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

摘要

Background Vitamin D is essential for proper neurodevelopment and cognitive and behavioral function. We examined newborn vitamin D in relation to later diagnosis of autism spectrum disorder (ASD) or developmental delay (DD). Methods Children aged 24-60 months enrolled in the population-based CHARGE case-control study were clinically confirmed to have ASD (n=373), DD (n=136), or typical development (TD, n=234) at the MIND Institute (Sacramento, CA) using standardized assessments. Total 25-hydroxyvitamin D (250HD) was measured using sensitive isotope dilution LC/MS/MS in archived dried blood spots collected for the California Department of Public Health's Newborn Screening Program. Associations between 20 nmol/L 250HD change and ASD and DD were assessed using unconditional multivariate polynomial logistic regression; associations between 250HD and Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS) scores were assessed using multivariate linear regression. Effect modification was examined using stratified models and interaction product terms. Results Neonatal 250HD was associated with significantly reduced ASD only in females (aORj=0.66; 95% CI: 0.48, 0.91, Pintxn=0.01). 250HD was significantly associated with reduced DD before (OR=0.84, 95% CI: 0.73, 0.97) but not after adjustment for maternal pre-pregnancy body mass index, prenatal vitamin intake, and education, and child race/ethnicity (aOR=0.91, 95% CI: 0.78,1.06). Similarly, MSEL and VABS were significantly associated before, but not after adjustment for several factors that could contribute to vitamin D status. Significant interaction by race/ethnicity was observed (p=0.02), with an association between 250HD and DD only in non-Hispanic white children (aOR=0.76; 95% CI: 0.61, 0.95). Conclusions This study provides evidence that newborn vitamin D could be associated with ASD in females and with DD in non-Hispanic white children. Future studies should investigate genetic interactions.