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Preeclampsia may be caused by an imbalance of angiogenic factors. We previously demonstrated that high serum levels of sFlt1 (an anti-angiogenic protein) and low levels of PGF (a pro-angiogenic protein) predict subsequent development of preeclampsia. While sFlt1 is too large a molecule (110 kD) to be filtered into the urine, PGF is much smaller (30 kD) and readily filtered. We hypothesized that urine PGF is altered prior to hypertension and proteinuria and may predict preeclampsia.
Nested case control study within the CPEP cohort of healthy nulliparas. Each woman who developed preeclampsia was matched to one normotensive control. 120 pairs were randomly chosen. Concentrations of PGF and creatinine were determined in 704 urine specimens obtained before labor.
Among normotensive controls urinary PGF increased during the first 2 trimesters, peaked at 29-32 weeks, and decreased thereafter. The pattern in cases before onset of preeclampsia was similar, but levels were significantly reduced beginning at 25-28 weeks. There were particularly large differences between controls and cases with subsequent early-onset preeclampsia or an SGA infant. The adjusted odds ratio for subsequent preeclampsia before 37 wks for specimens obtained at 21-32 weeks which were in the lowest quartile of control PGF concentrations (<118 pg/mL), as compared to all other quartiles, was 22.5 (95% CI 7.4-67.8).
Decreased urinary PGF increases greatly the risk of preeclampsia.