Mother-level random effect in the association between PM_2.5 and fetal growth: A population-based pregnancy cohort

Background: A growing body of literature reports associations between exposure to particulate matter with diameter ≤2.5 μm (PM_2.5) during pregnancy and birth outcomes. However, findings are inconsistent across studies. Objectives: To assess the association between PM_2.5 and birth outcomes of fetal growth in a cohort with high prevalence of siblings by multilevel models accounting for geographical- and mother-level correlations. Methods: In Israel, we used Maccabi Healthcare Services data to establish a population-based cohort of 381,265 singleton births reaching 24–42 weeks’ gestation and birth weight of 500–5000 g (2004–2015). Daily PM_2.5 predictions from a satellite-based spatiotemporal model were linked to the date of birth and maternal residence. We generated mean PM_2.5 values for the entire pregnancy and for exposure periods during pregnancy. Associations between exposure and birth outcomes were modeled by using multilevel logistic regression with random effects for maternal locality of residence, administrative census area (ACA) and mother. Results: In fully adjusted models with a mother-level random intercept only, a 10-μg/m³ increase in PM_2.5 over the entire pregnancy was positively associated with term low birth weight (TLBW) (Odds ratio, OR = 1.25, 95% confidence interval, CI: 1.09,1.43) and small for gestational age (SGA) (OR = 1.15, 95% CI: 1.06,1.26). Locality- and ACA-level effects accounted for <0.4% of the variance while mother-level effects explained ∼50% of the variability. Associations varied by exposure period, infants’ sex, birth order, and maternal pre-pregnancy BMI. Conclusions: Consideration of mother-level variability in a region with high fertility rates provides new insights on the strength of associations between PM_2.5 and birth outcomes.