Dataset Information

Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring: prenatal androgen exposure or genetic confounding?

ABSTRACT:

Background

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.

Methods

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.

Results

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.

Conclusions

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.

SUBMITTER: Cesta CE

PROVIDER: S-EPMC7093321 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring: prenatal androgen exposure or genetic confounding?

Cesta Carolyn E CE Öberg Anna S AS Ibrahimson Abraham A Yusuf Ikram I Larsson Henrik H Almqvist Catarina C D'Onofrio Brian M BM Bulik Cynthia M CM Fernández de la Cruz Lorena L Mataix-Cols David D Landén Mikael M Rosenqvist Mina A MA

Psychological medicine 20190312 4

<h4>Background</h4>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.<h4>Methods</h4>A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confo ...[more]

PMID: 30857571

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Project description:There is emerging evidence demonstrating an association between maternal polycystic ovary syndrome (PCOS) and autism spectrum disorder (ASD) in children, however, the cumulative effect of maternal PCOS on the development of ASD or other neuropsychiatry disorders (NPD) in children and separately for males and females has not been examined. We sought to systematically evaluate the influence of maternal PCOS on a wide range of NPD including ASD, attention deficit hyperactivity disorder (ADHD), chronic tic disorder (CDT), other behavior disorders, anxiety, depression, bipolar disorder, schizophrenia in children as well as in women of reproductive age only. We queried electronic databases including PubMed, EMBASE, and Google Scholar, until March 2021. We used DerSimonian and Laird (D-L) random effects method to compute pooled effect size in terms of odds ratio (OR). Nineteen studies (1667851 mothers, 2260622 children) were included in this study. Mothers with PCOS had an increased odds of children diagnosed with ASD (OR = 1.40, p < 0.001), ADHD (OR = 1.42, p < 0.001), CTD (OR = 1.44, p = 0.001), anxiety (OR = 1.33, p < 0.001), as well as other behavioral symptoms (OR = 1.45, p < 0.001) in the adjusted analysis. The association between maternal PCOS and ASD (OR: 1.43 vs. 1.66), ADHD (OR: 1.39 vs. 1.54), and CTD (OR: 1.42 vs. 1.51) was found to be significantly consistent between males and females, respectively. Our data do not suggest increased fetal testosterone exposure is associated with increased autistic traits in children. However, PCOS was significantly associated with increased odds of a wide range of NPD in women themselves. Maternal PCOS is a risk factor for various NPD with a similar extent in their children regardless of their underlying comorbidities. Managing PCOS is essential for women's health as well as for their children's health. More research is needed to determine the mechanisms and links between maternal PCOS and NPD in children.

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Dataset Information

Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring: prenatal androgen exposure or genetic confounding?

Background

Methods

Results

Conclusions

Publications

Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring: prenatal androgen exposure or genetic confounding?

Similar Datasets

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