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

• We evaluated the relative excess risk due to biological interaction (RERI) for PE.
• HR in high sFlt-1/PlGF, high BP and abnormal UAD (all risk) at 19–25 weeks was 107.
• HR in women with all risks at 26–31 weeks was 69.
• The RERI for PE at 19–25 weeks and 26–31 weeks was 84 and 54, respectively.
• We found a trio of risk factors for PE, which showed the biological interaction.

ObjectiveWe 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 designA prospective cohort study.Main outcome measuresIn 1239 pregnant women, MBP and UAD were measured at 16–23 weeks of gestation, and plasma levels of the sFlt-1/PlGF ratio at 19–25 weeks and 26–31 weeks. 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.ResultsAt 19–25 weeks, 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 26–31 weeks, 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.ConclusionsWe 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.