Outcomes of pregnancies that screened positive for sex chromosome aneuploidy ascertained via cell-free DNA screening

Abstract

Cell-free DNA screening (cfDNA), also referred to as noninvasive prenatal screening (NIPS), is utilized to screen for fetal chromosomal aneuploidies during pregnancy, including sex chromosome aneuploidies (SCAs). All patients within our center are offered diagnostic testing following a positive cfDNA for an SCA, but not all patients pursue this testing. This retrospective chart review aims to improve understanding of how often patients undergo confirmatory diagnostic testing when cfDNA is positive or inconclusive for an SCA and the pregnancy outcomes, including pregnancy termination and live birth rates. We also describe the outcomes of cases where patients had a normal cfDNA result; however, the cfDNA-predicted fetal sex is discrepant from the ultrasound-predicted fetal sex. The study found that 56 patients had a positive or inconclusive cfDNA for SCA, and 36/56 (64.3%) pursued confirmatory testing either via prenatal (19 patients) or postnatal (17 patients) diagnostic testing. For the cases where confirmatory diagnostic information was available, an SCA was confirmed in 16/36 (44.4%). A birthing parent SCA was discovered to be the likely cause of a positive cfDNA in two cases. The positive predictive value (PPV) of cfDNA was 41.7% for all SCAs, 27.8% for Turner syndrome, 50.0% for triple X syndrome, 100% for Klinefelter syndrome, 100% for Jacobs syndrome, and 0% for inconclusive results. Nine patients had a negative cfDNA; however, the cfDNA-predicted fetal chromosomal sex was discrepant from the fetal phenotypic sex predicted by ultrasound. In 3/9 cases, this led to a fetal ascertainment of a difference of sex development (DSD), which would not have been possible without the cfDNA result.