| Background Preeclampsia(PE)is a common disease unique to pregnancy,with a clinical incidence of 2.3% Mel 7.6%,which is one of the important causes of adverse pregnancy outcomes and seriously threatens the life safety of pregnant women and perinatal infants [1].Preeclampsia is characterized by elevated blood pressure,edema,proteinuria and other related symptoms of organ dysfunction,and will affect the normal growth and development of intrauterine fetus,resulting in fetal ischemia and hypoxia,and then increase the probability of preterm delivery [2].At present,the etiology and pathogenesis of preeclampsia are not completely clear,and there is a lack of effective predictive indicators of preeclampsia,so it is very difficult to carry out early prediction,identification and related intervention in clinic.Most pregnant women will only give a series of diagnosis and treatment measures after the emergence of related symptoms to increase the risk of perinatal and maternal adverse pregnancy outcome and death.It has a great impact on the health of mother and child [3].In the early stage of pregnancy,if the occurrence of preeclampsia can be predicted and appropriate preventive intervention measures can be taken in advance,the incidence of preeclampsia can be reduced,the progress of the disease can be curbed and the prognosis of mother and infant can be improved.Some foreign scholars have confirmed that the relevant indexes in the serum of pregnant women with preeclampsia have changed abnormally in the early and second trimester of pregnancy [4].In recent years,most scholars at home and abroad believe that preeclampsia is a placental disease,and pregnancy-associated plasma protein A(PAPP-A)and placental growth factor(PLGF)are closely related to the growth and development of placental trophoblasts and vascular endothelial damage,so PAPP-An and PLGF can be used as predictive indicators of preeclampsia [5].In previous clinical studies,PAPP-An and PLGF are mostly used to evaluate the severity of preeclampsia,but there are few studies on their application in the prediction of the incidence of preeclampsia [6].Previous studies have shown that the incidence of hypertensive disorder complicating pregnancy is negatively correlated with the slight increase of serum bilirubin level,and in the early stage of the disease,the serum bilirubin level of pregnant women has decreased [7].Therefore,serum bilirubin can be used as a potential predictor of preeclampsia.At present,there is no study on the predictive value of serum bilirubin in preeclampsia.Under this background,this paper adopts a prospective clinical research method to explore the predictive value of serum PAPP-A,PLGF and bilirubin in early and second trimester pregnant women for preeclampsia,and to provide reference for early clinical prediction,screening and intervention.Objective To study the combined predictive value of pregnancy associated plasma protein A(PAPP-A),placental growth factor(PLGF)and bilirubin in preeclampsia(PE).The purpose of this study is to provide a theoretical basis for the clinical prediction of preeclampsia(PE).The predictive value of serum PAPP-A,PLGF and bilirubin levels in preeclampsia will open up new ideas for clinical diagnosis and treatment.Object of study and Methods1.Object of study and groups A total of 170 pregnant women who underwent regular prenatal examination and hospital delivery in the obstetrics clinic of the third affiliated Hospital of Zhengzhou University from August 2018 to August 2019 were followed up from 11 weeks of pregnancy to 3 months after delivery.according to the follow-up results and the diagnostic criteria in the 9th edition of Obstetrics and Gynecology,they were divided into three groups: preeclampsia group,gestational hypertension group and control group,that is,after 20 weeks of pregnancy.Preeclampsia was defined as preeclampsia with systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg,accompanied by positive urine protein(24-hour quantitative ≥ 0.3g).If urinary protein was negative and returned to normal within 12 weeks after delivery,gestational hypertension was found in 32 cases of preeclampsia group,54 cases of gestational hypertension group,82 cases of normal pregnant women as control group and 2 cases of loss of follow-up.Inclusion criteria:(1)singleton pregnancy(2)with high risk factors for preeclampsia: obesity,BMI ≥ 24;age ≥ 35 years old;previous history of preeclampsia;family history of preeclampsia;previous adverse pregnancy outcome;history of recurrent abortion;delivery history of infants with low birth weight or less gestational age;in this pregnancy,in vitro fertilization was adopted.The interval from the previous pregnancy was more than 10 years.(3)there were no other complications during pregnancy.(4)the informed consent was signed after the hospital ethics committee certified and obtained the informed consent of the pregnant woman.Exclusion criteria:(1)this pregnancy is twins or multiple pregnancies(2)suffer from chronic hypertension before pregnancy(3)complicated with heart disease,diabetes,nephropathy and other complications during pregnancy(4)termination of pregnancy by abortion or induced labor(5)those who have previously suffered from liver disease or abnormal changes in liver function(6)the clinical data of the selected cases are incomplete.There were no significant differences among the three groups in terms of age,gestational weeks,gestational times,parturition times and abortion times among the three groups(P > 0.05).2.method(1)Detection of serological indexes: 3ml of elbow venous blood was taken from all pregnant women during the 20 th week of pregnancy,and the anticoagulant tube was stored in the refrigerator at-80 ℃ for examination.It was taken out from the refrigerator 2 hours before the test and melted slowly and naturally.After 15 min was placed in the centrifuge,the supernatant was centrifuged with 12000r/min for 10 min,and the supernatant was detected.The levels of PAPP-A,PLGF,TB,DB and IB in serum were detected by enzyme-linked immunosorbent assay((ELISA)).The detection instrument was Bio Tek ELx800 universal enzyme labeling instrument,and all the detection steps were strictly in accordance with the instructions of the kit.(2)observation index: the data of age,pregnancy,delivery,miscarriage,gestational week,delivery mode,birth weight and neonatal asphyxia of all pregnant women were collected,and the difference among the three groups was statistically significant(P < 0.05).3.Statistical methods The data are inputted and statistically analyzed by SPSS24.0 software.All measurement data in accordance with normal distribution are expressed by mean ±standard deviation(x ±s)and tested by LSD-t.Measurement data that do not conform to normal distribution are expressed by median(25th percentile,75 th percentile)[M(P25th P75)] and Wilcoxon rank sum test is used.The counting data rate(%)indicated that χ 2 test was used,t test was used for comparison between groups,Pearson correlation method was used to test the correlation between the two variables,and relative specificity,sensitivity and risk were used to test the predictive value of serum PAPP-A,PLGF and bilirubin levels in the early and second trimester of pregnancy for preeclampsia.The predictive value of serum PAPP-A,PLGF and bilirubin in the first and second trimester of pregnancy and the predictive value of combined test for PE were evaluated by receiver working characteristic curve(ROC)and Yoden index.Result1.Comparison of serum levels of PAPP-A,PLGF and bilirubin among the three groups at 11-20 weeks of gestation,the levels of serum PAPP-A,PLGF and total bilirubin in preeclampsia group were significantly lower than those in hypertensive disorder complicating pregnancy group and control group.The levels of serum direct bilirubin and indirect bilirubin in preeclampsia group were lower than those in pregnancy hypertension group and control group,and the difference was not statistically significant(p > 0.05).2.Comparison of serum levels of PAPP-A,PLGF and bilirubin among the three groups at 11-20 weeks of gestation,the levels of serum PAPP-A,PLGF and total bilirubin in preeclampsia group were significantly lower than those in hypertensive disorder complicating pregnancy group and control group.The levels of serum direct bilirubin and indirect bilirubin in preeclampsia group were lower than those in pregnancy hypertension group and control group,and the difference was not statistically significant(p > 0.05).3.The predictive value of single index of serum PAPP-A,PLGF and TB and combined detection of three items for preeclampsia from 11 to 20 weeks of gestation.The analysis of single index of serum PAPP-A,PLGF and TB has certain predictive value for preeclampsia,among which the area under ROC curve of PAPP-An is 0.826 and the best cut-off value is 36.540 ng/ml.The area under the ROC curve of PLGF is 0.924,the best cut-off value is 0.091 ng/ml;TB under the ROC curve is 0.901,and the best cut-off value is 7.520 μ mol/L;.The maximum area(AUC)under the ROC curve is 0.957,indicating that the predictive value of the combined detection of the above three indexes for preeclampsia is higher than that of any single index.4.The gestational age,natural delivery rate and birth weight of newborn in preeclampsia group were significantly lower than those in hypertension group and control group(p < 0.05).The incidence of cesarean section and neonatal asphyxia in preeclampsia group was significantly higher than that in hypertension group and control group(p < 0.05).There was no significant difference in vaginal delivery rate among the three groups(p > 0.05).Conclusions 1.In the early and second trimester of pregnancy,the serum levels of PAPP-A,PLGF and TB in pregnant women with preeclampsia were significantly lower than those in normal pregnant women.2.The detection of serum PAPP-A,PLGF and TB in the early and second trimester of pregnancy has a certain predictive value for the occurrence of preeclampsia,while the combined detection of the three indicators has the highest predictive efficiency.3.Early pregnancy to predict the risk of preeclampsia,as early as possible for high-risk pregnant women to develop effective intervention measures can improve the adverse pregnancy outcome. |