Vitamin D supplementation in the first 2 years and autism spectrum traits at 6–8 years – a randomized clinical trial

Abstract

Background: Early life vitamin D levels may be associated with autism spectrum disorder (ASD) and related traits, but causality is unknown. We examine whether higher-than-standard vitamin D3 supplementation during the first 2 years, as well as higher pregnancy and childhood 25-hydroxyvitamin D (25(OH)D) levels and their trajectories, are associated with lower ASD trait scores at ages 6–8 years in a non-clinical cohort. Methods: This secondary analysis of the double-blind randomized clinical trial vitamin D intervention in infants (VIDI) comprised 366 Finnish children aged 6–8 years, 177 of whom were randomized to receive 400-IU and 189 to receive 1,200-IU daily oral vitamin D3 supplementation between ages 2 weeks and 2 years. ASD-related traits were assessed at mean age 7.2 years (SD 0.4) using the parent-reported Autism Spectrum Screening Questionnaire (ASSQ). Predictor variables were supplementation group, 25(OH)D concentrations measured during pregnancy and at ages 1 and 2 years, as well as 25(OH)D trajectories (high vs. low) derived from these time points. Results: None of the predictor variables of interest were associated with the outcome in the full sample. After sex stratification, among boys, 25(OH)D concentrations at 1 and 2 years were inversely associated with ASSQ scores (mean difference −0.2 of normalized SD score (95% CI −0.3 to −0.1, p =.003) and −0.2 (95% CI −0.3 to −0.05, p =.01) per 10 ng/mL 25(OH)D) after adjustment for age, breastfeeding, parental education, maternal depressive symptoms, and season of 25(OH)D assessment as was belonging to the higher 25(OH)D trajectory, −0.45 SD (95% CI −0.79 to −0.10, p =.01). Conclusions: We found no indication that higher-than-normal vitamin D3 supplementation between ages 0 and 2 years decreases ASD-related trait scores at ages 6–8 years. Sex-stratified analysis suggested an inverse association, among boys, between early life 25(OH)D concentrations and ASD-related traits, warranting further studies on potential causal direction and sex specificity of associations.