Green spaces
The exposure of interest was the amount of greenness in the residential
environment. Green space was assessed using the mean Normalized
Difference Vegetation Index (NDVI) within 100 m, 300 m, 500 m, and 1000
m of the participant’s residence during pregnancy and the first two
years of life in both spring and summer seasons. These area sizes were
selected to cover immediate areas of exposure, containing accessible
green spaces in accordance with the World Health Organization (WHO)
recommendations and within five to ten minute walking
distances.20-23 We selected the 300 m buffer for NDVI
for the main analyses, in accordance with the WHO and UNICEF
recommendations.23,24 The calculation of the NDVI was
based on land surface reflectance of visible red (VISR) and
near-infrared (NIR) wavelengths,25 applying the
following equation (Eq. (1)):
\(NDVI=\ \frac{NIR-VISR}{NIR+VISR}\) (1)
The values range between -1 (water) through zero (rock, sand and snow)
to 1, with higher positive values indicating denser green vegetation
(i.e., photosynthetically active and healthy
vegetation).25 Only cloud-free images from Landsat 5
(spatial resolution: 30 m) during the
spring (April–May) and summer
(June–August) periods were used from conception (1983-90) to the first
two years of life (1984-92) to capture maximum spatial contrasts in
greenness (Appendix). In Finland, spring begins in April and summer
usually begins in late May in southern Finland
(https://en.ilmatieteenlaitos.fi/seasons-in-finland).
Negative NDVI values were not included in the calculation. ArcMap 10.5
was used to process satellite images, and QGIS 3.8 was used to extract
the average NDVI within each buffer size.
Covariates
Any determinant of allergic rhinitis was considered a potential
confounder of the studied associations between green spaces and
occurrence of allergic rhinitis.18,26-32 We were able
to adjust for the following confounders: age, sex, socioeconomic status
measured by parental education level and occupation, maternal smoking
during pregnancy and environmental tobacco smoke exposure (Appendix).
Data on the covariates was obtained from the baseline questionnaire.
Statistical analysis
The statistical inference was based on estimation of the time of onset
of allergic rhinitis in relation to the green space in residential
surroundings during pregnancy and the first two years of life.
Hazard ratio (HR) was used as the
measure of effect. We applied Cox proportional hazards regression models
to estimate crude and adjusted hazard ratios for the association
between green space, measured as
the cumulative exposure to NDVI (during pregnancy and during the first
two years of life), and the risk of allergic rhinitis, measured as the
time of onset of allergic rhinitis up to six, 12 and 27 years of age.
Both crude and adjusted models were fitted, and the effect estimates
were expressed for a 1 NDVI-month
change in exposure. The final model was adjusted for participants’ sex
and age, parental socioeconomic status, maternal smoking, and
environmental tobacco smoke exposure, and NDVI during pregnancy (spring
and summer) or early-life NDVI exposure (spring and summer). We
hypothesized that air pollution (PM2.5,
PM10, O3, NO2 and
SO2) modifies the association between NDVI and allergic
rhinitis through several potential underlying mechanisms (see
Discussion).32 The CAUSALMED procedure in SAS was used
to calculate the proportions of the mediated effect based on theoretical
assumptions proposed by Valeri et al. 33. Based on
exploratory analyses, we used the
cut-off based on the highest
quartile of air pollutant level during pregnancy and early-life to
define lower (air pollutants level <4thquartile) or higher air pollution (air pollutant level
≥4th quartile) levels. We stratified the associations
between NDVI and allergic rhinitis by air pollution levels. Sensitivity
analysis using different buffer sizes (100 m, 500 m, and 1000 m) and
quartiles of exposure to NDVI (Table S1) were performed to evaluate the
robustness of our findings. Statistical analyses were performed using
SAS software version 9.4 TS Level 1M5.