Urinary placental growth factor and risk of preeclampsia.
BACKGROUND
Preeclampsia may be caused by an imbalance of angiogenic factors. We previously demonstrated that high serum levels of soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein, and low levels of placental growth factor (PlGF), a proangiogenic protein, predict subsequent development of preeclampsia. In the absence of glomerular disease leading to proteinuria, sFlt1 is too large a molecule to be filtered into the urine, while PlGF is readily filtered.


OBJECTIVE
To test the hypothesis that urinary PlGF is reduced prior to onset of hypertension and proteinuria and that this reduction predicts preeclampsia.


METHODS
Nested case-control study within the Calcium for Preeclampsia Prevention trial of healthy nulliparous women enrolled at 5 US university medical centers during 1992-1995. Each woman with preeclampsia was matched to 1 normotensive control by enrollment site, gestational age at collection of the first serum specimen, and sample storage time at -70 degrees C. One hundred twenty pairs of women were randomly chosen for analysis of serum and urine specimens obtained before labor.


METHODS
Cross-sectional urinary PlGF concentrations, before and after normalization for urinary creatinine.


RESULTS
Among normotensive controls, urinary PlGF increased during the first 2 trimesters, peaked at 29 to 32 weeks, and decreased thereafter. Among cases, before onset of preeclampsia the pattern of urinary PlGF was similar, but levels were significantly reduced beginning at 25 to 28 weeks. There were particularly large differences between controls and cases of preeclampsia with subsequent early onset of the disease or small-for-gestational-age infants. After onset of clinical disease, mean urinary PlGF in women with preeclampsia was 32 pg/mL, compared with 234 pg/mL in controls with fetuses of similar gestational age (P<.001). The adjusted odds ratio for the risk of preeclampsia to begin before 37 weeks of gestation for specimens obtained at 21 to 32 weeks, which were in the lowest quartile of control PlGF concentrations (<118 pg/mL), compared with all other quartiles, was 22.5 (95% confidence interval, 7.4-67.8).


CONCLUSIONS
Decreased urinary PlGF at mid gestation is strongly associated with subsequent early development of preeclampsia.
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, USA.
Thadhani
Ravi
R
Qian
Cong
C
Lam
Chun
C
Lim
Kee-Hak
KH
Yu
Kai F
KF
Blink
Anastasia L
AL
Sachs
Benjamin P
BP
Epstein
Franklin H
FH
Sibai
Baha M
BM
Sukhatme
Vikas P
VP
Karumanchi
S Ananth
SA
D000328:Adult; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000175:diagnosis / Q000517:prevention & control* / Q000652:urine; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000652:urine*; D011264:Pregnancy Trimesters / Q000652:urine; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000652:urine; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1