孕期邻苯二甲酸酯暴露水平及其对妊娠结局的影响

发布时间：2018-09-04 20:35

【摘要】：研究目的 PAEs作为一种全球范围使用的塑料制品增塑剂,通过空气、土壤、饮水、食物等多种环境介质进入人体,危害身体健康。有研究表明孕妇PAEs暴露不仅可以引发孕期合并症,而且对胎儿的生长发育及生殖系统造成潜在的影响。目前我国人群孕期PAEs暴露水平及其对妊娠结局影响的研究资料有限,本研究在评价孕期PAEs暴露水平的基础上,初步探讨了孕期PAEs暴露对胎儿生长发育及男性生殖系统的潜在影响,为预防出生前PAEs暴露的危害提供科学依据。 研究内容和方法 1、孕期人群尿液中PAEs代谢产物含量测定：采集孕妇孕晚期尿液,运用固相萃取-三重四级杆高效液相色谱联用质谱法测定孕妇尿液中5种PAEs代谢产物水平。 2、孕期PAEs暴露与妊娠结局之间关联性研究：建立母亲-胎儿队列,采用线性回归模型分析母亲尿液中5种PAEs代谢产物水平与胎儿生长发育指标(身长、体重)间的关系。1：2匹配病例对照研究中,运用条件logistic回归模型分析母亲PAEs暴露与早产的关系。 3、孕期PAEs暴露与男性胎儿性激素水平之间关联性研究：采用线性模型进行孕期PAEs暴露与男性胎儿脐带血中性激素水平关联分析,探讨孕期PAEs暴露对男性生殖系统发育的潜在影响。 研究结果 1、孕期人群尿液中5种PAEs代谢产物含量测定：232名孕妇孕晚期尿液中MMP、MEP、MBP、MBzP和MEHP中位数分别为49.51μg/L、13.19μg/L、7.22μg/L、0.30μg/L、30.03μg/L,经肌酐调整后含量中位数分别为110.40μg/g、27.61μg/g、16.90μg/g、0,53μg/g、56.23μg/g。 2、孕期PAEs暴露与妊娠结局之间关联性研究：211名胎儿生长发育与母亲PAEs暴露的相关分析中,新生儿体重与母亲尿液中MMP、MEP和∑PAEs含量呈负相关(r=-0.28,P0.05；r=-0.14,P0.05；r=-0.25,P0.001),新生儿身长与MEP水平呈负相关(r=-0.14,P=0.05);排除早产因素影响后,进一步分析孕期PAEs暴露与176名足月儿生长发育结局的关系,Pearson相关分析及多元线性回归分析均未发现新生儿体重、身长与母亲尿液中5种PAEs代谢产物含量间存在统计学关联。单因素logistic回归分析发现孕期DEHP暴露降低早产发生的风险OR=0.31(0.17～0.57)。经协变量调整后,多因素logistic回归分析结果显示孕期DEHP暴露与早产间关系仍然存在统计学意义OR=0.23(0.08～0.64)。 3、孕期PAEs暴露与男性胎儿性激素水平之间关联性研究：男性胎儿脐带血中T、E2、P、FSH、LH、INSL3和SHBG含量均数分别为182.76ng/dl、5078.62pg/ml、779.18ng/ml、1.50IU/L、3.11IU/L、135.29pg/ml和98.78nmol/L。经母亲年龄、孕前BMI、孕次及分娩孕周调整后,多元线性回归分析发现男性胎儿脐血清中E2含量与孕期BBzP暴露呈正相关(β=0.083,P=0.03)。T/E2与BBzP暴露呈负相关趋势(β=-0.065,P=-0.07)。 研究结论 本研究中,5种PAEs代谢产物检出率较高(63.8%～99.1%),说明天津地区孕妇普遍暴露于多种PAEs。孕期不同类型PAEs暴露均对胎儿生长发育和生殖系统造成危害,其中MMP和MEP可能影响新生儿体重、身长,母亲DEHP暴露降低早产发生风险,孕期BBzP暴露影响男性新生儿性激素水平。
[Abstract]:research objective
PAEs, as a plasticizer used worldwide, enter the human body through air, soil, drinking water, food and other environmental media. Studies have shown that pregnant women exposed to PAEs can not only cause complications during pregnancy, but also have a potential impact on the growth and development of the fetus and reproductive system. In this study, the potential effects of prenatal exposure to PAEs on fetal growth and male reproductive system were preliminarily explored on the basis of evaluating the level of prenatal exposure to PAEs.
Research contents and methods
1. Determination of PAEs metabolites in the urine of pregnant women during pregnancy: The urine of pregnant women in late pregnancy was collected, and the levels of 5 kinds of PAEs metabolites in the urine of pregnant women were determined by solid phase extraction-triple four-stage high performance liquid chromatography-mass spectrometry.
2. Correlation between maternal and fetal PAEs exposure during pregnancy: A maternal-fetal cohort was established, and the relationship between maternal urinary 5 kinds of PAEs metabolites and fetal growth and development indicators (length, weight) was analyzed by linear regression model. In a 1:2 matched case-control study, conditional logistic regression model was used to analyze maternal PAEs exposure and fetal outcomes. The relationship between preterm delivery.
3. Study on the relationship between pregnant PAEs exposure and male fetal sex hormone level: Linear model was used to analyze the relationship between pregnant PAEs exposure and male fetal umbilical cord blood sex hormone level, and to explore the potential impact of pregnant PAEs exposure on male reproductive system development.
Research results
1. Determination of 5 kinds of PAEs metabolites in urine of pregnant women: Medians of MMP, MEP, MBzP, MEHP in urine of 232 pregnant women in the third trimester of pregnancy were 49.51 ug/L, 13.19 ug/L, 7.22 ug/L, 0.30 ug/L, 30.03 ug/L, and 110.40 ug/g, 27.61 ug/g, 16.90 ug/g, 0, 53 ug/g, 56.23 ug/g, respectively.
2. Correlation between PAEs exposure during pregnancy and pregnancy outcomes: In the correlation analysis between fetal growth and maternal PAEs exposure, neonatal weight was negatively correlated with maternal urinary MMP, MEP and_PAEs (r =-0.28, P 0.05; R =-0.14, P 0.05; P 0.05; R =-0.25, P 0.001), and neonatal length was negatively correlated with MEP level (r =-0.14, P = 0.05). After preterm delivery, the relationship between PAEs exposure during pregnancy and the growth and development outcomes of 176 full-term infants was further analyzed. Pearson correlation analysis and multiple linear regression analysis showed no neonatal weight. There was a statistical correlation between body length and the contents of five PAEs metabolites in mother's urine. The risk of premature delivery was reduced by OR = 0.31 (0.17-0.57). Multivariate logistic regression analysis showed that the relationship between DEHP exposure during pregnancy and premature delivery was still statistically significant OR = 0.23 (0.08-0.64).
3. Correlation between maternal exposure to PAEs and male fetal sex hormone levels: The mean levels of T, E2, P, FSH, LH, INSL 3 and SHBG in umbilical cord blood of male fetuses were 182.76ng/dl, 5078.62 pg/ml, 779.18 ng/ml, 1.50 IU/L, 3.11 IU/L, 135.29 pg/ml and 98.78 nmol/L, respectively. The results showed that the level of E2 in umbilical cord serum of male fetus was positively correlated with BBzP exposure during pregnancy (beta = 0.083, P = 0.03). T/E2 was negatively correlated with BBzP exposure (beta = - 0.065, P = - 0.07).
research conclusion
In this study, the detection rate of 5 kinds of PAEs metabolites was high (63.8% ~ 99.1%), indicating that pregnant women in Tianjin were generally exposed to a variety of PAEs. Different types of PAEs during pregnancy were harmful to fetal growth and reproductive system. MMP and MEP may affect neonatal weight, body length, maternal DEHP exposure reduced the risk of premature delivery, and BBzP outbreak during pregnancy. Exposure affects the level of sex hormones in male newborns.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R114

【引证文献】

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1 陈燕芬;PVC密封圈中ESBO的迁移研究和TTC安全评估方法的初步建立[D];暨南大学;2015年

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