Abstract

Background:

Studies have shown that air pollution exposures during pregnancy are associated with an increased risk of autism spectrum disorder (ASD) in children, and the risk appears to be greater for boys. However, studies assessing gestational windows of susceptibility have been mostly limited by trimesters.

Objective:

We identified sensitive windows of exposure to regional air pollution and risk of ASD and examined sex differences in a large birth cohort.

Methods:

This population-based retrospective cohort study included 294,937 mother–child pairs with singleton deliveries in Kaiser Permanente Southern California (KPSC) hospitals from 2001 to 2014. Children were followed using electronic medical records until clinical ASD diagnosis, non-KPSC membership, death, or 31 December 2019, whichever came first. Weekly mean fine particulate matter [PM with an aerodynamic diameter of $\le 2.5\mathrm{\mu }\mathrm{m}$ (${\mathrm{PM}}_{2.5}$)], nitrogen dioxide (${\mathrm{NO}}_2$), and ozone (${\mathrm{O}}_3$) pregnancy exposures were estimated using spatiotemporal prediction models. Cox proportional hazard models with distributed lags were used to estimate weekly pollutant exposure associations with ASD risk for the entire cohort, and separately for boys and for girls. Models were adjusted for child sex (for full cohort), maternal race/ethnicity, maternal age at delivery, parity, maternal education, maternal comorbidities, medical center, census tract median household income, birth year, and season.

Results:

There were 5,694 ASD diagnoses (4,636 boys, 1,058 girls). Sensitive ${\mathrm{PM}}_{2.5}$ exposure windows associated with ASD were found early in pregnancy, statistically significant throughout the first two trimesters [1–27 wk of gestation, cumulative $\text{hazard ratio\hspace{0.17em}}\left(\text{HR}\right)=1.14$ [95% confidence interval (CI): 1.06, 1.23] per interquartile range (IQR) ($7.4\text{-}{\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$) increase]. ${\mathrm{O}}_3$ exposure during 34–37 wk of gestation was associated with increased risk [$\text{HR}=1.06$ (95% CI: 1.01, 1.11) per IQR ($17.4\text{\hspace{0.17em}ppb}$) increase] but with reduced risk during 20–28 wk of gestation [$\text{HR}=0.93$ (95% CI: 0.89, 0.98)]. No associations were observed with ${\mathrm{NO}}_2$. Sex-stratified early gestational ${\mathrm{PM}}_{2.5}$ associations were stronger among boys [boys $\text{HR}=1.16$ (95% CI: 1.08, 1.26); girls $\text{HR}=1.06$ (95% CI: 0.89, 1.26)]. ${\mathrm{O}}_3$ associations in later gestation were observed only in boys [boys $\text{HR}=1.10$ (95% CI: 1.04, 1.16); girls $\text{HR}=0.94$ (95% CI: 0.84, 1.05)].

Conclusions:

Exposures to ${\mathrm{PM}}_{2.5}$ in the first two gestational trimesters were associated with increased ASD risk in children, with stronger associations observed for boys. The role of ${\mathrm{O}}_3$ exposure on ASD risk merits further investigation. https://doi.org/10.1289/EHP9509

中文翻译：

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产前暴露于空气污染和自闭症谱系障碍：暴露和性别差异的敏感窗口

摘要

背景：

研究表明，怀孕期间暴露于空气污染与儿童患自闭症谱系障碍 (ASD) 的风险增加有关，而男孩的风险似乎更大。然而，评估妊娠期易感性窗口的研究大多受到妊娠期的限制。

客观的：

我们确定了暴露于区域空气污染和 ASD 风险的敏感窗口，并检查了大型出生队列中的性别差异。

方法：

这项基于人群的回顾性队列研究包括 2001 年至 2014 年期间在 Kaiser Permanente Southern California (KPSC) 医院进行的 294,937 对单胎分娩的母婴。使用电子病历对儿童进行随访，直至临床 ASD 诊断、非 KPSC 会员、死亡或2019 年 12 月 31 日，以先到者为准。每周平均细颗粒物 [PM，空气动力学直径为$\le 2.5\mathrm{\mu }\mathrm{米}$(${\mathrm{下午}}_{2.5}$）]， 二氧化氮 （${\mathrm{不}}_2$) 和臭氧 (${\mathrm{○}}_3$) 使用时空预测模型估计怀孕暴露。使用具有分布滞后的 Cox 比例风险模型来估计每周污染物暴露与整个队列的 ASD 风险的关联，并分别对男孩和女孩进行评估。模型针对儿童性别（全队列）、产妇种族/民族、产妇分娩年龄、产次、产妇教育、产妇合并症、医疗中心、人口普查区家庭收入中位数、出生年份和季节进行了调整。

结果：

有 5,694 名 ASD 诊断（4,636 名男孩，1,058 名女孩）。敏感的${\mathrm{下午}}_{2.5}$与 ASD 相关的暴露窗口在妊娠早期发现，在妊娠的前两个三个月中具有统计学意义[妊娠 1-27 周，累积$\text{危险几率\hspace{0.17em}}\left(\text{人力资源}\right)=1.14$[95% 置信区间 (CI): 1.06, 1.23] 每四分位距 (IQR) ($7.4\text{-}{\mathrm{\mu }\mathrm{G}/\mathrm{米}}^3$） 增加]。${\mathrm{○}}_3$妊娠 34-37 周期间的暴露与风险增加有关 [$\text{人力资源}=1.06$(95% CI: 1.01, 1.11) 每个 IQR ($17.4\text{\hspace{0.17em}ppb}$) 增加] 但在妊娠 20-28 周期间风险降低 [$\text{人力资源}=0.93$(95% CI: 0.89, 0.98)]。没有观察到与${\mathrm{不}}_2$. 性别分层早孕${\mathrm{下午}}_{2.5}$男孩之间的关联更强[男孩$\text{人力资源}=1.16$(95% CI: 1.08, 1.26); 女孩们$\text{人力资源}=1.06$(95% CI: 0.89, 1.26)]。${\mathrm{○}}_3$仅在男孩中观察到妊娠后期的关联[男孩$\text{人力资源}=1.10$(95% CI: 1.04, 1.16); 女孩们$\text{人力资源}=0.94$(95% CI: 0.84, 1.05)]。

结论：

暴露于${\mathrm{下午}}_{2.5}$在前两个妊娠期中，与儿童 ASD 风险增加相关，而在男孩中观察到的相关性更强。的作用${\mathrm{○}}_3$ASD 风险的暴露值得进一步调查。https://doi.org/10.1289/EHP9509