Association between maternal polycystic ovary syndrome and major congenital anomalies: a hospital-based cohort study in Shanghai, China

Congenital anomalies (CAs) are a leading cause of perinatal mortality and childhood disability. Evidence regarding the association between maternal polycystic ovary syndrome (PCOS) and major CAs remains inconsistent. We examined this association using linked birth and medical records from Shanghai, China. This data-linkage cohort study included 152,889 live births delivered between 2012 and 2023 at four regional hospitals in Shanghai, China, Records from the Shanghai Birth Medical Information System were linked to the Shanghai Health Information Network (SHIN). Maternal PCOS was identified from physician-recorded diagnoses code E28.2. Major CAs diagnosed for livebirths through 1 year one age were classified according to EUROCAT Guide 1.5. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated using modified Poisson regression with cluster-robust standard errors clustered by maternal identity. Models adjusted were adjusted for birth year, maternal age, education level, infant sex, gravidity, plurality, pregestational diabetes mellitus (PGDM), gestational diabetes mellitus (GDM), pregnancy‑induced hypertension (PIH), delivery institution, and use of assisted reproductive technology (ART). Among 152,889 live births, 3,026(1.98%) were born to mothers with PCOS, and 4,627 (3.03%) offspring had at least one major CA; congenital heart defects (CHD) were the largest subgroup (1,719; 37.2%). After full adjustment, PCOS was not significantly associated with overall major CAs (adjusted RR [aRR] 1.12, 95% CI 0.95–1.32; P = 0.166). For CHD, the association was of borderline significance (aRR 1.33, 95% CI 1.04–1.71; P = 0.023) and did not survive correction for multiple comparisons ( q = 0.160). Severe CHDs were the only outcome that remained significant after correction (aRR 2.33, 95% CI 1.39–3.92; P = 0.001; q = 0.013; E-value 4.09), corresponding to 46.3 versus 15.2 cases per 10,000 live births. This association was stronger in ART-conceived than in spontaneously conceived pregnancies (aRR 5.23, 95% CI 2.30–11.92 vs. 1.41, 95% CI 0.63–3.13; P for interaction = 0.027). No statistically significant associations were observed for the other modeled subgroups. Sensitivity analyses (ART stratification and restricting the birth year to 2018–2023) were consistent with the main findings. In this hospital-based data-linkage cohort study, maternal PCOS was not associated with overall major CAs or most subgroup anomalies after multivariable adjustment. A possible excess of severe CHDs, particularly among ART-conceived pregnancies, should be considered hypothesis-generating and requires confirmation in larger studies.