妊娠期高血压疾病预测指标的筛查及早期预测模型的构建

发布时间：2018-06-13 12:39

本文选题：妊娠期高血压疾病 + 子痫前期　；参考：《第三军医大学》2017年硕士论文

【摘要】：目的妊娠期高血压疾病是一种发病机制尚不明确的妊娠期特有疾病。它是引起妊娠期妇女及胎儿病死率高的重要原因之一,给家庭与社会带来精神伤害和经济损失。国内外医学者致力寻找能在早期预测妊娠期高血压疾病的指标,但是目前仍然没有一个公认的指标被临床工作者所接受及广泛使用。因此,本研究致力于在我们产前检查常用的血清学指标和孕妇一般临床资料中寻求单个或多个早期预测指标,既不增加孕妇的经济负担,又能运用于基层医院。我们通过研究孕妇妊娠早期及妊娠中期唐氏筛查四项[抑制素A(INHA)、游离雌三醇(u E3)、甲胎蛋白(AFP)、血清人绒毛膜促性腺激素(β-hCG)]和血清学指标[血常规、肝功、肾功、凝血象、甲功、空腹血糖(FPG)、糖化血红蛋白Hb A1c]以及孕妇一般临床资料,来评价这些指标在早期预测妊娠期高血压疾病发生中的意义,最终构建妊娠期高血压疾病早期预测模型。主要方法及结果第一部分:抑制素A与常用血清学指标在妊娠期高血压疾病中变化的研究方法:本研究为回顾性病例对照研究,已通过第三军医大学大坪医院野战外科研究所伦理委员会。研究对象为2014年8月-2016年12月来我院定期规律产检及分娩的所有孕妇。收集妊娠期高血压疾病160例,其中妊娠期高血压27例、子痫前期-子痫组133例(包括轻度子痫前期45例、重度子痫前期-子痫88例);正常对照组78例。采集孕妇分娩前7天内、产后48-72小时的静脉血留取血清于-80℃储存,应用化学发光法检测血清INHA水平。并收集孕妇分娩前实验室常规检验的血常规、肝功、肾功、FPG、HbA1c、凝血象及甲功的指标及孕妇一般临床资料。应用SPSS19.0对血常规、肝功、肾功、HbA1c、凝血象及甲功及一般临床资料指标行单因素方差分析。结果:与正常组比较,妊娠期高血压疾病组及子痫前期-子痫组血清学指标中大型血小板比率P-LCR、血小板平均比积(PCT)、天门冬酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆红素(TBIL)、直接胆红素(DBIL)、乳酸脱氢酶(LDH)、5'-核苷酸酶(5'-NT)、总胆汁酸(TBA)、腺苷脱氨酶(ADA)、前白蛋白(PA)、肌酐(CREA)、尿酸(URIC)、胱抑素C(CYC)、β_2-微球蛋白(β_2-mG)、视黄醇结合蛋白(RBP)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、促甲状腺素(TSH)、Hb A1c水平及孕妇一般临床资料SBP、DBP、体重、BMI均升高(P0.05或P0.01);红细胞平均体积(MCV)、血小板平均体积(MPV)、单核细胞百分数(MONO%)、白蛋白(ALB)、球蛋白(GLB)、国际标准比率(PT-INR)、纤维蛋白原(FIB)、凝血酶原时间(PT-1)、游离甲状腺素(FT4)水平在血清中下降且分娩孕周小(P0.05或P0.01)。妊娠期高血压疾病组的INHA水平(1347.06±262.02pg/ml)和子痫前期-子痫组的INHA水平(1361.23±253.75pg/ml)均高于正常组(1152.58±310.59pg/ml)且有统计学意义(P0.05)。第二部分:妊娠期高血压疾病早期预测模型的构建方法:本研究为回顾性病例对照研究,已通过第三军医大学大坪医院野战外科研究所伦理委员会。采集孕妇孕11-14周、孕16-20周的静脉血留取血清于-80℃储存,应用化学发光法检测唐氏筛查四项,并收集孕11-14周、孕16-20周、孕24-28周实验室常规检验的血常规、肝功、肾功、空腹血糖、糖化血红蛋白、凝血象及甲功的指标及孕妇一般临床资料。最终孕11-14周妊娠期高血压疾病87例[妊娠期高血压20例、子痫前期组67例(子痫0例)],正常对照组55例;孕16-20周妊娠期高血压疾病28例[妊娠期高血压3例、子痫前期组25例(子痫0例)],正常对照组20例;孕24-28周妊娠期高血压疾病90例[妊娠期高血压17例、子痫前期组73例(子痫0例)],正常对照组67例。应用SPSS19.0对血常规、肝功、肾功、FPG、HbA1c、凝血象及甲功血清学指标及孕妇一般临床资料行单因素方差分析。并结合Logistic回归方法评价血清学指标及孕妇一般临床资料对妊娠期高血压疾病的预测价值,构建妊娠期高血压疾病及子痫前期-子痫的早期预测模型。结果:1.孕11-14周妊娠期高血压疾病组血清AST水平(21.77±7.88U/L)和子痫前期组血清AST水平(21.98±7.84U/L)均较正常组血清AST水平(18.40±4.93U/L)升高且有统计学差异(P0.05)。妊娠期高血压疾病组血清胆碱酯酶(CHE)水平(6882.37±1339.41U/L)和子痫前期组的血清胆碱酯酶水平(6840.21±1302.51U/L)均较正常组的水平(6212.84±925.94U/L)升高且有统计学差异(P0.05);妊娠期高血压疾病组血清5'-NT水平(5.73±2.82U/L)和子痫前期组血清5'-NT水平(6.03±2.94U/L)均较正常组的水平(3.77±1.86 U/L)升高有统计学意义(P0.01)。而且5'-NT存在子痫前期早期预测价值,5'-NT、AST及CHE存在娠期高血压疾病早期预测价值。2.孕16-20周妊娠期高血压疾病组血清INHA水平(329.08±88.03pg/ml)和子痫前期组血清INHA水平(337.03±101.26pg/ml)均较正常组的水平(232.74±82.77pg/ml)升高(P0.01)。妊娠期高血压疾病组的基础舒张压(DBP(73.80±8.00mm Hg)和子痫前期组的基础舒张压(DBP)(74.17±8.12mm Hg)均较正常组的水平(66.83±8.25mm Hg)增高(P0.01)。妊娠期高血压疾病组的孕前BMI值(23.41±5.81Kg/m~2)和子痫前期组的孕前BMI值(23.72±4.37Kg/m~2)均较正常组的值(20.57±2.73Kg/m~2)增高(P0.05)。而且血清INHA、基础DBP及孕前BMI存在子痫前期早期预测价值,血清INHA存在娠期高血压疾病早期预测价值。3.孕24-28周妊娠期高血压疾病FPG水平(4.93±0.53umol/L)和子痫前期组FPG水平(4.95±0.55umol/L)较正常组水平(4.67±0.35umol/L)升高且均有统计学差异(P0.01)。妊娠期高血压疾病基础收缩压(SBP)水平(116.51±10.15mmHg)和子痫前期组基础收缩压水平(116.18±10.07mmHg)较正常组的值(106.18±11.95mmHg)升高且有统计学差异(P0.01),而且FPG结合基础SBP有妊娠期高血压疾病和子痫前期早期预测价值。4.经Logistics回归分析得到孕11-14周有妊娠期高血压疾病预测价值的指标是5'-NT、AST及CHE,有子痫前期预测价值的指标是5'-NT;最终构建妊娠期高血压疾病预测模型如下:Y=0.512(AST)+0.510(5'-NT)+0.482(CHE)-3.667,准确率67.5%;子痫前期预测模型:Y=0.624(5'-NT)-1.785,准确率63.5%。孕16-20周有妊娠期高血压疾病预测价值的指标是INHA,有子痫前期预测价值的指标是INHA、孕前BMI及基础DBP;最终构建妊娠期高血压疾病预测模型:Y=1.162(INHA)-3.327,准确率79.3%;子痫前期预测模型如下:Y=1.164(INHA)+1.804(基础DBP)+1.695(孕前BMI)-12.967,准确率84.6%。孕24-28周对妊娠期高血压疾病、子痫前期预测价值的指标均是FPG及基础SBP;最终构建妊娠期高血压疾病预测模型如下:Y=0.443(FPG)+0.767(基础SBP)-2.7,准确率71.2%;子痫前期预测模型:Y=0.375(FPG)+0.739(基础SBP)-2.676,准确率71.2%。结论1、系统地研究了孕妇一般临床资料和临床常用的血清学指标(血常规、肝功、肾功、凝血象、甲功、空腹血糖、糖化血红蛋白)及抑制素A在妊娠期高血压疾病孕妇血清中的变化;筛查出了差异有统计学意义的指标如下:INHA、血常规中P-LCR、PCT、MONO%、MPV,肝功中AST、ALT、TBI、LDH、5'-NT、TBA、ADA、PA、ALB、GLB,肾功中CREA、URIC、CYC、β2-m G、RBP,凝血象中APTT、TT、PT-INR、FIB、PT-1,甲功中TSH、FT4,HbA1c及孕妇一般临床资料中的基础收缩压SBP、基础舒张压DBP、体重、BMI、分娩孕周。2、系列序贯研究了孕11-14周、孕16-20周、孕24-28周孕妇一般临床资料和临床常用的血清学指标及唐氏筛查四项(抑制素A、血清人绒毛膜促性腺激素、游离雌三醇、甲胎蛋白)在妊娠期高血压疾病孕妇血清中的变化,筛查出了差异有统计学意义的指标如下:抑制素A、血常规中的PLT、PCT,肝功中AST、ALT、5'-NT、GGT、CHE,肾功中的URIC,FPG以及孕妇一般临床资料中的基础收缩压、基础舒张压、孕前BMI。这些指标可能对妊娠期高血压疾病有早期预测价值。3、通过Logistic回归分析建立了不同孕周的妊娠期高血压疾病及子痫前期的早期预测模型:孕11-14周妊娠期高血压疾病早期预测模型:Y=0.512(AST)+0.510(5'-NT)+0.482(CHE)-3.667,准确率67.5%;子痫前期早期预测模型:Y=0.624(5'-NT)-1.785,准确率分别为63.5%;孕16-20周妊娠期高血压疾病早期预测模型:Y=1.162(INHA)-3.327,准确率为79.3%;子痫前期早期预测模型:Y=1.164(INHA)+1.804(基础DBP)+1.695(孕前BMI)-12.967,准确率为84.6%;孕24-28周妊娠期高血压疾病早期预测模型:Y=0.443(FPG)+0.767(基础SBP)-2.7,子痫前期早期预测模型:Y=0.375(FPG)+0.739(基础SBP)-2.676,准确率均为71.2%。其中孕16-20周血清抑制素A、基础DBP、孕前BMI联合预测模型准确率最高(84.6%),该早期预测模型将应用于临床进一步验证,有望成为一种经济、有效、可广泛应用于基层医院的子痫前期早期预测方法,以达到早发现、早预防、早监管、早治疗,最终降低妊娠期高血压疾病在孕产妇中发病率和死亡率的目的。
[Abstract]:Objective pregnancy induced hypertension (gestation) is an unambiguous pregnancy specific disease. It is one of the important causes of high mortality in pregnant women and fetus. It brings mental and economic damage to family and society. There is still no recognized indicator accepted and widely used by clinical workers. Therefore, this study seeks to seek individual or multiple early predictors in the common serological indicators and general clinical data of pregnant women for prenatal examination. It does not increase the economic burden of pregnant women, but also can be used in grass-roots hospitals. To evaluate four items [inhibin A (INHA), free female three alcohol (U E3), alpha fetoprotein (AFP), serum human chorionic gonadotropin (beta -hCG)] and serological indexes [blood routine, liver function, renal function, renal function, thyroid function, FPG, FPG), glycosylated hemoglobin Hb A1c], and general clinical data of pregnant women, were evaluated. The significance of these indicators in the early prediction of pregnancy induced hypertension and the construction of an early prediction model of pregnancy induced hypertension. Main methods and results: the study method of inhibin A and common serological indexes in pregnancy induced hypertension: This study was a retrospective case control study, which had passed through The ethics committee of the Department of field surgery research, Daping Hospital of the Third Army Medical University, was studied in all pregnant women of regular regular production and childbirth in our hospital in December -2016 August 2014. 160 cases of pregnancy induced hypertension were collected, including 27 cases of pregnancy induced hypertension and 133 cases of preeclampsia - eclampsia (45 cases of mild preeclampsia, severe preeclampsia) 88 cases of eclampsia, 78 cases of normal control group, were collected in 7 days before childbirth and 48-72 hours after delivery, the serum was stored at -80 C, and the serum INHA level was detected by chemiluminescence. The blood routine test, liver function, kidney work, FPG, HbA1c, coagulation hematogram and thyroid function and general clinical capital of pregnant women before delivery were collected. Material. Single factor variance analysis was performed on blood routine, liver function, renal function, HbA1c, hemogram and thyroid function and general clinical data. Results: compared with the normal group, the large platelet ratio in the pregnancy induced hypertension group and the preeclampsia and eclampsia group was P-LCR, the average platelet ratio (PCT), and aspartate aminotransferase (SPSS19.0). AST) alanine aminotransferase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL), lactate dehydrogenase (LDH), 5'- nucleotidase (5'-NT), total bile acid (TBA), adenosine deaminase (ADA), prealbumin (PA), creatinine (CREA), uric acid (URIC), cystatin, retinol binding protein, retinol binding protein, activated partial thromboplastin APTT, thrombin time (TT), thyrotropin (TSH), Hb A1c level and general clinical data of pregnant women, SBP, DBP, weight, BMI (P0.05 or P0.01); average volume of red blood cells (MCV), average volume of platelets (MPV), percentage of mononuclear cells, albumin, globulin, international standard ratio, fibrinogen, coagulation The level of plasma protin (PT-1) and free thyroxine (FT4) decreased in serum and was small (P0.05 or P0.01). The level of INHA (1347.06 + 262.02pg/ml) and the INHA level (1361.23 + 253.75pg/ml) in the group of preeclampsia and eclampsia (1361.23 + 253.75pg/ml) were higher than those of the normal group (1152.58 + 310.59pg/ml) and were statistically significant (P0.05). The two part: the construction method of the early prediction model of pregnancy induced hypertension: This study is a retrospective case control study, which has passed the ethics committee of the Department of field surgery research in Daping Hospital of Third Military Medical University. To collect pregnant women for 11-14 weeks and 16-20 weeks of pregnancy, the blood serum was stored at -80 C, and down screening was detected by chemiluminescence. Four items, including 11-14 weeks of pregnancy, 16-20 weeks of pregnancy, 24-28 weeks of pregnancy, routine laboratory test, liver function, renal function, fasting blood glucose, glycosylated hemoglobin, hemogram and thyroid function and general clinical data of pregnant women. 87 cases of pregnancy induced hypertension in 11-14 weeks of pregnancy [20 cases of pregnancy hypertension, 67 cases of preeclampsia (0 cases)] were normal. There were 55 cases in the control group; 28 cases of pregnancy induced hypertension (3 cases of pregnancy hypertension, 25 cases of preeclampsia group (0 cases of eclampsia)], 20 cases of normal control group, 90 pregnant 24-28 weeks pregnancy hypertension disease [17 cases of pregnancy hypertension, 73 cases of preeclampsia (eclampsia 0 cases)], 28 cases in normal control group. The application of SPSS19.0 to blood routine, liver work, renal work, FPG, HbA1c, a single factor variance analysis of the hemogram and the serological indexes of the thyroid function and the general clinical data of pregnant women. Combined with the Logistic regression method, the predictive value of the serological index and the general clinical data of pregnant women on hypertensive disorders in pregnancy was evaluated, and the early prediction model of pregnancy induced hypertension and preeclampsia and eclampsia was constructed. Results: 1. pregnancy 11 Serum levels of AST (21.77 + 7.88U/L) and serum AST level (21.98 + 7.84U/L) in the group of -14 weeks pregnancy induced hypertension were higher than those of normal group (18.40 + 4.93U/L) and there were statistically significant differences (P0.05). Serum cholinesterase (CHE) level (6882.37 + 1339.41U/L) and serum of preeclampsia group in the group of hypertensive patients with pregnancy The level of cholinesterase (6840.21 + 1302.51U/L) was higher than that of the normal group (6212.84 + 925.94U/L) and had statistical difference (P0.05). The serum level of 5'-NT (5.73 + 2.82U/L) and the serum 5'-NT level (6.03 + 2.94U/L) in the preeclampsia group were significantly higher than those of the normal group (3.77 + 1.86 U/L) (P0.01). And 5'-NT had early predictive value for preeclampsia, 5'-NT, AST and CHE had early predictive value for hypertensive disease in pregnancy. The serum INHA level (329.08 + 88.03pg/ml) and serum INHA level (337.03 + 101.26pg/ml) in the group of pregnancy induced hypertension in 16-20 weeks and preeclampsia group were higher than those of normal group (232.74 + 82.77pg/ml) (P0.01). Basic diastolic pressure (DBP (73.80 + 8.00mm Hg) and basic diastolic pressure (DBP) (74.17 + 8.12mm Hg) in preeclampsia group were higher than that of normal group (66.83 + 8.25mm Hg) (P0.01). The pre pregnancy BMI value (23.41 + 5.81Kg/m~2) and pre pregnancy BMI value (23.72 +)) of preeclampsia group were all (23.72 +). The value of (20.57 + 2.73Kg/m~2) was higher than that of the normal group (P0.05). Moreover, serum INHA, basal DBP and pre pregnancy BMI had early predictive value for preeclampsia, serum INHA had early predictive value for hypertensive disease of pregnancy, FPG level of.3. pregnancy (4.93 + 0.53umol/L) and FPG level (4.95 + 0.55umol/L) in pre eclampsia group (4.95 + 0.55umol/L) were more positive. The level of normal group (4.67 + 0.35umol/L) increased and had statistical difference (P0.01). The level of basal systolic pressure (SBP) of pregnancy induced hypertension (116.51 + 10.15mmHg) and basic systolic pressure in preeclampsia group (116.18 + 10.07mmHg) were higher than those of normal group (106.18 + 11.95mmHg) and had statistical difference (P0.01), and FPG combined basis SBP had pregnancy induced pregnancy. The predictive value of hypertensive disease and preeclampsia at the early stage of pregnancy.4. was analyzed by Logistics regression analysis to predict the value of pregnancy induced hypertension by 11-14 weeks of pregnancy, 5'-NT, AST and CHE, and the index of preeclampsia predictive value was 5'-NT; the final pretest model for pregnancy induced hypertension was as follows: Y=0.512 (AST) +0.510 (5'-NT) +0.482 (CH) E) -3.667, accuracy rate 67.5%; preeclampsia prediction model: Y=0.624 (5'-NT) -1.785, accurate rate of 63.5%. pregnancy for pregnancy induced hypertension, the predictive value of pregnancy is INHA. The index of predictive value for preeclampsia is INHA, pre pregnancy BMI and basic DBP; finally, the prediction model of hypertensive disorder in pregnancy: Y=1.162 (INHA), accuracy rate 79. 3%, the preeclampsia prediction model is as follows: Y=1.164 (INHA) +1.804 (base DBP) +1.695 (pre pregnancy BMI) -12.967, accurate rate of 24-28 weeks of pregnancy with pregnancy induced hypertension, the predictive value of preeclampsia are all FPG and basic SBP; finally, the prediction model for pregnancy induced hypertension is as follows: Y=0.443 (FPG), accuracy rate 71. 2%; preeclampsia prediction model: Y=0.375 (FPG) +0.739 (base SBP) -2.676, accurate rate 71.2%. conclusion 1, systematically study the changes of pregnant women's general clinical data and clinical common serological indexes (blood routine, liver function, kidney work, hemogram, thyroid function, fasting blood glucose, glycated hemoglobin) and inhibin A in pregnant women with hypertension. INHA, P-LCR, PCT, MONO%, MPV, AST, ALT, TBI, LDH, 5'-NT, TBA, ALT, 5'-NT, TBA. DBP, weight, BMI, and birth week.2. A series of sequential studies were carried out in the series of 11-14 weeks of pregnancy, 16-20 weeks of pregnancy, and 24-28 weeks of pregnant women's general clinical data and clinical routine serological indexes and four down screening (inhibin A, serum human chorionic gonadotropin, free female three alcohol, alpha fetoprotein) in pregnant women with hypertensive disorder complicating pregnancy. The results are as follows: inhibin A, PLT in blood routine, PCT, AST, ALT, 5'-NT, GGT, CHE, URIC, FPG, and basic systolic blood pressure in general clinical data of pregnant women, basic diastolic pressure, and pre pregnancy BMI., which can have an early predictive value for pregnancy induced hypertension. Regression analysis established an early prediction model of pregnancy induced hypertension and preeclampsia: early prediction model of pregnancy induced hypertension at 11-14 weeks of pregnancy: Y=0.512 (AST) +0.510 (5'-NT) +0.482 (CHE) -3.667, accuracy rate 67.5%; early preeclampsia prediction model: Y=0.624 (5'-NT) -1.785, 63.5%, respectively; pregnancy 16-20 weeks of pregnancy. Early prediction model of hypertensive disease of pregnancy: Y=1.162 (INHA) -3.327, accuracy rate 79.3%; early preeclampsia prediction model: Y=1.164 (INHA) +1.804 (basal DBP) +1.695 (pre pregnancy BMI) -12.967, accuracy rate 84.6%; early pregnancy model of pregnancy induced hypertension disease: Y=0.443 (FPG), early prediction model for preeclampsia Type: Y=0.375 (FPG) +0.739 (base SBP) -2.676, the accuracy rate is 71.2%. 16-20 weeks serum inhibin A, basic DBP, pre pregnancy BMI joint prediction model is the highest (84.6%), the early prediction model will be applied to clinical further validation, it is expected to be a kind of economic, effective, and can be widely used in primary pre eclampsia prediction in grass-roots hospitals. Methods: to achieve early detection, early prevention, early supervision, early treatment, and ultimately reduce the incidence and mortality of hypertensive disorder complicating pregnancy in pregnant women.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R714.246

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