Adverse pregnancy outcomes as early indicators of long-term maternal atrial fibrillation: a systematic review and meta-analysis

Abstract

Adverse pregnancy outcomes (APOs) - including hypertensive disorders of pregnancy (HDP), preeclampsia, gestational diabetes mellitus (GDM), preterm birth, and fetal growth deviations - are emerging female-specific cardiovascular risk factors, but their association with long-term maternal atrial fibrillation (AF) remains unclear. We aim to assess the association between APOs and subsequent maternal AF. We searched MEDLINE, Embase, and Cochrane Central. We included population-based cohort studies comparing women with and without APOs and reporting incident maternal atrial fibrillation during follow-up. Time-to-event associations were synthesized, pooling hazard ratios (HR) and corresponding 95% confidence intervals (CI). Statistical analysis was performed using R statistical software, version 4.5.0. Eleven population-based cohort studies including nearly 11 million women were analyzed. Hypertensive disorders of pregnancy were associated with higher long-term risk of AF (HR 1.52; 95% CI 1.32-1.75), as was preeclampsia (HR 1.47; 95% CI 1.23-1.76). Preterm birth was also associated with increased AF risk (HR 1.29; 95% CI 1.13-1.48). Delivery of a large-for-gestational-age infant was associated with higher AF risk (HR 1.23; 95% CI 1.13-1.34), whereas small-for-gestational-age delivery showed an inverse association (HR 0.88; 95% CI 0.80-0.97). For GDM, the association was more uncertain, with wide confidence intervals and effect estimates suggesting an increased risk (HR 1.20; 95% CI 0.84-1.72). Hypertensive and vascular pregnancy complications are associated with elevated long-term maternal AF risk. Associations for GDM and fetal growth phenotypes were heterogeneous and should be interpreted cautiously. These findings support APOs as markers of later arrhythmic vulnerability.Graphical Abstract