Newborn Vitamin D Levels in Relation to Autism Spectrum Disorders; A Case-Control Study in California

Background: Explanations for the continuing rise in the prevalence of Autism Spectrum Disorder (ASD) are urgently needed, so environmental factors are important to consider, as well as gene-environment (GxE) interactions. Vitamin D deficiency/insufficiency also appears to be increasing over recent decades. Emerging evidence suggests vitamin D may be related to risk of ASD, given advances in the understanding of its role in brain and immune function. Prior studies of ASD have generally examined surrogates of vitamin D (e.g. latitude, season) or levels in children already diagnosed, rather than the more likely susceptibility period during early development.

Objectives: To investigate the association between measured perinatal vitamin D deficiency/insufficiency and ASD in the Early Markers for Autism (EMA) study.

Methods: We conducted a population-based case-control study among children born in 2000-2003 in Southern California whose mothers had participated in prenatal and newborn screening and had banked biospecimens available. Autism (N=563) was identified from the Department of Developmental Services (DDS) and confirmed by expert clinician record review. General population controls (N=436) were randomly selected from birth certificates of children not served by DDS born in the same region and years. 25-Hydroxyvitamin D (25OHD) metabolites were measured in newborn dried blood spots by a sensitive assay, and hematocrit-corrected. The distribution of total 25OHD was compared between ASD cases and controls, and by potential confounding factors. For this presentation we categorized vitamin D levels as deficient (<50nmol/L), insufficient (50-74 nmol/L) and sufficient (≥75 nmol/L). Crude and adjusted odds ratios (AOR) and 95% confidence intervals (CI) were calculated by logistic regression. Further, we examined associations by newborn genotype for SNPs associated with vitamin D levels, and in subgroups defined by maternal race/ethnicity, parity, and child sex.

Results:  The median OHD level was 85.3 nmol/L; 14% of infants were classified deficient and 26% insufficient. OHD levels were lower (or deficiency more frequent) for winter births, higher birth order, non-White maternal race/ethnicity, and lower maternal education, as well as shorter time to blood draw. OHD levels were similar between cases and controls. Adjusting for a number of potential confounders did not change these patterns; the AOR (95%CI) for deficiency was 0.95 (0.64-1.4) and for insufficiency was 1.2 (0.86-1.6). While some variation in effect estimates were observed among the sub-groups examined, including the genotype at missense SNP rs4588 in vitamin D transport gene GC, confidence intervals were relatively wide and overlapped.

Conclusions: This is the first large study to examine newborn vitamin D in relation to autism, with no association seen. The relatively low rate of Vitamin D deficiency limited small sub-group analyses. Prior studies reporting lower Vitamin D levels in children with autism or their mothers, after diagnosis, may reflect current lifestyle and diet. In the more developmentally relevant time period, studies have found lower prenatal maternal OHD levels associated with language difficulties and mental and psychomotor outcomes in offspring, supporting the need for additional research on autism. We plan to examine second trimester maternal vitamin D levels in this study population in the future.