A systematic review and meta-analysis of the association between maternal polycystic ovary syndrome and neuropsychiatric disorders in children

Abstract

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.

Association between maternal polycystic ovary syndrome and attention-deficit/hyperactivity disorder in offspring aged 3–6 years: A Chinese population-based study

“…Significant associations between maternal PCOS and ADHD symptoms in offspring have been reported (10)(11)(12)(13)(14)(15)(16). For instance, three nationwide registry-based cohort studies with thousands of children in Sweden and Finland reported 42-46% greater odds of being diagnosed with ADHD in offspring with maternal PCOS (10,13,14).…”

“…High levels of circulating androgen exposure may affect fetal brain development during pregnancy (9). As a result, there is growing awareness that PCOS may increase the risk of neurodevelopmental disorders in offspring (10)(11)(12)(13)(14)(15)(16). For example, a national registry-based study in Sweden reported 42% greater odds of offspring ADHD associated with maternal PCOS (10).…”

New insights into the interaction between polycystic ovary syndrome and psychiatric disorders: A narrative review

“…54 Poor body image, fear of health problems, hormonal disturbances, metabolic disorders, chronic inflammation, altered gut microbiota, genetic polymorphism, and epigenetic factors were closely related with the pathogenesis of psychiatric disorders. 26,[55][56][57] PCOS-related clinical manifestations Known risk factors for psychiatric disorders include family history, stressful life events, and childhood physical or emotional abuse.…”

“…greater odds of depression, anxiety disorder, [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] bipolar affective disorder, schizophrenia, social phobia, obsessive-compulsive disorder, eating disorders, sleep disturbance, and attention deficit hyperactivity disorder (ADHD), 4,[24][25][26][27][28][29][30][31][32][33][34][35] as well as an increased prevalence of ADHD, autism spectrum disorder (ASD), chronic tic disorder, and other behavior disorders in their children. 26,[36][37][38][39][40][41][42][43] Furthermore, women with PCOS have a higher risk of both persistence of existing psychiatric disorders and the emergence of new psychiatric disorders during follow up. 17,44,45 Concurrently, psychological disorders may make PCOS treatment more challenging.…”

Anti-Müllerian Hormone and Polycystic Ovary Syndrome in Women and Its Male Equivalent

“…The main traits observed in fathers, brothers, and sons of women with PCOS are metabolic disturbances such as impaired glucose intolerance, reduced insulin sensitivity, obesity, and dyslipidemia, resulting in a higher prevalence of T2DM and cardiovascular diseases [ 8 , 9 , 10 ]. As for women with PCOS, psychiatric disorders have also been reported [ 11 ]. An increased prevalence of early-onset (<35 years) androgenic alopecia (AGA) is observed in male relatives of women with PCOS, which has been proposed as a phenotypic sign of the male PCOS equivalent [ 12 ].…”