A trio of risk factors for the onset of preeclampsia in the second and early third trimesters.

OBJECTIVE: We evaluated the biological interaction among mean blood pressure (MBP), uterine artery Doppler (UAD), and the soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio for preeclampsia (PE) risk. STUDY DESIGN: A prospective cohort study. MAIN OUTCOME MEASURES: In 1239 pregnant women, MBP and UAD were measured at 16-23weeks of gestation, and plasma levels of the sFlt-1/PlGF ratio at 19-25weeks and 26-31weeks. A Cox proportional hazard model was used. Women with a low sFlt-1/PlGF ratio and either low BP or normal UAD were set as controls. The relative excess risk due to biological interaction (RERI) was calculated using the following equation: RERI=hazard ratio (HR) in women with high sFlt-1/PlGF and both high BP and abnormal UAD (group 3) - HR in women with both high BP and abnormal UAD alone (group 1) - HR in women with high sFlt-1/PlGF alone (group 2)+1. RERI⩾10 was considered to be strong. RESULTS: At 19-25weeks, the HR and 95% confidence intervals (CI) in group 1, group 2, and group 3 were 7.4 (3.1-17.4), 15.3 (4.5-52.2), and 107.0 (41.0-279), respectively, and the RERI for PE was 85.3. At 26-31weeks, the HR and 95% CI in each group were 8.3 (2.9-23.2), 7.5 (0.97-57.8), and 69.0 (18.5-256), respectively; the RERI for PE was 54.2. CONCLUSIONS: We found a trio of risk factors for the onset of PE in the second and early third trimesters: high BP, abnormal UAD, and high sFlt-1/PlGF ratio.