Pollen as a mediator between environmental greenness during pregnancy and infancy periods and childhood persistent asthma: A nationwide retrospective birth cohort study in Japan

The association between environmental greenness and childhood asthma remains unclear. Pollen has been proposed as a potential mechanism of detrimental associations. This study aimed to elucidate the mechanisms underlying the association between environmental greenness during the pre-, peri-, and postnatal periods and childhood persistent asthma. A nationwide retrospective birth cohort study was conducted using data from the Japan Medical Data Center (JMDC). Child-mother dyads between January 2010 and January 2017 were identified, and four subcohorts were developed based on the timing of exposure to the highest greenness season. The exposure of interest was environmental greenness levels between June and September, quantified using the normalized difference vegetation index (NDVI). The primary outcome was persistent asthma in children aged 4-5 years. Causal mediation analysis was conducted to evaluate pollen as a mediator between NDVI and asthma. In these analyses, linear and modified Poisson regression models were used to evaluate the association of NDVI with pollen levels and childhood persistent asthma. The analyses were stratified by metropolitan and non-metropolitan areas. Clinically meaningful confounders and predictors of asthma were adjusted in the statistical models. A total of 100,273 child-mother dyads were included in the entire cohort, with 24.1% of the children having persistent asthma at the ages of 4-5 years. Higher environmental greenness was associated with higher pollen levels. The modified Poisson regression models showed higher environmental greenness was associated with a slightly higher risk of persistent childhood asthma. In metropolitan areas, significant detrimental natural direct effects of NDVI were observed; however, the natural indirect effects were uncertain. A large part of the association between environmental greenness and childhood persistent asthma in metropolitan areas was attributed to mechanisms other than those involving pollen. The associations in non-metropolitan areas remain uncertain. Further studies are required to elucidate the underlying mechanisms.