trisomies.
• Variations in PPV among NIPT methods highlight the necessity of confirmatory invasive testing for positive results.
• Combining NIPT with ultrasound screening for structural abnormalities may enhance the overall clinical utility of non-invasive prenatal testing.