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Androgens and Neurodevelopmental Disorders: Maternal Polycystic Ovarian Syndrome As a Risk Factor for ASD and ADHD
ASD and ADHD are neurodevelopmental disorders that are becoming increasingly common in childhood. The two conditions are highly co-morbid and are skewed by sex, with rates being considerably higher for boys. It may be that the two conditions share genetic and environmental risk factors. It has been hypothesized that ASD and ADHD are partially caused by prenatal androgen exposure. Recent evidence supports the hypothesis that fetal steroid exposure is associated with the risk of ASD.
Objectives:
We hypothesized that maternal polycystic ovary syndrome (PCOS), a condition associated with excess androgens, would increase the risk of ASD in the offspring. We furthermore tested whether risk attributable to PCOS is specific for ASD or if the condition is also associated with risk of ADHD.
Methods:
Here we compare the results of two matched case-control studies, for ASD and ADHD, both nested within the total population of Sweden (children aged 4-17 who were born in Sweden from 1984 to 2007). PCOS, ASD, and ADHD were defined from ICD codes through linkage to healthcare registers. Controls were matched by birth month and year, sex, and region of birth. Conditional logistic regression was used to evaluate the association between maternal diagnosis with PCOS and offspring outcomes.
Results:
We identified 23 748 ASD cases and 208 796 matched controls, as well as 58 938 ADHD cases and 504 983 matched controls. 16% of ADHD cases also had a diagnosis of ASD. Maternal PCOS increased the odds of ASD in the offspring by 59%, after adjustment for confounders (OR 1.59, 95% CI 1.34 – 1.88). However, maternal PCOS increased the odds of ADHD in offspring by 41% (OR 1.41, 1.26 – 1.58). After exclusion of the 16% of ADHD cases who also had a diagnosis of ASD, the OR for maternal PCOS was somewhat attenuated, though the association remained (OR 1.32, 1.17 – 1.51).
Conclusions:
These studies indicate that maternal PCOS is a risk factor for both ASD and ADHD, independent of co-morbidity between the disorders. Further studies are necessary to determine the mechanisms by which the metabolic and hormonal disturbances of maternal PCOS may influence fetal neurodevelopment.