Prenatal exposure to PM2.5 and childhood cognition: Accounting for between-site heterogeneity in a pooled analysis of ECHO cohorts in the Northeastern United States.

BACKGROUND: Emerging studies have investigated the adverse health effects of PM2.5 using data from multiple cohorts, and results often are not generalizable across cohorts. We aimed to assess associations between prenatal PM2.5 and childhood cognition in two U.S. cohorts while accounting for between-site heterogeneity. METHODS: Analyses included 348 mother-child dyads enrolled in the dual site (New York City and Boston) PRogramming of Intergenerational Stress Mechanisms (PRISM) cohort and in the First Thousand Days of Life (FTDL) study (Northern Virginia) participating in the Environmental influences on Child Health Outcomes (ECHO) national consortium. Residential prenatal PM2.5 exposure was estimated using a validated satellite-based model and childhood cognition was measured using the NIH Toolbox Cognition Battery at three to eight years of age. We used a log-linear model applied to contingency tables formed by cross-classifying covariates by site to examine between-site heterogeneity using 3rd trimester PM2.5 exposure, age-corrected cognition scores, and covariates potentially causing heterogeneities. Multivariable linear regression models informed by the combinability analysis were used to estimate the coefficients and 95% confidence intervals (CIs) for the association between 3rd trimester PM2.5 exposure and age-corrected cognition scores (mean = 100, SD = 15). RESULTS: The log-linear model indicated that inter-study associations were similar between PRISM-NYC and FTDL, which were different from those in PRISM-Boston. Accordingly, we combined the data of PRISM-NYC and FTDL cohorts. We observed associations between 3rd trimester PM2.5 and cognition scores, findings were varying by site, childsex, and test. For example, a 1 µg/m3 increase of 3rd trimester PM2.5 was associated with -4.35 (95% CI = -8.73, -0.25) mean early childhood cognition scores in females in PRISM-Boston. In the pooled NYC + FTDL site, the association between PM2.5 and childhood cognition may be modified by maternal education and urbanicity. CONCLUSIONS: We found associations between prenatal PM2.5 and impaired childhood cognition. Since multi-site analyses are increasingly conducted, our findings suggest the needed awareness of between-site heterogeneity.

Prenatal fine particulate exposure and early childhood asthma: Effect of maternal stress and fetal sex.

BACKGROUND: The impact of prenatal ambient air pollution on child asthma may be modified by maternal stress, child sex, and exposure dose and timing. OBJECTIVE: We prospectively examined associations between coexposure to prenatal particulate matter with an aerodynamic diameter of less than 2.5 microns (PM2.5) and maternal stress and childhood asthma (n = 736). METHODS: Daily PM2.5 exposure during pregnancy was estimated using a validated satellite-based spatiotemporally resolved prediction model. Prenatal maternal negative life events (NLEs) were dichotomized around the median (high: NLE ≥ 3; low: NLE < 3). We used Bayesian distributed lag interaction models to identify sensitive windows for prenatal PM2.5 exposure on children's asthma by age 6 years, and determine effect modification by maternal stress and child sex. RESULTS: Bayesian distributed lag interaction models identified a critical window of exposure (19-23 weeks' gestation, cumulative odds ratio, 1.15; 95% CI, 1.03-1.26; per interquartile range [1.7 µg/m3] increase in prenatal PM2.5 level) during which children concomitantly exposed to prenatal PM2.5 and maternal stress had increased risk of asthma. No significant association was seen in children born to women reporting low prenatal stress. When examining modifying effects of prenatal stress and fetal sex, we found that boys born to mothers with higher prenatal stress were most vulnerable (19-21 weeks' gestation; cumulative odds ratio, 1.28; 95% CI, 1.15-1.41; per interquartile range increase in PM2.5). CONCLUSIONS: Prenatal PM2.5 exposure during sensitive windows is associated with increased risk of child asthma, especially in boys concurrently exposed to elevated maternal stress.

Prenatal nitrate air pollution exposure and reduced child lung function: Timing and fetal sex effects.

BACKGROUND: Prenatal particulate air pollution exposure may alter lung growth and development in utero in a time-sensitive and sex-specific manner, resulting in reduced lung function in childhood. Such relationships have not been examined for nitrate (NO3-). METHODS: We implemented Bayesian distributed lag interaction models (BDLIMs) to identify sensitive prenatal windows for the influence of NO3- on lung function at age 7 years, assessing effect modification by fetal sex. Analyses included 191 mother-child dyads. Daily ambient NO3- exposure over pregnancy was estimated using a hybrid chemical transport (Geos-Chem)/land-use regression model. Spirometry was performed at mean (SD) age of 6.99 (0.89) years, with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) z-scores accounting for child age, sex, height and race/ethnicity. RESULTS: Most mothers were Hispanic (65%) or Black (22%), had ≤ high school education (67%), and never smoked (71%); 17% children had asthma. BDILMs adjusted for maternal age and education and child's asthma identified an early sensitive window of 6-12 weeks gestation, during which increased NO3- was significantly associated with reduced FEV1 z-scores specifically among boys. BDLIM analyses demonstrated similar sex-specific patterns for FVC. CONCLUSION: Early gestational NO3- exposure is associated with reduced child lung function, especially in boys.

Prenatal and postnatal stress and asthma in children: Temporal- and sex-specific associations.

BACKGROUND: Temporal- and sex-specific effects of perinatal stress have not been examined for childhood asthma. OBJECTIVES: We examined associations between prenatal and/or postnatal stress and children's asthma (n = 765) and effect modification by sex in a prospective cohort study. METHODS: Maternal negative life events were ascertained prenatally and postpartum. Negative life event scores were categorized as 0, 1 to 2, 3 to 4, or 5 or greater to assess exposure-response relationships. We examined effects of prenatal and postnatal stress on children's asthma by age 6 years, modeling each as independent predictors, mutually adjusting for prenatal and postnatal stress, and finally considering interactions between prenatal and postnatal stress. Effect modification by sex was examined in stratified analyses and by fitting interaction terms. RESULTS: When considering stress in each period independently, among boys, a dose-response relationship was evident for each level increase on the ordinal scale prenatally (odds ratio [OR], 1.38; 95% CI, 1.06-1.79; P value for trend = .03) and postnatally (OR, 1.53; 95% CI, 1.16-2.01; P value for trend = .001); among girls, only the postnatal trend was significant (OR, 1.60; 95% CI, 1.14-2.22; P value for trend = .005). Higher stress in both the prenatal and postnatal periods was associated with increased odds of receiving a diagnosis of asthma in girls (OR, 1.37; 95% CI, 0.98-1.91; Pinteraction = .07) but not boys (OR, 1.08; 95% CI, 0.82-1.42; Pinteraction = .61). CONCLUSIONS: Although boys were more vulnerable to stress during the prenatal period, girls were more affected by postnatal stress and cumulative stress across both periods in relation to asthma. Understanding sex and temporal differences in response to early-life stress might provide unique insight into the cause and natural history of asthma.