Context: Preeclampsia may be caused by an imbalance of angiogenic factors. We previously demonstrated that high serum levels of soluble fms-like tyrosine kin ase 1 (sFlt1), an antiangiogenic protein, and low levels of...Context: Preeclampsia may be caused by an imbalance of angiogenic factors. We previously demonstrated that high serum levels of soluble fms-like tyrosine kin ase 1 (sFlt1), an antiangiogenic protein, and low levels of placental growth fac tor (PIGF), a proangiogenic protein, predict subsequent development of preeclamp sia. In the absence of glomerular disease leading to proteinuria, sFlt1 is too l arge a molecule to be filtered into the urine, while PIGF is readily filtered. O bjective: To test the hypothesis that urinary PIGF is reduced prior to onset of hypertension and proteinuria and that this reduction predicts preecla-mpsia. De sign, Setting, and Patients: Nested case-control study within the Calcium for P reeclampsia Prevention trial of healthy nulliparous women enrolled at 5 US unive rsity medical centers during 1992-1995. Each woman with preeclampsia was matche d to 1 normotensive control by enrollment site, gestational age at collection of the first serum specimen, and sample storage time at -70℃. One hundred twenty pairs of women were randomly chosen for analysis of serum and urine specimens o btained before labor. Main Outcome Measure: Cross-sectional urinary PIGF concen trations, before and after normalization for urinary creatinine. Results: Among normotensive controls, urinary PIGF increased during the first 2 trimesters, pea ked at 29 to 32 weeks, and decreased thereafter. Among cases, before onset of pr eeclampsia the pattern of urinary PIGF was similar, but levels were significantl y reduced beginning at 25 to 28 weeks. There were particularly large differences between controls and cases of preeclampsia with subsequent early onset of the d isease or small-for-gestational-age infants. After onset of clinical disease, mean urinary PIGF 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 o dds 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 cont rol PIGF concentrations (<118 pg/mL), compared with all other quartiles, was 22. 5 (95%confidence interval, 7.4-67.8). Conclusion: Decreased urinary PIGF at mi d gestation is strongly associated with subsequent early development of preeclam psia.展开更多
文摘Context: Preeclampsia may be caused by an imbalance of angiogenic factors. We previously demonstrated that high serum levels of soluble fms-like tyrosine kin ase 1 (sFlt1), an antiangiogenic protein, and low levels of placental growth fac tor (PIGF), a proangiogenic protein, predict subsequent development of preeclamp sia. In the absence of glomerular disease leading to proteinuria, sFlt1 is too l arge a molecule to be filtered into the urine, while PIGF is readily filtered. O bjective: To test the hypothesis that urinary PIGF is reduced prior to onset of hypertension and proteinuria and that this reduction predicts preecla-mpsia. De sign, Setting, and Patients: Nested case-control study within the Calcium for P reeclampsia Prevention trial of healthy nulliparous women enrolled at 5 US unive rsity medical centers during 1992-1995. Each woman with preeclampsia was matche d to 1 normotensive control by enrollment site, gestational age at collection of the first serum specimen, and sample storage time at -70℃. One hundred twenty pairs of women were randomly chosen for analysis of serum and urine specimens o btained before labor. Main Outcome Measure: Cross-sectional urinary PIGF concen trations, before and after normalization for urinary creatinine. Results: Among normotensive controls, urinary PIGF increased during the first 2 trimesters, pea ked at 29 to 32 weeks, and decreased thereafter. Among cases, before onset of pr eeclampsia the pattern of urinary PIGF was similar, but levels were significantl y reduced beginning at 25 to 28 weeks. There were particularly large differences between controls and cases of preeclampsia with subsequent early onset of the d isease or small-for-gestational-age infants. After onset of clinical disease, mean urinary PIGF 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 o dds 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 cont rol PIGF concentrations (<118 pg/mL), compared with all other quartiles, was 22. 5 (95%confidence interval, 7.4-67.8). Conclusion: Decreased urinary PIGF at mi d gestation is strongly associated with subsequent early development of preeclam psia.
