Abstract
Maternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences. A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models. PCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31-1.99), ASD: aHR = 2.02 (95% CI 1.45-2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19-1.57), ASD: aHR = 1.46 (95% CI 1.21-1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys. Estimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.
Highlights
autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD), and Tourette’s disorder and chronic tic disorders (TD/CTD) were more prevalent in polycystic ovary syndrome (PCOS)-exposed offspring compared with PCOS-unexposed offspring born to unrelated mothers from the general population, but prevalence estimates were similar to their PCOS-unexposed cousins
Associations were stronger in girls than in boys for both ADHD and ASD when compared with PCOS-unexposed unrelated offspring from the general population
Outpatient coverage – Estimates calculated for children with follow-up in outpatient care were similar to those in the main analysis. In this national register-based study of mothers and their offspring, we found that children born to mothers with PCOS had a higher risk of being diagnosed with ADHD, ASD, and TD/ CTD, compared with children born to mothers from the general population without PCOS
Summary
Prenatal androgen exposure has been hypothesized to be associated with the development of neuropsychiatric disorders including autism spectrum disorders (ASD) (Baron-Cohen et al, 2011), attention-deficit/hyperactivity disorder (ADHD) (de Bruin et al, 2006; Baron-Cohen et al, 2011), and Tourette’s disorder and chronic tic disorders (TD/CTD) (Peterson et al, 1992; Alexander and Peterson, 2004; Martino et al, 2013). A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette’s disorder and chronic tic disorders (TD/CTD). Estimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v.
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