Maternal factors shaping the fetal environment and the occurrence of autism spectrum disorders

Abstract

Maternal stress response, micronutrient deficiency and maternal immune activation have all been implicated in the etiology of autism spectrum disorders (ASD). We evaluated several maternal factors that might act through one or more of these mechanisms. Specifically, we assessed the independent effects of maternal illness before and during pregnancy (Study 1) and maternal pre-pregnancy obesity (Study 2) on the risk of ASD using a case-control design among patients born into the General Practice Research Database from 1993-2008. We also assessed the effects of short interpregnancy interval and maternal history of pregnancy loss (Study 3) on the risk of ASD through age 3 years using a cohort design among individuals born to multigravida in Massachusetts from 2000-2010. Conditional logistic regression (Studies 1 and 2) or log-binomial regression models (Study 3) were used to analyze the data. In study 1, we found modest associations with maternal bacterial infection (aOR: 1.5, 95% CI: 1.1, 2.0) and asthma (aOR: 1.3, 95% CI: 1.1, 1.5), which were consistent across the ASD subtypes. No association was found between maternal autoimmune disease and ASDs. In study 2, we observed a nonlinear association between maternal BMI and ASD that suggested extremes in maternal BMI (underweight and obesity) are associated with modest increases in the risk for ASD among offspring. In study 3, we found a non-linear association with IPI, where IPI lengths less than 18 months and longer than 60 months were associated with an increased risk for ASD. This association was restricted to consecutive live births and stronger for younger mothers than older mothers. A history of pregnancy loss among multigravida was also associated with a modest increase in ASD risk. Together these findings contribute important information about the etiology of autism spectrum disorders and provide additional support for the maternal immune activation and nutritional depletion hypotheses.