Research On Adiponectin,MMP–9,Placental Growth Factor Combined Ultrasonic Blood Flow Indices In Severe Preeclampsia Perinatal Outcomes

Brackground Severe preeclampsia(PE) is a pregnancy-associated disorder and is also a serious condition with increasing significant maternal and perinatal morbidity and mortality.Along with the progress of severe PE, delivery is needed for the benefit of the mother.However, the premature delivery has adverse effects on perinatal outcomes. And it is limited to the most premature infants.So Severe PE is a difficult problem in perinatal medicine.The etiology of PE is still unknown. Reports show that Adiponectin has pround effects including protecting endothelial cells,regulating insulin sensitivity,anti-inflammatory and anti-atherogenetic actions, and protecting endothelial cells.Matrix metalloproteinase-9(MMP-9) plays an important role in human trophoblast invasion. Placental growth factor(PLGF) is one of the angiogenic factors, and it could active the endothelial cells,and improve proliferation of trophoblast. Thus these three factors might play an important role in the pathogenesis of severe PE.The flow wave abnormalities precede clinical manifestations of PE and they can be detected by Doppler ultrasound, so Doppler ultrasound has been regarded as a useful method for prediction of PE.In recent years,with the continuous development of ultrasound imaging technology,studies on quantitative analysis of placental blood flow using three-dimensional power Doppler ultrasound have been increasingly reported,indicating the unique advantages of this technology for the evaluation of placental blood flow.However, this technology has not been extensively applied in clinical practice.Severe preeclampsia patients show incomplete trophoblastic invasion on spiral arteries, decreasing placental blood flow infusion, placental ischemia and hypoxia,increasing the resistance in uterus-placental-fetal circulation, and intrauterine fetal hypoxia,resulting in adverse perinatal outcomes.However, almost studies only include one ultrasonic index or two ultrasonic indices and they do not identify effective,unified prediction index.The aim of this investigation was to evaluate the relationship between Adiponectin,MMP-9,PLGF combined ultrasonic blood flow indices and perinatal outcome in pregnant women with severe PE.And this investigation was divided into three parts.Part I Research on Doppler blood flow indices and placental blood flow perfusion in patients with severe preeclampsia and the control groupObjective The aim of this study was to assess the prognostic value of ultrasonic Doppler blood flow indices of uterine artery(Ut A), umbilical artery(UA), middle cerebral artery(MCA), ductus venosus(DV) and the placental blood perfusion indices between severe preeclampsia and normotensive pregnant women.Methods The case group included 120 pregnant women with severe preeclampsia and 120 normotensive pregnant women with the same gestation as the control group.Application of Doppler ultrasound monitored the flow of Ut A,UA,MCA,DV,UV.And application of three-dimensional power Doppler ultrasound monitored placental perfusion indices including vascularization index(VI), flow index(FI), and vascularization flow index(VFI).Results The resistance indices of UA, Ut A, DV of severe PE were higher than the control group, and the resistance indices of MCA of severe PE were lower than the control group.The rate of abnormal blood flows(absence or reversal of end-diastolic flow of UA, early diastolic notch of Ut A flows, absence or reversal of “a” wave of DV flow,pulsatile flow in the free UV) of severe PE were higher than the control group.VI, FI,VFI of case group were lower than the control group.The indicator with the largest area under the ROC curve was the FI, which had a cutoff value of 34.6.Conclusions Doppler ultrasound had important value in the hemodynamic aspects of severe PE.This research provided Doppler flow resistance data of Ut A,UA,MCA,DV in different gestational age.Flow index was the most predictive value,and three-dimensional power Doppler ultrasound technology might become one of the important methods of prenatal detection in severe PE.Part II Research on the expression of Adiponectin, MMP-9,placental growth factor in the placenta of severe preeclampsia and the control groupObjective This study aimed to evaluate the expression of Adiponectin, matrix metalloproteinase-9, placental growth factor in the placenta of severe preeclampsia and the normotensive pregnant women, and to discuss the possible pathogenesis of severe preeclampsia.Methods Immunohistochemical method was applied to detect the localization and protein expression level of Adiponectin, matrix metalloproteinase-9, placental growth factor,and the m RNA expression level of Adiponectin, matrix metalloproteinase-9,placental growth factor were detected by real-time fluorescent PCR technique.Results The positive cell of adiponectin, MMP-9, placental growth factor could be observed in trophoblast of the severe PE group and the control group. The protein expression and m RNA expression level of adiponectin were significantly higher in the case group compared with the control group,while the level of MMP-9 and placental growth factor were lower than that of control group. There was a negative correlation between the m RNA expression level of adiponectin and placental growth factor(r=-0.845,P<0.001), while there was a positive correlation between the m RNA expression level of MMP-9 and placental growth factor(r=0.572,P<0.001).Conclusions This study suggested that the increase of adiponectin expression and the decrease of MMP-9, placental growth factor in the placenta of the severe PE lead to the irregulation of trophoblast function and in collaboration to the onset of severe preeclampsia.Part III Research on relationship between perinatal outcome and adiponectin, MMP-9, placental growth factor and ultrasonic blood flow indicesObjective The goal of our current study was to explore the correlation between perinatal outcome and expression of adiponectin, matrix metalloproteinase-9, placental growth factor in the placenta and ultrasonic blood flow indices.Methods The perinatal outcomes were followed up.The correlation between gestational age at birth and the m RNA expression level of Adiponectin, matrix metalloproteinase-9,placental growth factor in the placenta were analysed. And the relationship between the ultrasonic blood flow with severe preeclampsia perinatal outcomes were analysed.Results The incidence of adverse perinatal outcomes of severe PE was 30%. There were positive correlation between the gestational age and birth weight, placental weight(r=0.899;0.921,P<0.001).There was a negative correlation between m RNA expression level of adiponectin and gestational age(r=-0.914,P<0.001), and there were a positive correlation between m RNA expression level of MMP-9, placental growth factor and gestational age(r=0.806;0.875,P<0.001).Flow index had the greatest value for the prediction of perinatal outcomes,and the cutoff value was 26.3.An absent or reversed DV “a” wave was an independent risk factor for perinatal death( OR=880.000).And bilateral Ut A early diastolic notch was the independent risk factor for admission to the neonatal intensive care unit(OR=98.667).The perinatal mortality rate of absent or reverse diastolic flow in umbilical artery is 69.2%,and that of absent or reverse “a” wave in ductus venous is 100%.Conclusions Increase of adiponectin expression level and the decrease of MMP-9, placental growth factor in the placenta of severe PE might lead to the worse perinatal outcome.Flow index had the greatest value for the prediction of perinatal outcomes. Abnormal arterial Doppler flow often appeared earlier, and abnormal venous Doppler flow resulted in adverse perinatal outcome compared to those whose Doppler abnormality were confined to the arterial flow. Thus when absent or reverse diastolic flow in umbilical artery is observed and the fetus has been the ability to survive outside,decision-to-delivery should be taken in order to avoid metabolic deterioration and to avoid increase adverse perinatal outcome.