Collaborative interaction of advanced maternal age and polycystic ovary syndrome on peripartum cardiovascular outcomes

Introduction Advanced maternal age (AMA, ≥35 years) and polycystic ovary syndrome (PCOS) are independently associated with adverse peripartum cardiovascular (CV) outcomes. Over 20% of deliveries in high income countries occur in women ≥ 35 years of age. This global rise in delayed childbearing combined with an 8-13% chance of developing polycystic ovary syndrome (PCOS) flags this growing population as high risk. Whether these exposures interact together to create excess peripartum cardiovascular risks beyond their independent effects remains unknown. Methods We analyzed hospitalizations from the 2016-2022 National Inpatient Sample (NIS) databases by identifying delivery hospitalizations with ICD-10-CM codes. The primary outcome of our study was preeclampsia, secondary outcomes included peripartum cardiomyopathy, arrhythmia, heart failure, pulmonary edema, VTE, and a composite CV endpoint. Survey-weighted logistic regressions were performed, taking into account the sampling design of the NIS database. Multiplicative interaction was assessed using ama and pcos interaction terms; additive interaction was quantified by the relative excess risk due to interaction (RERI) using a four-level exposure group approach. All models adjusted for necessary comorbidities and confounders. Results Among 5,006,094 delivery hospitalizations (representing ~25 million nationally weighted encounters), 943,113 (18.8%) had AMA, 38,997 (0.78%) had PCOS, and 9,098 (0.18%) had both. PCOS prevalence rose from 0.99% (2016) to 1.85% (2022). The AMA+PCOS group exhibited the highest metabolic burden: 31.2% had diabetes, 28.3% obesity, and 12.9% chronic hypertension. For preeclampsia, PCOS conferred an adjusted OR (aOR) of 1.32 (95% CI 1.28 - 1.38) and AMA aOR 1.09 (95% CI 1.08-1.10; p<0.001). The multiplicative AMA×PCOS interaction was non-significant (p=0.203). However, RERI = 0.117 (95% CI −0.003 to 0.236; p=0.056) demonstrated borderline positive additive interaction, indicating excess joint risk approaching but not yet exceeding conventional significance thresholds in the adjusted model. For arrhythmia, PCOS was the dominant risk factor (aOR 1.99, 95% CI 1.73-2.30), nearly doubling odds independent of AMA (aOR 1.15, 95% CI 1.11-1.21; both p<0.001). AMA was the dominant driver for heart failure (aOR 1.84, 95% CI 1.65-2.05) and PPCM (aOR 1.53, 95% CI 1.32-1.78). Conclusion We found both AMA and PCOS independently heightened peripartum cardiovascular risk. The borderline additive interaction for preeclampsia identified (RERI=0.117, p=0.056) suggests a synergistic collaboration between AMA and PCOS. PCOS predominantly drove arrhythmia while AMA led to heart failure and PPCM. Given the rise in AMA and PCOS prevalence, integrating PCOS into cardio-obstetrics risk models alongside AMA is an important, evidence based step, towards improving pre-pregnancy counseling and peripartum surveillance.