Association of maternal air pollution exposure and infant lung function is modified by genetic propensity to oxidative stress.

IntroductionThe association between air pollution and poor respiratory health outcomes is well established, however less is known about the biological mechanisms, especially in early life. Children are particularly at risk from air pollution, especially during the prenatal period as their organs and systems are still undergoing crucial development. Therefore, our study aims to investigate if maternal exposure to air pollution during pregnancy is associated with oxidative stress (OS) and inflammation in pregnancy or infant lung function at 4 weeks of age, and the extent to which the association is modified by an infants genetic risk of OS. MethodsThe Barwon Infant Study (BIS) is a longitudinal study of Australian children from the region of Geelong, Victoria. A total of 314 infants had available lung function and maternal OS markers. Exposure to annual air pollutants (NO2 and PM2.5) were estimated using validated, satellite-based, land-use regression models. Infant lung function was measured by multiple-breath washout, and the ratio of peak tidal expiratory flow over expiratory time was calculated at 4 weeks of age. An inflammation biomarker, glycoprotein acetyls (GlycA), was measured in maternal (36 weeks) and cord blood, and oxidative stress (OS) biomarkers, 8-hydroxyguanine (8-OHGua) and 8-hydroxy-2-deoxyguanosine (8-OHdG) were measured in maternal urine at 28 weeks. A genetic pathway score for OS (gPFSox) was calculated for each infant participant in the BIS cohort, and high risk defined as score >8. Linear regression was used to explore the association of maternal air pollution exposure with infant lung function, and potential modification by OS genotype was tested through use of interaction terms and other methods. ResultsThere was no evidence of a relationship between maternal exposure to air pollution and infant lung function in the whole population. We did not find an association between air pollution and GlycA or OS during pregnancy. We found evidence of an association between NO2 and lower in functional residual capacity (FRC) for children with a high genetic risk of OS ({beta}=-5.3 mls, 95% CI (-9.3, -1.3), p=0.01). We also found that when NO2 was considered in tertiles, the highest tertile of NO2 was associated with increase in lung clearance index (LCI) ({beta}=0.46 turnovers, (95% CI 0.10, 0.82), p=0.01) in children with a genetic propensity to OS. ConclusionOur study found that high prenatal levels of exposure to ambient NO2 levels is associated with lower FRC and higher LCI in infants with a genetic propensity to oxidative stress. There was no relationship between maternal exposure to air pollution with maternal and cord blood inflammation or OS biomarkers.