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The association between prenatal greenspace exposure and Autism spectrum disorder, and the potentially mediating role of air pollution reduction: A population-based birth cohort study
Environment International ( IF 11.8 ) Pub Date : 2022-07-30 , DOI: 10.1016/j.envint.2022.107445
Lief Pagalan 1 , Tim F Oberlander 2 , Gillian E Hanley 3 , Laura C Rosella 4 , Celeste Bickford 5 , Whitney Weikum 6 , Nancy Lanphear 7 , Bruce Lanphear 8 , Michael Brauer 5 , Matilda van den Bosch 9
Affiliation  

Background

Autism spectrum disorder (ASD) incidence has increased in past decades. ASD etiology remains inconclusive, but research suggests genetic, epigenetic, and environmental contributing factors and likely prenatal origins. Few studies have examined modifiable environmental risk factors for ASD, and far fewer have examined protective exposures. Greenspace has been associated with positive child development, but very limited greenspace research has examined ASD risk or prenatal exposures. Only one ecological study in 2017 has evaluated the association between greenspace and ASD, observing protective benefits. Greenspace may have direct effects on ASD risk and indirect effects by reducing air pollution exposure, a growing suspected ASD risk factor.

Objectives

To measure the association between prenatal greenspace exposure and ASD risk and examine if reduced air pollution levels in areas of higher greenspace mediate this association.

Methods

We linked a population-based birth cohort of all deliveries in Metro Vancouver, Canada, from 2004 to 2009, with follow-up to 2014. Diagnoses were based on Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised instruments. Greenspace was quantified as the average of the annual mean Normalized Difference Vegetation Index (NDVI) within a 250 m buffer of a residential postal code. Air pollutant exposures—particulate matter with a diameter less than 2.5 µm (PM2.5), nitric oxide (NO), and nitrogen dioxide (NO2)—were derived from previously developed and temporally adjusted land use regression models. We estimated air pollutant exposures as the mean concentration per month during pregnancy. We calculated odds ratios (ORs) using logistic regression per NDVI interquartile range (IQR) increase, adjusting for child sex, birth month and year, maternal age and birthplace, and neighborhood-level urbanicity and income. To estimate the health impact of greenspace on ASD at the population level, we used the logistic regression model and marginal standardization to derive risk differences (RDs). Lastly, to quantify the mediating effect of greenspace on ASD risk through air pollution reduction, we used marginal structural models and a potential outcomes framework to calculate marginal risk differences (RDs) to decompose the total effect of greenspace on ASD into natural direct and indirect effects.

Results

Of 129,222 births, 1,921 (1.5 %) children were diagnosed with ASD. The adjusted OR for ASD per NDVI IQR (0.12) increase was 0.96 (95 % CI: 0.90, 1.02) in 250 m buffer zones and 0.94 (95 % CI: 0.89, 1.00) in 100 m buffer zones. On the additive scale, the adjusted RDs were null. Natural direct, natural indirect, and total effect RDs were null for PM2.5, NO, and NO2 mediation models.

Conclusion

Prenatal greenspace exposure was associated with reduced odds of ASD, but in the additive scale, this effect was null at the population level. No mediating effect was observed through reduced air pollution, suggesting that air pollution may act as a confounder rather than as a mediator.



中文翻译:

产前绿地暴露与自闭症谱系障碍之间的关联,以及减少空气污染的潜在中介作用:基于人群的出生队列研究

背景

自闭症谱系障碍 (ASD) 的发病率在过去几十年中有所增加。ASD 病因尚无定论,但研究表明遗传、表观遗传和环境影响因素以及可能的产前起源。很少有研究检查 ASD 的可改变环境风险因素,而检查保护性暴露的研究要少得多。绿地与儿童的积极发展有关,但非常有限的绿地研究检查了 ASD 风险或产前暴露。2017 年只有一项生态研究评估了绿地与 ASD 之间的关联,观察到了保护效益。绿地可能对 ASD 风险产生直接影响,并通过减少空气污染暴露而产生间接影响,空气污染是一个越来越多的疑似 ASD 风险因素。

目标

测量产前绿地暴露与 ASD 风险之间的关联,并检查绿地较高地区空气污染水平的降低是否介导了这种关联。

方法

我们将 2004 年至 2009 年加拿大大温哥华地区所有分娩的基于人口的出生队列与 2014 年的随访联系起来。诊断基于自闭症诊断观察计划和自闭症诊断访谈修订工具。绿地被量化为住宅邮政编码 250 m 缓冲区内的年平均归一化差异植被指数 (NDVI) 的平均值。空气污染物暴露——直径小于 2.5 µm 的颗粒物 (PM 2.5 )、一氧化氮 (NO) 和二氧化氮 (NO 2)——源自先前开发和经过时间调整的土地利用回归模型。我们将空气污染物暴露估计为怀孕期间每月的平均浓度。我们使用逻辑回归计算了每个 NDVI 四分位间距 (IQR) 增加的优势比 (OR),并调整了儿童性别、出生月份和年份、母亲年龄和出生地以及社区水平的城市化和收入。为了在人群层面估计绿地对 ASD 的健康影响,我们使用逻辑回归模型和边际标准化来推导风险差异 (RDs)。最后,通过减少空气污染来量化绿地对 ASD 风险的中介作用,

结果

在 129,222 名新生儿中,有 1,921 名(1.5%)儿童被诊断为患有 ASD。每个 NDVI IQR (0.12) 增加的 ASD 的调整 OR 在 250 m 缓冲区中为 0.96 (95 % CI: 0.90, 1.02),在 100 m 缓冲区中为 0.94 (95 % CI: 0.89, 1.00)。在加性量表上,调整后的 RD 为空。PM 2.5、NO 和 NO 2中介模型的自然直接、自然间接和总效应 RD 均为零。

结论

产前绿地暴露与 ASD 几率降低有关,但在加性量表中,这种影响在人群水平上是无效的。通过减少空气污染没有观察到中介效应,这表明空气污染可能是一个混杂因素而不是一个中介因素。

更新日期:2022-07-31
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