The Role of Obesity in Preeclampsia

Abstract

The incidence of obesity is increasing at an alarming rate. There is compelling evidence that obesity increases the risk of preeclampsia about 3-fold, and in developed countries is the leading attributable risk for the disorder. In this presentation we explore this relationship and propose targets for future studies guided by the much more extensively studied relationship of obesity to cardiovascular disease. We further address the hypothesis that asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, may be one convergence point for the mechanism by which obesity increases the risk of preeclampsia. We conclude with consideration of the clinical implications of this information.

Figure 1. Prepregnancy BMI is associated with an increased risk of preeclampsia

Data from the Perinatal Collaborative Study including more than 19,000 Black and 19,000 white women was analyzed and the unadjusted prevalence of preeclampsia as related to prepregnancy BMI presented. The prevalence of preeclampsia increased with increasing prepregnancy BMI for mild and severe preeclampsia and in blacks and whites.

Figure 2. Asymmetric Dimethylarginine (ADMA) has been proposed as the “Uber Risk Factor” where many of the risk factors for cardiovascular disease and we propose for obesity and preeclampsia converge

Multiple risk factors can increase ADMA. Although these are shown as acting directly to increase ADMA it is most likely they act to reduce the activity the degradatory enzyme, dimethylarginine dimethylaminohydrolase (DDAH). With an increase in ADMA, nitric oxide synthase activity is competitively inhibited and the enzyme uncoupled leading to the production of superoxide. The resulting increased oxidative stress further decreases the activity of DDAH.