Abstract 20038: Maternal Pre-Pregnancy Overweight is Associated with Increased Cardiovascular Disease Mortality in the Framingham Heart Study

Abstract

Introduction: In the U.S., obesity among women of childbearing age is highly prevalent. Maternal obesity is associated with offspring obesity and cardiovascular disease (CVD) risk factors, potentially through epigenetic and early developmental mechanisms. There is limited evidence on the association of maternal overweight with offspring CVD events and mortality. Methods: We analyzed prospectively collected data from 1971 to 2012 on 879 Framingham Heart Study Offspring cohort participants with either directly measured pre-pregnancy maternal body mass index (BMI) (n=361) or offspring-reported maternal pre-pregnancy overweight status (n=518). Our outcomes included a composite measure of any CVD event or mortality, CVD mortality and all-cause mortality. Cox proportional hazard models were conducted, initially age and sex adjusted, and then additionally adjusted for potential mediators including traditional CVD risk factors. Pharmacologic treatments for diabetes, hypertension, and/or dyslipidemia were included as time-varying covariates. Results: Maternal pre-pregnancy overweight (BMI >= 85th percentile or self-report) was available for 879 Framingham Offspring Study participants (mean age [SD] at baseline 30 [5] years; 49% female; mean follow-up [SD] 32 [8] years). There were 193 CVD events, 28 CVD deaths, and 138 total deaths among the offspring. Maternal overweight was associated with an increased hazard ratio (HR) with CVD mortality (HR 10.5 [2.6-43]; p=0.001), all-cause mortality (HR 3.1 [1.5-6.4]; p=0.002), and marginally associated with the composite endpoint of CVD events and mortality (HR 1.7 [95% CI 0.99-2.8]; p=0.05). Adjustment for offspring BMI, diabetes, hypertension, and dyslipidemia attenuated the associations. In sensitivity analyses restricted to only those with directly measured maternal pre-pregnancy BMI, effect estimates remained robust (similar hazard ratios but larger confidence intervals). Conclusions: Maternal pre-pregnancy overweight is associated with offspring CVD mortality. The association is likely mediated in part through classical CVD risk factors such as offspring obesity, hypertension, diabetes, and dyslipidemia.