Mother’s PCOS Diagnosis Is Not Associated With Behavioral Symptoms in Offspring at 4-5 years

Introduction: Variation in prenatal sex steroid concentrations has been linked to child behavioral problems, with higher maternal total and free testosterone associated with child internalizing and externalizing symptoms. Polycystic Ovary Syndrome (PCOS) is a hyperandrogenic disorder that results in elevated testosterone levels during pregnancy among affected women. Population-based analyses suggest a higher risk of depression and anxiety diagnosis in children of women with PCOS. Animal models of prenatal hyperandrogenism further support an association with increased anxiety in offspring. Within the context of a multi-center U.S. pregnancy cohort, we examined early childhood behavioral and social responsiveness in children born to mothers with and without PCOS. Methods: Pregnant women were recruited in their first trimester for The Infant Development and Environment Study (TIDES). PCOS status was determined by maternal reports of PCOS diagnosis or history of hirsutism/oligomenorrhea. Women who reported neither a history of PCOS or symptoms of hirsutism or oligomenorrhea served as a comparison group. When participating children were age 4, mothers completed the Behavioral Assessment System for Children, 2(nd) Edition (BASC-2), a measure of child behavior problems, and the Social Responsiveness Scale, 2(nd) Edition (SRS-2), a measure of social impairment consistent with autistic traits. We fit linear regression models considering three outcomes: (1) BASC-2 externalizing composite score (e.g., hyperactivity, aggression); (2) BASC internalizing composite score (e.g., anxiety, depression, somatization); and (3) SRS-2 total score, adjusting for covariates, maternal age, child age, race, study center, income, education, alcohol and tobacco use, child sex, maternal depression. For all outcomes, higher scores indicate more problematic behaviors. Results: A total of 360 mother/child pairs completed the 4-year assessment and were included in this analysis. This included 81 mothers with PCOS (37 male, 44 female) and 279 comparison mothers (132 male, 147 female). Mean maternal age at delivery was 30.7 years (±4.7) for PCOS cases and 31.9 years (±5.4) for comparison mothers. Interaction terms indicated no effect modification by child sex. In analyses combining both sexes, maternal PCOS was not associated with externalizing behaviors (β=1.81; 95% CI: ‐2.37, 6.0; p=0.40), internalizing behaviors (β=2.20; 95% CI: ‐2.14, 6.53; p=0.32), or social impairment (β=-0.34; 95% CI: ‐3.34, 2.65; p=0.82). Conclusions: In this prospective evaluation, we observed no association between maternal PCOS and neurobehavioral symptoms in children at age 4. Given that prior literature using population databases suggested increased behavioral symptoms in school-aged and older children of PCOS mothers, these symptoms may become more apparent with development and continued assessment is warranted.