Abstract
BACKGROUND: Despite accumulating evidence linking greenness with the decreased risk of low birthweight (LBW), the potential modification and mediation effects of ambient air pollution remain unstudied. METHODS: We conducted a nationwide birth cohort analysis using nearly 3.9 million registry-based mother-infant records across 31 provinces in Iran during 2013-2018. Greenness exposure during pregnancy was assessed utilizing the normalized difference vegetation index (NDVI) within multiple buffers (500-3000 m). Logistic regression model was used to analyze the associations of maternal greenness exposure with LBW and small for gestational age (SGA). Modification effects of PM(2.5) and O(3) levels were checked via comparing greenness-related risks in stratified analyses by grouping maternal air pollution exposure into low, medium, and high levels based on cut-points at tertiles. Mediation analysis was adopted to quantify the degree to which PM(2.5) and O(3) exposure mediated the associations of greenness exposure with LBW and SGA. RESULTS: We observed consistently lower LBW and SGA risks in relation to greater greenness within buffers of 500-3000 m. Each 0.1-unit rise of NDVI within the 3000-m buffer (NDVI-(3000 m)) was associated with an estimated odds of 0.902 (95% confidence interval [CI]: 0.900-0.905) for LBW and 0.887 (95% CI: 0.886-0.889) for SGA. Stratified analyses provided consistent evidence for greater greenness-related protective effects in lowering LBW and SGA risks at higher PM(2.5) and O(3) levels in multiple age subgroups. Among the entire group with maternal age of 15-49 years, for instance, LBW risk for each 0.1-unit rise in NDVI-(3000 m) declined by 6.8% (95% CI: 6.4%-7.2%), 10.1% (95% CI: 9.7%-10.6%), and 10.9% (95% CI: 10.4%-11.3%) in the 1st to 3rd tertile stratum of PM(2.5) levels, respectively. The mediation analysis suggested a significant mediating role of ambient air pollution in greenness-LBW/SGA association, where reduced PM(2.5) and O(3) mediated 2.2%-3.4% and 7.3%-12.1% risks during the pregnancy. CONCLUSIONS: This study provided national evidence for greater health benefits of greenness in alleviating LBW and SGA risks among pregnant women being exposed to higher PM(2.5) and O(3) pollution levels. Reduced PM(2.5) and O(3) may partially mediate the association of greenspace exposure with fetal growth.