基于出生队列的农村孕妇环境烟草烟雾暴露异质性与婴儿生长发育关系研究

Numerous scientific evidence has proved that tobacco smoking and passive smoking could seriously harm to human health. Recent researches in China suggest the exposure to Environmental Tobacco Smoke (ETS) in rural areas was higher than the one in the urban areas. This exposure to ETS among pregnant women is a big problem in Yunnan province which is main base tobacco production in China and tobacco makes up a big part of the provincial GDP. No report however has focused on the effects of cumulative ETS exposure on pregnancy outcomes, infant growth and metabolic disorders. This study will be based on a birth cohort established in rural Xuanwei and follows pregnant women and their infants to examine how prenatal exposure to ETS influence birth outcomes, infant growth and other metabolic disorders while taking into longitudinal data and population heterogeneity in data analysis procedures account. Firstly, this study will recruit 700 pregnant women in rual Xuanwei, during their first trimester, and follow them each trimester. And their newborn children are also followed until their 1 year old. Moreover, ETS exposure to pregnant women and infant will be measured by duplicate detection of the biomarkers (nicotine and cotinine) in urine of pregnant women at three trimester, 6-month and 12-month baby as well as in meconium respectively. Both Nicotinine and Cotinine will be determined by Ultra-performance Liquid Chromatography Couple with Tandem Mass Spectrometer(HPLC-MS/Ms). Secondly, a questionnaire on the behavior of passive smoking and dietary survey will be collected during pregnancy to 1-year infant. In addition birth weight, height, head circumference,and metabolic indicators (insulin, glucose, lipid, leptin, adiponectin C-peptide, TSH and GH) in umbilical cord blood will simultaneously be measured to assess the influence of infant growth, developing obesity, diabetes and other metabolic disorders. Finally, in order to explore and quantify the complex causal relationship between ETS cumulative exposure and birth outcome, fetal glucose and lipid metabolism, as well as dynamic growth and development trajectory of infant, we plan to integrate exposures with outcomes into one full model using two statistical methods: Latent Variable Growth Curve Modeling （LGM） and Latent Class Analysis （LCA）with Distal Outcomes. All the analysis use Bayesian Markov Chain Monte Carlo（MCMC） stochastic simulation algorithm iteration by Stata and Mplus software. Findings from this study will help to provide evidence and reference to developing effective interventions and appropriate strategies to decrease the accumulation of ETS exposure in pregnant women and reduce the adverse effects on infant growth and development.

众多科学证据表明，被动吸烟危害人类健康。中国农村环境烟草烟雾（ETS）暴露高于城市，作为烟草生产大省云南农村孕妇ETS暴露严重。国内外以往队列研究多为孕期ETS暴露对出生结局的影响，农村孕妇ETS暴露异质性与婴儿生长发育相关研究少见。本研究基于农村的出生队列，整合孕期宫内ETS暴露及出生后婴儿ETS暴露，于孕早期、中期和晚期重复测量孕妇被动吸烟行为与尿液ETS生物标志物（尼古丁和可替宁）含量，监测孕妇中、晚期营养素摄入情况；追踪婴儿分娩至1岁，检测胎便中以上生物标志物含量；检测脐血中血糖、胰岛素、C肽、血脂、脂联素、瘦素和生长素等相关指标；测量6月龄和12月龄婴儿ETS暴露水平，观察出生结局和婴儿生长发育。运用Mplus 软件进行数据建模，探讨孕期ETS暴露异质性与妊娠结局、胎儿糖脂代谢和婴儿生长发育的关系。研究结果可为制定减少孕妇ETS暴露和降低婴儿生长发育不良影响干预措施提供科学依据。

本研究聚焦农村孕妇环境烟草烟雾（ETS）暴露异质性与婴儿生长发育关系。基于云南宣威农村的出生队列，继续建立出生队列712对，观察至儿童1岁。结果发现：.1.妇女孕期ETS暴露普遍。妇女自我报告孕早、中、晚期二手烟（SHS）暴露率分别为53.29%、52.11%和53.29%。各孕期ETS暴露率分别为82.58%、83.31%和81.47%，各期尿液可替宁（UC）浓度平均为6.28ng/mL、5.83ng/mL和5.41ng/mL。胎便可替宁检出率为97.50%，浓度平均为91.49ng/g。使用潜变量增长曲线模型发现孕期UC暴露异质性三个模式：无明显变化型、递增型、递减型。婴儿出生后6月龄和1岁时ETS暴露率分别为57.49%和65.31%。其平均UC浓度分别为0.42ng/ml和0.69ng/ml。居住乡镇1，家中同住吸烟者均增加自我报告孕期SHS暴露率；居住乡镇2，家中同住吸烟者增加孕期UC暴露的风险；文化程度小学及以下妇女增加孕中期UC暴露风险。.2. 孕期UC暴露异质性模式中，递增型与出生体重负相关，递减型与出生身长、新生儿脐带血生长激素、胰岛素样因子（IGF-1）和甘油三酯浓度水平正相关。未发现与出生头围和不良出生结局相关。孕期异质性、儿童6月龄和1岁UC浓度与婴儿身长、体重、头围、神经心理行为发育无关联。但半岁儿童UC浓度与婴儿社会情绪得分呈负相关。.综上，妇女孕期和婴儿ETS暴露普遍。但总体暴露水平低于多数国外报道。家中同住吸烟者可增加自我报告和UC暴露的风险。孕期UC暴露异质性模式中递增型可减少出生体重，递减型可增加出生身长、新生儿的生长激素、IGF-1和甘油三酯。研究提示，妇女孕期要尽量减少ETS暴露，实施家中禁烟的规定。本研究结果可为制定降低婴儿生长发育不良影响干预措施提供科学依据。