环境危险因素和代谢酶基因多态性与早产关系的病例对照研究
|
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。
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 birth
1.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 birth
1.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 birth
1.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.
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。
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 birth
1.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 birth
1.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 birth
1.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.
引文
1.张玉华,单若冰,于海青.青岛地区早产儿流行病学十年回顾调查分析.中国优生与遗传杂志,1995,3(5):47-48.
2.黄醒华.早产的防治.中华围产医学杂志,2003,6(6):363-364.
3.徐海,张益诚,林明理,等.围产期和环境因素对早产儿体格发育的影响.中国优生与遗传杂志.1991,5(1):35-37.
4.乐杰.妇产科学.第6版.北京:人民卫生出版社,2004,129.
5.曾蔚越主编.早产与早产儿.北京:人民军医出版社,2006,9.
6.Patel RR,Steer P,Doyle P.Does gestation vary by ethnic group? A London-based study of over 122000 pregnancies with spontaneous onset of labour.Inter J Epidemiol,2004,33(1):107-113.
7.黄志碧,姜岳明,韦业平.3245例新生儿早产危险因素研究,中国初级卫生保健,2001,16(6):37-39.
8.Dole N,Savitz DA,Hertz Picciotto I,et al.Maternal stress and preterm birth.Am J Epidemiol,2003,157(1):14-24.
9.Chien P F,Khan K S,Ogston S,et al.The diagnostic accuracy of cervicovaginal fetal fibronectin in predicting preterm delivery:An overview.British Journal of Obstetrics and Gynaecology,1997,104(4):436-444.
10.Ponce NA,Hoggatt KJ,Wilhelm M,et al.Preterm birth:the interaction of traffic-related air pollution with economic hardship in Los Angeles neighborhoods.Am J Epidemiol,2005,162(2):140-148.
11.龚建华,早产危险因素的研究进展.国外医学保健分册,1990,1:11.
12.乐杰.妇产科学.第5版.北京:人民卫生出版社,2000,129-131.
13.王金元,李英旭.早产的危险因素及其相关并发症关系的探讨.小儿急救医学.2004,11(4):238-239.
14.Lagerstrom M.School performance and IQ-test scores at age 13 as related to birth weight and gestational age.Stand J Psychd.1991,32 (4):316-329.
15.杨军,尹晓娟,罗分平,等.早产儿视网膜病变高危因素的多因素分析.南方医科大学学报,2007,27(8):1136-1238.
16.汤学专,钟礼立,贺湘玲,等.早产儿脑性瘫痪发病危险因素分析.中国临床康复,2005,9(11):162-163.
17.Gilbeit C,Rahi J,Eckstein M,et al.Retinopaihy of prematurity in middle-income countries.Lancet,1997,350(9770):12-14
18.李志斌,周笑聘,王志瑾,等.广州市早产危险因素的病例对照研究.广东卫生防疫,2001,27(2):11-12.
19.陆惠萍.早产218例临床分析.医学理论与实践.2007,20(10):1195-1196.
20.许慧琳,赵耐青,纪海燕.我国早产危险因素的meta分析.中国初级卫生保健.2006,20(9):34-36.
21.栾荣生主编.流行病学研究原理与方法.成都:四川大学出版社,2005,95.
22.Lao TT,Ho LF.Obstetric outcome of teenage pregnancies.Hum Reprod,1998,13(11):3228-3232.
23.Ziadeh S.Obstetric outcome of teenage pregnancies in North Jordan.Arch Gynecol Obstet,2001,265(1):26-29.
24.Romero-Maldonado S,Quezada-Salazar CA,Lopez Barrera MD,Arroyo Cabrales LM.Effect of risk on the child of an older mother(case-control study).Ginecol Obstet Mex,2002,70(24):295-302.
25.Eliyahu S,Weiner E,Nachum Z,et al.L,Epidemiologic risk factors for preterm delivery,ISr Med Assoc,J,2002,4(12):1 115-1 117.
26.王宏韬,段建华,吕秀翠,等.早产低出生体质量儿影响因素的Logistic回归分析.青岛大学医学院学报,2004,40(3):237-239.
27.Millar WJ,ChenJ.Maternal education and risk factors for small-for-gestational-age births.Health Rep,1998,10(2):43.
28.Peters HR,Vince CD,Friesen H.Low birth weight at a Papua New Guinea highlands hospitals.J Trp Pediatr,2001,47(1):17.
29.Begum F,Buckshe K,Pande JN.Risk factors associated with preterm labour.Bangladesh.Med Res Counc Bull,2003,29(2):59-66.
30.Ehrenberg HM,Dierker L,Milluzzi C,et al.Low maternal weight failure to thrive in pregnancy,and adverse pregnancy outcomes.Am J Obstet Gynecol,2003,189(6):1726-1730.
31.Schieve LA,Cogswell ME,Scanlon KS,et al.Prepregnancy body mass index and pregnancy weight gain:associations with preterm delivery.Obstet Gynecol,2000,96(2):194-200.
32.龚建华.早产有关因素的研究,中华妇产科杂志,1992,27(1):22-24.
33.Delgado RM.Perez IR,Gomez OM.et al.Risk factors for low birth weight:results from a case control study in southern Spain.Am J Phys A nthropol,1998,105(4):419.
34.张东峰,姜秀波,李红彩.父母亲社会经济状况与早产儿发生的关系.青岛大学医学院学报,2004,40(1):54-56.
35 章丽燕,陈烈平,Zina Luutai,等.早产危险因素病例一对照研究.海峡预防医学杂志,2003,9(4):17-19.
36.吕慧玲,许小幸,徐白壮,等.产前保健因素对早产的影响.青岛医学院学报,1997,(3):253.
37.Boy E,Bruce N,Delgado H.Birth weight and exposure to kitchen wood smoke during pregnancy in rural Guatemala.Environ Health Perspect.2002,110(1):109-114.
38.John EM,Savitz DA,Shy CM.Spontaneous abortions among cosmetologist,Epidemiology,1994,5:147-155.
39.Blackmore C,Harlow SD,Gargiullo P,et al.Chemical hair treatments and adverse pregnancy outcome among Black women in central North Carolina.Am J Epidemiol.1999,149(8):712-716.
40.保毓书,朱文宇,鲍桂芳,等.公共汽车女司乘人员生育机能状况的调查研究.工业卫生与职业病,1996,22(4):211-214.
41.保毓书,胡永华,符绍莲,等.应用医院资料进行职业有害因素对妊娠经过和结局影响的研究.中华劳动卫生职业病杂志,2001,19(2):83-86.
42.林向华,王锦珍,王治明,等.塑料作业女工的生殖健康危害调查.工业卫生与职业病,2004,30(1):19-21.
43.辽宁省联合调查组.铅对女工月经、妊娠及子代健康影响的调查报告.工业卫生与职业病,1995,21(5):301-303.
44.刘淑敏.379例早母亲女危险因素分析.中国初级卫生保健,2000,14(2):34-36.
45.罗亚莉,费春媛,车众.早产及其影响因素研究.甘肃科学学报,2007,19(2):81-83.
46.姚荣英,韩慧,张玉媛.早产相关危险因素的调查分析.蚌埠医学院学报,2005,30(6):500-501.
47.Hanke W,Kallinka J,Florek E,et al.Passive smoking and pregnancy outcome in central Poland.Hum Exp Toxicol,1999,18(4):265.
48.Winfham GC,Hopkins B,Fenster L,et al.Prenatal active passive tobacco smoke exposure and risk of preterm delivery or low birth weight.Epidemiology,2000,11(4):427-433.
49.Chan A,Keane RJ,Robinson JS.The contribution of maternal smoking to preterm birth,small for gestational age and low birth weight among Aboriginal and non-Aboriginal birth in South Australia.Med J A ust,2001,174(8):389.
50.Ferguson SE,Smith GN,Salenieks ME.Preterm premature rupture of membranes:nutritional and socioeconomic factors.Obstet Gynecol,2002,100(6):1250-1256.
51.Stang J,Brown J,Jacobs D.Effect of iron and folic acid supplements on serum zinc levels among a cohort of pregnant women.Clinic Nutrition,2002,17(4):15-26.
52.Moutquin JM.Socio-economic and psychosocial factors in the management and prevention of preterm labour.BJOG 2003,110 Suppl 20:56-60.
53.Whitehead N,Hill HA,Brogan DJ,et al.Exploration of threshold analysis in the relation between stressful life events and preterm delivery.Am J Epidemiol,2002,155(2):117-24.
54.温宏式,尹玲,董悦.异常孕产史妇女120例再次妊娠结局.北京医学,1994,16(4):213-215.
55.Tough SC,Newburn-Cook CV,White DE,et al.maternal characteristics and past pregnancy experiences preterm delivery among women aged 20 to 34 predict J Obstet Gynaecol Can,2003,25(8):656-666.
56.Sagiv SK,Mendola P,Loomis D,et al.A time-series analysis of air pollution and preterm birth in Pennsylvania,1997-2001.Environ Health Perspect.2005,113(5):602-606.
57.Wilhelm M,Ritz B.Local variations in CO and particulate air pollution and adverse birth outcomes in Los Angeles County,California,USA.Environ Health Perspect,2005,113(9):1212-1221.
58.Huynh M,Woodruff TJ,Parker JD,et al.Relationships between air pollution and preterm birth in California.Paediatr Perinat Epidemiol.2006,20(6):454-461.
59.Liu S,Krewski D,Shi Y,et al.Association between gaseous ambient air pollutants and adverse pregnancy outcomes in Vancouver,Canada.Environ Health Perspect.2003,111(14):1773-1778.
60.Ritz B,Yu F,Chapa G et al.Effect of air pollution on preterm birth among children born in Southern California between 1989 and 1993.Epidemiology.2000,11(5):502-511.
61.蒋秋静.太原市煤烟型大气污染现状及治理对策.科技情报开发与经济,2000,10(2):75-76.
62.时红.太原市大气环境污染现状及防治管理.山西经济管理干部学院学报,2001,9(2):28-30.
63.金银龙.我国煤烟型大气污染对人群健康危害的定量研究论文集.2001.
64.丁昌明,刘娅,张淼,等.高效液相色谱法测定尿样中的卜羟基芘.卫生研究.2007,36(5):616-617.
65.Hatch M C,Warburton D,Santella R M.Polycyclic aromatic hydrocarbon- DNA adducts in spontaneously aborted fetal tissue.Carcinogen,1990,11(9):1673-1675.
66.Perera F P,Tang D,Rauh V,et al.Relationships among Polycyclic aromatic hydrocarbon-DNA adducts,proximity to the world trade center,and effects on fetal growth.Environ Health Persp,2005,113(8):1062-1067.
67.Dejmek J,Solansky I,Benes I,et al.The impact of polycyclic aromatic hydrocarbons and fine particles on pregnancy outcome.Environ Health Persp,2000,108(12):1159-1164.
68.Wang X,Ding H,Ryan L,et al.Association between air pollution and low birth weight:a community-based study.Environ Health Perspect,1997,105(5):514-520.
69.徐东群,张文丽,王焱,等.大气颗粒物污染特征研究.中国预防医学杂志,2004,5(1):7-9.
70.杨文敏,吴炳耀,马亚萍等.不同粒径颗粒物中PAHs含量与致突变性关系的研究.环境与健康杂志,1997,(11)1:10-13.
71.赵振华.厨房空气中多环芳烃及炊事员尿中1-羟基芘的测定.中华预防医学杂志,1992,(4):193-196.
72.Claude Viau,Aissata Diakite.Is 1-hydroxyoyrene a Reliable Bioindicator of Measured Dietary Polycyelic Aromatic Hydrocarbon under Normal Conditions.Journal of Chromatography B,2002,778:165-177.
73.毛惠琴,陈小琳,洪传沽,等.含煤燃料对家庭妇女尿中1-羟基芘排泄的影响.上海医科大学学报,1995,22(1):58-60.
74.冷曙光,郑玉新,李晓华,等.焦炉工外暴露等级与尿中1-轻基芘水平的关系.工业卫生与职业病,2003,29(5):288-291.
75.张瑾峰,安魁,朱晓芳,等.尿中1-OH芘和血细胞SCE检测显示环境污染因素对人体影响.中国优生与遗传杂志,2001,9(4):28-29.
76.段小丽,魏复盛,张军锋,等.人尿中1-轻基花浓度与多环芳烃日暴露量的关系.环境化学,2005,24(1):86-88.
77.王劲,闫卫利,郜舟顺,等.尿中1-羟基芘作为焦炉工多环芳烃暴露监测指 标研究.职业卫生与病伤.2006,21(1):8-9.
78.马西林,丁中华,刘瑞莲等.大同市空气中多环芳烃与人尿中1-羟基芘的分析.环境化学,1994,13(6):536-542.
79.段小丽,魏复盛,Zhang Jim等,用尿中1-羟基芘评价人体暴露PAHs的肺癌风险.中国环境科学,2005,25(3):275-278.
80.李敏,杨秀群,陈淑明,等.脐带血铅含量与新生儿出生体重关系的探讨.中国儿童保健杂志,2000,8(3):165.
81.叶艳,张勤.个旧地区学前集体儿童铅损害现状及其防治对策中国儿童保健杂志.2004,12(6):533.
82.Shukla R,Dietrich KN,et al.Lead exposure and growth in the early preschool child:A follow-up report from the Cincinnati lead study.Pediatrics,1991,88(5):886-893.
83.Litvak PF,Graziano JH,et al.A p rospective study of birth weight and length of Gestation in a population Surrounding a lead smelter in Kosovo,Yugoslavi.Int J Epidemiol,1991,20(3):722-728.
84.王舜钦,张金良.我国儿童血铅水平分析研究.环境与健康杂志,2004,21(6):355-360.
85.薛向阳,贾卉,李芳,等。产妇脐带血、静脉血微量元素的含量分析.中国优生与遗传杂志,2005,13(7):73-74.
86.刘艳云.新生儿脐血铅水平与血红细胞系统变化的相关性研究.黑龙江医学,2006,30(1):11
87.沈晓明,颜崇淮,吴圣相,等.胎儿时期低水平血铅暴露对婴儿发育影响的前瞻性研究.中华儿科杂志,1997,35:174-176.
88.彭荣飞,甘平胜,黄聪.ICP-MS直接测定儿童全血中Pb、Cd、Cu、Zn、Mn、Fe 和Ca.中国卫生检验杂志,2006,16(11):1303-1309.
89.张卫,任爱国,杨孜,等.产妇毛发、静脉血及胎儿脐血微量元素相关性分析.中国生育健康杂志,2005,16(4):209-212
90.李万立,罗海吉.微量元素铜与人类疾病关系的研究进展.微量元素与健康研究,2008,25(1):62-64.
91.岳瑛,乐杰.必需微量元素与妊娠的关系,实用妇产科杂志,1996,12(5):238-239.
92.各红,李洞,石蕾.婴幼儿的铜营养状况,国外医学地理分册,1998,19(4):167-169.
93.李芳,薛向阳,梁虹.孕妇血清及胎儿脐带血中微量元素与新生儿体重的关系.陕西医学杂志,2005,34(8):952-954.
94.Arnaud J,Preziosi P,Mashjako L,et al.Serum-traneelenentein Zairianmnthere and their new borns.Eur J Clin Nutr,1994;48(5):341.
95.罗劲,谷红丽.正常妊娠妇女血清中微量元素变化的研究.中国医师杂志,2005,增刊,316-317.
96.尹卓莲,周咏梅.母血常微量元素与胎儿宫内发育迟缓关系的研究.滨州医学院学报,2006,29(1):18-20.
97.顾景范,邵继智.临床营养学.上海:科学技术出版社,1990.
98.Guyer B,Hoyert DL,Martin JA,et al.Annual summary of vital statistics 1998.Pediatrics,1999,104:1229-1246.
99.Berkowitz GS,Papiemik E.Epidemiology of PTD.Epidemiologic Reviews,1993,15:414-443.
100.邓光辉.韶关市早产危险因素病例一对照研究.中国初级卫生保健,1997,11(6):27-28.
101.Wang X B,Zuckerman B,Coffman G A,et al.Aggregation of low birth weight among whites and blacks in the United States.New England Journal of Medicine,1995,333(26):1744-1749.
102.Savtz D A,Blackmore C A,Thorp J M.Epidemiologic characteristics of preterm delivery:etiologic heterogeneity.American Journal of Obstetrics and Gynecology,1991,164:467-471.
103.Stacy AG Andrew F.GSTM1,GSTT1 and risk of squamous cell carcinoma of the head and neck.Am J Epidemiol,2001,154:95-105.
104.Cotton SC,Sharp L,Little J,et al.GlutathioneS-transferase p olymorphisms and colorectal Cancer.Am J Epidemiol,2000,151:7-32.
105.Lin GF,Ma QW,Zha YL,et al.Genetic polymorphism of glutathione S-transferase T1 and M1 in Shanghai "indigene" population[J].Carcinogenesis Teratogenesis Mutagenesis,2001,13:10-12.
106.陆敦,印木泉.细胞色素P450、谷胱甘肽转移酶多态性及其与肿瘤的关系.癌变.畸变.畸变,2001,13(2):121-129.
107.王建,刘悼霖,黎锦如,等.中国广东籍汉族人细胞色素P4502E1基因5'侧翼区多态性.中山医科大学学报,1999,20(1):29-31.
108.龚建平,高长明,Takezaki Toshiro,等.细胞色素P4502E1基因多态性、烟酒习惯与直肠癌易感性的关系.南京医科大学学报(自然科学版),2006,26(12):1163-1167.
109.Kawajiri K,Nakachi K,Imai K,et al.The CYP1A1 gene and cancer susceptibility.Crit Rev Oncol Hematol.1993,14(1):77-87.
110.Shields PG,Caporaso NE,Falk RT.Lung cancer,race,and a CYP1A1genetic polymorphism.Cancer Epidemiol Biomarkers Prey.1993,2(5):481-5.
111.Masson LF,Sharp L,Cotton SC,etal.Cytochrome P4501A1 gene polymerphisms and risk of breast cancer:A Huge reviews.Am J Epidemiol 2005,161(10):901-915.
112.刘春莲,顾继伟,彭亮,等.中国人群CYP1A1 SNPrs4646903遗传多态性研究.中国热带医学,2008,8(1):13-15.
113.Maurizio T,Davide M,AlbertoI.Drug metabolism polymorphisms as modulators of cancer,1999,2:158-164.
114.Ishibe N,Wiencke JK,Zuo ZF,et al.Susceptibility to lung cancer in light smokers associated with CYP1A1 polymorphisms in Mexican-and African-Americans.Cancer Epidemiol Biomarkers Prey.1997,6:1075-1080.
115.Xu X,Kelsey KT,Wiencke JK,et al.Cytochrome P450 CYP1A1 MspI polymorphism and lung cancer susceptibility.Cancer Epidemiol Biomarkers Prey.1996,5:687-692.
116.Watanabe J,Hayashi S,Kawajiri K.Different regulation and expression of the human CYP2E1 gene due to the RsaI polymorphism in the 5'-flanking region.J Biochem,1994,116:321-326.
117.Kiyohara C,Nakanishi Y,Inutsuka S,et al.The relationship between CYP1A1 aryl hydrocarbon hydroxylase activity and lung cancer in a Japanese population.Pharmacogenetics,1998,8(4):315-323.
118.金莹,陈大方,杨帆,等.细胞P450氧化酶基因MSPI位点多态性与早产的关联性研究.北京大学学报,2004,36(6):595-599.
119.Xiaobin Wang,l Dafang Chen,2 Tianhua Niu,et al.Genetic Susceptibility to Benzene and Shortened Gestation:Evidence of Gene-Environment Interaction
120.Cotton SC,Sharp L,Little J,et al.Glutathione S-transferase polymorphisms and colorectal cancer:a huge review,2000,15(1):7-31.
121.Heather HN.Ethnic differences in the prevalence if the homozygous deleted genotype of glutathione s-transferase theta.Carcinogenesis,1995,18(5):1243-1245.
122.Xiaobin Wang,Barry Zuckerman,Colleen Pearson,et al.Maternal cigarette smoking,metabolic gene polymorphism,and infant birth weight.JAMA,2002,287(2):195-202.
[1]黄醒华.早产的防治.中华围产医学杂志,2003,6(6):363-364.
[2]有风芝,徐冬梅.早产的防治探讨,中国社区医师,2004,6(4):76.
[3]曾蔚越主编.早产与早产儿.北京:人民军医出版社,2006,9.
[4]徐海,张益诚,林明理,等.围产期和环境因素对早产儿体格发育的影响.中国优生与遗传杂志.1991,5(1):35-37.
[5]乐杰.妇产科学.第6版.北京:人民卫生出版社,2004.129.
[6]Lao TT,Ho LF.Obstetric outcome of teenage pregnancies.Hum Reprod,1998,13(11):3228-3232.
[7]Monaghan SC,Little RE,Hulchiy O,Strassner H,Gladen BC.Risk factors for spontaneous preterm birth in two urban areas of Ukraine.Paediatr Perinat Epidemiol,2001,15(2):123-130.
[8]Ziadeh S.Obstetric outcome of teenage pregnancies in North Jordan.Arch Gynecol Obstet,2001,265(1):26-29.
[9]Romero-Maldonado S,Quezada-Salazar CA,Lopez Barrera MD,Arroyo Cabrales LM.Effect of risk on the child of an older mother(case-control study).Ginecol Obstet Mex,2002,70(24):295-302.
[10]Schieve LA,Cogswell ME,Scanlon KS,et al.Prepregnancy body mass index and pregnancy weight gain:associations with preterm delivery.Obstet Gynecol,2000,96(2):194-200.
[11]Begum F,Buckshe K,Pande JN.Risk factors associated with preterm labour.Bangladesh.Med Res Counc Bull,2003,29(2):59-66.
[12]Ehrenberg HM,Dierker L,Milluzzi C,et al.Low maternal weight failure to thrive in pregnancy,and adverse pregnancy outcomes.Am J Obstet Gynecol,2003,189(6):1726-1730.
[13]Begum F,Buckshe K,Pande JN.Risk factors associated with preterm labour.Bangladesh.Med Res Counc Bull,2003,29(2):59-66.
[14]姚荣英,韩慧,张玉媛.早产相关危险因素的调查分析,蚌埠医学院学报,2005,30(6):500-501.
[15]张东峰,姜秀波,李红彩,等.父母亲社会经济状况与早产儿发生的关系.青岛大学医学院学报,2004,40(1):54-56.
[16]Ritz B,Yu F,Chapa G et al.Effect of air pollution on preterm birth among children born in Southern California between 1989 and 1993.Epidemiology.2000,11(5):502-511.
[17]Liu S,Krewski D,Shi Y,et al.Association between gaseous ambient air pollutants and adverse pregnancy outcomes in Vancouver,Canada.Environ Health Perspect.2003,111(14):1773-1778.
[18]Tsai SS,Yu HS,Chang CC,et al.Increased risk of preterm delivery in women residing near thermal power plants in Taiwan.Arch Environ Health.2004,59(9):478-483.
[19]Yang CY,Chang CC,Tsai SS,et al.Preterm delivery among people living around Portland cement plants.Environ Res.2003,92(1):64-68.
[20]Yang CY,Chang CC,Chuang HY,et al.Evidence for increased risks of preterm delivery in a population residing near a freeway in Taiwan.Arch Environ Health.2003,58(10):649-654.
[21]Xu X,Ding H,Wang X.Acute effects of total suspended particles and sulfur dioxides on preterm delivery:a community-based cohort study.Arch Environ Health.1995,50(6):407-15.
[22]Wang X,Ding H,Ryan L et al.Association between air pollution and low birth weight:a community-based study.Environ Health Perspect.1997,105(5):514-520.
[23]Mishra V,Dai X,Smith KR,et al.Maternal exposure to biomass smoke and reduced birth weight in Zimbabwe.Ann Epidemiol.2004,14(10):740-747.
[24]Boy E,Bruce N,Delgado H.Birth weight and exposure to kitchen wood smoke during pregnancy in rural Guatemala.Environ Health Perspect.2002,110(1):109-114.
[25]Winfham GC,Hopkins B,Fenster L,et aI.prenatal active passive tobacco smoke exposure and risk of preterm delivery or low birth weight.Epidemiology,2000,11(4):427-433.
[26]Hanke W,Kallmka J,Florek L,et al.Passive somking and pregnancy outcome in central Poland,Hum Exp Toxicol,1999,18(4):265.
[27]Goldhaber MK,Polen MR,Hiatt RA.The risk of miscarriage and birth defects among women who use visual display terminals during pregnancy.Am.J.Ind.Med,1988,13(6):695-706.
[28]Hruba D,Kukla L,Tyrlik M.Occupational risks for human reproduction :ELSPAC Study.European Longitudinal Study of Pregnancy and Childhood.Cent Eur J Public Health,1999,7(4):210-215.
[29]Grajewski B,Schnorr TM,Reefhuis J,Roeleveld N,Salvan A,Mueller CA,Conover DL,Murray WE.Work with video display terminals and the risk of reduced birthweight and preterm birth.Am J Ind Med,1997,32(6):681-688.
[30]保毓书,朱文宇,鲍桂芳,郭秀敏,赵淑芬,郑青,叶爱萍,张秀池.公共汽车女司乘人员生育机能状况的调查研究.工业卫生与职业病,1996,22 (4):211-214.
[31]保毓书,胡永华,符绍莲,李宏.应用医院资料进行职业有害因素对妊娠经过和结局影响的研究.中华劳动卫生职业病杂志,2001,19(2):83-86.
[32]林向华,王锦珍,王治明,等.塑料作业女工的生殖健康危害调查,工业卫生与职业病,2004,30(1):19-21.
[33]辽宁省联合调查组.铅对女工月经、妊娠及子代健康影响的调查报告.工业卫生与职业病,1995,21(5):301-303.
[34]Shah NR,Bracken MB.A systematic review and meta-analysis of prospective studies on the association between maternal cigarette smoking and preterm delivery.Am J Obstet Gynecol,2000,182(2):465-472.
[35]Kesmodel U,Olsen SF.Smoking habits among pregnant Danish women:reliability of information recorded after delivery.J Epidemiol Community Health,1999,53(4):239-242.
[36]Jaakkola J,Jaakkola N,Zahlsen K.Fetal growth and length of gestation in relationto pregnantal exposure tobacco smoke assessed by hair nicotine concentration.Environ Health Perspect,2001,109(6):557-561.
[37]Ahem J,Pickett KE,Selvin S,Abrams B.Preterm birth among African American and white women:a multilevel analysis of socioeconomic characteristics and cigarette smoking.J Epidemiol Community Health,2003,57(8):606-611.
[38]Parazzini F,Chatenoud L,Surace M,Tozzi L,Salerio B,Bettoni G,Benzi G.Moderate alcohol drinking and risk of preterm birth.Eur J Clin Nutr,2003,57(10):1345-1349.
[39]Ferguson SE,Smith GN,Salenieks ME.Preterm premature rupture of membranes:nutritional and socioeconomic factors.Obstet Gynecol,2002,100(6):1250-1256.
[40]Stang J,Brown J,Jacobs D.Effect of iron and folic acid supplements on serum zinc levels among a cohort of pregnant women.Clinic Nutrition, 2002,17(4):15-26.
[41]Moutquin JM.Socio-economic and psychosocial factors in the management and prevention of preterm labour.BJOG 2003,110 Suppl 20:56-60.
[42]Dole N,Savitz DA,Hertz-picciotto I,et al.Maternal stress and preterm birth.Obstet Gynecol Surv,2003,58(6):365-366.
[43].Whitehead N,Hill HA,Brogan DJ,et al.Exploration of threshold analysis in the relation between stressful life events and preterm delivery.Am J Epidemiol,2002,155(2):117-24.
[44]胡成平,刘树仁,黄正南,孙振球.早产危险因素病例对照研究.湖南医科大学学报,2000,25(5):446-448.
[45]Ezechi OC,Makinde ON,Kalu BE,Nnatu SN.Risk actors for preterm delivery in south western Nigeria.Ann Periodontol,2001,6(1):183-188.
[46]Escriba-Aguir V,Perez-Hoyos S,Saurel-Cubizolles MJ.Physical load and psychological demand at work during pregnancy and preterm birth.Int Arch Occup Environ Health,2001,4(8):583-588.v[47]Pickett KE,Ahern JE,Selvin S,Abrams B.Neighborhood socioeconomic status,maternal race and preterm a case-control study.Ann Epidemiol,2002,12(6):410-418.
[48]Fergusun SL,Smith GN,Salenieks ML,et al.preterm premature rupture of membranes.Nutritional and socioeconomic factors,Obstet Gynecol,2002,100(6):1250-1256.
[49]章丽燕,陈烈平,Zina Luutai,等.早产危险因素病例一对照研究.海峡预防医学杂志,2003,9(4):17-19.
[50]Leitich H,Kiss H.Asymptomatic bacterial vaginosis and intermediate flora as risk factors for adverse pregnancy outcome.Best Pract Res Clin Obstet Gynaecol,2007,21(3):375-90.
[51]Eliyahu S,Weiner E,Nachum Z,et al.L,Epidemiologic risk factors for preterm delivery,ISr Med Assoc,J,2002,4(12):1 115-1 117.
[52]Mamell N,Laumon B,Laza RP,etal.Prematurity and occupation activeity during pregnancy.AM J Epideniol,1984,309-322.
[53]Patel RR,Steer P,Doyle P.Does gestation vary by ethnic group? A London-based study of over 122000 pregnancies with spontaneous onset of labour.Inter J Epidemiol,2004,33(1):107-113.
[54]温宏式,尹玲,董悦.异常孕产史妇女120例再次妊娠结局.北京医学,1994,16(4):213-215.
[55]Tough SC,Newburn-Cook CV,White DE,et al.maternal characteristics and past pregnancy experiences preterm delivery among women aged 20 to 34 predict J Obstet Gynaecol Can,2003,25(8):656-666.
[56]蒲杰,曾蔚越.肿瘤坏死因子基因多态性与早产.实用妇产科杂志,2005,21(11):650-652.
[57]梁红业,吴白燕,陈大方,等.新生儿PON2基因多态性与早产的关系.遗传,2002,24(5):515-518.
[1]黄醒华.早产的防治.中华围产医学杂志,2003,6(6):363-364.
[2]有风芝,徐冬梅.早产的防治探讨,中国社区医师,2004,6(4):76
[3]chien P F,Khan K S,Ogston S,et al.The diagnostic accuracy of cervicovaginal fetal fibronectin in predicting preterm delivery:An overview.British Journal of Obstetrics and Gynaecology,1997,104(4):436-444.
[4]Ponce NA,Hoggatt KJ,Wilhelm M,et al.Preterm birth:the interaction of traffic-related air pollution with economic hardship in Los Angeles neighborhoods.Am J Epidemiol,2005,162(2):140-148.
[5]龚建华,早产危险因素的研究进展.国外医学保健分册,1990,1:11.
[6]乐杰.妇产科学,第五版.北京:人民卫生出版社,2001,129.
[7]Ritz B,Yu F,Chapa G et al.Effect of air pollution on preterm birth among children born in Southern California between 1989 and 1993.Epidemiology.2000,11(5):502-511.
[8]Sagiv SK,Mendola P,Loomis D,et al.A time-series analysis of air pollution and preterm birth in Pennsylvania,1997-2001.Environ Health Perspect.2005,113(5):602-606.
[9]Hansen C,Neller A,Williams G,et al.Maternal exposure to low levels of ambient air pollution and preterm birth in Brisbane,Australia.BJOG.2006,113(8):935-941.
[10]Leem JH,Kaplan BM,Shim YK,et al.Exposures to air pollutants during pregnancy and preterm delivery.Environ Health Perspect.2006,114(6): 905-10.
[11]Wilhelm M,Ritz B.Local variations in CO and particulate air pollution and adverse birth outcomes in Los Angeles County,California,USA.Environ Health Perspect,2005,113(9):1212-1221.
[12]Huynh M,Woodruff TJ,Parker JD,et al.Relationships between air pollution and preterm birth in California.Paediatr Perinat Epidemiol.2006,20(6):454-461.
[13]Liu S,Krewski D,Shi Y,et al.Association between gaseous ambient air pollutants and adverse pregnancy outcomes in Vancouver,Canada.Environ Health Perspect.2003,111(14):1773-1778.
[14]Maroziene L,Grazuleviciene R.Maternal exposure to low-level air pollution and pregnancy outcomes:a population-based study.Environ Health.2002,1(1):6.
[15]Tsai SS,Yu HS,Chang CC,et al.Increased risk of preterm delivery in women residing near thermal power plants in Taiwan.Arch Environ Health.2004,59(9):478-483.
[16]Yang CY,Chang CC,Tsai SS,et al.Preterm delivery among people living around Portland cement plants.Environ Res.2003,92(1):64-68.
[17]Yang CY,Chang CC,Chuang HY,et al.Evidence for increased risks of preterm delivery in a population residing near a freeway in Taiwan.Arch Environ Health.2003,58(10):649-654.
[18]Xu X,Ding H,Wang X.Acute effects of total suspended particles and sulfur dioxides on preterm delivery:a community-based cohort study.Arch Environ Health.1995,50(6):407-15.
[19]张扬,王爱英,郑戈.低出生体重儿及其影响因素,河南预防医学杂志,1994,5(6):344-345.
[20]李强,刘运广,黄月艳.低出生体重儿远期听力、视力与智力随访.实用儿科临床杂志,2000,15(3):143-144.
[21]Ver Yiu,Stephen Buka,David Zurakowski,et al.Relationship between birthweight and blood pressure in childhood.American Journal of kidney diseases,1999,33(2):253-260.
[22]Bobak M.Richards M,Wadsworth M.Air pollution and birth weight in Britain in 1946.Epidemiol,2001,12(3):358-359.
[23]Dugandzic R,Dodds L,Stieb D,et al.The association between low level exposures to ambient air pollution and term low birth weight:a retrospective cohort study.Environ Health.2006,5:3.
[24]Chen L,Yang W,Jennison BL,et al.Air pollution and birth weight in northern Nevada,1991-1999.Inhal Toxicol.2002,14(2):141-157.
[25]Ritz B,Yu F.The effect of ambient carbon monoxide on low birth weight among children born in southern California between 1989 and 1993.Environ Health Perspect 1999,107(1):17-25.
[26]Bobak M.Outdoor air pollution,low birth weight,and prematurity.Environ Health Perspect 2000,108(2):173-176.
[27]Ha EH,Hong YC,Lee BE,et al.Is air pollution a risk factor for low birth weight in Seoul?Epidemiology 2001,12(6):643-648.
[28]Vassilev ZP,Robson MG,Klotz JB.Associations of polycyclic organic matter in outdoor air with decreased birthweight:a pilot cross-sectional analysis.J Toxicol Environ Health 2001,64(8):595-605.
[29]Lin CM,Li CY,Mao IF.Increased risks of term low birth weight infants in a petrochemical industrial city with high air pollution levels.Arch Environ Health.2004,59(12):663-668.
[30]Wang X,Ding H,Ryan L et al.Association between air pollution and low birth weight:a community-based study.Environ Health Perspect.1997,105(5):514-520.
2.黄醒华.早产的防治.中华围产医学杂志,2003,6(6):363-364.
3.徐海,张益诚,林明理,等.围产期和环境因素对早产儿体格发育的影响.中国优生与遗传杂志.1991,5(1):35-37.
4.乐杰.妇产科学.第6版.北京:人民卫生出版社,2004,129.
5.曾蔚越主编.早产与早产儿.北京:人民军医出版社,2006,9.
6.Patel RR,Steer P,Doyle P.Does gestation vary by ethnic group? A London-based study of over 122000 pregnancies with spontaneous onset of labour.Inter J Epidemiol,2004,33(1):107-113.
7.黄志碧,姜岳明,韦业平.3245例新生儿早产危险因素研究,中国初级卫生保健,2001,16(6):37-39.
8.Dole N,Savitz DA,Hertz Picciotto I,et al.Maternal stress and preterm birth.Am J Epidemiol,2003,157(1):14-24.
9.Chien P F,Khan K S,Ogston S,et al.The diagnostic accuracy of cervicovaginal fetal fibronectin in predicting preterm delivery:An overview.British Journal of Obstetrics and Gynaecology,1997,104(4):436-444.
10.Ponce NA,Hoggatt KJ,Wilhelm M,et al.Preterm birth:the interaction of traffic-related air pollution with economic hardship in Los Angeles neighborhoods.Am J Epidemiol,2005,162(2):140-148.
11.龚建华,早产危险因素的研究进展.国外医学保健分册,1990,1:11.
12.乐杰.妇产科学.第5版.北京:人民卫生出版社,2000,129-131.
13.王金元,李英旭.早产的危险因素及其相关并发症关系的探讨.小儿急救医学.2004,11(4):238-239.
14.Lagerstrom M.School performance and IQ-test scores at age 13 as related to birth weight and gestational age.Stand J Psychd.1991,32 (4):316-329.
15.杨军,尹晓娟,罗分平,等.早产儿视网膜病变高危因素的多因素分析.南方医科大学学报,2007,27(8):1136-1238.
16.汤学专,钟礼立,贺湘玲,等.早产儿脑性瘫痪发病危险因素分析.中国临床康复,2005,9(11):162-163.
17.Gilbeit C,Rahi J,Eckstein M,et al.Retinopaihy of prematurity in middle-income countries.Lancet,1997,350(9770):12-14
18.李志斌,周笑聘,王志瑾,等.广州市早产危险因素的病例对照研究.广东卫生防疫,2001,27(2):11-12.
19.陆惠萍.早产218例临床分析.医学理论与实践.2007,20(10):1195-1196.
20.许慧琳,赵耐青,纪海燕.我国早产危险因素的meta分析.中国初级卫生保健.2006,20(9):34-36.
21.栾荣生主编.流行病学研究原理与方法.成都:四川大学出版社,2005,95.
22.Lao TT,Ho LF.Obstetric outcome of teenage pregnancies.Hum Reprod,1998,13(11):3228-3232.
23.Ziadeh S.Obstetric outcome of teenage pregnancies in North Jordan.Arch Gynecol Obstet,2001,265(1):26-29.
24.Romero-Maldonado S,Quezada-Salazar CA,Lopez Barrera MD,Arroyo Cabrales LM.Effect of risk on the child of an older mother(case-control study).Ginecol Obstet Mex,2002,70(24):295-302.
25.Eliyahu S,Weiner E,Nachum Z,et al.L,Epidemiologic risk factors for preterm delivery,ISr Med Assoc,J,2002,4(12):1 115-1 117.
26.王宏韬,段建华,吕秀翠,等.早产低出生体质量儿影响因素的Logistic回归分析.青岛大学医学院学报,2004,40(3):237-239.
27.Millar WJ,ChenJ.Maternal education and risk factors for small-for-gestational-age births.Health Rep,1998,10(2):43.
28.Peters HR,Vince CD,Friesen H.Low birth weight at a Papua New Guinea highlands hospitals.J Trp Pediatr,2001,47(1):17.
29.Begum F,Buckshe K,Pande JN.Risk factors associated with preterm labour.Bangladesh.Med Res Counc Bull,2003,29(2):59-66.
30.Ehrenberg HM,Dierker L,Milluzzi C,et al.Low maternal weight failure to thrive in pregnancy,and adverse pregnancy outcomes.Am J Obstet Gynecol,2003,189(6):1726-1730.
31.Schieve LA,Cogswell ME,Scanlon KS,et al.Prepregnancy body mass index and pregnancy weight gain:associations with preterm delivery.Obstet Gynecol,2000,96(2):194-200.
32.龚建华.早产有关因素的研究,中华妇产科杂志,1992,27(1):22-24.
33.Delgado RM.Perez IR,Gomez OM.et al.Risk factors for low birth weight:results from a case control study in southern Spain.Am J Phys A nthropol,1998,105(4):419.
34.张东峰,姜秀波,李红彩.父母亲社会经济状况与早产儿发生的关系.青岛大学医学院学报,2004,40(1):54-56.
35 章丽燕,陈烈平,Zina Luutai,等.早产危险因素病例一对照研究.海峡预防医学杂志,2003,9(4):17-19.
36.吕慧玲,许小幸,徐白壮,等.产前保健因素对早产的影响.青岛医学院学报,1997,(3):253.
37.Boy E,Bruce N,Delgado H.Birth weight and exposure to kitchen wood smoke during pregnancy in rural Guatemala.Environ Health Perspect.2002,110(1):109-114.
38.John EM,Savitz DA,Shy CM.Spontaneous abortions among cosmetologist,Epidemiology,1994,5:147-155.
39.Blackmore C,Harlow SD,Gargiullo P,et al.Chemical hair treatments and adverse pregnancy outcome among Black women in central North Carolina.Am J Epidemiol.1999,149(8):712-716.
40.保毓书,朱文宇,鲍桂芳,等.公共汽车女司乘人员生育机能状况的调查研究.工业卫生与职业病,1996,22(4):211-214.
41.保毓书,胡永华,符绍莲,等.应用医院资料进行职业有害因素对妊娠经过和结局影响的研究.中华劳动卫生职业病杂志,2001,19(2):83-86.
42.林向华,王锦珍,王治明,等.塑料作业女工的生殖健康危害调查.工业卫生与职业病,2004,30(1):19-21.
43.辽宁省联合调查组.铅对女工月经、妊娠及子代健康影响的调查报告.工业卫生与职业病,1995,21(5):301-303.
44.刘淑敏.379例早母亲女危险因素分析.中国初级卫生保健,2000,14(2):34-36.
45.罗亚莉,费春媛,车众.早产及其影响因素研究.甘肃科学学报,2007,19(2):81-83.
46.姚荣英,韩慧,张玉媛.早产相关危险因素的调查分析.蚌埠医学院学报,2005,30(6):500-501.
47.Hanke W,Kallinka J,Florek E,et al.Passive smoking and pregnancy outcome in central Poland.Hum Exp Toxicol,1999,18(4):265.
48.Winfham GC,Hopkins B,Fenster L,et al.Prenatal active passive tobacco smoke exposure and risk of preterm delivery or low birth weight.Epidemiology,2000,11(4):427-433.
49.Chan A,Keane RJ,Robinson JS.The contribution of maternal smoking to preterm birth,small for gestational age and low birth weight among Aboriginal and non-Aboriginal birth in South Australia.Med J A ust,2001,174(8):389.
50.Ferguson SE,Smith GN,Salenieks ME.Preterm premature rupture of membranes:nutritional and socioeconomic factors.Obstet Gynecol,2002,100(6):1250-1256.
51.Stang J,Brown J,Jacobs D.Effect of iron and folic acid supplements on serum zinc levels among a cohort of pregnant women.Clinic Nutrition,2002,17(4):15-26.
52.Moutquin JM.Socio-economic and psychosocial factors in the management and prevention of preterm labour.BJOG 2003,110 Suppl 20:56-60.
53.Whitehead N,Hill HA,Brogan DJ,et al.Exploration of threshold analysis in the relation between stressful life events and preterm delivery.Am J Epidemiol,2002,155(2):117-24.
54.温宏式,尹玲,董悦.异常孕产史妇女120例再次妊娠结局.北京医学,1994,16(4):213-215.
55.Tough SC,Newburn-Cook CV,White DE,et al.maternal characteristics and past pregnancy experiences preterm delivery among women aged 20 to 34 predict J Obstet Gynaecol Can,2003,25(8):656-666.
56.Sagiv SK,Mendola P,Loomis D,et al.A time-series analysis of air pollution and preterm birth in Pennsylvania,1997-2001.Environ Health Perspect.2005,113(5):602-606.
57.Wilhelm M,Ritz B.Local variations in CO and particulate air pollution and adverse birth outcomes in Los Angeles County,California,USA.Environ Health Perspect,2005,113(9):1212-1221.
58.Huynh M,Woodruff TJ,Parker JD,et al.Relationships between air pollution and preterm birth in California.Paediatr Perinat Epidemiol.2006,20(6):454-461.
59.Liu S,Krewski D,Shi Y,et al.Association between gaseous ambient air pollutants and adverse pregnancy outcomes in Vancouver,Canada.Environ Health Perspect.2003,111(14):1773-1778.
60.Ritz B,Yu F,Chapa G et al.Effect of air pollution on preterm birth among children born in Southern California between 1989 and 1993.Epidemiology.2000,11(5):502-511.
61.蒋秋静.太原市煤烟型大气污染现状及治理对策.科技情报开发与经济,2000,10(2):75-76.
62.时红.太原市大气环境污染现状及防治管理.山西经济管理干部学院学报,2001,9(2):28-30.
63.金银龙.我国煤烟型大气污染对人群健康危害的定量研究论文集.2001.
64.丁昌明,刘娅,张淼,等.高效液相色谱法测定尿样中的卜羟基芘.卫生研究.2007,36(5):616-617.
65.Hatch M C,Warburton D,Santella R M.Polycyclic aromatic hydrocarbon- DNA adducts in spontaneously aborted fetal tissue.Carcinogen,1990,11(9):1673-1675.
66.Perera F P,Tang D,Rauh V,et al.Relationships among Polycyclic aromatic hydrocarbon-DNA adducts,proximity to the world trade center,and effects on fetal growth.Environ Health Persp,2005,113(8):1062-1067.
67.Dejmek J,Solansky I,Benes I,et al.The impact of polycyclic aromatic hydrocarbons and fine particles on pregnancy outcome.Environ Health Persp,2000,108(12):1159-1164.
68.Wang X,Ding H,Ryan L,et al.Association between air pollution and low birth weight:a community-based study.Environ Health Perspect,1997,105(5):514-520.
69.徐东群,张文丽,王焱,等.大气颗粒物污染特征研究.中国预防医学杂志,2004,5(1):7-9.
70.杨文敏,吴炳耀,马亚萍等.不同粒径颗粒物中PAHs含量与致突变性关系的研究.环境与健康杂志,1997,(11)1:10-13.
71.赵振华.厨房空气中多环芳烃及炊事员尿中1-羟基芘的测定.中华预防医学杂志,1992,(4):193-196.
72.Claude Viau,Aissata Diakite.Is 1-hydroxyoyrene a Reliable Bioindicator of Measured Dietary Polycyelic Aromatic Hydrocarbon under Normal Conditions.Journal of Chromatography B,2002,778:165-177.
73.毛惠琴,陈小琳,洪传沽,等.含煤燃料对家庭妇女尿中1-羟基芘排泄的影响.上海医科大学学报,1995,22(1):58-60.
74.冷曙光,郑玉新,李晓华,等.焦炉工外暴露等级与尿中1-轻基芘水平的关系.工业卫生与职业病,2003,29(5):288-291.
75.张瑾峰,安魁,朱晓芳,等.尿中1-OH芘和血细胞SCE检测显示环境污染因素对人体影响.中国优生与遗传杂志,2001,9(4):28-29.
76.段小丽,魏复盛,张军锋,等.人尿中1-轻基花浓度与多环芳烃日暴露量的关系.环境化学,2005,24(1):86-88.
77.王劲,闫卫利,郜舟顺,等.尿中1-羟基芘作为焦炉工多环芳烃暴露监测指 标研究.职业卫生与病伤.2006,21(1):8-9.
78.马西林,丁中华,刘瑞莲等.大同市空气中多环芳烃与人尿中1-羟基芘的分析.环境化学,1994,13(6):536-542.
79.段小丽,魏复盛,Zhang Jim等,用尿中1-羟基芘评价人体暴露PAHs的肺癌风险.中国环境科学,2005,25(3):275-278.
80.李敏,杨秀群,陈淑明,等.脐带血铅含量与新生儿出生体重关系的探讨.中国儿童保健杂志,2000,8(3):165.
81.叶艳,张勤.个旧地区学前集体儿童铅损害现状及其防治对策中国儿童保健杂志.2004,12(6):533.
82.Shukla R,Dietrich KN,et al.Lead exposure and growth in the early preschool child:A follow-up report from the Cincinnati lead study.Pediatrics,1991,88(5):886-893.
83.Litvak PF,Graziano JH,et al.A p rospective study of birth weight and length of Gestation in a population Surrounding a lead smelter in Kosovo,Yugoslavi.Int J Epidemiol,1991,20(3):722-728.
84.王舜钦,张金良.我国儿童血铅水平分析研究.环境与健康杂志,2004,21(6):355-360.
85.薛向阳,贾卉,李芳,等。产妇脐带血、静脉血微量元素的含量分析.中国优生与遗传杂志,2005,13(7):73-74.
86.刘艳云.新生儿脐血铅水平与血红细胞系统变化的相关性研究.黑龙江医学,2006,30(1):11
87.沈晓明,颜崇淮,吴圣相,等.胎儿时期低水平血铅暴露对婴儿发育影响的前瞻性研究.中华儿科杂志,1997,35:174-176.
88.彭荣飞,甘平胜,黄聪.ICP-MS直接测定儿童全血中Pb、Cd、Cu、Zn、Mn、Fe 和Ca.中国卫生检验杂志,2006,16(11):1303-1309.
89.张卫,任爱国,杨孜,等.产妇毛发、静脉血及胎儿脐血微量元素相关性分析.中国生育健康杂志,2005,16(4):209-212
90.李万立,罗海吉.微量元素铜与人类疾病关系的研究进展.微量元素与健康研究,2008,25(1):62-64.
91.岳瑛,乐杰.必需微量元素与妊娠的关系,实用妇产科杂志,1996,12(5):238-239.
92.各红,李洞,石蕾.婴幼儿的铜营养状况,国外医学地理分册,1998,19(4):167-169.
93.李芳,薛向阳,梁虹.孕妇血清及胎儿脐带血中微量元素与新生儿体重的关系.陕西医学杂志,2005,34(8):952-954.
94.Arnaud J,Preziosi P,Mashjako L,et al.Serum-traneelenentein Zairianmnthere and their new borns.Eur J Clin Nutr,1994;48(5):341.
95.罗劲,谷红丽.正常妊娠妇女血清中微量元素变化的研究.中国医师杂志,2005,增刊,316-317.
96.尹卓莲,周咏梅.母血常微量元素与胎儿宫内发育迟缓关系的研究.滨州医学院学报,2006,29(1):18-20.
97.顾景范,邵继智.临床营养学.上海:科学技术出版社,1990.
98.Guyer B,Hoyert DL,Martin JA,et al.Annual summary of vital statistics 1998.Pediatrics,1999,104:1229-1246.
99.Berkowitz GS,Papiemik E.Epidemiology of PTD.Epidemiologic Reviews,1993,15:414-443.
100.邓光辉.韶关市早产危险因素病例一对照研究.中国初级卫生保健,1997,11(6):27-28.
101.Wang X B,Zuckerman B,Coffman G A,et al.Aggregation of low birth weight among whites and blacks in the United States.New England Journal of Medicine,1995,333(26):1744-1749.
102.Savtz D A,Blackmore C A,Thorp J M.Epidemiologic characteristics of preterm delivery:etiologic heterogeneity.American Journal of Obstetrics and Gynecology,1991,164:467-471.
103.Stacy AG Andrew F.GSTM1,GSTT1 and risk of squamous cell carcinoma of the head and neck.Am J Epidemiol,2001,154:95-105.
104.Cotton SC,Sharp L,Little J,et al.GlutathioneS-transferase p olymorphisms and colorectal Cancer.Am J Epidemiol,2000,151:7-32.
105.Lin GF,Ma QW,Zha YL,et al.Genetic polymorphism of glutathione S-transferase T1 and M1 in Shanghai "indigene" population[J].Carcinogenesis Teratogenesis Mutagenesis,2001,13:10-12.
106.陆敦,印木泉.细胞色素P450、谷胱甘肽转移酶多态性及其与肿瘤的关系.癌变.畸变.畸变,2001,13(2):121-129.
107.王建,刘悼霖,黎锦如,等.中国广东籍汉族人细胞色素P4502E1基因5'侧翼区多态性.中山医科大学学报,1999,20(1):29-31.
108.龚建平,高长明,Takezaki Toshiro,等.细胞色素P4502E1基因多态性、烟酒习惯与直肠癌易感性的关系.南京医科大学学报(自然科学版),2006,26(12):1163-1167.
109.Kawajiri K,Nakachi K,Imai K,et al.The CYP1A1 gene and cancer susceptibility.Crit Rev Oncol Hematol.1993,14(1):77-87.
110.Shields PG,Caporaso NE,Falk RT.Lung cancer,race,and a CYP1A1genetic polymorphism.Cancer Epidemiol Biomarkers Prey.1993,2(5):481-5.
111.Masson LF,Sharp L,Cotton SC,etal.Cytochrome P4501A1 gene polymerphisms and risk of breast cancer:A Huge reviews.Am J Epidemiol 2005,161(10):901-915.
112.刘春莲,顾继伟,彭亮,等.中国人群CYP1A1 SNPrs4646903遗传多态性研究.中国热带医学,2008,8(1):13-15.
113.Maurizio T,Davide M,AlbertoI.Drug metabolism polymorphisms as modulators of cancer,1999,2:158-164.
114.Ishibe N,Wiencke JK,Zuo ZF,et al.Susceptibility to lung cancer in light smokers associated with CYP1A1 polymorphisms in Mexican-and African-Americans.Cancer Epidemiol Biomarkers Prey.1997,6:1075-1080.
115.Xu X,Kelsey KT,Wiencke JK,et al.Cytochrome P450 CYP1A1 MspI polymorphism and lung cancer susceptibility.Cancer Epidemiol Biomarkers Prey.1996,5:687-692.
116.Watanabe J,Hayashi S,Kawajiri K.Different regulation and expression of the human CYP2E1 gene due to the RsaI polymorphism in the 5'-flanking region.J Biochem,1994,116:321-326.
117.Kiyohara C,Nakanishi Y,Inutsuka S,et al.The relationship between CYP1A1 aryl hydrocarbon hydroxylase activity and lung cancer in a Japanese population.Pharmacogenetics,1998,8(4):315-323.
118.金莹,陈大方,杨帆,等.细胞P450氧化酶基因MSPI位点多态性与早产的关联性研究.北京大学学报,2004,36(6):595-599.
119.Xiaobin Wang,l Dafang Chen,2 Tianhua Niu,et al.Genetic Susceptibility to Benzene and Shortened Gestation:Evidence of Gene-Environment Interaction
120.Cotton SC,Sharp L,Little J,et al.Glutathione S-transferase polymorphisms and colorectal cancer:a huge review,2000,15(1):7-31.
121.Heather HN.Ethnic differences in the prevalence if the homozygous deleted genotype of glutathione s-transferase theta.Carcinogenesis,1995,18(5):1243-1245.
122.Xiaobin Wang,Barry Zuckerman,Colleen Pearson,et al.Maternal cigarette smoking,metabolic gene polymorphism,and infant birth weight.JAMA,2002,287(2):195-202.
[1]黄醒华.早产的防治.中华围产医学杂志,2003,6(6):363-364.
[2]有风芝,徐冬梅.早产的防治探讨,中国社区医师,2004,6(4):76.
[3]曾蔚越主编.早产与早产儿.北京:人民军医出版社,2006,9.
[4]徐海,张益诚,林明理,等.围产期和环境因素对早产儿体格发育的影响.中国优生与遗传杂志.1991,5(1):35-37.
[5]乐杰.妇产科学.第6版.北京:人民卫生出版社,2004.129.
[6]Lao TT,Ho LF.Obstetric outcome of teenage pregnancies.Hum Reprod,1998,13(11):3228-3232.
[7]Monaghan SC,Little RE,Hulchiy O,Strassner H,Gladen BC.Risk factors for spontaneous preterm birth in two urban areas of Ukraine.Paediatr Perinat Epidemiol,2001,15(2):123-130.
[8]Ziadeh S.Obstetric outcome of teenage pregnancies in North Jordan.Arch Gynecol Obstet,2001,265(1):26-29.
[9]Romero-Maldonado S,Quezada-Salazar CA,Lopez Barrera MD,Arroyo Cabrales LM.Effect of risk on the child of an older mother(case-control study).Ginecol Obstet Mex,2002,70(24):295-302.
[10]Schieve LA,Cogswell ME,Scanlon KS,et al.Prepregnancy body mass index and pregnancy weight gain:associations with preterm delivery.Obstet Gynecol,2000,96(2):194-200.
[11]Begum F,Buckshe K,Pande JN.Risk factors associated with preterm labour.Bangladesh.Med Res Counc Bull,2003,29(2):59-66.
[12]Ehrenberg HM,Dierker L,Milluzzi C,et al.Low maternal weight failure to thrive in pregnancy,and adverse pregnancy outcomes.Am J Obstet Gynecol,2003,189(6):1726-1730.
[13]Begum F,Buckshe K,Pande JN.Risk factors associated with preterm labour.Bangladesh.Med Res Counc Bull,2003,29(2):59-66.
[14]姚荣英,韩慧,张玉媛.早产相关危险因素的调查分析,蚌埠医学院学报,2005,30(6):500-501.
[15]张东峰,姜秀波,李红彩,等.父母亲社会经济状况与早产儿发生的关系.青岛大学医学院学报,2004,40(1):54-56.
[16]Ritz B,Yu F,Chapa G et al.Effect of air pollution on preterm birth among children born in Southern California between 1989 and 1993.Epidemiology.2000,11(5):502-511.
[17]Liu S,Krewski D,Shi Y,et al.Association between gaseous ambient air pollutants and adverse pregnancy outcomes in Vancouver,Canada.Environ Health Perspect.2003,111(14):1773-1778.
[18]Tsai SS,Yu HS,Chang CC,et al.Increased risk of preterm delivery in women residing near thermal power plants in Taiwan.Arch Environ Health.2004,59(9):478-483.
[19]Yang CY,Chang CC,Tsai SS,et al.Preterm delivery among people living around Portland cement plants.Environ Res.2003,92(1):64-68.
[20]Yang CY,Chang CC,Chuang HY,et al.Evidence for increased risks of preterm delivery in a population residing near a freeway in Taiwan.Arch Environ Health.2003,58(10):649-654.
[21]Xu X,Ding H,Wang X.Acute effects of total suspended particles and sulfur dioxides on preterm delivery:a community-based cohort study.Arch Environ Health.1995,50(6):407-15.
[22]Wang X,Ding H,Ryan L et al.Association between air pollution and low birth weight:a community-based study.Environ Health Perspect.1997,105(5):514-520.
[23]Mishra V,Dai X,Smith KR,et al.Maternal exposure to biomass smoke and reduced birth weight in Zimbabwe.Ann Epidemiol.2004,14(10):740-747.
[24]Boy E,Bruce N,Delgado H.Birth weight and exposure to kitchen wood smoke during pregnancy in rural Guatemala.Environ Health Perspect.2002,110(1):109-114.
[25]Winfham GC,Hopkins B,Fenster L,et aI.prenatal active passive tobacco smoke exposure and risk of preterm delivery or low birth weight.Epidemiology,2000,11(4):427-433.
[26]Hanke W,Kallmka J,Florek L,et al.Passive somking and pregnancy outcome in central Poland,Hum Exp Toxicol,1999,18(4):265.
[27]Goldhaber MK,Polen MR,Hiatt RA.The risk of miscarriage and birth defects among women who use visual display terminals during pregnancy.Am.J.Ind.Med,1988,13(6):695-706.
[28]Hruba D,Kukla L,Tyrlik M.Occupational risks for human reproduction :ELSPAC Study.European Longitudinal Study of Pregnancy and Childhood.Cent Eur J Public Health,1999,7(4):210-215.
[29]Grajewski B,Schnorr TM,Reefhuis J,Roeleveld N,Salvan A,Mueller CA,Conover DL,Murray WE.Work with video display terminals and the risk of reduced birthweight and preterm birth.Am J Ind Med,1997,32(6):681-688.
[30]保毓书,朱文宇,鲍桂芳,郭秀敏,赵淑芬,郑青,叶爱萍,张秀池.公共汽车女司乘人员生育机能状况的调查研究.工业卫生与职业病,1996,22 (4):211-214.
[31]保毓书,胡永华,符绍莲,李宏.应用医院资料进行职业有害因素对妊娠经过和结局影响的研究.中华劳动卫生职业病杂志,2001,19(2):83-86.
[32]林向华,王锦珍,王治明,等.塑料作业女工的生殖健康危害调查,工业卫生与职业病,2004,30(1):19-21.
[33]辽宁省联合调查组.铅对女工月经、妊娠及子代健康影响的调查报告.工业卫生与职业病,1995,21(5):301-303.
[34]Shah NR,Bracken MB.A systematic review and meta-analysis of prospective studies on the association between maternal cigarette smoking and preterm delivery.Am J Obstet Gynecol,2000,182(2):465-472.
[35]Kesmodel U,Olsen SF.Smoking habits among pregnant Danish women:reliability of information recorded after delivery.J Epidemiol Community Health,1999,53(4):239-242.
[36]Jaakkola J,Jaakkola N,Zahlsen K.Fetal growth and length of gestation in relationto pregnantal exposure tobacco smoke assessed by hair nicotine concentration.Environ Health Perspect,2001,109(6):557-561.
[37]Ahem J,Pickett KE,Selvin S,Abrams B.Preterm birth among African American and white women:a multilevel analysis of socioeconomic characteristics and cigarette smoking.J Epidemiol Community Health,2003,57(8):606-611.
[38]Parazzini F,Chatenoud L,Surace M,Tozzi L,Salerio B,Bettoni G,Benzi G.Moderate alcohol drinking and risk of preterm birth.Eur J Clin Nutr,2003,57(10):1345-1349.
[39]Ferguson SE,Smith GN,Salenieks ME.Preterm premature rupture of membranes:nutritional and socioeconomic factors.Obstet Gynecol,2002,100(6):1250-1256.
[40]Stang J,Brown J,Jacobs D.Effect of iron and folic acid supplements on serum zinc levels among a cohort of pregnant women.Clinic Nutrition, 2002,17(4):15-26.
[41]Moutquin JM.Socio-economic and psychosocial factors in the management and prevention of preterm labour.BJOG 2003,110 Suppl 20:56-60.
[42]Dole N,Savitz DA,Hertz-picciotto I,et al.Maternal stress and preterm birth.Obstet Gynecol Surv,2003,58(6):365-366.
[43].Whitehead N,Hill HA,Brogan DJ,et al.Exploration of threshold analysis in the relation between stressful life events and preterm delivery.Am J Epidemiol,2002,155(2):117-24.
[44]胡成平,刘树仁,黄正南,孙振球.早产危险因素病例对照研究.湖南医科大学学报,2000,25(5):446-448.
[45]Ezechi OC,Makinde ON,Kalu BE,Nnatu SN.Risk actors for preterm delivery in south western Nigeria.Ann Periodontol,2001,6(1):183-188.
[46]Escriba-Aguir V,Perez-Hoyos S,Saurel-Cubizolles MJ.Physical load and psychological demand at work during pregnancy and preterm birth.Int Arch Occup Environ Health,2001,4(8):583-588.v[47]Pickett KE,Ahern JE,Selvin S,Abrams B.Neighborhood socioeconomic status,maternal race and preterm a case-control study.Ann Epidemiol,2002,12(6):410-418.
[48]Fergusun SL,Smith GN,Salenieks ML,et al.preterm premature rupture of membranes.Nutritional and socioeconomic factors,Obstet Gynecol,2002,100(6):1250-1256.
[49]章丽燕,陈烈平,Zina Luutai,等.早产危险因素病例一对照研究.海峡预防医学杂志,2003,9(4):17-19.
[50]Leitich H,Kiss H.Asymptomatic bacterial vaginosis and intermediate flora as risk factors for adverse pregnancy outcome.Best Pract Res Clin Obstet Gynaecol,2007,21(3):375-90.
[51]Eliyahu S,Weiner E,Nachum Z,et al.L,Epidemiologic risk factors for preterm delivery,ISr Med Assoc,J,2002,4(12):1 115-1 117.
[52]Mamell N,Laumon B,Laza RP,etal.Prematurity and occupation activeity during pregnancy.AM J Epideniol,1984,309-322.
[53]Patel RR,Steer P,Doyle P.Does gestation vary by ethnic group? A London-based study of over 122000 pregnancies with spontaneous onset of labour.Inter J Epidemiol,2004,33(1):107-113.
[54]温宏式,尹玲,董悦.异常孕产史妇女120例再次妊娠结局.北京医学,1994,16(4):213-215.
[55]Tough SC,Newburn-Cook CV,White DE,et al.maternal characteristics and past pregnancy experiences preterm delivery among women aged 20 to 34 predict J Obstet Gynaecol Can,2003,25(8):656-666.
[56]蒲杰,曾蔚越.肿瘤坏死因子基因多态性与早产.实用妇产科杂志,2005,21(11):650-652.
[57]梁红业,吴白燕,陈大方,等.新生儿PON2基因多态性与早产的关系.遗传,2002,24(5):515-518.
[1]黄醒华.早产的防治.中华围产医学杂志,2003,6(6):363-364.
[2]有风芝,徐冬梅.早产的防治探讨,中国社区医师,2004,6(4):76
[3]chien P F,Khan K S,Ogston S,et al.The diagnostic accuracy of cervicovaginal fetal fibronectin in predicting preterm delivery:An overview.British Journal of Obstetrics and Gynaecology,1997,104(4):436-444.
[4]Ponce NA,Hoggatt KJ,Wilhelm M,et al.Preterm birth:the interaction of traffic-related air pollution with economic hardship in Los Angeles neighborhoods.Am J Epidemiol,2005,162(2):140-148.
[5]龚建华,早产危险因素的研究进展.国外医学保健分册,1990,1:11.
[6]乐杰.妇产科学,第五版.北京:人民卫生出版社,2001,129.
[7]Ritz B,Yu F,Chapa G et al.Effect of air pollution on preterm birth among children born in Southern California between 1989 and 1993.Epidemiology.2000,11(5):502-511.
[8]Sagiv SK,Mendola P,Loomis D,et al.A time-series analysis of air pollution and preterm birth in Pennsylvania,1997-2001.Environ Health Perspect.2005,113(5):602-606.
[9]Hansen C,Neller A,Williams G,et al.Maternal exposure to low levels of ambient air pollution and preterm birth in Brisbane,Australia.BJOG.2006,113(8):935-941.
[10]Leem JH,Kaplan BM,Shim YK,et al.Exposures to air pollutants during pregnancy and preterm delivery.Environ Health Perspect.2006,114(6): 905-10.
[11]Wilhelm M,Ritz B.Local variations in CO and particulate air pollution and adverse birth outcomes in Los Angeles County,California,USA.Environ Health Perspect,2005,113(9):1212-1221.
[12]Huynh M,Woodruff TJ,Parker JD,et al.Relationships between air pollution and preterm birth in California.Paediatr Perinat Epidemiol.2006,20(6):454-461.
[13]Liu S,Krewski D,Shi Y,et al.Association between gaseous ambient air pollutants and adverse pregnancy outcomes in Vancouver,Canada.Environ Health Perspect.2003,111(14):1773-1778.
[14]Maroziene L,Grazuleviciene R.Maternal exposure to low-level air pollution and pregnancy outcomes:a population-based study.Environ Health.2002,1(1):6.
[15]Tsai SS,Yu HS,Chang CC,et al.Increased risk of preterm delivery in women residing near thermal power plants in Taiwan.Arch Environ Health.2004,59(9):478-483.
[16]Yang CY,Chang CC,Tsai SS,et al.Preterm delivery among people living around Portland cement plants.Environ Res.2003,92(1):64-68.
[17]Yang CY,Chang CC,Chuang HY,et al.Evidence for increased risks of preterm delivery in a population residing near a freeway in Taiwan.Arch Environ Health.2003,58(10):649-654.
[18]Xu X,Ding H,Wang X.Acute effects of total suspended particles and sulfur dioxides on preterm delivery:a community-based cohort study.Arch Environ Health.1995,50(6):407-15.
[19]张扬,王爱英,郑戈.低出生体重儿及其影响因素,河南预防医学杂志,1994,5(6):344-345.
[20]李强,刘运广,黄月艳.低出生体重儿远期听力、视力与智力随访.实用儿科临床杂志,2000,15(3):143-144.
[21]Ver Yiu,Stephen Buka,David Zurakowski,et al.Relationship between birthweight and blood pressure in childhood.American Journal of kidney diseases,1999,33(2):253-260.
[22]Bobak M.Richards M,Wadsworth M.Air pollution and birth weight in Britain in 1946.Epidemiol,2001,12(3):358-359.
[23]Dugandzic R,Dodds L,Stieb D,et al.The association between low level exposures to ambient air pollution and term low birth weight:a retrospective cohort study.Environ Health.2006,5:3.
[24]Chen L,Yang W,Jennison BL,et al.Air pollution and birth weight in northern Nevada,1991-1999.Inhal Toxicol.2002,14(2):141-157.
[25]Ritz B,Yu F.The effect of ambient carbon monoxide on low birth weight among children born in southern California between 1989 and 1993.Environ Health Perspect 1999,107(1):17-25.
[26]Bobak M.Outdoor air pollution,low birth weight,and prematurity.Environ Health Perspect 2000,108(2):173-176.
[27]Ha EH,Hong YC,Lee BE,et al.Is air pollution a risk factor for low birth weight in Seoul?Epidemiology 2001,12(6):643-648.
[28]Vassilev ZP,Robson MG,Klotz JB.Associations of polycyclic organic matter in outdoor air with decreased birthweight:a pilot cross-sectional analysis.J Toxicol Environ Health 2001,64(8):595-605.
[29]Lin CM,Li CY,Mao IF.Increased risks of term low birth weight infants in a petrochemical industrial city with high air pollution levels.Arch Environ Health.2004,59(12):663-668.
[30]Wang X,Ding H,Ryan L et al.Association between air pollution and low birth weight:a community-based study.Environ Health Perspect.1997,105(5):514-520.