title: PP058. The additive effect of plasma levels of sFlt-1/PLGF ratio following the risk classification using both blood pressure levels and uterine artery blood flow impedance in the second trimester on the later occurrence of preeclampsia.
abstract: BACKGROUND
  The multivariate model including circulating levels of soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratios, maternal factors, blood pressure (BP) levels and uterine artery (UtA) doppler in the first to second trimester has been reported to be clinically useful to predict PE more accurately. However, the effects of levels of sFlt-1/PlGF ratio after the stratification of women using two major risk factors for PE, BP levels and UtA blood flow imdedance (BFI) have not been evaluated.
  
  
  OBJECTIVE
  Our aim was to evaluate the additive effect of plasma levels of sFlt-1/PlGF ratio following the risk classification using both mean blood pressure (MBP) levels and the combination of two UtABFI, mean pulsatility index (mPI) and mean notch depth index (mNDI), on the later occurrence of PE.
  
  
  METHODS
  1161 women were recruited into a prospective cohort study during 2004 and 2008. Clinical BPs were measured twice during 16 and 23 weeks, UtA doppler was performed twice during 16 and 23 weeks, and the mPI and mNDI was measured. Plasma samples were drawn once at 20-23weeks, and were stored at -20°C until use. The levels of sFlt-1/PlGF ratio were measured by automated electrochemiluminescent immunoassay (Roche Diagnostics K.K.). The cutoff value of mean BP (MBP) was determined as 91.3mmHg using ROC curve, and that of sFlt-1/PlGF ratio was 13.0, the 97.5th percentile of log10(sFlt-1/PlGF) at 20-23 weeks in normal pregnant women. If the mPI was <90th percentile of the gestational-age specific reference range of mPI, or the mNDI was <90th percentile of the gestational-age specific reference range of mNDI, we defined that the UtABFI was low; if the mPI was ⩾90th percentile and the mNDI was ⩾90th percentile, we defined that the UtABFI was high.
  
  
  RESULTS
  When women were stratified to 4 groups: low BP and low UtABFI, high BP but low UtABFI, high UtABFI but low BP, high BP and high UtABFI, the PPVs were 0.7%, 6.9%, 6.2% and 39.1%, respectively. In women with low BP and low UtABFI, the high sFlt-1/PlGF changed the PPV to 11.1%; the interval from the sampling to the onset of PE in women with high sFlt-1/PlGF ratio was significantly shorter than in those with low sFlt-1/PlGF ratio (mean±SD [weeks]: 5.9±1.5 vs. 16.5±2.1, p<0.01). In women with high BP but low UtABFI, the high sFlt-1/PlGF changed the PPV to 18.2%; the interval from the sampling to the onset of PE in women with high sFlt-1/PlGF ratio was significantly shorter than in those with low sFlt-1/PlGF ratio (8.0±5.7 vs. 12.6±3.7, p<0.05). Although these effects of sFlt-1/PlGF ratio on the occurrence of PE were not confirmed in women with high BP and high UtABFI, PE occurred in all women with three risk factors (5/5), and the interval from the sampling to the onset of PE was6.8±4.1 weeks.
  
  
  CONCLUSIONS
  Women with both high BP and high UtABFI, especially those with additional risk of high sFlt-1/PlGF ratio, were the highest risk of PE. In the lowest risk group of low BP and low UtABFI, the addition of sFlt-1/PlGF ratio improved the PPV and the interval from the sampling to the onset of PE. These results clearly indicated the clinical importance of measuring sFlt-1/PlGF ratio in addition to BP levels and UtABFI in all pregnant women in the second trimester.
authors.affiliation: Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ohkuchi
authors.affiliation: Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Hirashima
authors.affiliation: Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Matsubara
authors.affiliation: Obstetrics and Gynecology, Jichi Medical University School of Medicine, Shimotsuke-shi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Suzuki