Non-Invasive Prenatal Testing (NIPT) Results for Participants of the eXtraordinarY Babies Study: Screening, Counseling, Diagnosis, and Discordance

Sex chromosome aneuploidies (SCAs), including 47,XXY, 47,XXX, 47,XYY, and supernumerary variants, occur collectively in approximately 1/500 livebirths. Clinical phenotypes are highly variable resulting in previous ascertainment rates have been estimated to be only 10-25% during a lifetime. Historically, prenatal SCA diagnoses were incidental findings, accounting for ≤10% of cases, with the majority of diagnoses occurring postnatally during evaluations for neurodevelopmental, medical, or infertility concerns. The initiation of noninvasive prenatal testing (NIPT) in 2012 and adoption into standardized obstetric care provides a unique opportunity to significantly increase prenatal ascertainment of SCAs. However, the impact NIPT has had on ascertainment of SCAs is understudied, particularly for those who may defer diagnostic testing until after birth. This study evaluates the timing of diagnostic testing following positive NIPT in 152 infants with SCAs and potential factors influencing this decision. Eighty-seven (57%) elected to defer diagnostic testing after a positive NIPT until birth, and 8% (7/87) of those confirmed after birth were found to have discordant results on postnatal diagnostic testing, most of which would have influenced genetic counseling.