Mother-level random effect in the association between PM2.5 and fetal growth: A population-based pregnancy cohort

Low birth weight and preterm birth have a substantial public health impact. Studies examining their association with outdoor air pollution were identified using searches of bibliographic databases and reference lists of relevant papers. Pooled estimates of effect were calculated, heterogeneity was quantified, meta-regression was conducted and publication bias was examined. Sixty-two studies met the inclusion criteria. The majority of studies reported reduced birth weight and increased odds of low birth weight in relation to exposure to carbon monoxide (CO), nitrogen dioxide (NO(2)) and particulate matter less than 10 and 2.5 microns (PM(10) and PM(2.5)). Effect estimates based on entire pregnancy exposure were generally largest. Pooled estimates of decrease in birth weight ranged from 11.4 g (95% confidence interval -6.9-29.7) per 1 ppm CO to 28.1g (11.5-44.8) per 20 ppb NO(2), and pooled odds ratios for low birth weight ranged from 1.05 (0.99-1.12) per 10 μg/m(3) PM(2.5) to 1.10 (1.05-1.15) per 20 μg/m(3) PM(10) based on entire pregnancy exposure. Fewer effect estimates were available for preterm birth and results were mixed. Pooled odds ratios based on 3rd trimester exposures were generally most precise, ranging from 1.04 (1.02-1.06) per 1 ppm CO to 1.06 (1.03-1.11) per 20 μg/m(3) PM(10). Results were less consistent for ozone and sulfur dioxide for all outcomes. Heterogeneity between studies varied widely between pollutants and outcomes, and meta-regression suggested that heterogeneity could be partially explained by methodological differences between studies. While there is a large evidence base which is indicative of associations between CO, NO(2), PM and pregnancy outcome, variation in effects by exposure period and sources of heterogeneity between studies should be further explored. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n=321,223) and offspring birth weight (n=230,069 mothers), we identified 190 independent association signals (129 novel). We used structural equation modelling to decompose the contributions of direct fetal and indirect maternal genetic effects, and then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of those alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

Ambient air pollution has been associated with restricted fetal growth, which is linked with adverse respiratory health in childhood. We assessed the effect of maternal exposure to low concentrations of ambient air pollution on birthweight. We pooled data from 14 population-based mother-child cohort studies in 12 European countries. Overall, the study population included 74 178 women who had singleton deliveries between Feb 11, 1994, and June 2, 2011, and for whom information about infant birthweight, gestational age, and sex was available. The primary outcome of interest was low birthweight at term (weight <2500 g at birth after 37 weeks of gestation). Mean concentrations of particulate matter with an aerodynamic diameter of less than 2·5 μm (PM2·5), less than 10 μm (PM10), and between 2·5 μm and 10 μm during pregnancy were estimated at maternal home addresses with temporally adjusted land-use regression models, as was PM2·5 absorbance and concentrations of nitrogen dioxide (NO2) and nitrogen oxides. We also investigated traffic density on the nearest road and total traffic load. We calculated pooled effect estimates with random-effects models. A 5 μg/m(3) increase in concentration of PM2·5 during pregnancy was associated with an increased risk of low birthweight at term (adjusted odds ratio [OR] 1·18, 95% CI 1·06-1·33). An increased risk was also recorded for pregnancy concentrations lower than the present European Union annual PM2·5 limit of 25 μg/m(3) (OR for 5 μg/m(3) increase in participants exposed to concentrations of less than 20 μg/m(3) 1·41, 95% CI 1·20-1·65). PM10 (OR for 10 μg/m(3) increase 1·16, 95% CI 1·00-1·35), NO2 (OR for 10 μg/m(3) increase 1·09, 1·00-1·19), and traffic density on nearest street (OR for increase of 5000 vehicles per day 1·06, 1·01-1·11) were also associated with increased risk of low birthweight at term. The population attributable risk estimated for a reduction in PM2·5 concentration to 10 μg/m(3) during pregnancy corresponded to a decrease of 22% (95% CI 8-33%) in cases of low birthweight at term. Exposure to ambient air pollutants and traffic during pregnancy is associated with restricted fetal growth. A substantial proportion of cases of low birthweight at term could be prevented in Europe if urban air pollution was reduced. The European Union. Copyright © 2013 Elsevier Ltd. All rights reserved.