Medical Findings in Infants Prenatally Identified With Sex Chromosome Trisomy in Year 1 of Life

BACKGROUND AND OBJECTIVE: Sex chromosome trisomies (SCT), including XXY, XYY, and XXX syndromes, have been historically underdiagnosed. Noninvasive prenatal cell-free DNA screening has significantly increased identification, leading to a need for pediatric care for a growing population of newborns with SCT. Our goal was to analyze and compare perinatal, medical, and physical features in infants with prenatal identification of SCT through 12 months of age. METHODS: The eXtraordinarY Babies Study is a prospective natural history study of prenatally identified children with SCT. Participants enroll prior to 12 months of age and have medical histories and examinations at 2-, 6-, and 12-month visits. Descriptive statistics were followed by comparisons between SCT groups (t tests, analysis of variance, Fisher exact tests). Relative risks were calculated compared to general population rates. RESULTS: A total of 309 infants are included (XXY = 182; XXX = 76; XYY = 51). Relative risk (RR) compared to general population is elevated for breastfeeding difficulties (51.1%; RR 2.7 [CI 2.1-3.4]), positional torticollis (29.4%; RR 7.5 [5.3-10.7]), eczema (47.6%; RR 3.5 [3.1-3.9]), food allergies (19.4%; RR 2.4 [1.9-3.1]), small cardiac septal defects (7.8%; RR 17.3 [11.8-25.3]), and structural renal abnormalities (4.5%; RR 10.1 [6.0-16.8]), all P < .001. Comparisons between groups show more similarities than differences; however, infants with an extra X chromosome are at higher risk for lower birth weight and length, infants with XXX have higher risk for renal and cardiac malformations, and the risk of eczema is higher in boys. DISCUSSION: Results inform care as pediatricians and families can be reassured that a prenatal diagnosis of SCT is not associated with complex medical or physical abnormalities within the first year of life, but proactive monitoring for select at-risk conditions is warranted.