Adverse Pregnancy Outcomes Linked to Long-Term Atrial Fibrillation Risk

Several hypertensive pregnancy outcomes have been associated with increased risk of atrial fibrillation (AF) ≤46 years later, indicating a need for early preventive actions and long-term clinical follow-up.1

Prior research has indicated a potential association between hypertensive disorders of pregnancy and increased risk of cardiovascular disease later in life. However, many of these studies have had insufficient follow-up periods, and few have examined multiple outcomes to allow for comparison. Additionally, it is unclear whether previously reported associations are explained by adverse pregnancy outcomes, revealing preexisting risk, or eliciting new risk.1,2

“To address these knowledge gaps, we conducted a national cohort study of more than 2 million women in Sweden,” Casey Crump, MD, PhD, department of family and community medicine, McGovern Medical School, the University of Texas Health Science Center, and colleagues wrote. “We hypothesized that women who experienced adverse pregnancy outcomes would have long-term increased risks of AF and that such risks would only be partially explained by shared familial factors.”1

Investigators initially identified 6 adverse pregnancy outcomes via prenatal and birth records in the Swedish Medical Birth Register. Preterm delivery, or gestational age <37 completed weeks, was based on maternal report of last menstrual period in the 1970s and ultrasonography estimation beginning in the 1980s. Small for gestational age was defined by infant birth weight <10th percentile, while large for gestational age was defined as >90th percentile. Preeclampsia, other hypertensive disorders of pregnancy, and gestational diabetes were identified from diagnostic codes in the Medical Birth Register.1

The study’s primary outcome was AF identified from nationwide inpatient and outpatient diagnoses through 2018. Investigators used Cox regression to compute hazard ratios (HRs) for AF associated with specific adverse pregnancy outcomes. Cosibling analysis was also utilized to assess for potential confounding by shared familial factors.1

The team analyzed 2,201,047 women over the course of the study; 865,912 (39.3%) experienced ≥1 of the 6 adverse pregnancy outcomes examined. The most common was large for gestational age (14.8%), followed by small for gestational age (14.3%) and preterm delivery (8.9%). During 54 million person-years of follow-up, 51,173 women (2.3%) were diagnosed with AF. Median age at first delivery was 27 years (interquartile range [IQR], 23-30), median age at AF diagnosis was 63 years (56-69), and median age at end of follow-up was 53 years (43-64).1

Over the course of follow-up, which ran for ≤46 years after delivery, all adverse pregnancy outcomes except small for gestational age were independently associated with increased AF risk. Following adjustment for all other adverse pregnancy outcomes, the HRs for AF associated with each outcome were as follows:

• Other hypertensive disorders: HR, 1.46 (95% CI, 1.34-1.58)
• Preeclampsia: HR, 1.36 (95% CI, 1.32-1.4)
• Large for gestational age: HR, 1.19 (95% CI, 1.16-1.22)
• Preterm delivery: HR, 1.14 (95% CI, 1.1-1.18
• Gestational diabetes: HR, 1.12 (95% CI, 1.01-1.24)
• Small for gestational age: HR, 0.98 (95% CI, 0.95-1)1

Within 10 years after delivery, adjusted HRs were significantly elevated among women with hypertensive disorders (HR, 1.69; 95% CI, 1.32-2.15), preterm delivery (HR, 1.46; 95% CI, 1.26-1.7), or large for gestational age (HR, 1.16; 95% CI, 1.01-1.32). At 30-46 years after delivery, adjusted HRs were substantially elevated among those with other hypertensive disorders (HR, 1.44; 95% CI, 1.24-1.66), preeclampsia (HR, 1.38; 95% CI, 1.33-1.5), gestational diabetes (HR, 1.19; 95% CI, 1.03-1.37), large for gestational age (HR, 1.17; 95% CI, 1.14-1.21), or preterm delivery (HR, 1.11; 95% CI, 1.07-1.16).1

“The present study’s findings have important clinical implications,” wrote Crump and colleagues. “Preeclampsia, other hypertensive disorders of pregnancy, large for gestational age, gestational diabetes, and preterm delivery should now be recognized as long-term risk factors for AF. High-quality preconception and prenatal care should be prioritized to reduce the prevalence of adverse pregnancy outcomes and their long-term sequelae.”1

References

1. Crump C, Wei J, Sundquist J, Sundquist K. Adverse pregnancy outcomes and long-term risk of atrial fibrillation. JAMA Cardiology. Published online October 22, 2025. doi:10.1001/jamacardio.2025.3951

2. Al Bahhawi T, Aqeeli A, Harrison SL, et al. Pregnancy-Related Complications and Incidence of Atrial Fibrillation: A Systematic Review. J Clin Med. 2023;12(4):1316. Published 2023 Feb 7. doi:10.3390/jcm12041316