孕早期被动吸烟致胎儿神经管缺陷发生的风险及机制研究

问卷调查研究提示，妇女孕早期被动吸烟可能增加胎儿神经管缺陷(NTD)发生风险。本研究拟以人群病例对照研究结合大鼠被动吸烟模型揭示孕早期被动吸烟与胎儿NTD发生风险的关系及两个可能的作用机制：1)叶酸代谢异常；2)DNA氧化损伤。人群研究在我国北方NTD高发地区进行。初选对象为孕中期B超筛查时发现的NTD疑似胎儿及配比选择的正常胎儿。采集孕妇发样和静脉血保存，收集孕早期被动吸烟及其它信息。随访妊娠结局，排除B超筛查错误的对象后，确定最终研究对象（200对）。通过测定和比较病例组和对照组之间孕早期发样尼古丁水平（被动吸烟标志物）、血液叶酸和8-羟基脱氧鸟苷水平（DNA氧化损伤标志物）、部分代谢酶多态性，以及各指标之间的相关性，揭示妇女被动吸烟与NTD发生的病因关联及可能的作用机制。通过构建大鼠孕早期被动吸烟模型及测定相关的生物标志物,直观、深入地验证被动吸烟致NTD发生的病因关联及作用机制。

Emerging evidence from questionnaire investigation suggests that women's passive smoking during early pregnancy may increase the risk of having a child with neural tube defects (NTD). We propose to conduct a human case-control study combined with rat experiment to examine the association of maternal passive smoking with the NTD risk in offspring and the two potential mechanisms: 1) folate metabolic disturbance, and 2) DNA oxidative damage. Epidemiological study will be conducted in the region of northern China with high NTD prevalence. The NTD cases and one matched control for each case will be recruited at the time of type-B ultrasound scanning in the second trimester of pregnancy. Women's hair samples, venous blood, information on women's passive smoking during early pregnancy and other variables will be collected in the recruitment. The recruited participants will be followed to verify the pregnancy outcome at delivery, and the final study subjects (200 pairs) will be confirmed at the time after exclusion of the subjects with false diagnosis by ultrasound scanning. Pregnant women's hair nicotine(Biomarker of passive smoking) in first trimester, blood folate and 8-hydroxydeoxyguanosine (Biomarker of DNA lesion) in second trimester, and relative genetic polymorphisms of metabolic enzymes will be measured. The association of maternal passive smoking with NTD risk and the potential mechanisms will be examined by analyzing the difference of hair nicotine, blood folate, and 8-hydroxydeoxyguanosine levels between case and control groups, and the correlation between these biomarkers. Rat passive smoking model will be established, together with measurement of various biomarkers, to directly and thoroughly verify the effects of passive smoking on NTD occurrence and the potential mechanisms by which passive smoking may result in NTD occurrence.