Risk Factors Associated with Preeclampsia in Healthy Nulliparous Women. The Calcium for Preeclampsia Prevention (CPEP) Study Group

Objective: Our goal was to identify risk factors for the development of preeclampsia in nulliparous women enrolled in a multicenter trial comparing calcium supplementation to a placebo.

Study Design: A total of 4589 women from five centers was studied. Analysis of risk factors for preeclampsia was performed in 4314 who carried the pregnancy to > 20 weeks. Baseline systolic and diastolic blood pressure, demographic characteristics, and findings after randomization were examined for the prediction of preeclampsia. Preeclampsia was defined as hypertension (diastolic blood pressure > or = 90 mm Hg on two occasions 4 hours to 1 week apart) and proteinuria (> or = 300 mg/24 hours, a protein/creatinine ratio > or = 0.35, one dipstick measurement > or = 2+ or two dipstick measurements > or = 1+ at an interval as specified for diastolic blood pressure).

Results: Preeclampsia developed in 326 women (7.6%). The first analysis treated each risk factor as a categoric variable in a univariate regression. Maternal age, blood group and Rh factor, alcohol use, previous abortion or miscarriage, private insurance, and calcium supplementation were not statistically significant. Risk factors initially found to be significant were body mass index, systolic blood pressure, diastolic blood pressure, non-white race (African-American and other), clinical center, and smoking. Adjusted odds ratios computed with a logistic regression model revealed that body mass index (odds ratio 3.22 for > or = 35 kg/m2 vs < 19.8 kg/m2), systolic blood pressure (odds ratio 2.66 for > or = 120 vs < 101 mm Hg), diastolic blood pressure (odds ratio 1.72 for > or = 61 mm Hg vs < 60 mm Hg), and clinical center (odds ratio 1.85 for Memphis vs the other clinical centers) were statistically significant predictors of preeclampsia. Results of the final model fit revealed that preeclampsia risk increases significantly (p < 0.0001) with increased body mass index at randomization, as well as with increased systolic and diastolic blood pressure at randomization. Calcium supplementation had no effect on the risks posed by body mass index and blood pressure. Among risk factors developing after randomization, an abnormal results of a glucose screen (plasma glucose > or = 140 mg/dl 1 hour after a 50 gm glucose challenge) was not found to be associated with a significant risk of preeclampsia.

Conclusion: These risk factors should be of value in counseling women regarding preeclampsia and should aid in understanding the pathophysiologic characteristics of this syndrome.