Author summaryWhy was this study done? Worldwide, in 2017, air pollution was thought to be responsible for an estimated 600,000 deaths of children aged under 5 years. Some, but not all, studies suggest an association between air pollution exposure and deaths during the first year of life. We investigated whether air pollution is associated with infant deaths after taking into account important factors such as deprivation, and also investigated which causes of death may be increased as a result of air pollution exposure. What did the researchers do and find? We used data for 7,984,366 babies born alive between 2001 and 2012 in England and Wales. We associated 3 air pollutants, namely particulate matter with aerodynamic diameter <= 10 mu m (PM10), nitrogen dioxide (NO2), and sulphur dioxide (SO2), with all-cause infant deaths (deaths in the first year of life), neonatal deaths (deaths occurring within the first 28 days of life), and postneonatal deaths (deaths occurring from 28 days up to 1 year of age), and with specific causes of infant deaths. Infant and postneonatal deaths were significantly associated with increased exposure to NO2, PM10, and SO2; however, risk of neonatal death was only significantly associated with SO2. The 3 air pollutants seemed to be associated with different underlying causes of deaths. What do these findings mean? We have shown that the 3 air pollutants are associated in different ways with neonatal and postneonatal deaths, with all 3 associated with infant deaths but only SO2 associated with neonatal deaths, suggesting that SO2 exposure is more likely to act via the mother. We also show that air pollutants are associated with deaths via different specific causes, thus suggesting that each acts in a unique way. Only by understanding how air pollutants act to cause increased infant mortality can prevention therapies be developed to prevent both fetal and newborn mortality. Background Many but not all studies suggest an association between air pollution exposure and infant mortality. We sought to investigate whether pollution exposure is differentially associated with all-cause neonatal or postneonatal mortality, or specific causes of infant mortality. Methods and findings We separately investigated the associations of exposure to particulate matter with aerodynamic diameter <= 10 mu m (PM10), nitrogen dioxide (NO2), and sulphur dioxide (SO2) with all-cause infant, neonatal, and postneonatal mortality, and with specific causes of infant deaths in 7,984,366 live births between 2001 and 2012 in England and Wales. Overall, 51.3% of the live births were male, and there were 36,485 infant deaths (25,110 neonatal deaths and 11,375 postneonatal deaths). We adjusted for the following major confounders: deprivation, birthweight, maternal age, sex, and multiple birth. Adjusted odds ratios (95% CI;p-value) for infant deaths were significantly increased for NO2, PM10, and SO2(1.066 [1.027, 1.107;p= 0.001], 1.044 [1.007, 1.082;p= 0.017], and 1.190 [1.146, 1.235;p< 0.001], respectively) when highest and lowest pollutant quintiles were compared; however, neonatal mortality was significantly associated with SO2(1.207 [1.154, 1.262;p< 0.001]) but not significantly associated with NO(2)and PM10(1.044 [0.998, 1.092;p= 0.059] and 1.008 [0.966, 1.052;p= 0.702], respectively). Postneonatal mortality was significantly associated with all pollutants: NO2, 1.108 (1.038, 1.182;p< 0.001); PM10, 1.117 (1.050, 1.188;p< 0.001); and SO2, 1.147 (1.076, 1.224;p< 0.001). Whilst all were similarly associated with endocrine causes of infant deaths (NO2, 2.167 [1.539, 3.052;p< 0.001]; PM10, 1.433 [1.066, 1.926;p= 0.017]; and SO2, 1.558 [1.147, 2.116;p= 0.005]), they were differentially associated with other specific causes: NO(2)and PM(10)were associated with an increase in infant deaths from congenital malformations of the nervous (NO2, 1.525 [1.179, 1.974;p= 0.001]; PM10, 1.457 [1.150, 1.846;p= 0.002]) and gastrointestinal systems (NO2, 1.214 [1.006, 1.466;p= 0.043]; PM10, 1.312 [1.096, 1.571;p= 0.003]), and NO(2)was also associated with deaths from malformations of the respiratory system (1.306 [1.019, 1.675;p= 0.035]). In contrast, SO(2)was associated with an increase in infant deaths from perinatal causes (1.214 [1.156, 1.275;p< 0.001]) and from malformations of the circulatory system (1.172 [1.011, 1.358;p= 0.035]). A limitation of this study was that we were not able to study associations of air pollution exposure and infant mortality during the different trimesters of pregnancy. In addition, we were not able to control for all confounding factors such as maternal smoking. Conclusions In this study, we found that NO2, PM10, and SO(2)were differentially associated with all-cause mortality and with specific causes of infant, neonatal, and postneonatal mortality.
