Prenatal nutritional supplementation and autism spectrum disorders in two European population-based cohorts

Objective: In two prospective population-based cohorts, we examined whether prenatal nutrient supplementation is protective against autism and its sub-components, and whether associations depend upon relevant genotypes. Study design: The Stockholm Youth Cohort (SYC) is a total population register-based cohort of children living in Stockholm County, Sweden. Self-reported supplement and drug use was assessed at first antenatal visit. ASD was ascertained after 4 to 15 years of follow-up covering all pathways to ASD care and services in Stockholm County. Intellectual disability was ascertained through two Stockholm-based registers. The Avon Longitudinal Study of Parents and their Children, UK (ALSPAC) is a population-based prospective birth cohort study based in Avon, England. Nutritional supplements were reported at 18-weeks gestation regarding use during pregnancy. Factor analysis produced seven factor scores related to autism and 1 combined score based on traits assessed at multiple ages, and IQ scores were obtained at 8.5 years of age. Methods: In the SYC, adjusted odds ratios (ORs) and 95% confidence intervals (CI) were estimated using multivariable regression, sibling controls, and propensity score matching. In ALSPAC, linear regression was used to calculate [beta] estimates with 95% confidence intervals (CI) for factor scores and IQ. Supplementation was examined in main effects models and in interaction models with maternal and child genetic variants involved in folate metabolism. Results: In the SYC, maternal multivitamin use was associated with lower odds of ASD with ID in the child relative to mothers who did not use folic acid, iron, or multivitamins in regression (OR: 0.69 [95% CI: 0.57 to 0.84], sibling control (0.77 [0.52 to 1.15]), and propensity score matched (0.68 [0.54 to 0.86]) analyses. Findings were not specific to ASD, as similar estimates were found for ID only. There was no consistent evidence that either iron or folic acid use were associated with lower risk of ASD. In ALSPAC, vitamin supplementation was associated with higher language acquisition skills, while folic acid use were associated with lower articulation scores; both of these relationships were also observed for higher dietary folate. Vitamin and folic acid supplementation were associated with higher IQ scores in the child; associations between folic acid supplementation and IQ appeared to depend upon child MTHFR677 genotype. There was no strong evidence of relationships between iron and ASD sub-components. Conclusions: Our findings suggest that maternal nutrition may be related to specific features of autism such as cognition and facets of language development, and may depend upon genes involved in folate metabolism, specifically child MTFHR677. Further scrutiny of maternal nutrition and its role in the etiology of autism, cognition, and language development is warranted.Ph.D., Public Health -- Drexel University, 201