Screening Predictive Biomarkers For Hypertensive Disorders Complicating Pregnancy And Constructing Early Prediction Model For Late-onset Hypertensive Disorders Complicating Pregnancy

Background and ObjectiveHypertensive disorders complicating pregnancy is a specific disease during pregnancy.The pathogenic mechanism of hypertensive disorders complicating pregnancy is unclear.It is an important reason of maternal and fetal death.Hypertensive disorders complicating pregnancy has brought heavily mental and economic damage to the family and society.Domestic and foreign medical scientists are looking for markers to predict the hypertensive disorders complicating pregnancy,but clinicians have not yet widely accepted and widely used.Therefore,the purpose of this study is to screen individual or multiple early predictors based on our usual maternal serum markers and general clinical data without increasing the financial burden of pregnant women and being used by primary hospitals.In this study,we investigated and evaluated the effects of inhibin A(INHA),free estriol(u E3),alpha-fetoprotein(AFP),serum human chorionic gonadotropin(?-hCG)and serological parameters(blood rountine,liver unction,renal function,coagulation function,glycosylated hemoglobin,thyroid function)and maternal general clinical data,and screened meaningful maternal serum markers.Establishment of early prediction model of hypertensive disorders complicating pregnancy.Methods and resultsSection 1: Study on the changes of inhibin A and common maternal serum markers in hypertensive disorder complicating pregnancyMethods: This study is a retrospective case-control study.Subjects in the study were the pregnant women who visit the Third Affiliated Hospital of Third Military Medical University between August 2014 and December 2016.Including 160 cases of hypertensive disorders complicating pregnancy,the normal pregnant 78 cases.The serum samples were stored at-80?.The levels of serum INHA were measured by Chemiluminescence method.And we collected blood routine,liver function,renal function,FPG,Hb A1 c,coagulation function and thyroid function.Apply SPSS19.0 to make single-factor variance analysis for the some markers.Results: large plarelet ratio,plateletocrit,aspartate amino transferase,alanine aminotransferase,total bilrubin,direct bilrubin,lactic dehydrogenase,5'-nuleotidase,total bile acid,adenosine deaminase,prealbumin,urine creatinine,uric acid,cystatin C,?2-microglobulin,retinol blinding protein,activated partal thromboplastin time,thrombin time,thyroid stimulating hormone,glycosylated hemglobin,body mass index,systolic blood pressure,diastolic blood pressure and weight of hypertensive disorders complicating pregnancy and preeclampsia-eclampsia were higher than that of normal pregnant(P <0.05);Mean corpuscular volume,mean platelet volume,monocyte percentage,albumin,globulin,the international ratio,fibrinogen,prothrombin time,free thyroxine,gestational age of hypertensive disorders complicating pregnancy and preeclampsia-eclampsia were lower than that of normal pregnant(P<0.05).Compared with normal pregnant(1152.58 ± 310.59 pg / ml),the level of INHA were higher in hypertensive disorders complicating pregnancy(1371.06 ± 262.02pg/ml)and preeclampsia-eclampsia(1361.23 ± 253.75pg/ml)(P<0.05).Compared with normal pregnant(7.48 ± 4.37U/L),the leve of 5'-NT were higher in hypertensive disease complications(10.26 ± 9.69U/L)and preeclampsia-eclampsia(10.86 ± 10.27U/L)(P<0.01).Section 2: Constructing early prediction model for late-onset hypertensive disorders complicating pregnancyMethods: Subjects in the study were the pregnant women who visit the Third Affiliated Hospital of Third Military Medical University between August 2014 and December 2016.Review the number of pregnant women in the first part and the blood samples of the number of pregnant women in the first part,as follows: At 11-14 weeks of pregnancy,hypertensive disorders complicating pregnancy 87 Cases,the normal pregnant 55 cases;At 16-20 weeks of pregnancy,hypertensive disorders complicating pregnancy 28 cases,the normal pregnant 20 cases.At 24-28 weeks of pregnancy,hypertensive disorders complicating pregnancy 90 cases,the normal pregnant 67 cases.All serum samples were collected from 11-14 weeks of pregnancy and 16-20 weeks of pregnancy and were stored at-80 ?.INHA,uE3,AFP,?-h CG were measured by Chemiluminescence method.And we also collected blood routine,liver function,renal function,FPG,Hb A1 c,coagulation function and thyroid function.Apply SPSS19.0.to make single-factor variance analysis and Logistics to analysis for the markers.Results:1.The levels of serum AST in the hypertensive disorders complicating pregnancy(21.77 ± 7.88U/L)and in the preeclampsia group(21.98 ± 7.84U/L)were higher than that of the normal group(18.40 ± 4.93U/L)(P<0.05)at 11-14 weeks of pregnancy.The levels of serum CHE in the hypertensive disorders complicating pregnancy(6882.37 ± 1339.41U/L)and in the preeclampsia group(6840.21 ± 1302.51U/L)were significantly higher than that of the normal group(6212.84 ± 925.94U/L)(P<0.05).The level of serum 5'-NT in the hypertensive disorders complicating pregnancy(5.73 ± 2.82U/L)and in the preeclampsia group(6.03 ± 2.94U/L)was significantly higher than that of the normal group(P <0.05)3.77 ± 1.86 U/L)(P <0.01).Moreover,the level of serum AST,CHE and 5'-NT would be useful for early prediction for hypertensive disorders complicating pregnancy and preeclampsia.2.The levels of serum INHA in the hypertensive disorders complicating pregnancy(329.08 ± 88.03pg/ml)and in the preeclampsia(337.03 ± 101.26pg/ml)were higher than that of the normal group(232.74 ± 82.77pg/ml)(P<0.01)at 16-20 weeks of pregnancy.The level of basal DBP in the hypertensive disorders complicating pregnancy(73.80 ± 8.00 mm Hg)and in the preeclampsia group(74.17 ± 8.12 mm Hg)was significantly higher than that of the normal group(66.83 ± 8.25 mmHg)(P <0.01).The levels of basal BMI in the hypertensive disorders complicating pregnancy(23.41 ± 5.81Kg/m~2)and in the preeclampsia(23.72 ± 4.37Kg/m~2)were higher than that of the normal group(20.57 ± 2.73Kg/m~2)(P<0.05).3.The levels of FPG and basal SBP were obviously higher in the hypertensive disorders complicating pregnancy and in the preeclampsia than that of the normal group(P<0.01)at 24-28 weeks of pregnancy.4.The early prediction models for hypertensive disorders complicating pregnancy: At 11-14 weeks of pregnancy Y=0.512(AST)+ 0.510(5'-NT)+ 0.482(CHE)-3.667(the rate of accuracy 67.5%);At 16-20 weeks of pregnancy Y=1.162(INHA)-3.327(the rate of accracy 79.3%);At 24-28 weeks of pregnancy Y=0.443(FPG)+ 0.767(SBP)-2.7(the rate of accracy 71.2%).The early prediction models for preeclampsia: At 11-14 weeks of pregnancy Y=0.624×(5'-NT)-1.785(the rate of accuracy 63.5%);At 16-20 weeks of pregnancy Y=1.164(INHA)+ 1.804(DBP)+ 1.695(BMI)-12.967(the rate of accuracy 84.6%);At 24-28 weeks of pregnancy Y=0.375(FPG)+ 0.739(SBP)-2.676(the rate of accuracy 71.2%)?Conclusions:1.Systematic study of the general clinical data and clinical commonly used biomarkers(blood,liver function,renal function,coagulation,thyroid function,fasting plasma glucose,glycosylated hemoglobin)and inhibin A in pregnant women with hypertensive disorders complicating pregnancy.The levels of AST,ALT,TBI,LDH,5'-NT,AST,ALT,TBI,LDH,5'-NT,TBA,ADA,PA,ALB,GLB,CREA,URIC,CYC,?2-mG,RBP,APTT,TT,PT-INR,FIB,PT-1,TSH,FT4,HbA1 c and the basic systolic blood pressure,the base diastolic blood pressure,body weight,BMI,gestational age were statistic difference between the hypertensive disorders complicating pregnancy and the normal pregnant(P <0.05).2.We studied the changes of general clinical data and clinical biomarkers and Four Indexes of Down 's Screening in pregnant women with hypertensive disorder at weeks 11-14,16-20 and 24-28 weeks,the differences were statistically significant as follows: inhibin A,blood routine in the PLT,PCT,liver function in the AST,ALT,5'-NT,GGT,CHE,renal function in the URIC and FPG,pregnant women in general clinical data in the base systolic blood pressure,basal diastolic blood pressure and pre-pregnancy BMI.These biomarkers may have early predictive value for hypertensive disorders complicating pregnancy.3.Establishment of hypertensive disorders complicating pregnancy and preeclampsia early prediction models of different gestational age through Logistic regression analysis: At 11-14 weeks of pregnancy,the early prediction model for hypertensive disorders complicating pregnancy : Y = 0.512(AST)+ 0.510(5'-NT)+ 0.482(CHE)-3.667,the accuracy rate was 67.5%;early prediction model for preeclampsia : Y = 0.624(5'-NT)-1.785,the accuracy rate was 63.5%;At 16-20 weeks of pregnancy,the early prediction model for hypertensive disorders complicating pregnancy: Y = 1.164(INHA)-3.327,the accuracy rate was 79.3%.The early prediction model for preeclampsia: Y= 1.164(INHA)+ 1.804(DBP)+ 1.695(BMI)-12.967,and the accuracy rate was 84.6%;At 24-28 weeks of pregnancy,the early prediction model for hypertensive disorders complicating pregnancy: Y = 0.443(FPG)+ 0.767(SBP)-2.7,the accuracy rate was 71.2%;Early prediction model for preeclampsia: Y = 0.375(FPG)+ 0.739(SBP)-2.676,the accuracy rate was 71.2%.The early prediction model for preeclampsia at 16-20 weeks of pregnancy was the highest(84.6%).The early predictive model for preeclampsia will be validated by clinical work,is expected to become economic,effective and can be widely used in primary hospital.Aim to early detection,early prevention,early supervision,early treatment,and ultimat ely reduce the incidence and mortality of hypertensive disorders complicating pregnancy.