Maternal Steroid Hormone Levels in Early Pregnancy and Autism in the Offspring: A Population-Based, Nested Case-Control Study.

Abstract

A role for prenatal steroid hormones in the etiology of autism has been proposed, but evidence is conflicting. Here, we examined serum levels of maternal estradiol, testosterone, 17-hydroxyprogesterone (OHP), and cortisol from the first trimester of gestation (mean= 10.1 weeks) in relation to the odds of diagnosed autism with and without co-occurring intellectual disability (ID) in the offspring (n= 118 autism with ID, n= 249 autism without ID, n= 477 control). Levels of maternal hormones were measured using highly sensitive liquid chromatography tandem mass spectrometry, standardized according to gestational timing of sample collection, and analyzed with restricted cubic spline logistic regression models adjusting for child's sex and maternal health, demographic, and socioeconomic factors. We observed significant nonlinear associations between maternal estradiol, 17-OHP, and cortisol with autism, which varied with the presence of co-occurring ID. Compared to mean levels, lower levels of estradiol were associated with higher odds of autism with ID (odds ratio for concentrations 1 SD below the mean= 1.66; 95% CI, 1.24-2.11), while higher cortisol levels were associated with lower odds (odds ratio for 1 SD above the mean= 0.55; 95% CI, 0.36-0.88). In contrast, higher 17-OHP was associated with increased odds of autism without ID (odds ratio for 1 SD above the mean= 1.49; 95% CI, 1.11-1.99). We observed no evidence for interaction with sex of the child. These findings support the notion that the maternal steroid hormonal environment in early pregnancy may contribute to autism, but also emphasize the complex relationship between early-life steroid exposure and autism.