Physiologic adaptations to a healthy pregnancy include marked insulin-resistance, atherogenic dyslipidemia, fat accretion, lowered blood pressure and increased inflammation.1 These manifestations are necessary to support fetal growth and development. While many effects are reversible after parturition, a worsened maternal cardiometabolic risk profile may persist years later, particularly after a first birth. Lower plasma high density lipoprotein cholesterol (HDL-C), greater weight retention and increased abdominal obesity are associated with primiparity or pre-pregnancy obesity.2-5 Increasing trends in pre-pregnancy weight and excessive gestational weight gain, and variable lactation practices may affect future disease risk in women during mid to late life.
The inability to meet the physiological demands of pregnancy may lead to complications such as gestational diabetes mellitus (GDM), hypertensive disorders, and premature deliveries. A history of pregnancy complications has been linked to future cardiometabolic diseases in women.6;7 Pregnancy may be viewed as a stress test that reveals underlying tendencies for cardiometabolic disease risk, or pregnancy may exert persistent adverse effects that heighten disease risk. The childbearing experience also affects maternal behaviors and lifestyle (i.e., sleep, reduced physical activity). However, few longitudinal studies have distinguished the biological effects of pregnancy from the social and behavioral effects of childrearing.
Women may possess unfavorable cardiometabolic risk factors before pregnancy that predict future pregnancy complications. Few longitudinal studies have obtained pre-pregnancy measurements. In the multi-center U.S. CARDIA study, impaired fasting glucose and hyperinsulinemia, individually or in combination with low HDL-C among non-diabetic women, were strong predictors of GDM.8 Pre- and inter-conceptual screening for cardiometabolic risk factors may be important for prevention of GDM and other complications during and after pregnancies. Preterm birth (PTB <37 weeks) has been associated with future maternal cardiovascular disease (CVD) risk. Dyslipidemia may be related to both PTB and CVD, but studies have rarely assessed pre-pregnancy plasma lipids in relation to PTB. Both low and high pre-pregnancy plasma total cholesterol were associated with higher PTB risk. These risk factors may represent distinct pathways to the heterogeneous outcome of PTB as well as later life sequelae.9
Risk factors for cardiovascular disease in women include a history of pregnancy complications (i.e., gestational diabetes, gestational hypertension, and preeclampsia).10 The characterization of the reproductive experience as unmasking future disease risk is a relatively new concept, and few studies have prospectively examined subclinical or clinical measures of cardiometabolic disease during the perinatal period through many years later. A history of pregnancy complications may reveal future risk of cardiometabolic diseases, including glucose intolerance and early atherosclerosis. Herein, we critically examine the scientific evidence for the role of reproductive history, including healthy pregnancies and a history of GDM, and their role in unmasking and/or development of future cardiometabolic disease and atherosclerosis in women. Modifiable risk factors, including pre-pregnancy and postpartum risk factors, may be important to early prevention of cardiometabolic diseases in women.
Funding Acknowledgment:
National Institutes of Health, National Institute of Child Health and Human Development, Bethesda, Maryland, United States;(Contracts # N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, and N01-HC-95095, from the National Heart, Lung, and Blood Institute, and K01 DK059944 and R01 DK090047 from the National Institute of Diabetes, Digestive and Kidney Diseases) and Kaiser Permanente Northern California.