| ObjectiveAngiogenic factors like placental growth factor(PGF), its antiangiogenic antagonist soluble fms-like tyrosine kinase 1 (sFlt1), and endogenous inhibitor of endothelial nitric oxide synthase like asymmetric dimethylarginine(ADMA) are closely related to the pathogenesis of pre-eclampsia. Because it is known that altered maternal sFlt1 and PGF, ADMA levels are detectable weeks before the onset of the pre-eclampsia complications. The aim of the study is to investigate the predictive value of these markers in early trimester pregnancy with pulse index (PI) in uterine perfusion and try to set predictive model and screening model for pre-eclampsia in early pregnancy.MethordsWe took all the women (n=770 persons) who received prenatal care in Shanghai First Maternity and Infant Health Hospital from 2007 to 2009. Exclusion criteria included histories of hypertension, renal disease, and diabetes et al. For the study, women with singletons enrolled in the study since 12-16weeks of gestation and followed until 6 weeks after delivery. All the persons were collected blood samples at pregnant 12-16 weeks and 20-24 weeks, doing the PI at 20-24 weeks. We made the devision according to the pregnant outcome. Cases (n=44) were defined as those with blood collections in the first and second trimester who subsequently developed pre-eclampsia, and controls (n=100) were contemporaneous women enrolled in the same study and remained normotensive, normoglycemic, and without evidence of proteinuria during pregnancy.Blood samples were collected from all women at the first prenatal care (pregnant 12-16 weeks) and repeated in the second trimester (pregnant 20-24 weeks). After collection, samples were stored in-80℃until analysis. Serum sFlt-1, PGF and ADMA were measured using ELISA kits. Doppler ultrasound of the uterine arteries was performed in second trimester (pregnant 20-24weeks). The same doctor took the average pulsatility index (PI) of the blood flow through both arteries.ResultsThe prospective study includes 740 pregnant women.44 of them developed new-onset pre-eclampsia. Pregnancies with adverse pregnancy outcome showed significantly higher sFlt1 (0.368±0.03 versus 0.320±0.022; P<0.01) in pregnant 20-24 weeks, significantly higher ADMA (0.84±0.205 versus 0.67±0.199, P<0.01) and lower PGF(115.86±59.1 versus 210±63.13, P<0.01) compared with those with normal outcome in pregnant 12-16weeks. From the analysis, we found that the combination of Doppler PI, PGF and ADMA increased the sensitivity and specificity of PI alone in early pregnancy. PI was obvious higher in case group in pregnant 20-24 weeks. When the specificity was 80%, sensitivity was 76%. From the analysis, we found that the combination of Doppler PI, PGF and ADMA increased the sensitivity and specificity of PI alone in early pregnancy. When the specificity was 80%, combined sensitivity was increased to 90%.On the other hand, we try to set a pre-eclampsia screening model. PI is a popular and steady related factor in pre-eclampsia. If we only use PI to predict the disease, positive predictive value was 61.5%. But it was too late. From the analysis, we found that ADMA, PGF and BMI were much more related for the screening. So we try to set the screening model(except PI). After screening, we can get the high risk women to take PI in the second trimester. It is showed that positive predictive value was increased to 80.9%.ConclusionWe conclude that the measurement of PI and some serum factors allows an efficient prediction and screening model in early second trimester pregnancy for pre-eclampsia. |
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