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Background Midlife women have a higher risk of cardiometabolic disease than younger women, but the lifelong biological/lifestyle factors responsible for this increase are unclear. Objectives We investigated whether pregnancy history is a risk factor for midlife overweight/obesity and evaluated potential hormonal mechanisms. Methods The Baltimore Midlife Women's Health Study, a prospective cohort, recruited 772 women aged 45–54 y. Women reported pregnancy characteristics via questionnaires, trained staff measured weight/height to calculate midlife BMI, and serum hormones were assessed by ELISA. Logistic regression models assessed associations of pregnancy history with risk of midlife overweight/obesity and BMI gain since age 18. We additionally explored whether associations differed by menopausal status, and whether midlife hormones mediated relationships of pregnancy history and midlife BMI. Results These premenopausal or perimenopausal women were 66% Caucasian/White and 30% African American/Black, with a median of 2 live births (range: 0–11) and median age at first birth of 27 y (range: 12–46 y). Women with 0 and ≥2 live births had lower odds of overweight/obesity than those with 1 birth (OR = 0.47; 95% CI: 0.23, 0.96; P = 0.04, and OR = 0.58; 95% CI: 0.35, 0.95; P = 0.03, respectively). Women with ≥2 live births also had lower odds of BMI gain than those with 1 birth (OR = 0.66; 95% CI: 0.41, 1.06; P = 0.08). Furthermore, women who were older at their first birth had lower odds of overweight/obesity (OR = 0.96; 95% CI: 0.92, 1.00; P = 0.03) and BMI gain (OR = 0.97; 95% CI: 0.93, 1.00; P = 0.06). Number of pregnancies and age at last pregnancy were not associated with midlife overweight/obesity or BMI gain. Associations did not differ by menopausal status and were not explained by midlife hormones. Conclusions Earlier childbirth and having 1 child increased women's risk of midlife overweight/obesity and BMI gain since age 18. Additional studies should focus on women's childbearing years as a critical determinant of midlife metabolic health.

Objectives In mid-life, women have elevated risks of cardiovascular and metabolic diseases. Pregnancy causes substantial metabolic changes in women, but it is unclear whether these changes persist life-long. Thus, we investigated associations between pregnancy history and mid-life overweight/obesity, accounting for the menopausal transition. Methods Pre- and peri-menopausal women (ages 45–54, n = 772) in the Baltimore Mid-Life Women's Health Study reported their demographics, health habits, and pregnancy history (numbers of live births/pregnancies and age at first birth/last pregnancy) via questionnaires. Height and weight were measured to calculate BMI. Multivariable logistic regression models assessed overall and stratified (by menopausal status) associations of pregnancy history and risk of mid-life overweight/obesity (BMI ≥ 25 kg/m2), controlling for race, employment, health, alcohol intake, smoking status, physical activity, and menopausal status (unstratified models). Results Women had a median age of 48, 65% were pre- and 35% were peri-menopausal, 65% were white, 63% had graduated college, and 74% had a family income ≥$50,000. Mean (SD) BMI was 28.5 (7.4) kg/m2, and was higher in peri- vs. pre-menopausal women (29.8 vs. 27.8 kg/m2; P < 0.005). Ages at first birth or last pregnancy were not associated with mid-life BMI. Women whose pregnancies either did or did not result in a live birth had 44% (OR: 0.56; 95% CI: 0.32, 0.99; P < 0.05) and 59% (OR: 0.41; 95% CI: 0.19, 0.87; P < 0.05), respectively, lower odds of being overweight/obese at age 45–54 compared to women who had never been pregnant. However, in women who had been pregnant, the odds of being overweight/obese increased by 19% with every live birth (OR: 1.19; 95% CI: 1.02, 1.40; P < 0.05). In stratified analyses, these associations remained significant only in pre-menopausal women. Conclusions In pre-menopausal women, having a history of pregnancy appears to be protective against overweight/obesity, but the protective effects diminish with every live birth. In peri-menopausal women, pregnancy history was not related to BMI, suggesting the importance of other lifestyle or physiological factors in determining BMI during menopause. The discrete findings in pre- vs. peri-menopausal women warrant studies examining relationships of pregnancy history with BMI after menopause. Funding Sources This study was made possible by funding from NIH/NIEHS, USDA, and Michigan AgBioResearch.