孕前和孕期大气NO2暴露与小于胎龄儿和大于胎龄儿发生风险关联的易感暴露窗口识别

Identifying susceptible exposure windows for ambient nitrogen dioxide before and during pregnancy and increased risks of small/large for gestational age

  • 摘要:
    背景 大气二氧化氮(NO2)暴露可能会增加小于胎龄儿(SGA)和大于胎龄儿(LGA)的发生风险。然而,既往研究在推测孕期大气污染暴露影响的易感窗口时,主要是将孕期划分为相对较长的暴露时期,如孕早、中、晚期或者妊娠月。目前尚无研究探索过怀孕前后大气NO2周均暴露水平与SGA和LGA发生风险的关联。

    目的 评估孕前和孕期大气NO2暴露对SGA和LGA发生风险的影响,并细化暴露窗口为每周,以更为准确地分析NO2暴露的易感窗口。

    方法 本研究依托在天津市开展的“环境和生活因素在人整个生命轨迹中对代谢健康的影响研究(ELEFANT)”项目建立出生队列,获取末次月经日期和分娩日期均在2014年6月至2016年6月期间且孕周为24~42周的10 916名单胎妊娠孕妇信息。基于中国空气质量再分析数据集(CAQRA),获得每名孕妇孕前和整个孕期NO2日均暴露水平。应用分布式滞后模型结合Cox比例风险回归模型,调整孕妇年龄、民族、文化程度、职业、孕前体重指数、居住地、怀孕次数、生产次数、吸烟和饮酒情况,丈夫吸烟情况,怀孕季节等潜在混杂因素,评估孕前12周和孕期NO2周均暴露水平与SGA和LGA发生风险的关系。回归结果以NO2每增加3 μg·m−3,SGA和LGA发生风险的危险比(HRs)及其95%置信区间(CIs)表示。

    结果 研究对象孕前期、孕早期、孕中期、孕晚期和整个孕期NO2平均暴露水平分别为(39.6±10.8)、(42.7±10.5)、(44.8±12.7)、(37.7±11.1)和(41.6±4.8) μg·m−3。孕早期NO2暴露水平每增加3 μg·m−3,SGA发生风险升高19.0%(95%CI:8.0%~32.0%)。孕前、孕早期和整个孕期NO2暴露水平每增加3 μg·m−3,LGA发生风险分别升高7.0%(95%CI:1.0%~13.0%)、37.0%(95%CI:29.0%~46.0%)和19.0%(95%CI:9.0%~31.0%)。SGA的NO2暴露易感窗口为怀孕前第7~12周和孕期第6~12周,其中在怀孕前第12周的估计效应值最大,NO2暴露水平每增加3 μg·m−3,SGA发生风险升高6.0%(95%CI:3.2%~8.9%)。LGA的NO2暴露易感窗口为怀孕前第1~12周和孕期第1~6周,其中在怀孕前第12周的估计效应值最大,NO2暴露水平每增加3 μg·m−3,LGA发生风险升高6.1%(95%CI:4.5%~7.8%)。

    结论 大气NO2暴露可增加SGA和LGA发生的风险,其细化到周的易感窗口期位于孕前12周和孕早期内。

     

    Abstract:
    Background Exposure to ambient nitrogen dioxide (NO2) could increase the risks of small for gestational age (SGA) and large for gestational age (LGA). Nevertheless, previous published studies usually use a time period over relatively long durations as the exposure window, such as trimester-specific or gestational months, to identify adverse pregnancy outcomes related susceptible exposure windows for ambient air pollution. At present, no study has explored associations of weekly-specific ambient air NO2 exposure around pregnancy with SGA and LGA.

    Objective To evaluate the associations of exposure to ambient NO2 over the preconception and entire pregnancy period with risks of SGA and LGA, as well as to explore critical windows of NO2 exposure by refining exposure period to specific weeks.

    Methods Based on a birth cohort established by the project Environmental and LifEstyle FActors iN metabolic health throughout life-course Trajectories (ELEFANT) situated in Tianjin, 10 916 singleton pregnant women whose dates of the last menstrual period and delivery were both between June 2014 and June 2016, and whose gestational age were within 24-42 completed gestational weeks were included in this study. Each pregnant woman's exposures to ambient NO2 throughout 12 weeks before pregnancy and pregnancy period were matched with daily average NO2 concentrations obtained from the Chinese air quality reanalysis datasets (CAQRA). Distributed lag models incorporated in Cox proportional hazard regression models were applied to explore the associations of maternal exposure to weekly ambient NO2 throughout 12 weeks before pregnancy and pregnancy period with risks of SGA and LGA after controlling for potential confounders including maternal age, ethnicity, educational level, occupation, body mass index before pregnancy, residence, times of gravidity and parity, smoking, alcohol consumption, husband smoking, and season of conception. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated per 3 μg·m−3 increase in ambient NO2 concentrations.

    Results The average levels of maternal exposure to NO2 over the preconception, first trimester, second trimester, third trimester, and entire pregnancy periods were (39.6±10.8), (42.7±10.5), (44.8±12.7), (37.7±11.1), and (41.6±4.8) μg·m−3, respectively. For a 3 μg·m−3 increase in NO2 over the first trimester, the risk of SGA increased by 19.0% (95%CI: 8.0%-32.0%). For a 3 μg·m−3 increase in NO2 over the preconception, first trimester, and entire pregnancy, the associated risks of LGA increased by 7.0% (95%CI: 1.0%-13.0%), 37.0% (95%CI: 29.0%-46.0%) and 19.0% (95%CI: 9.0%-31.0%), respectively. For SGA, the susceptible exposure windows for NO2 were observed during the 7th to 12th preconceptional weeks and the 6th to 12th gestational weeks, with the strongest association found at the 12th preconceptional week, when the risk of SGA increased by 6.0% (95%CI:3.2%-8.9%) for a 3 μg·m−3 increase in NO2. For LGA, the susceptible exposure windows for NO2 were observed during the 1st to 12th preconceptional weeks and the 1st to 6th gestational weeks, with the strongest association found at the 12th preconceptional week, when the risk of LGA increased by 6.1% (95%CI: 4.5%-7.8%) for a 3 μg·m−3 increase in NO2.

    Conclusion Exposure to ambient NO2 is associated with increased risks of both SGA and LGA, and the most susceptible weekly exposure windows are nested within the 12 weeks before pregnancy and early pregnancy.

     

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