Altered Metabolic Profiles among Older Mothers with a History of Preeclampsia

Abstract

Preeclampsia has been linked to increased risk for cardiovascular disease and, more recently, to reduced risk for breast cancer later in life. The altered chronic disease risk associated with prior preeclampsia may reflect underlying metabolic differences. In this case-control study, we examined the metabolic profiles of older mothers with and without a history of preeclampsia in their first pregnancies. At the time of the study, subjects were non-pregnant, non-smoking women who completed their first pregnancies at age 30 or older, were pre-menopausal, and were free of serious chronic disease. Cases were 13 women who experienced preeclampsia in their first pregnancies; controls were 13 women with uncomplicated first pregnancies, frequency matched to cases on race/ethnicity, current age, and age at delivery. A fasting blood sample was collected from each subject during the luteal phase (day 19–22) of the menstrual cycle and assayed for specific factors thought to be linked to hypertensive disease or breast cancer. Compared to women with uncomplicated pregnancies, those with a history of preeclampsia had significantly elevated levels of fasting serum triglycerides, insulin and glucose, and a higher fasting insulin resistance index, suggesting that women with prior preeclampsia were relatively insulin resistant. In addition, cases had higher levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) and a higher molar ratio of IGFBP-3 to IGF-1 than did controls. Adjustment for obesity and other potential confounders did not appreciably alter the magnitude of these associations. This preliminary study suggests that women with a history of preeclampsia have persistent metabolic abnormalities consistent with their observed excess risk for cardiovascular morbidity and mortality, and their apparent reduced risk for breast cancer later in life.