Prenatal ambient air pollutant mixture exposure and neurodevelopment in urban children in the Northeastern United States

Background: Studies of prenatal air pollution (AP) exposure on child neurodevelopment have mostly focused on a single pollutant. We leveraged daily exposure data and implemented novel data-driven statistical approaches to assess effects of prenatal exposure to a mixture of seven air pollutants on cognitive functioning in school-age children from an urban pregnancy cohort. Methods: Analyses included 236 children born at ≥37 weeks gestation. Maternal prenatal daily exposure levels for nitrogen dioxide (NO₂), ozone (O₃), and constituents of fine particles [elemental carbon (EC), organic carbon (OC), nitrate (NO₃⁻), sulfate (SO₄²⁻), ammonium (NH₄⁺)] were estimated based on residential addresses using validated satellite-based hybrid models or global 3-D chemical-transport models. Children completed Wide Range Assessment of Memory and Learning (WRAML-2) and Conners’ Continuous Performance Test (CPT-II) at 6.5 ± 0.9 years of age. Time-weighted levels for mixture pollutants were estimated using Bayesian Kernel Machine Regression Distributed Lag Models (BKMR-DLMs), with which we also explored the interactions in the exposure-response functions among pollutants. Resulting time-weighted exposure levels were used in Weighted Quantile Sum (WQS) regressions to examine AP mixture effects on outcomes, adjusted for maternal age, education, child sex, and prenatal temperature. Results: Mothers were primarily ethnic minorities (81% Hispanic and/or black) reporting ≤12 years of education (68%). Prenatal AP mixture (per unit increase in WQS estimated AP index) was associated with decreased WRAML-2 general memory (GM; β = −0.64, 95%CI = −1.40, 0.00) and memory-related attention/concentration (AC; β = −1.03, 95%CI = −1.78, −0.27) indices, indicating poorer memory functioning, as well as increased CPT-II omission errors (OE; β = 1.55, 95%CI = 0.34, 2.77), indicating increased attention problems. When stratified by sex, association with AC index was significant among girls, while association with OE was significant among boys. Traffic-related pollutants (NO₂, OC, EC) and SO₄²⁻ were major contributors to these associations. There was no significant evidence of interactions among mixture components. Conclusions: Prenatal exposure to an AP mixture was associated with child neurocognitive outcomes in a sex- and domain-specific manner.