Application of Non-Invasive Prenatal Testing for Dominant Single-Gene Disorders in an Intermediate-Risk Population: A...

To assess the feasibility and efficiency of applying non-invasive prenatal testing for single-gene disorders (NIPT-SGD) in an intermediate-risk population.

We conducted a prospective cohort study of 2000 pregnant women at intermediate risk for SGDs in China. NIPT-SGD was conducted using a cfDNA-SGD panel targeting 155 genes associated with 202 dominant SGDs. Genetic validation was conducted via amniocentesis followed by Sanger sequencing, or through exome sequencing using newborn dried blood spot samples. Postnatal clinical follow-up was performed in both positive and negative cases through physical examination of the infants.

Out of 2000 participants, 3 cases experienced library preparation failures, leaving 1997 pregnancies for analysis. NIPT-SGD identified 10 positives and 1987 negatives. Subsequent diagnostic testing confirmed 7 true positives, 2 false positives, 988 true negatives, and no false negatives, yielding a sensitivity of 100% (95% CI: 59.0%-100%), specificity of 99.8% (95% CI: 99.3%-100%), positive predictive value of 77.8% (95% CI: 40.0%-97.2%), and negative predictive value of 100% (95% CI: 99.6%-100%). Among the 7 true-positive cases, 4 exhibited clinical features consistent with the identified genetic conditions or adverse pregnancy outcomes.

NIPT-SGD is a reliable and effective strategy for the detection of fetal dominant SGDs in an intermediate-risk population. However, the implementation still needs caution due to clinical ambiguity introduced by variants in fetuses without phenotypic manifestations.