Abstract and Introduction
Study Question: Do children whose mothers have polycystic ovary syndrome (PCOS) have an increased risk of morbidity?
Summary Answer: Maternal PCOS is associated with an increased risk of infection, allergy and other childhood morbidity.
What is Known Already: PCOS is associated with higher rates of gestational diabetes, pre-eclampsia and preterm delivery, but the long-term impact on child health is poorly understood.
Study Design, Size, Duration: We conducted a retrospective longitudinal cohort study of 1 038 375 children in Quebec between 2006 and 2020.
Participants/Materials, Setting, Methods: We included 7160 children whose mothers had PCOS and 1 031 215 unexposed children. Outcomes included child hospitalization for infectious, allergic, malignant and other diseases before 13 years of age. We estimated hazard ratios (HRs) and 95% CI for the association of PCOS with childhood morbidity in adjusted Cox proportional hazards regression models.
Main Results and the Role of Chance: Children exposed to PCOS were hospitalized at a rate of 68.9 (95% CI 66.2–71.8) per 1000 person-years, whereas unexposed children were hospitalized at a rate of 45.3 (95% CI 45.1–45.5) per 1000 person-years. Compared with no exposure, maternal PCOS was associated with 1.32 times the risk of any childhood hospitalization (95% CI 1.26–1.40), 1.31 times the risk of infectious disease hospitalization (95% CI 1.25–1.38) and 1.47 times the risk of allergy-related hospitalization (95% CI 1.31–1.66). Risk of hospitalization was also elevated for childhood metabolic (HR 1.59, 95% CI 1.16–2.18), gastrointestinal (HR 1.72, 95% CI 1.53–1.92), central nervous system (HR 1.74, 95% CI 1.46–2.07) and otologic disorders (HR 1.34, 95% CI 1.26–1.43). Subgroup analyses suggested that there was little difference in the association of PCOS with hospitalization among boys (HR 1.31, 95% CI 1.24–1.39) and girls (HR 1.34, 95% CI 1.26–1.43).
Limitations, Reasons for Caution: We analyzed severe childhood morbidity requiring hospitalization, not mild diseases treated in ambulatory clinics. We lacked data on ethnicity, education and physical activity, and cannot rule out residual confounding.
Wider Implications of the Findings: Our findings suggest that maternal PCOS is associated with an increased risk of childhood morbidity.
Study Funding/Competing Interest(S): This study was supported by grant PJT-162300 from the Canadian Institutes of Health Research. N.A. acknowledges a career award from the Fonds de recherche du Québec-Santé (296785). The authors declare no competing interests.
Trial Registration Number: N/A.
Polycystic ovary syndrome (PCOS) is a common reproductive disorder, characterized by ovarian dysfunction, hyperandrogenism, polycystic ovary morphology and metabolic complications (Witchel et al., 2019). PCOS affects up to 10% of women of reproductive age (Bozdag et al., 2016). Women with PCOS are at risk of obesity, type 2 diabetes and cardiovascular disease, and a number of studies suggest that there may be associations with adverse pregnancy outcomes such as gestational diabetes, pre-eclampsia and preterm birth (Palomba et al., 2015; McDonnell and Hart, 2017). Although an impact on birth outcomes has been documented, the long-term health of children whose mothers have PCOS has received limited attention.
Owing to elevated circulating androgen levels, metabolic dysfunction and the potential for a suboptimal intrauterine environment in women with PCOS, researchers have raised concern over the somatic and neurodevelopmental health of children who are exposed to these conditions in utero (Palomba et al., 2015; Bell et al., 2018a). Hyperandrogenism and insulin resistance may affect fetal neuroendocrine and immune programming, possibly impacting the long-term health of offspring (Cardoso and Padmanabhan, 2019). Studies have found that maternal PCOS is associated with faster catch-up growth and greater BMI in childhood (Recabarren et al., 2008; Finnbogadóttir et al., 2017). Children of women with PCOS are more likely to have insulin resistance, abnormal lipid profiles and diabetes (Wilde et al., 2018; Gunning et al., 2020; Chen et al., 2021), as well as attention deficit disorders (Kosidou et al., 2017), autism spectrum disorder (Kosidou et al., 2016; Cherskov et al., 2018; Chen et al., 2020) and developmental delay (Bell et al., 2018b). We assessed the association between maternal PCOS and risk of child morbidity requiring hospitalization before 13 years of age.
Hum Reprod. 2022;37(9):2135-2142. © 2022 Oxford University Press