47: Associations with preeclampsia: lessons from the hyperglycemia and adverse pregnancy outcome (HAPO) study


      To examine associations of maternal glucose levels, BMI and fasting serum C-peptide with the risk of preeclampsia (PE), in the multicenter multinational HAPO Study.

      Study Design

      Secondary analysis of double blinded prospective observational cohort study. Eligible pregnant women underwent a standard 75-g oral glucose tolerance test (OGTT) between 24 and 32 weeks gestation (mean 27.8 weeks). Preeclampsia includes PE, severe PE, eclampsia, and PE superimposed on chronic HTN. Women with gestational or chronic HTN were excluded. Associations between PE and maternal glucose, fasting serum C-peptide and BMI (measured at the OGTT) were assessed using multiple logistic regression analyses, with adjustment for potential confounders including field center, family history of hypertension and diabetes, maternal age, parity, height, gestational age at OGTT, smoking, alcohol use, and baby′s sex.


      1) Overall, 21,364 of 23,316 blinded HAPO participants were eligible for analysis, of whom 1,116 (5.2%) developed PE. 2) Fully adjusted odds ratios (OR) for PE associated with a 1 SD higher fasting (6.9 mg/dl), 1-hour (30.9 mg/dl), and 2-hour plasma glucose (23.5 mg/dl) were 1.08 (95% CI 1.00-1.16)), 1.19 (95% CI 1.11-1.28), 1.21 (1.13-1.30), respectively). 3) For each 1 SD increment in maternal BMI (5.1 kg/m2) the adjusted OR was 1.60 (95% CI 1.50-1.71). 4)) For maternal fasting C-peptide the adjusted OR was 3.08 (95% CI 1.84-5.16) for the highest versus lowest category of C-peptide (>4.8 vs. <1.2 ug/L).


      Our results indicate generally strong, continuous associations of maternal hyperinsulinemia, BMI and maternal glucose levels below those diagnostic of diabetes with preeclampsia. These findings support a possible role of insulin resistance in the pathogenesis of PE.