Impact of Prenatal Cell‐Free DNA Screening on Sex Chromosome Aneuploidy Diagnoses in Infants and Children

OBJECTIVE: Prenatal cell-free DNA (cfDNA) screening increasingly includes sex chromosome aneuploidy (SCA) screening, despite variation in test accuracy and expressivity. This study evaluated changes in pediatric SCA diagnostic rates before and after the introduction of cfDNA screening. METHOD: A controlled interrupted time series analysis was conducted using Clinformatics Data Mart claims data (2008-2019). Two cohorts were analyzed: infants (< 2 years) and children (2-18 years). The primary outcome was quarterly SCA diagnostic rates. RESULTS: During the pre-intervention period (2008-2013), 197 infants and 1477 children were diagnosed with an SCA, compared with 373 infants and 1300 children post-intervention (2014-2019). Introduction of prenatal cfDNA screening was associated with an immediate increase in SCA diagnosis rates among infants (3.55-6.56 cases per 100,000 persons), followed by a post-intervention average increase of 0.233 cases per 100,000 persons per quarter. Both the level (p = 0.03) and trend (p = 0.002) changes were statistically significant for infants compared with children. CONCLUSIONS: Prenatal cfDNA screening was associated with an immediate and sustained increase in SCA diagnosis rates among infants, whereas no meaningful change was observed among children, suggesting that cfDNA screening may contribute to more frequent detection of SCAs earlier in life.