Serum sFlt1 concentration during preeclampsia and mid trimester blood pressure in healthy nulliparous women.
OBJECTIVE
The purpose of this study was to determine whether serum fms-like tyrosine kinase 1 (sFlt1) concentration during preeclampsia were associated with mid trimester blood pressure, other maternal characteristics, or pregnancy outcomes.


METHODS
We performed a nested case-control study within the Calcium for Preeclampsia Prevention study cohort. Each woman with preeclampsia (case) was matched to 1 normotensive control. A total of 120 pairs of women was chosen randomly. Serum concentrations of sFlt1 and placental growth factor were measured throughout pregnancy, but before labor and delivery. We focused on data from 40 women with blood specimens that were obtained after the onset of preeclampsia. After logarithmic transformation, we determined mean serum sFlt1 concentrations of all control specimens within gestational age windows during which case specimens had been obtained after the onset of preeclampsia. Within each of these gestational age windows, we computed an upper bound for the control specimens equal to 2 standard deviations above the mean. After the onset of preeclampsia, 16 women with log-transformed serum sFlt1 values greater than the upper bound of the control specimens were considered to have high preeclampsia serum sFlt1 levels. The 24 other women were considered to have low preeclampsia serum sFlt1 levels.


RESULTS
Women with high or low concentrations of serum sFlt1 during preeclampsia (arithmetic means, 5746 and 3007 pg/mL, respectively) had similar pregnancy outcomes and similar maternal characteristics, except for blood pressure at Calcium for Preeclampsia Prevention study enrollment. Systolic and diastolic blood pressure at enrollment at 13 to 21 weeks of gestation were significantly higher in the 24 women with low serum sFlt1 concentrations during preeclampsia (systolic blood pressure, 114 mm Hg; diastolic blood pressure, 65 mm Hg) than in the 16 women who had preeclampsia at high serum sFlt1 concentrations (systolic blood pressure, 106 mm Hg; diastolic blood pressure, 59 mm Hg). Blood pressure at 13 to 21 weeks among the women with high preeclampsia serum sFlt1 concentrations was identical to the blood pressure among normotensive control subjects. In linear regression analyses of data from all 40 women, both systolic (P < .0001) and diastolic (P = .014) blood pressures at enrollment were correlated negatively with natural logarithm serum sFlt1 concentration after onset of preeclampsia.


CONCLUSIONS
Women with higher mid trimester blood pressure had preeclampsia at lower serum sFlt1 concentrations. Because higher blood pressure may reflect occult endothelial damage, these observations may explain increased susceptibility to preeclampsia among women with pre-existing vascular disease.
Levine
Richard J
RJ
Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, Department of Health and Human Services, Bethesda, MD 20892, USA. LevineRJ@mail.nih.gov
Qian
Cong
C
Maynard
Sharon E
SE
Yu
Kai F
KF
Epstein
Franklin H
FH
Karumanchi
S Ananth
SA
D000328:Adult; D001794:Blood Pressure; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D010298:Parity; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1