Windows of susceptibility and joint effects of prenatal and postnatal ambient air pollution and temperature exposure on asthma and wheeze in Mexican children

Introduction: Prenatal and early-life exposure to air pollution and extreme temperatures are associated with childhood asthma and wheeze. However, potential windows of susceptibility and their sex-specific and interactive effects have not been fully elucidated. We aimed to identify critical windows of susceptibility and evaluate sex-specific effects in these associations, and evaluate exposure interactions. Methods: We analyzed data from 468 mother-child pairs enrolled in the PROGRESS birth cohort in Mexico City. Daily residential levels of PM2.5, NO2, and temperature were generated from our validated spatiotemporally resolved models from conception to age 4 years. Childhood asthma and wheeze outcomes were collected at 4-6 and 7-8 years. Distributed lag nonlinear models (DLNMs) were used to identify susceptible windows for prenatal weekly-specific and postnatal monthly-specific associations of air pollution and temperature with respiratory outcomes adjusting for covariates. To evaluate sex-specific effects, DLNMs were stratified. Joint effects were assessed using relative excess risk due to interaction and attributable proportion. Results: Mid-gestation was a critical window for both PM 2.5 (weeks 20-28, cumulative OR: 1.18 [95% CI: 1.01, 1.37]; weeks 19-26, cumulative OR: 1.18 [95% CI: 1.02, 1.36]) and NO2 (weeks 18-25, cumulative OR: 1.16 [95% CI: 1.02, 1.31]) exposure, associated with higher odds of wheeze. Postnatal exposure to PM 2.5 and NO2 during the first year of life was also linked to higher odds of wheeze. The warmer and colder temperatures showed mixed effects on respiratory outcomes. We observed a synergistic interaction between high PM 2.5 and high temperature exposure during the first year of life, associated with higher odds of current wheeze. The associations of prenatal air pollution and temperature exposure with respiratory outcomes were more pronounced in males.