Neonatal vitamin D status in relation to autism spectrum disorder and developmental delay in the CHARGE case–control study

Vitamin D appears essential for normal neurodevelopment and cognitive and behavioral function. We examined neonatal vitamin D in relation to the child's later diagnosis of autism spectrum disorder (ASD) or developmental delay (DD). Children aged 24–60 months enrolled in the population‐based CHARGE case–control study were evaluated clinically for ASD (n = 357), DD (n = 134), or typical development (TD, n = 234) at the MIND Institute (Sacramento, CA) using standardized assessments. Total 25‐hydroxyvitamin D (25[OH]D) was measured using sensitive isotope dilution liquid chromatography–tandem mass spectrometry in archived dried blood spots collected for the California Department of Public Health's Newborn Screening Program. Multinomial logistic regression was used to calculate ORs as measures of the associations between 25 nmol/L change in 25(OH)D and ASD and DD. Associations between 25(OH)D and scores on Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales were assessed using robust linear regression. Effect modification was examined using stratified models and interaction product terms. Unadjusted mean (SD) 25(OH)D was lower for DD (73.2 [37.6]) than for TD (82.7 [39.3]) and ASD (80.1 [37.4]). After adjustment for maternal prepregnancy body mass index and education, a 25 nmol/L increase in total 25(OH)D was not associated with ASD (OR = 0.97; CI: 0.87–1.08) or DD (OR = 0.91; 95% CI: 0.78–1.06). Neonatal 25(OH)D was associated with significantly reduced ASD only in females (adjusted OR = 0.74; 95% CI: 0.55–0.99, Pinteraction = 0.03), and significantly reduced DD only in non‐Hispanic white children (adjusted OR = 0.79; 95% CI: 0.63–0.98, Pinteraction = 0.11 for Hispanic, Pinteraction = 0.31 for other), driven by DD children with trisomy 21. This study provides evidence that neonatal vitamin D could be associated with ASD in females and with DD in non‐Hispanic white children. Autism Res 2019, 12: 976–988. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Vitamin D appears essential for brain development and function. We examined neonatal total 25‐hydroxyvitamin D (25[OH]D) measured in dried blood spots in relation to later diagnoses of autism spectrum disorder (ASD) or developmental delay (DD) and related assessment scores. Higher neonatal 25(OH)D was associated with a 26% reduction in the odds for ASD only in females. After taking into account factors that could contribute to vitamin D status, a significant