Prepregnancy Adiposity, Adverse Pregnancy Outcomes, and Cardiovascular Disease Risk in Midlife

BACKGROUND Prepregnancy obesity is a key modifiable risk factor for both adverse pregnancy outcomes (APOs) and cardiovascular disease (CVD). However, whether APOs represent a marker or mediator between body mass index (BMI) and CVD risk is unclear. OBJECTIVES This study sought to determine the extent to which the association between prepregnancy BMI and CVD risk factors in midlife is mediated by APOs. METHODS Pregnant participants aged ≥18 years enrolled at 28 weeks' gestation (range: 24-32 weeks) in the HAPO FUS (Hyperglycemia and Adverse Pregnancy Outcomes Follow-Up Study) without prepregnancy hypertension or diabetes were included in analyses. Participants had a follow-up visit 11.6 ± 1.3 years after delivery. 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). Analyses were adjusted for maternal and gestational age, parity, field center, alcohol and smoking status in pregnancy, and fetal sex. RESULTS Among 4,269 study participants, mean maternal age was 30.1 ± 5.6 years, and 10.6% had prepregnancy obesity. GDM and new-onset HDP occurred in 13.8% and 10.7% of participants, respectively. Compared with those with a normal prepregnancy BMI, those with prepregnancy obesity had higher MAP (7.0 mm Hg; 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 41.7 ± 5.6 years. GDM partially mediated the association between obesity and HbA1c (24.6%; 95% CI: 20.9%-28.4%), whereas new-onset HDP partially mediated the association between obesity and MAP (12.4%; 95% CI: 10.6%-14.2%). CONCLUSIONS In this multinational cohort of pregnant individuals, APOs mediated a small proportion of the association between prepregnancy obesity and CVD risk in mid-life. Prioritizing weight management earlier in the life course before pregnancy may promote maternal and midlife cardiovascular health.