In a recent study published in the journal Circulation Research, researchers examined the associations between body mass index (BMI), adverse pregnancy outcomes (APOs), and cardiovascular disease (CVD) risk.
In the United States (US), one in four pregnancies is complicated by an APO. APOs represent heterogeneous syndromes, including gestational diabetes, small-for-gestational-age birth, preterm birth, and hypertensive disorders of pregnancy. APOs are associated with increased short-term risks of maternal morbidity and mortality, with emerging evidence supporting the association between APOs and lifetime CVD risk.
Study: Body Mass Index, Adverse Pregnancy Outcomes, and Cardiovascular Disease Risk. Image Credit: Kaspars Grinvalds / Shutterstock
The association between CVD and APOs might be related to shared upstream risk factors preceding the onset of CVD risk factors. Individuals with elevated BMI in early pregnancy or pre-pregnancy have higher odds of APOs. Further, evidence suggests that obesity in early adulthood is associated with future CVD risk. Nonetheless, it remains unknown whether APOs are markers of underlying risk associated with obesity and if they mediate the association with future CVD risk.
“We’re finding that certain pregnancy complications are unmasking and then increasing cardiovascular disease risks, such as obesity, that were already present. This study provides insight into potential timing for interventions for people with overweight or obesity who are thinking about pregnancy,” said Victoria L. Pemberton, R.N.C., a study author and researcher in the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH.
About the study
In the present study, researchers assessed the associations between maternal obesity, hypertensive disorders of pregnancy, other APOs, and postpartum cardiovascular health. Nulliparous pregnant individuals with singleton pregnancies were recruited during 2014-17 between the sixth and thirteenth gestational weeks. Adults without a history of pre-pregnancy diabetes or hypertension were included, while those with stillbirth or spontaneous/inducted abortion were excluded.
BMI was measured at the baseline visit, which served as the exposure. The primary mediator was hypertensive disorders of pregnancy, defined as preeclampsia, gestational hypertension, and eclampsia. Secondary mediators were APO subtypes (small-for-gestational age birth, preterm birth, and gestational diabetes). The primary outcome was the incident development of CVD risk factors (hypertension, diabetes, and hyperlipidemia).
Secondary outcomes were continuous measures of fasting glucose, total cholesterol, and systolic blood pressure (SBP). Confounders included maternal age, race/ethnicity, smoking status, physical activity, diet quality, perceived stress, sleep duration, depression, and CVD risk factor levels. The team used generalized linear models to separately estimate exposure-mediator, exposure-outcome, and mediator-outcome associations.
The study recruited 4,216 pregnant individuals at an average gestational age of 11.4 weeks. The average maternal age was 27 at baseline in early pregnancy; more than half the participants (53%) had a normal BMI (of < 25 kg/m2), 25% were overweight (BMI: 25 kg/m2 to < 30 kg/m2), and 22% were obese (BMI ≥ 30 kg/m2).
The mean gestational period and birth weight were 39 weeks and 3.3 kg, respectively. About 15% of individuals had hypertensive disorders of pregnancy. Specifically, 9% of participants had eclampsia or preeclampsia, and 6% had hypertension. Around 8% of subjects had a preterm birth, 4% had gestational diabetes, and 11% had small-for-gestational-age birth.
The follow-up visit occurred about 3.7 years post-baseline visit. Overweight and obese individuals had a higher risk of hypertensive disorders of pregnancy than those with normal BMI, with similar results for gestational diabetes, gestational hypertension, and eclampsia or preeclampsia. Obesity and overweight were not associated with small-for-gestational age and preterm births.
Hypertensive disorders of pregnancy were associated with elevated risk of incident hyperlipidemia, hypertension, and increased SBP and total cholesterol. Gestational hypertension was not associated with total cholesterol or incident hyperlipidemia. On the other hand, gestational diabetes was associated with a higher risk of incident diabetes, hyperlipidemia, and increased fasting glucose and total cholesterol levels.
There were no associations between small-for-gestational-age birth and CVD risk factors. Preterm birth was associated with increased risks of incident diabetes, hypertension, and hyperlipidemia. Individuals who were overweight or obese in early pregnancy had a higher risk of incident diabetes, hyperlipidemia, and hypertension than those with normal BMI. The differences between normal BMI and obesity were significantly higher for fasting glucose levels and SBP.
The researchers observed some (degree of) mediation between obesity and incident hypertension by hypertensive disorders of pregnancy. However, associations with diabetes and hyperlipidemia were independent and not mediated by hypertensive disorders of pregnancy. Preterm and small-for-gestational-age births did not mediate associations between obesity and incident CVD risk factors. Similar results were evident for overweight relative to normal BMI across APO subtypes.
The team found that two APOs – gestational diabetes and hypertensive disorders of pregnancy – mediated a small but significant association of obesity or overweight in early pregnancy with fasting glucose levels and incident hypertension around 3.7 years postpartum, respectively. The findings indicate that APOs may broadly represent a marker for pre-existing CVD risk that may be unmasked during pregnancy, suggesting an emphasis on pre-pregnancy or early pregnancy interventions before the onset of APOs.