Exposure assessment
We measured exposure to greenness in the residential environment as our exposure of interest. Greenness was measured using the mean Normalized Difference Vegetation Index (NDVI) within 100 m, 300 m, 500 m, and 1000 m of the participant’s residence(s) during pregnancy and the first two years of life in both spring and summer seasons., We selected the 300 m radius for NDVI for the main analyses, as this has been recommended by the WHO and UNICEF. The calculation of the NDVI was based on land surface reflectance of visible red (VISR) and near-infrared (NIR) wavelengths, applying the following equation (Eq. (1)):
\(NDVI=\ \frac{NIR-VISR}{NIR+VISR}\) (1)
The NDVI values range from -1 to 1, where negative values represent water, zero values rock, sand or snow (without vegetation), and positive values indicate density of green vegetation (i.e., the highest NDVI values are observed from photosynthetically active and healthy vegetation). We used only cloud-free images during the spring (April–May) and summer (June–August) seasons from Landsat 5 (spatial resolution: 30 m) between conception (1983-90) and the first two years of life (1984-92) to capture maximum spatial contrasts in greenness (Figure 1). The used images represented the highest available quality and processing level (https://earthexplorer.usgs.gov/). We included NDVI values higher than zero to investigate the role of green vegetation on the risk of asthma. In southern Finland, the spring usually begins in April and the summer begins in late May (https://en.ilmatieteenlaitos.fi/seasons-in-finland). ArcMap 10.5 was used to process satellite images, and QGIS 3.8 was used to extract the average NDVI within each buffer size.
We calculated individual-level cumulative exposure to NDVI (cumNDVI) during pregnancy and early life (first two years of life) by taking the average of monthly exposure over the residential history, while weighting by the days spent in each residential address and time of pregnancy in the spring and summer seasons. Estimates were based on the number of pregnancy or early-life days during spring and summer [Eq. (2)].
\(\text{\ Cumulative\ exposure\ to\ NDVI}_{\ residence,\ \ i}=\ \sum{\text{mean\ exposure\ to\ NDVI}_{j}*duration\ of\ exposure}_{j}\text{\ \ \ \ \ \ \ \ \ \ \ \ }\)(2)
where residencei corresponds to ith participant, mean exposure to NDVIj corresponds to the mean exposure to NDVI in jth residential addresses during months 4-5 (April-May) for spring and during months 6-8 (June-August) for summer, and the duration of exposurej corresponds to the number of estimated days within specific month during spring/summer periods in jth residential addresses during pregnancy or early life.
We defined individual cumNDVI during the entire pregnancy, the first trimester (defined as gestational months 1 to 3), the second trimester (gestational months 4 to 6) and the third trimester (gestational months 7 to the end of pregnancy) by taking the average of exposure during each pregnancy month. The child was exposed to the average spring NDVI level during pregnancy months from April to May, to the average summer NDVI level during pregnancy months from June to August, and to NDVI level 0 from September to March. The latter corresponded to a lack of exposure outside of the growing season when NDVI values decrease significantly for all types of land use in vegetation zones like southern Finland in the Baltic Sea region.
We conducted a sensitivity analysis where mean exposure to NDVIj corresponded to the mean exposure to NDVI in jth residential address during the months 3-5 (March-May) for spring and the months 6-9 (June-September) for summer.