Prenatal air pollution and neurodevelopment: a longitudinal neuroimaging study of mechanisms and early risk for ADHD in Puerto Rican children

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This study aims to examine the neurodevelopmental consequences (specifically risk for ADHD phenotypes) of prenatal maternal air pollution exposure and to examine two potential mechanisms, prenatal maternal inflammation and offspring sleep disruptions. Epidemiological studies support this association; however, studies have yet to determine (1) important exposure periods, (2) pollutant exposure effects independent of socio-economic status and adversity, (3) offspring sex effects, and (4) the underlying mechanisms. Air pollution exposure is often higher in disadvantaged communities; studies that do not consider the socioeconomic and adversity history of participants run the risk of reporting confounded effects. We will address gaps by examining the influence of prenatal PM2.5 exposure on neurodevelopment (via MRI) while controlling for postnatal PM2.5, critical environmental aspects (intergenerational adversity, SES, family functioning), and polygenetic ADHD risk. We will examine offspring brain white matter twice, in infancy (~2 weeks) and in childhood (2-9 yrs). We will work within a two-generation, epidemiological cohort of Puerto Ricans that has been followed since 2000 and carefully characterized for adversity, family functioning, and psychiatric illness. We will study BYS-ECHO children (Generation 2; G2's), who are currently being scanned during infancy (UH3OD023328) and propose to re-assess white matter development in toddlerhood (n=84; 12-24 mos) or childhood (n=98; 6-9yrs). We will index the effects of mother’s prenatal PM2.5 exposure estimated using highly resolved spatio-temporal prediction models (and supplemented by real-time air quality data via portable sensors in a sub-sample) on G2’s ADHD-related neurocircuitry and phenotypes, while controlling for the aforementioned variables. The overarching aim of this study is to examine the neurodevelopmental consequences of prenatal PM2.5 exposure and test two proposed underlying mechanisms: (Aim1) prenatal maternal inflammation, OR (Aim 2) sleep deficits in offspring (measured via in-home actigraphy assessments). Maternal inflammation is a prenatal mechanism, thus we hypothesize in Aim 1 that neurocircuitry alterations will be present in both infancy and toddler/childhood MRIs. Because offspring sleep is a postnatal mechanism, in this alterative (Aim 2) hypothesis we predict alterations in ADHD neurocircuitry in toddler/childhood, but not in newborns. It is also possible we find support for both aims, in which case we would be uniquely poised to examine cumulative and interactive effects. We will also test the moderating role of infant sex (Aim 3), and based on pre-clinical studies, hypothesize that males would demonstrate more susceptibility to prenatal air pollution. This study will be the first to utilize infant longitudinal neuroimaging to understand prenatal air pollution exposure. We will be uniquely able to disassociate the effects of prenatal PM2.5 exposure from those of postnatal factors and PM2.5 on brain development, and to test two putative mechanisms, both of which are potential modifiable targets for intervention.