Human chorionic gonadotropin, angiogenic factors, and preeclampsia risk: a nested case–control study

Objective To study whether human chorionic gonadotropin concentrations during pregnancy or combinations of human chorionic gonadotropin and other angiogenic factors, soluble fms‐like tyrosine kinase 1 and placental growth factor (PlGF), are associated with preeclampsia risk. Design Nested case–control study. Setting Population cohort of pregnant women. Sample A total of 121 cases of preterm (<37 weeks) and 158 cases of term preeclampsia (≥37 weeks of gestation) and 356 women without preeclampsia (controls). Methods Women with preeclampsia were identified by linkage to the Medical Birth Registry of Norway. Concentrations of human chorionic gonadotropin, soluble fms‐like tyrosine kinase 1 and PlGF were measured in maternal serum samples collected in each trimester of pregnancy. Main outcome measures Odds ratios of preterm and term preeclampsia. Results High human chorionic gonadotropin concentrations (highest quartile) in the first trimester were associated with reduced risk for preterm preeclampsia (OR 0.3, 95% CI 0.1–0.9), compared with low human chorionic gonadotropin (lowest quartile), whereas high human chorionic gonadotropin concentrations in the second trimester were associated with increased risk for preterm preeclampsia (OR 4.0, 95% CI 1.8–8.9). High human chorionic gonadotropin concentrations in the third trimester were associated with increased risk for term preeclampsia (OR 4.8, 95% CI 1.8–13.3). Concentrations of human chorionic gonadotropin above the median value combined with PlGF below the median in the second trimester were associated with very high risk for preterm preeclampsia (OR 36.9, 95% CI 8.2–165.8). Conclusions The results suggest an important role of human chorionic gonadotropin in the pathophysiological processes that lead to preeclampsia. The combined association of human chorionic gonadotropin and PlGF indicates a possible synergism between underlying biological pathways.