Identifying sensitive windows of exposure to NO2 and fetal growth trajectories in a Spanish population-based birth cohort

Abstract

Background: The epidemiologic literature supports an association between air pollution exposure and adverse fetal development. Our group previously published associations between maternal exposure to nitrogen dioxide (NO2), averaged across pregnancy trimesters, and reduced fetal growth in the INMA (INfancia y Medio Ambiente) project. Here, we apply novel statistical methods with greater flexibility to identify narrower (i.e., weekly) periods of potential sensitivity of fetal growth to NO2 exposure. Methods: This study includes 2,141 women from three INMA regions: Valencia, Sabadell, and Gipuzkoa. Abdominal circumference (AC), biparietal diameter (BPD), femur length (FL), and estimated fetal weight (EFW) were assessed via ultrasounds at 12, 20, and 34 weeks. Linear mixed models produced growth curves from which standard deviation scores were calculated to describe growth trajectories in the first 12, 12-20, and 20-34 weeks of pregnancy. Weekly NO2 exposures were estimated using temporally adjusted land-use regression models and assigned to women based on their addresses during pregnancy. We used distributed lag non-linear models to identify gestational weeks during which fetal growth is sensitive to NO2 exposure (per 10-µg/m3), adjusted for relevant covariates. Results: NO2 exposure during gestational week 4 was associated with reduced EFW trajectories in the first 12 weeks (β=-0.019; 95%CI: -0.037,-0.001), while exposure during gestational week 5 was associated with reduced EFW during weeks 20-34 (β=-0.004; 95%CI: -0.007,0.00). NO2 exposure during gestational week 11 was associated with reduced AC growth in the first 12 weeks (β=-0.051; 95%CI: -0.097,-0.006), while exposures during weeks 7 and 8 were associated with reduced AC growth during weeks 12-20 (β=-0.010, 95%CI: -0.020,0.00; β=-0.024; 95%CI: -0.008,0.00, respectively). NO2 exposure in each of gestational weeks 6-16 was associated with decreased BPD trajectories during weeks 20-34. Conclusions: Our results suggest NO2 exposures during specific weeks in early and mid, but not late, pregnancy are associated with reduced fetal growth.