Neonatal Vitamin D Status in Relation to Autism Spectrum Disorder and Developmental Delay in the Charge Case-Control Study

Abstract

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 (LC/MS/MS) 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 (MSEL) and Vineland AdaptiveBehavior Scales (VABS) 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 pre-pregnancy body mass index and education, a AUTHORS' CONTRIBUTIONS RJS conceived of and designed the study, helped secure funding, helped guide statistical analyses, interpreted results and drafted the manuscript; QN conducted preliminary statistical analysis; DE conducted measurements of dried blood spot vitamin D. RLH provided clinical oversight for the study and contributed clinical diagnoses; AMI designed the analytical plan and oversaw the preliminary statistical analyses and conducted final analyses. All authors reviewed and approved the final manuscript.