Maternal PCOS Linked to Increased Risk of Neuropsychiatric Disorders in Offspring

Catharina Lavebratt, MSc, PhD

New research from an international team of investigators has uncovered a potential link between presence of polycystic ovary syndrome (PCOS) in mothers and the incidence of neuropsychiatric disorders among offspring.

The study, which was conducted by investigators from Sweden, China, and Finland, found children were at a 1.3-fold greater risk of developing a neuropsychiatric disorder if born to mothers who had PCOS and this risk became even greater if their mothers were obese, had gestational diabetes, had a cesarean delivery, or experienced other medical problems.

“The higher risk applied to a number of psychiatric diagnoses, including mood, anxiety, eating and sleeping disorders, intellectual disabilities, specific developmental, autism spectrum, attention deficit hyperactivity, conduct and tic disorders, and other behavioral and emotional disorders. This is the first study to report an increased risk of a wide range of neuropsychiatric disorders in offspring exposed to maternal PCOS, indicating a broad adverse effect of PCOS on neurodevelopment,” said Catharina Lavebratt, MSc, PhD, an associate professor at the Karolinska Institutet, Stockholm, Sweden, in a statement.

With previous studies indicating associations between maternal PCOS and increased risk autism spectrum disorder, attention-deficit/hyperactivity disorders (ADHD), and development delay in offspring, investigators sought to further explore potential associations between maternal PCOS and anovulatory infertility through a population-based cohort study. To do so, Lavebratt and colleagues from the Finnish Institute for Health and Welfare and Shandong University designed their study to investigate this topic using national registries from Finland.

Using a time frame lasting from 1996-2014, investigators identified more than 1.1 million live births followed through 2018 for possible inclusion in their study. After excluding births to mothers with symptoms similar to PCOS, investigators were left with a cohort of 1,097,753 births by 590,939 mothers. Of these 1,097,753 births, 105,409 (9.8%) children were diagnosed with a neurodevelopmental or psychiatric disorder during the study period.

For the purpose of their study, investigators conducted stratified analyses to assess the role of PCOS and joint effects of PCOS with maternal obesity, perinatal problems, cesarean delivery, gestational diabetes, and use of fertility treatment. Of note, investigators pointed out these analyses were adjusted for maternal age, county of birth, marriage status at birth, smoking, parity, psychiatric disorders, prescription of psychotropic N05/N06 during pregnancy, and systemic inflammatory diseases when applicable.

Upon analysis, results suggested presence of maternal PCOS was associated with a 32% increased in risk of a psychiatric disorder in offspring (HR, 1.32; 95% CI, 1.27-1.38). Specifically, maternal PCOS was associated with increased risk for sleeping disorders (HR 1.46; 95% CI 1.27-1.67), ADHD and conduct disorders (HR, 1.42; 95% CI 1.33-1.52), tic disorders (HR, 1.42; 95% CI 1.21-1.68), intellectual disabilities (HR, 1.41; 95% CI 1.24-1.60), autism spectrum disorder (HR, 1.40; 95% CI 1.26-1.57), specific developmental disorders (HR 1.37; 95% CI 1.30-1.43), eating disorders (HR 1.36; 95% CI 1.15-1.61), anxiety disorders (HR, 1.33; 95% CI 1.26-1.41), and mood disorders (HR, 1.27; 95% CI 1.18-1.35).

Further analysis indicated children born to mothers with maternal PCOS and normal body weight were at an increased risk (HR, 1.20; 95% CI, 1.09-1.32), but investigators noted this risk was even greater among children born to severely obese mothers with PCOS (HR, 2.11; 95% CI, 1.76-2.53) when compared to children born to normal-weight mothers without PCOS. Additionally, when excluding those with perinatal problems, investigators found children born to mothers with PCOS were at an increased risk of any neuropsychiatric disorders (HR, 1.28; 95% CI, 1.22-1.34) when compared to those born to mothers without PCOS.

Investigators also pointed out excluding cases with maternal gestational diabetes (HR 1.30; 95% CI, 1.25-1.36), cesarean delivery (HR 1.29; 95% CI, 1.23-1.35) or fertility treatment (HR 1.31; 95% CI, 1.25-1.36) did not mitigate the apparent associations between maternal PCOS and diagnosis of any neuropsychiatric disorder among offspring.

This study, “Association of polycystic ovary syndrome or anovulatory infertility with offspring psychiatric and mild neurodevelopmental disorders: a Finnish population-based cohort study,” was published in Human Reproduction.