title: A trio of risk factors for the onset of preeclampsia in the second and early third trimesters.
abstract: 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.
  
  
  METHODS
  A prospective cohort study.
  
  
  METHODS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Japan. Electronic address: okuchi@jichi.ac.jp.
authors.forename: Akihide
authors.initials: A
authors.lastname: Ohkuchi
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Hirashima
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Division of Inflammation Research, Center of Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Koumei
authors.initials: K
authors.lastname: Shirasuna
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Japan.
authors.forename: Hirotada
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Ariga
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Hirose
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Matsubara
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Suzuki
keywords: Mean arterial pressure; Placental growth factor; Prediction; Preeclampsia; Soluble fms-like tyrosine kinase 1; Uterine artery Doppler