Pregnancy-Related Risk Factors and Glucose Intolerance in Women during Midlife

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 DESCRIPTION (provided by applicant): Over 50% of U.S. women enter pregnancy overweight or obese, and almost 50% gain more weight during pregnancy than is recommended. Maternal excess adiposity not only leads to greater perinatal morbidity and mortality, but higher weight retention and greater disease risk. Randomized interventions to modify gestational weight gain (GWG), especially among overweight or obese women, have been largely ineffective. Excess maternal adiposity before, during and after pregnancy may result in worse cardiometabolic health for women during the childbearing years. These periods are referred to as "pregnancy-related risk factor changes" that involve increased adiposity, as well as alterations in metabolic risk factors during the preconception, gestational, and post-pregnancy periods. We hypothesize that maternal cardiometabolic risk factor changes (i.e., "trajectories") before pregnancy may increase the risk of excessive GWG and adverse perinatal outcomes (APOs), and that maternal BMI and subsequent weight changes throughout the childbearing years may adversely affect maternal cardiometabolic risk factor development post-pregnancy, and thereby accelerate the progression to glucose intolerance in women during midlife. We propose an ancillary study to the NHLBI funded CARDIA Study, a multi-center longitudinal cohort of 5,115 black and white women and men (18-30 y) enrolled in 1985-1986, and re-examined up to 8 times as of 2011 with retention of 72% of the surviving cohort. Exams included metabolic risk factor (body weight, waist girth, fasting glucose and lipids) measurements every 2-5 years (both before and after pregnancies) in 1986-2011, including oral glucose tolerance testing via 2-hr 75 g OGTTs up to four times from 1996-2011. Women also reported GWG and perinatal outcomes (birth weight, gestational age, GDM, preterm birth) which were validated via medical record abstractions. The proposed study will coincide with the Year 30 CARDIA exam (June 2015-2016) to collect new data on reproductive and offspring health histories, administer a fifth 2-hr 75 g OGTT and measure HbA1c. This study leverages the unique CARDIA datasets that include prospective risk factor measurements from before to after pregnancies, existing GWG and APO data, and additional new data collection to assess progression to glucose tolerance in women. The specific aims are: 1) To evaluate the impact of pre-pregnancy cardiometabolic risk factor trajectories on pregnancy outcomes; 2) To characterize the contributions of weight changes from before, during and after pregnancy to the development of cardiometabolic risk factors for glucose intolerance and 3) To evaluate the independent associations of maternal pre-pregnancy BMI, GWG, and post-pregnancy weight changes on the progression to glucose intolerance. These findings can be translated into individual risk stratification to optimize prevention efforts by identifying women at high- risk fo perinatal morbidity, and subsequent progression to glucose intolerance during the reproductive years.