母亲孕期空气污染物混合暴露对子代先天性心脏病的联合作用

目的：探索母亲孕期空气污染物中可入肺颗粒物（PM₁）、细颗粒物（PM_2.5）、可吸入颗粒物（PM₁₀）和二氧化氮（NO₂）混合暴露对子代先天性心脏病发生风险的影响，并估计上述几种污染物的作用权重。方法：纳入广东省先天性心脏病防治登记网（GRCHD）2007—2016年登记的来自21个地市、40家医疗机构的6038例先天性心脏病患儿（病例组）及5227名健康对照儿童（对照组）。采用logistic回归模型评估母亲暴露于单个空气污染物对子代先天性心脏病发生的影响，采用spearman相关系数分析各种污染物之间的相关性。并采用Quantile g-computation评估空气污染物混合暴露对先天性心脏病发生的联合效应及各种污染物的权重。结果：病例组PM₁、PM_2.5、PM₁₀和NO₂的暴露浓度显著高于对照组（均P<0.01）。PM₁、PM_2.5、PM₁₀、NO₂之间的相关系数均大于0.80。母亲孕期PM₁、PM_2.5、PM₁₀和NO₂暴露均与子代先天性心脏病发生风险显著升高有关。当这些紧密相关的污染物混合暴露时，先天性心脏病的发生风险较其独立暴露时更高。混合暴露物与先天性心脏病风险之间呈单调递增关系，混合暴露每升高一个分位数，先天性心脏病的发生风险增加47%（OR=1.47，95%CI：1.34~1.61）。母亲孕早期空气污染物混合暴露对先天性心脏病发生的影响最大，但孕早、中、晚期任一时间段的暴露效应均不及整个孕期的混合暴露效应强。混合暴露中PM₁₀的作用权重最大（81.3%）。结论：母亲孕期空气污染物混合暴露会增加子代先天性心脏病的发生风险，且较各污染物独立暴露时效应更强。PM₁₀在混合暴露中的作用权重最大。

Risk of maternal exposure to mixed air pollutants during pregnancy for congenital heart diseases in offspring

Objective: To explore the risk of maternal exposure to mixed air pollutants of particulate matter 1 (PM₁), particulate matter 2.5 (PM_2.5), particulate matter 10 (PM₁₀) and NO₂ for congenital heart disease (CHD) in offspring, and to estimate the ranked weights of the above pollutants. Methods: 6038 CHD patients and 5227 healthy controls from 40 medical institutions in 21 cities in Guangdong Registry of Congenital Heart Disease (GRCHD) from 2007 to 2016 were included. Logistic regression model was used to estimate the effect of maternal exposure to a single air pollutant on the occurrence of CHD in offspring. Spearman correlation coefficient was used to analyze the correlation between various pollutants, and Quantile g-computation was used to evaluate the joint effects of mixed exposure of air pollutants on CHD and the weights of various pollutants. Results: The exposure levels of PM₁, PM_2.5, PM₁₀ and NO₂ in the CHD group were significantly higher than those in the control group (all P<0.01). The correlation coefficients among PM₁, PM_2.5, PM₁₀ and NO₂ were greater than 0.80. PM₁, PM_2.5, PM₁₀ and NO₂ exposure were associated with a significantly increased risk of CHD in offspring. Mixed exposure of these closely correlated pollutants presented much stronger effect on CHD than exposure of any single pollutants. There was a monotonic increasing relationship between mixed exposure and CHD risk. For each quantile increase in mixed exposure, the risk of CHD increased by 47% (OR=1.47, 95%CI: 1.34–1.61). Mixed exposure had greater effect on CHD in the early pregnancy compared with middle and late pregnancy, but the greatest effect was the exposure in the whole pregnancy. The weight of PM₁₀ is the highest in the mixed exposure (81.3%). Conclusions: Maternal exposure to the mixture of air pollutants during pregnancy increases the risk of CHD in offspring, and the effect is much stronger than that of single exposure of various pollutants. PM₁₀ has the largest weights and the strongest effect in the mixed exposure.