【作者】 张美云；

【导师】 金银龙；

【作者基本信息】 中国疾病预防控制中心 ， 劳动卫生与环境卫生学， 2008， 博士

【摘要】 研究背景无论是在发展中国家还是发达国家,早产是导致围生儿发病和死亡的重要原因之一,同时也是导致婴幼儿发生诸如生长发育迟缓、视力损害、听力障碍、慢性肺部疾病、脑瘫以及运动功能受限等并发症和后遗症的重要因素,以及可能与成年后的高血压、冠心病、Ⅱ型糖尿病等密切相关,并由此对个人的身心健康产生长远影响,给社会和家庭造成巨大的经济负担。近二十年来世界各国采用了各种预防不良妊娠结局的措施,但效果并不十分明显,一些国家早产的发生率没有下降反而有上升趋势。早产的发生率随地域、种族和国家等的不同而存在差异,有数据显示早产占分娩总数的5%-15%,美国和加拿大近年早产的发生率呈上升趋势,我国的早产发生率尚缺乏全国统一研究资料,估计约为10%左右。因此,深入探究早产的病因,降低早产发生率仍是摆在人们面前的一个严峻的课题。早产问题引起了国内外学者的广泛关注,也开展了一系列有关早产危险因素的流行病学研究,但是多数研究集中在一个或几个因素上,如临床因素、营养、心理和社会经济等方面。随着社会经济的发展,人们生存环境的不断变化,以及环境因素的复杂性,人们应该在更大的范围内探讨环境危险因素对早产的影响。除环境因素和社会经济状况的影响外,遗传因素也可能是早产的一个重要的影响因素。研究发现,早产在黑种人中有显著的家庭聚集性;有早产史的母亲再次分娩早产儿的概率增大,这提示早产的发生受到遗传因素的影响。有关早产的遗传因素的研究较少;有关环境因素和遗传易感性交互作用对早产的影响研究则更少。本研究从多因素的角度出发,研究早产的环境危险因素(突出了目前生活环境暴露情况)和代谢酶基因遗传易感性,同时探讨环境化学污染物内暴露量与早产的关系。为预防和减少不良妊娠结局的发生提供科学依据,对降低婴儿死亡率,提高人口素质具有重要的现实意义。研究目的1、探讨早产的环境危险因素;2、探讨环境化学污染物的生物内暴露量与早产的关系;3、探讨新生儿及其母亲的毒物代谢酶基因的多态性对早产的影响,筛选早产的遗传危险因素,同时了解在早产发生中基因与基因、环境与基因的交互作用。研究方法1、应用流行病学的方法研究早产的环境危险因素采用1:2匹配的病例对照研究,选择太原市现患早产病例和对照进行环境危险因素的流行病学调查。同时利用条件Logistic回归模型筛选坏境危险因素。2、应用分析化学的方法检测生物样品中的化学污染物的含量采用酶水解—高效液相色谱法(HPLC)测定病例和对照组母亲尿样中1-OH-Py的含量;采用全自动生化仪测定尿肌酐;采用电感耦合等离子体质谱法(ICP-MS)测定病例和对照组母亲静脉血和新生儿脐带血中重金属Pb及微量元素的含量。3、应用分子流行病学的方法研究代谢酶基因多态性应用多重PCR法检测母亲和新生儿GSTM1、GSTT1基因多态性;采用限制性内切酶PCR(RFLP-PCR)技术检测CYP1A1基因MspI位点多态性和CYP2E1基因Rsa I位点多态性。应用条件Logistic回归模型分析基因多态性,筛选遗传危险因素。研究结果第一部分早产的环境危险因素1:2病例对照研究1、单因素的条件Logistic回归模型分析结果1.1新生儿父母亲一般情况:早产的可能环境危险因素:母亲职业为农民(OR=4.176,95%CI 1.920-9.082)或母亲职业为无业者(OR=1.447,95%CI 1.006-2.081)以及父亲的职业为农民(OR=10.851,95%CI3.674-32.058),父亲身高低(OR=1.137,95%CI1.016-1.708),母亲孕期体重增加少(OR=1.771,95%CI 1.282-2.445)。母亲及父亲文化程度高是早产的保护因素,OR分别为0.731(95%CI0.621-0.860),0.692(95%CI 0.591-0.811)。而母亲身高、体重、体质指数及父亲体重和体质指数均与早产未见关联。1.2家庭经济收入高是早产的保护因素(OR=0.750,95%CI 0.649-0.867);产前检查次数少是早产的危险因素(OR=3.362,95%CI 2.238-5.051)。1.3新生儿母亲孕期生活居住环境暴露与早产结果显示早产的危险因素有:常驻地在农村和工矿区发生早产的危险较大,OR值分别为2.447(95%CI 1.587-3.773)和4.368(95%CI 1.166-16.365);做饭时油烟多(OR=1.656,95%CI 1.275-2.150);家中使用烟煤燃料(OR=3.447,95%CI 1.956-6.074);家中使用燃煤取暖(OR=2.664,95%CI 1.764-4.022)家中使用井水或简易自来水(OR=1.608,95%CI 1.173-2.205);怀孕期间装修(OR=2.213,95%CI 1.035-4.734)。使用排油烟设备是早产的保护因素(OR=0.519,95%CI 0.364-0.740)。生活中接触微波炉和电磁炉,以及使用手机、孕期饲养宠物和孕期染烫发等未见与早产有关联(P＞0.05)。1.4新生儿父母亲吸烟饮酒情况:早产的可能危险因素有:母亲孕期被动吸烟(OR=1.237,95%CI 1.030-1.485),父亲吸烟(OR=1.170,95%CI 1.016-1.135);1.5新生儿母亲孕期营养与饮食习惯与早产的关系:孕期经常食用肉类食物(OR=0.729,95%CI 0.561-0.949)、孕前和孕期服用叶酸制剂(OR=0.681,95%CI0.521-0.892)是早产的保护因素;而孕期补充其他维生素以及经常食用蔬菜水果、蛋奶等未见与早产有关联。1.6新生儿母亲其他情况:孕期胎教(OR=0.667,95%CI 0.499-0.891)是早产的保护因素,孕期心理因素和家族出生史等仍待进一步的探讨。2、多因素的条件Logistic回归模型分析结果在控制了其他混杂因素后,家庭使用非清洁燃料(OR=2.083,95%CI1.126-3.855)、产前检查次数少(OR=2.581,95%CI 1.710-3.897)可能是早产的主要危险因素;家庭经济收入高(OR=0.831,95%CI 0.701-0.986)和母亲无早产史(OR=0.107,95%CI 0.013-0.911)是早产的保护因素。第二部分环境化学污染物的生物内暴露量与早产的关系1、新生儿母亲尿样1-OH-Py的含量与早产的关系早产组母亲尿样的1-OH-Py含量(中位数)为1.0521μmol/mol肌酐,对照组产妇尿样的1-OH-Py含量(中位数)为0.7792μmol/mol肌酐;配对病例和对照组母亲尿样1-OH-Py含量的值经对数转换后,然后应用配对t-检验进行分析,t=1.982,P=0.051,按照a=0.05的水平,两组1-OH-Py含量是否存在统计学差异,还不能下结论,有待进一步扩大样本量进行研究。2、病例和对照组母亲静脉血中元素的含量病例与对照组母亲静脉血铅含量在统计学上没有显著性差异(Z=-0.144,P=0.886);病例与对照组母亲静脉血铬含量在统计学上存在显著性差异,对照组血铬含量高于病例组(Z=-2.462,P=0.014);病例与对照组母亲静脉血铜含量在统计学上存在显著性差异(Z=-2.247,P=0.025),对照组母亲血铜含量高于病例组。3、病例和对照组新生儿脐带血元素含量病例与对照组新生儿脐带血铅含量在统计学上没有显著性差异(Z=-0.309,P=0.757);病例与对照组新生儿脐带血血铬含量在统计学上没有显著性差异(Z=-1.634,P=0.102);病例与对照组新生儿脐带血铜含量在统计学上存在显著性差异(Z=-2.993,P=0.003),对照组新生儿脐带血铜含量高于病例组。第三部分母亲与新生儿代谢酶基因多态性与早产的关系1、母亲代谢酶基因多态性与早产关系的单因素条件Logistic分析GSTT1缺失基因型与早产有关,携带GSTT1缺失基因型的个体发生早产的危险性大,OR=1.704(95%CI为1.059-2.740);CYP1A1突变基因型与早产有关,携带CYP1A1突变基因型(突变杂合和突变纯合)的个体发生早产的危险性大,OR值分别为2.259(95%CI 1.229-4.152),2.384(95%CI 1.083-5.250):GSTM1和CYP2E1基因Rsa I位点多态性与早产未见关联(P＞0.05)。2、母亲GSTM1、GSTT1、CYP2E1和CYP1A1的不同基因型联合作用GSTM1和CYP1A1联合基因型与早产有关联(P＜0.05),同时携带GSTM1非缺失型和CYP1A1杂合突变基因型的个体较同时携带GSTM1非缺失型和CYP1A1野生基因型的个体发生早产的危险性增加。GSTT1和CYP1A1联合基因型与早产有关联(P＜0.05),同时携带GSTT1非缺失型和CYP1A1突变基因型以及同时携带GSTT1缺失型和CYP1A1野生型或突变型基因的个体,较同时携带GSTT1非缺失型和CYP1A1野生型基因的个体发生早产的危险性显著增加。3、母亲不同基因多态性的多因素条件Logistic回归分析结果在控制了其他混杂因素的影响,GSTT1和CYP1A1基因多态性与早产的发生有关联(P＜0.05),其OR值分别为1.700(95%CI 1.042-2.772)、2.250(95%CI1.215-4.169)和2.391(95%CI 1.066-5.367)。4、新生儿代谢酶基因多态性与早产关系的单因素条件Logistic回归分析新生儿GSTT1基因与早产有关联(P＜0.05),携带GSTT1缺失基因型的个体发生早产的危险性大,OR=1.818(95%CI 1.081-3.059);CYP1A1突变基因型与早产可能有关联(P=0.0658),按a=0.05水平,有待进一步研究;GSTM1和CYP2E1基因多态性与早产未见关联(P＞0.05)。5、新生儿GSTM1、GSTT1、CYP2E1和CYP1A1的不同基因型联合作用与早产关系新生儿GSTM1和CYP1A1联合基因型与早产有关联(P＜0.05),携带GSTM1非缺失型和CYP1A1突变基因型以及同时携带GSTM1缺失型和CYP1A1杂合基因型的个体较同时携带GSTM1缺失型和CYP1A1野生型的个体发生早产的危险性显著增加。GSTT1和CYP1A1联合基因型与早产有关联(P＜0.05),同时携带GSTT1缺失型和CYP1A1突变基因型的个体,较同时携带GSTT1非缺失型和CYP1A1野生基因型的个体发生早产的危险性显著增加。6、新生儿不同基因的多态性的多因素条件Logistic回归分析在控制了其他混杂因素的影响,新生儿GSTT1基因多态性与早产的发生有关联(P＜0.05),其OR值分别为1.755(95%CI 1.040-2.962);新生儿CYP1A1突变纯合基因型与早产可能有关联(P=0.0566),按a=0.05水平,有待进一步的深入研究。7、环境危险因素和母亲代谢酶基因多态性与早产关系的多因素分析在控制了其他混杂因素的影响,与发生早产有关的环境危险因素为家用燃料(OR=4.758,95%CI 1.859-2.178),是否使用排油烟设备(OR=0.368,95%CI0.147-0.920);与发生早产有关的遗传因素为CYP1A1基因,其中携带CYP1A1突变杂合基因型个体较携带CYP1A1野生纯合基因型个体发生早产的危险性大,其OR值为2.433,95%CI为1.170-5.058。8、环境危险因素与母亲代谢酶基因的交互作用对早产的影响家用燃料与母亲CYP1A1基因多态性存在交互作用,在家中使用非清洁燃料,且母亲携带CYP1A1 MspI一个或两个突变等位基因,即突变杂合或突变纯合基因型时,能够增加发生早产的危险性(携带突变杂合基因型:OR=14.467,95%CI为3.618-57.852;携带突变纯合基因型:OR=26.708,95%CI为2.804-254.430)。进一步应用相乘模型做两因素的交互作用检验,发现两因素之间存在显著的交互作用(P＜0.01)。研究结论1、与早产有关的主要环境危险因素:在控制了其他混杂因素的影响,家庭使用非清洁燃料、产前检查次数少可能是早产的主要危险因素;家庭经济收入高和母亲无早产史是早产的保护因素。2、母亲及父亲职业与文化程度、烹调油烟,使用抽油烟设备、家庭取暖方式、孕期装修、被动吸烟、父亲吸烟、孕前期是否服用叶酸制剂、孕期是否进行胎教、孕期经常食用肉类食物、孕期体重增加少等可能与早产有关。3、早产组母亲尿中1-羟基芘含量稍高于对照组,虽然按a=0.05水平,在统计学上暂不能下定论,但是太原产妇尿中1-羟基芘含量偏高,这说明太原市产妇暴露较高的多环芳烃;这可能与太原市一直以来空气污染严重有关系,提示关注空气污染对妊娠结局的影响。4、母亲静脉血铅含量和新生儿脐带血铅含量在病例组和对照组中均没有统计学上的显著性差异,但是总体血铅含量偏高,可能与环境铅污染有关。另外,母亲和新生儿病例组血铜含量低于对照组,这提示关注孕产妇微量元素缺乏,可能对于预防不良妊娠结局有意义。有关这方面的研究有待进一步的深入。5、在控制了其他的混杂因素影响,母亲以及新生儿的GSTT1不同基因型与早产的发生有关联;携带GSTT1缺失基因型的个体较携带非缺失基因型的个体发生早产危险性增加;母亲CYP1A1 MspI位点基因多态性与早产的发生有关联,携带CYP1A1一个或两个突变(突变杂合和突变纯合)基因型的个体较携带野生纯合基因型的个体,发生早产的危险性增加。这提示我们关注孕产妇的个体差异,预防早产的发生。6、母亲GSTT1和CYP1A1联合基因型与早产有关联;新生儿GSTT1和CYP1A1联合基因型与早产也有关联。同时携带GSTT1缺失型和CYP1A1突变基因型的个体较同时携带GSTT1非缺失型和CYP1A1野生基因型的个体,发生早产的危险性显著增加;他们的联合基因型有增加早产的危险性作用。7、在控制其他环境与基因混杂因素后,发现家庭使用燃煤燃料是早产的危险因素,使用排油烟设备是早产的保护因素;母亲携带CYP1A1 MspI突变杂合基因型是早产的危险因素。8、环境与基因之间对早产的影响存在交互作用,家中使用非清洁燃料与母亲携带CYP1A1 MspI一个或两个突变基因型之间存在交互作用,它们的联合作用增加了发生早产的危险性。更多还原

【Abstract】 Background:Whether in developing or developed counties,preterm birth is still one of the important reasons that cause perinatal infants’ morbidity and mortality,also leads to children complications and sequelaes,such as growth retardation,visual impairment, hearing impairment,chronic lung disease,cerebral palsy and movement dysfunction etc.,as well as cause hypertension,coronary heart disease,Ⅱdiabetes etc.after they grow up.Thus preterm birth has a profound impact on individual’s physical and mental health and causes huge financial burden on social and family.In recent 20 years,prevention measures used by the various adverse pregnancy outcomes are not very effective.The incidence of preterm birth has not declined but in some countries there is an upward trend.The incidences of preterm birth are different with different areas,ethnic and nationality.The data show that the incidence rate of preterm birth is 5%-15%,while the incidences of preterm of the United States and Canada in recent years are upward trend.China’s incidence rate of preterm birth is still a lack of unified national research datum,and about 10 percent.Therefore,it is still an significant subject to further explore causes of preterm birth and reduce its incidence.The problem of preterm birth has aroused extensive attention of scholars at home and abroad and epidemiological studies on risk factors for preterm birth have also been carried out,but mainly concentrated in one or several factors,such as clinical factors,nutrition,psychological and socio-economic aspects.However,with the constant deterioration of the people’s living environment and the complexity of environmental factors,people should study in a larger range of environmental risk factors impact on preterm birth.In addition to environmental factors and the impact of socio-economic conditions, genetic factors may also be an important factor on preterm birth.The studies found that preterm birth of black people are significantly families gathered;a mother who has a history of preterm birth increased the probability of having preterm infants again, which suggested that the occurence of preterm birth is affected by genetic factors. Now,the researches on genetic factors related to preterm birth are less and more less on environmental pollution and genetic susceptibility of preterm birth.From the perspective of multifactor,this study explored the effects of environmental risk factors,which highlights the life of the current environmental exposure,the metabolism enzyme of genetic susceptibility factors and internal exposure content of chemical pollutants in the environment on preterm birth,to provide a scientific references for preventing and reducing the occurrence of adverse pregnancy outcomes and infant mortality.Objectives:1.To explore the environmental risk factors of preterm birth in Taiyuan City;2.To explore the relationship between internal exposure content of chemical pollutants and preterm birth;3.To explore the impact of the neonatal infants and their mothers toxic metabolic enzymes gene polymorphism on preterm birth,while understanding the interaction of gene-gene and gene-environment in preterm birth.Methods:1.To survey the environmental risk factors on preterm birth by epidemiological investigation. Using a 1:2 match case-control method to choose preterm birth cases and the control,a epidemiological investigation were carried out about environmental risk factors of preterm birth.At the same time using Logistic regression model to screen environmental risk factors.2.To detect the content of chemical pollutants in biological samples by method of chemical analysis.Using enzyme hydrolysis -High Performance Liquid Chromatography(HPLC) to detect the content of 1-OH-Py in mothers’ urine in cases and the control groups; Using automatic biochemical analyzer to detect urine creatinine;Using Inductively Coupled Plasma Mass Spectrometry(ICP-MS) to detect the heavy metals and trace element in mothers’ vein blood and neonate umbilical cord blood in cases and the control groups.3.To detect metabolic enzyme gene polymorphism by the method of molecular epidemiology.Using Multiplex PCR to detect GSTM1,GSTT1 gene polymorphism;Using RFLP-PCR to detect MspI polymorphism on CYP1A1 gene and RsaI polymorphism on CYP2E1 gene.Using logistic regression model to analyses genetic polymorphism and screen genetic risk factors.Results:The partⅠ:A 1:2 matched case-control study on environmental risk factors for preterm birth1.The results of singie-factor logistic regression model analysis.1.1 General situation of neonates’ parents:Possible risk factors of Preterm birth:The mother’s occupation that is farmer (OR=4.176,95%CI 1.920-9.082) or the mother who is unemployed(OR=1.447,95% CI 1.006-2.081) or the father’s occupation that is farmer(OR=10.851,95%CI 3.674-32.058);The father’s height(OR=1.137,95%CI 1.016-1.708);Less weight gain during pregnancy(OR=1.771,95%CI for 1.282-2.445).High education level of mother and father is a protective factor for preterm birth, which OR are 0.731(95%CI 0.621-0.860) and 0.692(95%CI 0.591-0.811) separately.The mother’s height,weight,BMI and father’s weight,BMI has no obvious relationship with preterm birth.1.2 High household income is a protective factor for preterm birth(OR=0.750, 95%CI 0.649-0.867);Times of less prenatal examination is a risk factor of preterm birth(OR=3.362,95%CI 2.238-5.051).1.3 The relationship between living environment exposure of pregnant women and preterm birth.The risk factors are:Permanent living places in factories and mines and in rural areas,OR are 2.447(95%CI 1.587-3.773) and 4.368(95%CI 1.166-16.365) separately,volume of fumes from cooking(OR=1.656,95%CI 1.275-2.150);the use of coal fuel in home(OR=3.447,95%CI 1.956-6.074),the ways of getting warm in home(OR=2.664,95%CI 1.764-4.022,the use of well water or simple tap water (OR=1.608,95%CI 1.173-2.205),decoration during pregnancy(OR=2.213,95%CI 1.035-4.734).Use of exhaust equipment is a preterm birth protective factor(OR=0.519,95% CI 0.364-0.740).There is not obvious relationship between use of microwave ovens, induction cooker,mobile phones,keeping of pets during pregnancy,dyeing hair during pregnancy and preterm birth.1.4 Passive smoking of pregnant mothers(OR=1.237,95%CI 1.030-1.485)and smoking fathers(OR=1.170,95%CI 1.016-1.135) are possible risk factors for preterm birth.1.5 Eating habits and nutrition during pregnancy.Regular consumption of meat food during pregnancy(OR=0.729,95%CI 0.561-0.949),taking folic acid before and during pregnancy(OR=0.681,95%CI 0.521-0.892) are protective factors of preterm birth;Regular consumption of supplementary vitamins,fruits,vegetables,eggs and milk during pregnancy is not associated with preterm birth obviously.1.6 Fetus education(OR=0.667,95%CI 0.499-0.891) is a protective factor of preterm birth.The relationship between pregnant women’s psychological factors and family history of birth with preterm birth still remain to be further explored.2.The results of multi-factors Logistic regression model analysis.After adjusted other bias factors,using of unclean fuels(OR=2.083,95%CI 1.126-3.855),less times of prenatal examination(OR=2.581,95%CI 1.710-3.897) may be the main risk factors for preterm birth;High family incomes(OR=0.831, 95%CI 0.701-0.986) and no the history of prematurity(OR=0.107,95%CI 0.013-0.911) are protective factors of preterm birth.The partⅡ:The relationship between the content of internal exposure of the environmental chemical pollutants and preterm birth1.The relationship between the content of 1-OH-Py in mothers’ urine and preterm birth.The content of 1-OH-Py in mothers urine samples in preterm group is(median) 1.0521μmol/mol creatinine,while in control group is(median) 0.7792μmol/mol creatinine;After logarithm conversion and using matched t-test,it is not enough to draw a conclusion that there is a statistic difference between the value of 1-OH-Py in mothers urine in cases and in matching the control group samples(t=1.982,P=0.051), and it remains to be further expanding sample sizes for research.2.Element content in mothers’ vein blood in the cases and the control groups.There is no statistically significant difference between mothers vein blood Pb content in the cases and that in the control groups(Z=-0.144,P=0.886).There is a statistically significant difference between mothers vein blood chromium content in the cases and that in the control groups,chromium content in control group is higher than that in the case group(Z=-2.462,P=0.014);There is a statistically significant difference between mothers vein blood Cu content in the Cases and that in the control group(Z=-2.247,P=0.025),Cu content in control group is higher than that in the case group.3.Neonate umbilical cord blood elements in cases and the control groups.There is no statistically significant difference between newborn infants umbilical cord blood Pb content in the Cases and that in the control groups(Z=-0.309,P= 0.757);There is no statistically significant difference between neonate umbilical cord blood chromium content in the Cases and that in the control groups,(Z=-1.634,P= 0.102);There is a statistically significant difference between neonate umbilical cord blood Cu content in the cases and that in the control groups(Z=-2.993,P=0.003), Cu content in control group is higher than that in the case group.The partⅢ:the relationship between the metabolic enzyme gene polymorphism of the mothers and the neonates and preterm birth1.The results of single-factor logistic regression model analysis of relationship between the mother’s metabolic enzyme genetic polymorphism and preterm birth.GSTT1 null genotypes are related to preterm birth.The individuals carrying GSTT1 null genotypes have higher risk on preterm birth,OR=1.704(95%CI 1.059-2. 740);CYP1A1 mutation genotypes are related to preterm birth,the individuals carrying CYP1A1 mutation genotypes(heterozygous and homozygous mutation) have higher risk on preterm birth,OR=2.259(95%CI 1.229-4.152),OR=2.384(95%CI 1.083-5.250);GSTM1 and CYP2E1 genotypes are not associated with preterm birth (P＞0.05).2.The combined effects of different genotypes in mothers’ GSTM1,GSTT1, CYP2E1 and CYP1A1.GSTM1 and CYP1A1 combined genotypes are associated with preterm birth(P＜0.05).The preterm birth risks of the individuals who carrying GSTT1 non-null genotypes and CYP1A1 heterozygous genotypes at the same time are higher than that of those who carrying GSTT1 non-null genotypes and CYP1A1 wild-genotypes.GSTT1 and CYP1A1 combined genotypes are related to preterm birth(P＜0.05). The preterm birth risks of the individuals who carrying GSTT1 non-null genotypes and CYP1A1 heterozygous or mutant genotypes at the same time and the individuals who carrying GSTT1 null genotypes and CYP1A1 wild or heterozygous or mutant genotypes at the same time are significantly increased,comparing with that of individuals who carrying GSTT1 non-null genotypes and CYP1A1 wild-genotypes at the same time.3.Mothers’ different genetic multi-factors conditional logistic regression analysis.After adjusted for other confounding factors,GSTT1 gene and CYP1A1 gene polymorphism are shown relationship with preterm birth(P＜0.05),OR values are 1.700(95%CI 1.042-2.772),2.250(95%CI 1.215-4.169),2.391(95%CI 1.066-5.367), separately.4.The results of single factor conditional logistic analysis on relationship between neonatal infant metabolic enzyme gene polymorphism and the preterm birth.Neonatal infant GSTT1 null genotypes are related to preterm birth(P＜0.05).The preterm birth risks of the individuals who carrying GSTT1 null genotypes are high, OR=1.818(95%CI 1.081-3.059);CYP1A1 mutant genotypes are may be related to preterm birth,it is not enough to draw a conclusion that neonatal infant CYP1A1 mutant genotypes is related to preterm birth(P=0.0658),and it remains to be further expanding sample sizes for research,according to a=0.05;GSTM1 and CYP2E1 genotypes are not shown relationship with preterm birth(P＞0.05).5.The relationship between combined effect of neonatal infant GSTM1,GSTT1, CYP2E1 and CYP1A1 genotypes and preterm birth.Neonatal infant GSTM1 and CYP1A1 joint genotypes are related to preterm birth(P＜0.05).The preterm birth risks of the individuals who carrying GSTT1 non-null genotypes and CYP1A1 mutant genotypes and the individuals who carrying GSTM1 null genotypes and CYP1A1 heterozygous genotypes at the same time are significantly increased,comparing with that of individuals who carrying GSTM1 null genotypes and CYP1A1 wild-genotypes at the same time.Neonatal infant GSTT1 and CYP1A1 joint genotypes are related to preterm birth(P＜0.05).The preterm birth risks of the individuals who carrying GSTT1 null genotypes and CYP1A1 or mutant genotypes at the same time are significantly increased,comparing with that of individuals who carrying GSTT1 non-null genotypes and CYP1A1 wild-genotypes at the same time.6.The results of different neonatal infant genes multifactor conditional logistic regression analysis.After adjusted the other genes effect,neonatal infant GSTT1 gene polymorphism is related to preterm birth,OR=1.755(95%CI 1.040-2.962);CYP1A1 mutant homozygous genotypes are may be related to preterm birth,it is not enough to draw a conclusion that neonatal infant CYP1A1 mutant genotypes is related to preterm birth(P=0.0566),and it remains to be further expanding sample sizes for research,according to a=0.05.7.Multifactor analysis of relationship between environmental risk factors and maternal metabolic enzyme gene polymorphism and preterm birth.After adjusted other confounding factors,environmental risk factors related to preterm birth are the fuel used by family(OR-4.758,95CI 1.859-12.178),the use of exhaust equipment(OR=0.368,95%CI 0.147-0.920);the genetic factors related to premature is the CYP1A1 gene,which carrying mutant heterozygous CYP1A1 genotype compared with CYP1A1 genotype homozygous wild has higher risk, OR=2.433,95%CI for 1.170-5.058.8.Interaction analysis on the environmental risk factors and mothers’ metabolic enzyme genes polymorphism in preterm birth.Domestic fuel and mother CYP1A1 gene polymorphism exists interaction,at home in the use of non-clean fuels,and the mother carrying CYP1A1 MspI one or two mutant alleles,mutant heterozygous or mutation homozygous genotype,could increase in the risk of premature(carrying mutant heterozygous genotypes:OR= 14.467,95%CI 3.618-57.852;carrying homozygous mutation genotypes:OR=26.708, 95%CI 2.804-254.430).Using the product model,to the further test the interaction of two factors,found that there was a significant difference on the interaction of two factors(P＜0.01).Conclusion:Through this research results can be considered:the occurence of preterm birth was affected by environmental factors and genetic factors.1.The main environmental factors related to preterm birth:After adjusted the other confounding factors,the use of unclean fuel,less times of prenatal examination may be the main risk factors for preterm birth;high-income of families and the mothers without preterm birth history is the protective factors. 2.The parents occupations and education degrees,Cooking Oil-Smoke,heating ways,house decoration during pregnancy,passive smoking,smoking of father, whether taking folic acid before pregnancy,fetus education during pregnancy,eating meat during pregnancy,less weight gain before pregnancy may be all association with preterm birth.3.The content of 1-OH-Py in maternal urinary in preterm birth groups were slightly higher than that in control groups,according to a=0.05 level,it was can not draw a conclusion temporary.But the contents of maternal urinary 1-OH-Py were slightly higher in Taiyuan City,which indicating that Taiyuan’s maternal were exposure to higher polycyclic aromatic hydrocarbons;That may be related to serious air pollution in Taiyuan,which prompted concern about air pollution’s impact on the outcome of pregnancy.4.There are not statistically significant differences of the mothers vein blood lead and the neonates umbilical cord blood lead between the cases and the controls.But that the whole blood lead levels are high may be related to environmental pollution.In addition,the mothers and neonates blood copper content in case groups are lower than that in the control groups,which prompted concern about the lack of maternal trace elements,which is meaningful for the prevention of possible adverse pregnancy outcomes.5.After adjusted for other gene confounding factors,the mothers’ and neonates’ GSTT1 gene polymorphism are related to preterm birth;The preterm birth risks of the individuals who carrying GSTT1 null genotype are higher than that of individuals carrying non-null genotypes;and the mothers’ CYP1A1 gene polymorphism are related to preterm birth;the preterm birth risks of the individuals who carrying CYP1A1 mutant genotypes(mutant heterozygous genotypes and homozygous mutation genotypes)are higher than that of the individual carrying wild genotypes; The results prompt our concern on maternal individual differences and prevent the incidence of premature delivery.6.The mothers’ GSTT1 and CYP1A1 combined genotypes are associated with preterm birth;Neonatal infant GSTT1 and CYP1A1 combined genotypes are associated with preterm birth.The preterm birth risks of the individuals who carrying GSTT1 null genotype and CYP1A1 genotype or mutant genotype at the same time are higher than that of those who carrying GSTT1 non-null genotypes and CYP1A1 wild-genotypes.7.After adjusted other confounding factors,the use of coal fuel in family is risk factor for preterm birth,the use of the exhausting cooking oil-smoke equipment is preterm birth protective factor;mothers carrying CYP1A1 mutant heterozygous genotypes are risk factors for preterm birth.8.An interaction was observed in gene-environment co-effect in the premature, Domestic fuel and mother CYP1A1 gene polymorphism exists interaction,at home in the use of non-clean fuels,and the mother carrying CYP1A1 MspI one or two mutant alleles,mutant heterozygous or mutation homozygous genotype,could increase in the risk of premature.更多还原