Study Finds Adverse Pregnancy Outcomes Mediate Association With CVD Risk, Prepregnancy Obesity in Midlife

Adverse pregnancy outcomes (APOs) mediated a small proportion of the association between the risk of cardiovascular disease (CVD) and prepregnancy obesity in midlife, according to findings published in the Journal of the American College of Cardiology. Prioritizing weight management earlier in life and prior to pregnancy may promote stronger midlife cardiovascular and maternal health, the authors suggested.¹

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Prepregnancy obesity is a key—and modifiable—risk factor for both APOs and CVD; however, whether APOs actually represent a marker or mediator between body mass index (BMI) and CVD risk is unclear, according to the investigators. For this reason, their study aimed to determine the extent to which the correlation between prepregnancy BMI and CVD risk factors in midlife is mediated by APOs.¹

“Understanding the connection between adverse pregnancy outcomes and CVD is important in the development of effective preventative strategies and determining the best timing for intervention to support long-term heart health,” lead study author Jaclyn Borrowman, PhD, researcher at Northwestern University, explained in a news release.²

This multinational, longitudinal, cohort study enrolled pregnant participants who were at least 18 years of age and at a median gestation of 28 weeks (range: 24-31 weeks) in the Hyperglycemia and Adverse Pregnancy Outcomes Follow-Up Study. These patients did not have prepregnancy hypertension or diabetes. Participants had a follow-up visit 11.6 ± 1.3 years following delivery.¹

Mediation analysis assessed the proportion of the association between self-reported prepregnancy BMI and CVD risk factors at follow-up (mean arterial pressure [MAP], triglycerides, and hemoglobin A1c [HbA1c]) mediated by gestational diabetes (GDM) and new-onset hypertensive disorders of pregnancy (HDP). Of note, analyses were adjusted for maternal and gestational age, parity, field center, alcohol and smoking statuses in pregnancy, and fetal sex.¹

A total of 4269 participants with a mean maternal age of 30.1 ± 5.6 years were enrolled in the study. Approximately 10.6% of patients had prepregnancy obesity. Additionally, GDM and new-onset HDP occurred in about 13.8% and 10.7% of participants, respectively. Compared with participants with a normal pre-pregnancy BMI, those with higher BMIs had higher MAP (7.0 mmHg; 95% CI: 6.0-8.1 mm Hg), triglycerides (28.5 mg/dL; 95% CI: 21.9-35.1 mg/dL), and HbA1c (0.3%; 95% CI: 0.2%-0.4%) at follow-up at a mean age of about 41.7 ± 5.6 years.¹

Further, the investigators observed that GDM partially mediated the association between obesity and HbA1c (24.6%; 95% CI: 20.9%-28.4%). New-onset HDP appeared to have less of an association between obesity and MAP (12.4%; 95% CI: 10.6%-14.2%).¹

“The study highlights the significance of AOPs as a risk-enhancing factor for CVD. Our results also suggest that prioritizing weight management among those considering pregnancy may promote both maternal and future cardiovascular health,” said Borrowman in the news release. “The results of the study underscore the value in addressing excess adiposity in the prepregnancy and postpartum period, particularly as there are options with emerging therapies such new anti-obesity medications.”²

These data suggest that APOs represent a potential clinically significant marker of future CVD risk that is unmasked during the stress of pregnancy, highlighting key vascular and metabolic pathways. These pathways have important implications in designing preventive strategies, according to the investigators. Interventions that target the prepregnancy period with the goal of achieving and maintaining a healthy weight should be evaluated in future research.

REFERENCES

1. Borrowman JD, Huang X, Petito LC, et al. Prepregnancy Adiposity, Adverse Pregnancy Outcomes, and Cardiovascular Disease Risk in Midlife. J Am Coll Cardiol. 2025;85(15):1536–1546. doi:10.1016/j.jacc.2025.02.033

2. American College of Cardiology. Pregnancy complications contribute to cardiovascular risk for overweight women, study finds. News release. April 14, 2025. Accessed April 14, 2025. https://www.eurekalert.org/news-releases/1080015