Air Pollution Exposures and Child Executive Function: A U.S. Multi-Cohort Study.

BACKGROUND: Executive function, which develops rapidly in childhood, enables problem solving, focused attention, and planning. Animal models describe executive function decrements associated with ambient air pollution exposure, but epidemiologic studies are limited. METHODS: We examined associations between early childhood air pollution exposure and school-aged executive function in 1,235 children from three U.S. pregnancy cohorts in the ECHO-PATHWAYS Consortium. We derived point-based residential exposures to ambient particulate matter ≤2.5µm in aerodynamic diameter (PM2.5) and nitrogen dioxide (NO2), and ozone (O3) at ages 0-4 years from spatiotemporal models with a 2-week resolution. We assessed executive function across three domains -- cognitive flexibility, working memory, and inhibitory control -- using performance-based measures and calculated a composite score quantifying overall performance. We fitted linear regressions to assess air pollution - child executive function associations, adjusting for sociodemographic characteristics, maternal mental health, and health behaviors, and examined modification by child sex, maternal education, and neighborhood educational opportunity. RESULTS: In the overall sample, we found hypothesized inverse associations in crude but not adjusted models. Modified associations between NO2 exposure and working memory by neighborhood education opportunity were present (P interaction = 0.05), with inverse associations more pronounced in the "High" and "Very high" categories. Associations of interest did not differ by child sex or maternal education. CONCLUSIONS: This work contributes to the evolving science regarding early-life environmental exposures and child development. There remains a need for continued exploration in future research endeavors, to elucidate the complex interplay between natural environment and social determinants influencing child neurodevelopment.

Maternal stressful life events during pregnancy and childhood asthma and wheeze.

BACKGROUND: Studies have linked prenatal maternal psychosocial stress to childhood wheeze/asthma but have rarely investigated factors that may mitigate risks. OBJECTIVE: To investigate associations between prenatal stress and childhood wheeze/asthma, evaluating factors that may modify stress effects. METHODS: Participants included 2056 mother-child dyads from Environmental influences on Child Health Outcomes (ECHO)-PATHWAYS, a consortium of 3 prospective pregnancy cohorts (the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study, The Infant Development and Environment Study, and a subset of the Global Alliance to Prevent Prematurity and Stillbirth study) from 6 cities. Maternal stressful life events experienced during pregnancy (PSLEs) were reported using the Pregnancy Risk Assessment Monitoring System Stressful Life Events questionnaire. Parents reported child wheeze/asthma outcomes at age 4 to 6 years using standardized questionnaires. We defined outcomes as ever asthma, current wheeze, current asthma, and strict asthma. We used modified Poisson regression with robust standard errors (SEs) to estimate risk ratios (RRs) and 95% CI per 1-unit increase in PSLE, adjusting for confounders. We evaluated effect modification by child sex, maternal history of asthma, maternal childhood traumatic life events, neighborhood-level resources, and breastfeeding. RESULTS: Overall, we observed significantly elevated risk for current wheeze with increasing PSLE (RR, 1.09 [95% CI, 1.03-1.14]), but not for other outcomes. We observed significant effect modification by child sex for strict asthma (P interaction = .03), in which risks were elevated in boys (RR, 1.10 [95% CI, 1.02-1.19]) but not in girls. For all other outcomes, risks were significantly elevated in boys and not in girls, although there was no statistically significant evidence of effect modification. We observed no evidence of effect modification by other factors (P interactions > .05). CONCLUSION: Risk of adverse childhood respiratory outcomes is higher with increasing maternal PSLEs, particularly in boys.

Individual and Neighborhood Level Predictors of Children's Exposure to Residential Greenspace.

Inequities in urban greenspace have been identified, though patterns by race and socioeconomic status vary across US settings. We estimated the magnitude of the relationship between a broad mixture of neighborhood-level factors and residential greenspace using weighted quantile sum (WQS) regression, and compared predictive models of greenspace using only neighborhood-level, only individual-level, or multi-level predictors. Greenspace measures included the Normalized Difference Vegetation Index (NDVI), tree canopy, and proximity of the nearest park, for residential locations in Shelby County, Tennessee of children in the CANDLE cohort. Neighborhood measures include socioeconomic and education resources, as well as racial composition and racial residential segregation. In this sample of 1012 mother-child dyads, neighborhood factors were associated with higher NDVI and tree canopy (0.021 unit higher NDVI [95% CI: 0.014, 0.028] per quintile increase in WQS index); homeownership rate, proximity of and enrollment at early childhood education centers, and racial composition, were highly weighted in the WQS index. In models constrained in the opposite direction (0.028 unit lower NDVI [95% CI: - 0.036, - 0.020]), high school graduation rate and teacher experience were highly weighted. In prediction models, adding individual-level predictors to the suite of neighborhood characteristics did not meaningfully improve prediction accuracy for greenspace measures. Our findings highlight disparities in greenspace for families by neighborhood socioeconomic and early education factors, and by race, suggesting several neighborhood indicators for consideration both as potential confounders in studies of greenspace and pediatric health as well as in the development of policies and programs to improve equity in greenspace access.

Long-term ozone exposure and lung function in middle childhood.

BACKGROUND: Ozone (O3) exposure interrupts normal lung development in animal models. Epidemiologic evidence further suggests impairment with higher long-term O3 exposure across early and middle childhood, although study findings to date are mixed and few have investigated vulnerable subgroups. METHODS: Participants from the CANDLE study, a pregnancy cohort in Shelby County, TN, in the ECHO-PATHWAYS Consortium, were included if children were born at gestational age >32 weeks, completed a spirometry exam at age 8-9, and had a valid residential history from birth to age 8. We estimated lifetime average ambient O3 exposure based on each child's residential history from birth to age 8, using a validated fine-resolution spatiotemporal model. Spirometry was performed at the age 8-9 year study visit to assess Forced Expiratory Volume in the first second (FEV1) and Forced Vital Capacity (FVC) as primary outcomes; z-scores were calculated using sex-and-age-specific reference equations. Linear regression with robust variance estimators was used to examine associations between O3 exposure and continuous lung function z-scores, adjusted for child, sociodemographic, and home environmental factors. Potential susceptible subgroups were explored using a product term in the regression model to assess effect modification by child sex, history of bronchiolitis in infancy, and allergic sensitization. RESULTS: In our sample (n = 648), O3 exposure averaged from birth to age 8 was modest (mean 26.6 [SD 1.1] ppb). No adverse associations between long-term postnatal O3 exposure were observed with either FEV1 (ß = 0.12, 95% CI: -0.04, 0.29) or FVC (ß = 0.03, 95% CI: -0.13, 0.19). No effect modification by child sex, history of bronchiolitis in infancy, or allergic sensitization was detected for associations with 8-year average O3. CONCLUSIONS: In this sample with low O3 concentrations, we did not observe adverse associations between O3 exposures averaged from birth to age 8 and lung function in middle childhood.

Associations of residential green space with internalizing and externalizing behavior in early childhood.

BACKGROUND: Green space exposures may promote child mental health and well-being across multiple domains and stages of development. The aim of this study was to investigate associations between residential green space exposures and child mental and behavioral health at age 4-6 years. METHODS: Children's internalizing and externalizing behaviors in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort in Shelby County, Tennessee, were parent-reported on the Child Behavior Checklist (CBCL). We examined three exposures-residential surrounding greenness calculated as the Normalized Difference Vegetation Index (NDVI), tree cover, and park proximity-averaged across the residential history for the year prior to outcome assessment. Linear regression models were adjusted for individual, household, and neighborhood-level confounders across multiple domains. Effect modification by neighborhood socioeconomic conditions was explored using multiplicative interaction terms. RESULTS: Children were on average 4.2 years (range 3.8-6.0) at outcome assessment. Among CANDLE mothers, 65% self-identified as Black, 29% as White, and 6% as another or multiple races; 41% had at least a college degree. Higher residential surrounding greenness was associated with lower internalizing behavior scores (-0.66 per 0.1 unit higher NDVI; 95% CI: -1.26, -0.07) in fully-adjusted models. The association between tree cover and internalizing behavior was in the hypothesized direction but confidence intervals included the null (-0.29 per 10% higher tree cover; 95% CI: -0.62, 0.04). No associations were observed between park proximity and internalizing behavior. We did not find any associations with externalizing behaviors or the attention problems subscale. Estimates were larger in neighborhoods with lower socioeconomic opportunity, but interaction terms were not statistically significant. CONCLUSIONS: Our findings add to the accumulating evidence of the importance of residential green space for the prevention of internalizing problems among young children. This research suggests the prioritization of urban green spaces as a resource for child mental health.

Prenatal polycyclic aromatic hydrocarbon exposure and asthma at age 8-9 years in a multi-site longitudinal study.

BACKGROUND AND AIM: Studies suggest prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) may influence wheezing or asthma in preschool-aged children. However, the impact of prenatal PAH exposure on asthma and wheeze in middle childhood remain unclear. We investigated these associations in socio-demographically diverse participants from the ECHO PATHWAYS multi-cohort consortium. METHODS: We included 1,081 birth parent-child dyads across five U.S. cities. Maternal urinary mono-hydroxylated PAH metabolite concentrations (OH-PAH) were measured during mid-pregnancy. Asthma at age 8-9 years and wheezing trajectory across childhood were characterized by caregiver reported asthma diagnosis and asthma/wheeze symptoms. We used logistic and multinomial regression to estimate odds ratios of asthma and childhood wheezing trajectories associated with five individual OH-PAHs, adjusting for urine specific gravity, various maternal and child characteristics, study site, prenatal and postnatal smoke exposure, and birth year and season in single metabolite and mutually adjusted models. We used multiplicative interaction terms to evaluate effect modification by child sex and explored OH-PAH mixture effects through Weighted Quantile Sum regression. RESULTS: The prevalence of asthma in the study population was 10%. We found limited evidence of adverse associations between pregnancy OH-PAH concentrations and asthma or wheezing trajectories. We observed adverse associations between 1/9-hydroxyphenanthrene and asthma and persistent wheeze among girls, and evidence of inverse associations with asthma for 1-hydroxynathpthalene, which was stronger among boys, though tests for effect modification by child sex were not statistically significant. CONCLUSIONS: In a large, multi-site cohort, we did not find strong evidence of an association between prenatal exposure to PAHs and child asthma at age 8-9 years, though some adverse associations were observed among girls.

Role of Air Pollution in the Development of Asthma Among Children with a History of Bronchiolitis in Infancy.

BACKGROUND: Infants experiencing bronchiolitis are at increased risk for asthma, but few studies have identified modifiable risk factors. We assessed whether early life air pollution influenced child asthma and wheeze at age 4-6 years among children with a history of bronchiolitis in the first postnatal year. METHODS: Children with caregiver-reported physician-diagnosed bronchiolitis were drawn from ECHO-PATHWAYS, a pooled longitudinal cohort from six US cities. We estimated their air pollution exposure from age 1 to 3 years from validated spatiotemporal models of fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ). Caregivers reported children's current wheeze and asthma at age 4-6 years. We used modified Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for child, maternal, and home environmental factors. We assessed effect modification by child sex and maternal history of asthma with interaction models. RESULTS: A total of 224 children had caregiver-reported bronchiolitis. Median (interquartile range) 2-year pollutant concentrations were 9.3 (7.8-9.9) µg/m 3 PM 2.5 , 8.5 (6.4-9.9) ppb NO 2 , and 26.6 (25.6-27.7) ppb O 3 . RRs (CI) for current wheeze per 2-ppb higher O 3 were 1.3 (1.0-1.7) and 1.4 (1.1-1.8) for asthma. NO 2 was inversely associated with wheeze and asthma whereas associations with PM 2.5 were null. We observed interactions between NO 2 and PM 2.5 and maternal history of asthma, with lower risks observed among children with a maternal history of asthma. CONCLUSION: Our results are consistent with the hypothesis that exposure to modest postnatal O 3 concentrations increases the risk of asthma and wheeze among the vulnerable subpopulation of infants experiencing bronchiolitis.

Placental transcriptomic signatures of spontaneous preterm birth.

BACKGROUND: Spontaneous preterm birth accounts for most preterm births and leads to significant morbidity in the newborn and childhood period. This subtype of preterm birth represents an increasing proportion of all preterm births when compared with medically indicated preterm birth, yet it is understudied in omics analyses. The placenta is a key regulator of fetal and newborn health, and the placental transcriptome can provide insight into pathologic changes that lead to spontaneous preterm birth. OBJECTIVE: This analysis aimed to identify genes for which placental expression was associated with spontaneous preterm birth (including early preterm and late preterm birth). STUDY DESIGN: The ECHO PATHWAYS consortium extracted RNA from placental samples collected from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood and the Global Alliance to Prevent Prematurity and Stillbirth studies. Placental transcriptomic data were obtained by RNA sequencing. Linear models were fit to estimate differences in placental gene expression between term birth and spontaneous preterm birth (including gestational age subgroups defined by the American College of Obstetricians and Gynecologists). Models were adjusted for numerous confounding variables, including labor status, cohort, and RNA sequencing batch. This analysis excluded patients with induced labor, chorioamnionitis, multifetal gestations, or medical indications for preterm birth. Our combined cohort contained gene expression data for 14,023 genes in 48 preterm and 540 term samples. Genes and pathways were considered statistically significantly different at false discovery rate-adjusted P value of <.05. RESULTS: In total, we identified 1728 genes for which placental expression was associated with spontaneous preterm birth with more differences in expression in early preterm samples than late preterm samples when compared with full-term samples. Of those, 9 genes were significantly decreased in both early and late spontaneous preterm birth, and the strongest associations involved placental expression of IL1B, ALPL, and CRLF1. In early and late preterm samples, we observed decreased expression of genes involved in immune signaling, signal transduction, and endocrine function. CONCLUSION: This study provides a comprehensive assessment of the differences in the placental transcriptome associated with spontaneous preterm birth with robust adjustment for confounding. Results of this study are in alignment with the known etiology of spontaneous preterm birth, because we identified multiple genes and pathways for which the placental and chorioamniotic membrane expression was previously associated with prematurity, including IL1B. We identified decreased expression in key signaling pathways that are essential for placental growth and function, which may be related to the etiology of spontaneous preterm birth. We identified increased expression of genes within metabolic pathways associated exclusively with early preterm birth. These signaling and metabolic pathways may provide clinically targetable pathways and biomarkers. The findings presented here can be used to understand underlying pathologic changes in premature placentas, which can inform and improve clinical obstetrics practice.

Prenatal exposure to polycyclic aromatic hydrocarbons is not associated with behavior problems in preschool and early school-aged children: A prospective multi-cohort study.

BACKGROUND: Epidemiological study findings are inconsistent regarding associations between prenatal polycyclic aromatic hydrocarbon (PAH) exposures and childhood behavior. This study examined associations of prenatal PAH exposure with behavior at age 4-6 years in a large, diverse, multi-region prospective cohort. Secondary aims included examination of PAH mixtures and effect modification by child sex, breastfeeding, and child neighborhood opportunity. METHODS: The ECHO PATHWAYS Consortium pooled 1118 mother-child dyads from three prospective pregnancy cohorts in six U.S. cities. Seven PAH metabolites were measured in prenatal urine. Child behavior was assessed at age 4-6 using the Total Problems score from the Child Behavior Checklist (CBCL). Neighborhood opportunity was assessed using the socioeconomic and educational scales of the Child Opportunity Index. Multivariable linear regression was used to estimate associations per 2-fold increase in each PAH metabolite, adjusted for demographic, prenatal, and maternal factors and using interaction terms for effect modifiers. Associations with PAH mixtures were estimated using Weighted Quantile Sum Regression (WQSR). RESULTS: The sample was racially and sociodemographically diverse (38% Black, 49% White, 7% Other; household-adjusted income range $2651-$221,102). In fully adjusted models, each 2-fold increase in 2-hydroxynaphthalene was associated with a lower Total Problems score, contrary to hypotheses (b = -0.80, 95% CI = -1.51, -0.08). Associations were notable in boys (b = -1.10, 95% CI = -2.11, -0.08) and among children breastfed 6+ months (b = -1.31, 95% CI = -2.25, -0.37), although there was no statistically significant evidence for interaction by child sex, breastfeeding, or neighborhood child opportunity. Associations were null for other PAH metabolites; there was no evidence of associations with PAH mixtures from WQSR. CONCLUSION: In this large, well-characterized, prospective study of mother-child pairs, prenatal PAH exposure was not associated with child behavior problems. Future studies characterizing the magnitude of prenatal PAH exposure and studies in older childhood are needed.

Intergenerational transmission of stress: Multi-domain stressors from maternal childhood and pregnancy predict children's mental health in a racially and socioeconomically diverse, multi-site cohort.

PURPOSE: Despite growing recognition that unfortunately common maternal stress exposures in childhood and pregnancy may have intergenerational impacts on children's psychiatric health, studies rarely take a life course approach. With child psychopathology on the rise, the identification of modifiable risk factors is needed to promote maternal and child well-being. In this study, we examined associations of maternal exposure to childhood traumatic events (CTE) and pregnancy stressful life events (PSLE) with child mental health problems in a large, sociodemographically diverse sample. METHODS: Participants were mother-child dyads in the ECHO-PATHWAYS consortium's harmonized data across three U.S. pregnancy cohorts. Women completed questionnaires regarding their own exposure to CTE and PSLE, and their 4-6-year-old child's mental health problems using the Child Behavior Checklist (CBCL). Regression analyses estimated associations between stressors and child total behavior problems, adjusting for confounders. RESULTS: Among 1948 dyads (child age M = 5.13 (SD = 1.02) years; 38% Black, 44% White; 8.5% Hispanic), maternal history of CTE and PSLE were independently associated with children's psychopathology: higher CTE and PSLE counts were related to higher total problems ([ßCTE = 0.11, 95% CI [.06, .16]; ßSLE = 0.21, 95% CI [.14, 0.27]) and greater odds of clinical levels of problems (ORCTE = 1.41; 95% CI [1.12, 1.78]; ORPSLE = 1.36; 95% CI [1.23, 1.51]). Tests of interaction showed PSLEs were more strongly associated with child problems for each additional CTE experienced. CONCLUSION: Findings confirm that maternal exposure to CTE and PSLE are independently associated with child mental health, and history of CTE exacerbates the risk associated with PSLE, highlighting intergenerational risk pathways for early psychopathology. Given the prevalence of these exposures, prevention and intervention programs that reduce childhood trauma and stress during pregnancy will likely positively impact women's and their children's health.

The association between duration of breastfeeding and childhood asthma outcomes.

BACKGROUND: Postnatal exposures, including breastfeeding, may influence asthma development. OBJECTIVE: To investigate the association between breastfeeding duration and child asthma. METHODS: We studied 2021 mother-child dyads in the ECHO PATHWAYS consortium of prospective pregnancy cohorts (GAPPS, CANDLE, TIDES). Women reported the duration of any and exclusive breastfeeding and child asthma outcomes during follow-up at child age 4 to 6 years. Outcomes included current wheeze (previous 12 months), ever asthma, current asthma (having ≥2 of current wheeze, ever asthma, medication use in past 12-24 months), and strict current asthma (ever asthma with either or both current wheeze and medication use in past 12-24 months). We used multivariable logistic regression to assess associations (odds ratios and 95% confidence intervals) between breastfeeding and asthma outcomes adjusting for potential confounders. We assessed effect modification by mode of delivery, infant sex, and maternal asthma. RESULTS: Among women, 33%, 13%, 9%, and 45% reported 0 to less than 2, 2 to 4, 5 to 6, and more than 6 months of any breastfeeding, respectively. The duration of any breastfeeding had a protective linear trend with ever asthma but no other outcomes. There was a duration-dependent protective association of exclusive breastfeeding and child asthma outcomes (eg, current asthma adjusted odds ratio [95% confidence interval], 0.64 [0.41-1.02], 0.61 [0.38-0.98], and 0.52 (0.31-0.87) for 2to 4 months, 5 to 6 months, and more than 6 months, respectively, compared with <2 months). For exclusive breastfeeding, protective associations were stronger in dyads with children born by vaginal vs cesarean delivery although interactions did not reach statistical significance (Pinteractions 0.12-0.40). CONCLUSION: Longer duration of exclusive breastfeeding had a protective association with child asthma.

Association of prenatal exposure to ambient air pollution with adverse birth outcomes and effect modification by socioeconomic factors.

BACKGROUND: Maternal exposure to air pollution has been associated with birth outcomes; however, few studies examined biologically critical exposure windows shorter than trimesters or potential effect modifiers. OBJECTIVES: To examine associations of prenatal fine particulate matter (PM2.5), by trimester and in biologically critical windows, with birth outcomes and assess potential effect modifiers. METHODS: This study used two pregnancy cohorts (CANDLE and TIDES; N = 2099) in the ECHO PATHWAYS Consortium. PM2.5 was estimated at the maternal residence using a fine-scale spatiotemporal model, averaged over pregnancy, trimesters, and critical windows (0-2 weeks, 10-12 weeks, and last month of pregnancy). Outcomes were preterm birth (PTB, <37 completed weeks of gestation), small-for-gestational-age (SGA), and continuous birthweight. We fit multivariable adjusted linear regression models for birthweight and Poisson regression models (relative risk, RR) for PTB and SGA. Effect modification by socioeconomic factors (maternal education, household income, neighborhood deprivation) and infant sex were examined using interaction terms. RESULTS: Overall, 9% of births were PTB, 10.4% were SGA, and mean term birthweight was 3268 g (SD = 558.6). There was no association of PM2.5 concentration with PTB or SGA. Lower birthweight was associated with higher PM2.5 averaged over pregnancy (ß -114.2, 95%CI -183.2, -45.3), during second (ß -52.9, 95%CI -94.7, -11.2) and third (ß -45.5, 95%CI -85.9, -5.0) trimesters, and the month prior to delivery (ß -30.5, 95%CI -57.6, -3.3). Associations of PM2.5 with likelihood of SGA and lower birthweight were stronger among male infants (p-interaction ≤0.05) and in those with lower household income (p-interaction = 0.09). CONCLUSIONS: Findings from this multi city U.S. birth cohort study support previous reports of inverse associations of birthweight with higher PM2.5 exposure during pregnancy. Findings also suggest possible modification of this association by infant sex and household income.

Maternal Plasma 25-Hydroxyvitamin D during Gestation Is Positively Associated with Neurocognitive Development in Offspring at Age 4-6 Years.

BACKGROUND: Vitamin D is critical to embryonic neuronal differentiation and other developmental processes that may affect future neurocognitive function. However, observational studies have found inconsistent associations between gestational vitamin D and neurocognitive outcomes. OBJECTIVES: We examined the association of gestational 25-hydroxyvitamin D [25(OH)D] with children's IQ at 4-6 y, and explored whether associations differed by race. METHODS: This study used data from the CANDLE (Conditions Affecting Neurocognitive Development and Learning in Early Childhood) cohort. Between 2006 and 2011, CANDLE recruited 1503 women in their second trimester of healthy singleton pregnancies. Inclusion criteria for this analysis were gestation of ≥34 wk and availability of 25(OH)D and IQ data. Associations between second-trimester 25(OH)D plasma concentration and Stanford-Binet IQ scores in offspring at 4-6 y were examined using multivariable linear regression; interaction terms were used to explore possible effect modification by race. RESULTS: Mean ± SD 25(OH)D concentration among 1019 eligible dyads was 21.6 ± 8.4 ng/mL, measured at a mean ± SD gestational age of 23.0 ± 3.0 wk. Vitamin D deficiency [25(OH)D < 20 ng/mL] was observed in 45.6%. Maternal 25(OH)D differed by race with a mean ± SD of 19.8 ± 7.2 ng/mL in Blacks sand 25.9 ± 9.3 ng/mL in Whites ( P  < 0.001). In adjusted models a 10-ng/mL increase in 25(OH)D was associated with a 1.17-point higher Full Scale IQ (95% CI: 0.27, 2.06 points), a 1.17-point higher Verbal IQ (95% CI: 0.19, 2.15 points), and a 1.03-point higher Nonverbal IQ (95% CI: 0.10, 1.95 points). We observed no evidence of effect modification by race. CONCLUSIONS: Second-trimester maternal 25(OH)D was positively associated with IQ at 4-6 y, suggesting that gestational vitamin D status may be an important predictor of neurocognitive development. These findings may help inform prenatal nutrition recommendations and may be especially relevant for Black and other dark-skinned women at high risk of vitamin D deficiency.

Associations Between Maternal Nutrition in Pregnancy and Child Blood Pressure at 4-6 Years: A Prospective Study in a Community-Based Pregnancy Cohort.

BACKGROUND: The intrauterine environment may influence offspring blood pressure, with effects possibly extending into adulthood. The associations between prenatal nutrition and offspring blood pressure, alone or in combination with other sociodemographic or behavioral factors, are unclear. OBJECTIVES: To investigate the associations of maternal dietary patterns and plasma folate concentrations with blood pressure in children aged 4-6 years, and assess the potential effect modifications by child sex, maternal race, pre-pregnancy overweight or obesity, maternal smoking, and breastfeeding. METHODS: Participants were 846 mother-child dyads from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study. Maternal nutrition was characterized by the Healthy Eating Index 2010 (HEI) scores and plasma folate concentrations in pregnancy. We calculated the systolic blood pressure (SBP) and diastolic blood pressure percentiles, incorporating sex, age, and height, and categorized children as either having high blood pressure (HBP; ≥90th percentile) or normal blood pressure. Linear regressions were performed to quantify the associations between maternal nutrition and continuous blood pressure percentiles, and Poisson regressions were used to estimate the incidence rate ratio (IRR) of binary HBP. We examined the effect modifications using interaction models. RESULTS: Mean HEI scores and folate concentrations were 60.0 (SD, 11.3) and 23.1 ng/mL (SD, 11.1), respectively. Based on measurements at 1 visit, 29.6% of the children were defined as having HBP. Maternal HEI scores and plasma folate concentrations were not associated with child blood pressure percentiles or HBP in the full cohort. Among mothers self-identified as white, there was an inverse relationship between maternal HEI score and child SBP percentile (ß, -0.40; 95%CI: -0.75 to -0.06). A maternal HEI score above 59 was associated with a reduced risk of HBP in girls (IRR, 0.53; 95% CI: 0.32-0.88). No modified associations by pre-pregnancy overweight or obesity, maternal smoking, or breastfeeding were indicated. CONCLUSIONS: We found little evidence for effects of maternal nutrition during pregnancy on childhood blood pressure, but detected sex- and race-specific associations. The study contributes to the evolving scientific inquiry regarding developmental origins of disease.

Exposure to ambient air pollution and early childhood behavior: A longitudinal cohort study.

BACKGROUND: Prenatal and early life air pollution exposure may impair healthy neurodevelopment, increasing risk of childhood behavioral disorders, but epidemiological evidence is inconsistent. Little is known about factors that determine susceptibility. METHODS: Participants were mother-child dyads from the CANDLE study, an ECHO PATHWAYS Consortium birth cohort set in the mid-South United States, who completed a preschool visit. We estimated prenatal and childhood exposures to nitrogen dioxide (NO2) and particulate matter less than 10 µm (PM10) at participants' residences using a national annual average universal kriging model (land-use regression with spatial smoothing). Distance to nearest major roadway was used as a proxy for traffic-related pollution. Primary outcomes were children's internalizing and externalizing behavior problems. Regression models were adjusted for individual- and neighborhood-level socioeconomic measures, maternal IQ, and multiple other potential confounders. We tested for effect modification by select maternal and child characteristics. RESULTS: The analytic sample (N = 975 of 1503 enrolled) was 64% African American and 53% had a household annual income below $35,000; child mean age was 4.3 years (SD: 0.4). Mean prenatal NO2 and PM10 exposures were 12.0 ppb (SD: 2.4) and 20.8 µg/m3 (SD: 2.0); postnatal exposures were lower. In fully adjusted models, 2 ppb higher prenatal NO2 was positively associated with externalizing behavior (6%; 95% CI: 1, 11%). Associations with postnatal exposure were stronger (8% per 2 ppb NO2; 95%CI: 0, 16%). Prenatal NO2 exposure was also associated with an increased odds of clinically significant internalizing and externalizing behaviors. We found suggestive evidence that socioeconomic adversity and African American race increases susceptibility. PM10 and road proximity were not associated with outcomes. CONCLUSIONS: Findings showed that air pollution exposure is positively associated with child behavior problems and that African American and low SES children may be more susceptible. Importantly, associations were observed at exposures below current air quality standards.

Prenatal air pollution and childhood IQ: Preliminary evidence of effect modification by folate.

OBJECTIVES: Animal studies suggest that air pollution is neurotoxic to a developing fetus, but evidence in humans is limited. We tested the hypothesis that higher air pollution is associated with lower child IQ and that effects vary by maternal and child characteristics, including prenatal nutrition. METHODS: We used prospective data collected from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study. Outdoor pollutant exposure during pregnancy was predicted at geocoded home addresses using a validated national universal kriging model that combines ground-based monitoring data with an extensive database of land-use covariates. Distance to nearest major roadway was also used as a proxy for traffic-related pollution. Our primary outcome was full-scale IQ measured at age 4-6. In regression models, we adjusted for multiple determinants of child neurodevelopment and assessed interactions between air pollutants and child sex, race, socioeconomic status, reported nutrition, and maternal plasma folate in second trimester. RESULTS: In our analytic sample (N = 1005) full-scale IQ averaged 2.5 points (95% CI: 0.1, 4.8) lower per 5 µg/m3 higher prenatal PM10, while no associations with nitrogen dioxide or road proximity were observed. Associations between PM10 and IQ were modified by maternal plasma folate (pinteraction = 0.07). In the lowest folate quartile, IQ decreased 6.8 points (95% CI: 1.4, 12.3) per 5-unit increase in PM10; no associations were observed in higher quartiles. CONCLUSIONS: Our findings strengthen evidence that air pollution impairs fetal neurodevelopment and suggest a potentially important role of maternal folate in modifying these effects.

Short-term ozone exposure and asthma severity: Weight-of-evidence analysis.

To determine whether evidence indicates that short-term exposure to ambient concentrations of ozone in the United States can affect asthma severity, we systematically reviewed published controlled human exposure, epidemiology, and animal toxicity studies. The strongest evidence for a potential causal relationship came from epidemiology studies reporting increased emergency department visits and hospital admissions for asthma following elevated ambient ozone concentrations. However, while controlled exposure studies reported lung function decrements and increased asthma symptoms following high ozone exposures 160-400 parts per billion [ppb]), epidemiology studies evaluating similar outcomes reported less consistent results. Animal studies showed changes in pulmonary function at high ozone concentrations (> 500ppb), although there is substantial uncertainty regarding the relevance of these animal models to human asthma. Taken together, the weight of evidence indicates that there is at least an equal likelihood that either explanation is true, i.e., the strength of the evidence for a causal relationship between short-term exposure to ambient ozone concentrations and asthma severity is "equipoise and above."

Ambient Ammonia Exposures in an Agricultural Community and Pediatric Asthma Morbidity.

BACKGROUND: Large-scale animal feeding operations compromise regional air quality in the rural US through emission of pollutants, such as ammonia gas. Exposure to airborne pollution from animal feeding operations may cause pediatric asthma exacerbations in surrounding communities. OBJECTIVES: To describe spatial and temporal patterns in ambient ammonia concentrations in an agricultural region, and to investigate associations between short-term fluctuations in ammonia and subsequent changes in respiratory health in children with asthma. METHODS: For 13 months in the Yakima Valley of Washington State, 14 monitors sampled ammonia in outdoor air for 24-hour periods every 6 days. School-age children with asthma (n = 51) were followed for two health outcomes: biweekly reports of asthma symptoms and quick relief medication usage, and daily measurements of forced expiratory volume in 1 second. We assessed associations between each outcome and ammonia using generalized estimating equations. RESULTS: Twenty-four-hour ammonia concentrations varied from 0.2 to 238.1 µg/m during the study period and displayed a strong correlation with proximity to animal feeding operations. The percentage of forced expiratory volume in 1 second was 3.8% lower (95% confidence interval = 0.2, 7.3) per interquartile increase in 1-day lagged ammonia concentration and 3.0% lower (95% confidence interval = 0.5, 5.8) for 2-day lagged concentration. We observed no associations between self-reported asthma symptoms or medication usage and estimated ammonia exposure. CONCLUSIONS: Ammonia concentrations were elevated in this community and strongly predicted by proximity to animal feeding operations. Ammonia's association with acute lung function decrements in children with asthma in the surrounding community may be causal or, alternatively, ammonia may be a marker for other pollutants from animal feeding operations associated with respiratory effects.

Regional PM2.5 and asthma morbidity in an agricultural community: a panel study.

BACKGROUND: Elevated pediatric asthma morbidity has been observed in rural US communities, but the role of the ambient environment in exacerbating rural asthma is poorly understood. OBJECTIVES: To investigate associations between particulate matter less than 2.5 µm in diameter (PM2.5) and pediatric asthma exacerbations in an agricultural community of Washington State. METHODS: School-aged children with asthma (n=58) were followed for up to 25 months with repeated measures of respiratory health. Asthma symptoms and quick-relief medication use were assessed biweekly through phone administered surveys (n=2023 interviews). In addition, subjects used home peak flow meters on a daily basis to measure forced expiratory volume in one second (FEV1) (n=7830 measurements). Regional PM2.5 was measured at a single air monitor located centrally in the study region. To assess relationships between PM2.5 and these outcomes we used linear regression with generalized estimating equations, adjusting for meteorological and temporal confounders. Effect modification by atopy was explored as well. RESULTS: An interquartile increase (IQR) in weekly PM2.5 of 6.7 µg/m(3) was associated with an increase in reported asthma symptoms Specific symptoms including wheezing, limitation of activities, and nighttime waking displayed the strongest associations. FEV1 as a percent of predicted decreased by 0.9% (95%CI: -1.8, 0.0) for an IQR increase in PM2.5 one day prior, and by 1.4% (95%CI: -2.7, -0.2) when restricted to children with atopic asthma. CONCLUSIONS: This study provides evidence that PM2.5 in an agricultural setting contributes to elevated asthma morbidity. Further work on identifying and mitigating sources of PM2.5 in the area is warranted.

Providing perspective for interpreting cardiovascular mortality risks associated with ozone exposures.

When identifying standards for air pollutants based on uncertain evidence, both science and policy judgments play critical roles. Consequently, critical contextual factors are important for understanding the strengths, limitations, and appropriate interpretation of available science, and potential benefits of risk mitigation alternatives. These factors include the relative magnitude and certainty of the risks posed by various factors and the impacts of other risk factors on air pollutant epidemiology study findings. This commentary explores ozone's status as a risk factor for cardiovascular mortality in contrast with decades of strong and consistent evidence for other established risk factors. By comparison, the ozone evidence is less conclusive, more heterogeneous, and subject to substantial uncertainty; ozone's potential effects, if any, are small and challenging to discern. Moreover, the absence of a demonstrated causal relationship calls into question efforts to quantify cardiovascular mortality risks attributed to ozone exposures on a population level and highlights the need to explicitly acknowledge this uncertainty if such calculations are performed. These concerns are relevant for other similar policy contexts - where multiple established risk factors contribute to the health impact of interest; exposure-effect associations are relatively small, weak, and uncertain; and a causal relationship has not been clearly established.