Trajectory analysis of rhinitis in a birth cohort from lower-income New York City neighborhoods.

BACKGROUND: Rhinitis is a prevalent, chronic nasal condition associated with asthma. However, its developmental trajectories remain poorly characterized. OBJECTIVE: We sought to describe the course of rhinitis from infancy to adolescence and the association between identified phenotypes, asthma-related symptoms, and physician-diagnosed asthma. METHODS: We collected rhinitis data from questionnaires repeated across 22 time points among 688 children from infancy to age 11 years and used latent class mixed modeling (LCMM) to identify phenotypes. Once children were between ages 5 and 12, a study physician determined asthma diagnosis. We collected information on the following asthma symptoms: any wheeze, exercise-induced wheeze, nighttime coughing, and emergency department visits. For each, we used LCMM to identify symptom phenotypes. Using logistic regression, we described the association between rhinitis phenotype and asthma diagnosis and each symptom overall and stratified by atopic predisposition and sex. RESULTS: LCMM identified 5 rhinitis trajectory groups: never/infrequent; transient; late onset, infrequent; late onset, frequent; and persistent. LCMM identified 2 trajectories for each symptom, classified as frequent and never/infrequent. Participants with persistent and late onset, frequent phenotypes were more likely to be diagnosed with asthma and to have the frequent phenotype for all symptoms (P < .01). We identified interaction between seroatopy and rhinitis phenotype for physician-diagnosed asthma (P = .04) and exercise-induced wheeze (P = .08). Severe seroatopy was more common among children with late onset, frequent and persistent rhinitis, with nearly 25% of these 2 groups exhibiting sensitivity to 4 or 5 of the 5 allergens tested. CONCLUSIONS: In this prospective, population-based birth cohort, persistent and late onset, frequent rhinitis phenotypes were associated with increased risk of asthma diagnosis and symptoms during adolescence.

Rhinorrhea and watery eyes in infancy and risk of attention-deficit hyperactivity disorder in school-age children.

Increased parasympathetic nervous system (PNS) activity is associated with attention-deficit/hyperactivity disorder (ADHD) inattentive symptoms, but not hyperactive-impulsive symptoms, and may contribute to inattentive subtype etiology. Guided by prior work linking infant rhinorrhea and watery eyes without a cold (RWWC) to PNS dysregulation, we examined associations between infant RWWC and childhood ADHD symptoms in a longitudinal cohort of Black and Latinx children living in the context of economic disadvantage (N = 301 youth: 158 females, 143 males). Infant RWWC predicted higher inattentive (relative risk [RR] 2.16, p < .001) but not hyperactive-impulsive (RR 1.53, p = .065) ADHD symptoms (DuPaul scale), administered to caregivers at child age 8-14 years. Stratified analyses revealed that these associations were present in females but not males, who were three times more likely to have higher ADHD current total symptoms if they had infant RWWC than if they did not. Additionally, associations between RWWC and inattention symptoms were observed only in females. RWWC may thus serve as a novel risk marker of ADHD inattentive-type symptoms, especially for females.

Report of prenatal maternal demoralization and material hardship and infant rhinorrhea and watery eyes.

BACKGROUND: Previously, we found that reported infant rhinorrhea and watery eyes without a cold (RWWC) predicted school age exercise-induced wheezing, emergency department visits, and respiratory-related hospitalizations for asthma. These findings appeared independent of infant wheezing and allergy. Overall, we theorize that prenatal material hardship and psychosocial distress can induce infant dysregulation in the autonomic nervous system leading to infant RWWC and school age exercise-induced wheezing. OBJECTIVE: To test the hypotheses that indicators of prenatal stress and measures of maternal demoralization, which can alter infant autonomic nervous system responses, would predict infant RWWC. METHODS: In a prospective birth cohort of urban children (n = 578), pregnant women were queried in the third trimester about material hardship and maternal demoralization using validated instruments. Child RWWC was queried every 3 months in infancy. RESULTS: Notably, 44% of the mothers reported not being able to afford at least one of the basic needs of daily living during pregnancy, and children of those mothers were more likely to have infant RWWC (P < .001). The children had an increased risk of RWWC with increasing maternal demoralization during pregnancy (P < .001). In models controlling for sex, race and ethnicity, maternal asthma, maternal allergy, smoker in the home (pre- or postnatal), prenatal pesticide exposure, and older siblings, RWWC was predicted by mother's report of material hardship (relative risk, 1.22; P = .021) and maternal demoralization (relative risk, 1.14; P = .030). CONCLUSION: These results suggest an association between material hardship and psychological distress during pregnancy and RWWC in infancy, further supporting a link between infant autonomic dysregulation and RWWC.

Infant rhinitis and watery eyes predict school-age exercise-induced wheeze, emergency department visits and respiratory-related hospitalizations.

BACKGROUND: Rhinitis and conjunctivitis are often linked to asthma development through an allergic pathway. However, runny nose and watery eyes can result from nonallergic mechanisms. These mechanisms can also underlie exercise-induced wheeze (EIW), which has been associated with urgent medical visits for asthma, independent of other indicators of asthma severity or control. OBJECTIVE: To test the hypothesis that rhinitis or watery eyes without cold symptoms (RWWC) in infancy predict development of EIW and urgent respiratory-related medical visits at school age, independent of seroatopy. METHODS: Within a prospective birth cohort of low-income, urban children (n = 332), RWWC was queried during the first year of life. Relative risks (RRs) for EIW, emergency department (ED) visits, and hospitalizations for asthma and other breathing difficulties at 5 to 7 years of age were estimated with multivariable models. Seroatopy was determined at 7 years of age. RESULTS: Infant RWWC was common (49% of children) and predicted school-age EIW (RR, 2.8; P < .001), ED visits (RR, 1.8; P = .001), and hospitalizations (RR, 9.8; P = .002). These associations were independent of infant wheeze. They were also independent of birth order, an indicator of increased risk of exposure to viruses in infancy, and infant ear infections, an indicator of sequelae of upper airway infections. The association between infant RWWC and ED visits at 5 to 7 years of age was attenuated (RR, 1.2; P = .23) when EIW at 5 to 7 years of age was included in the model, suggesting EIW mediates the association. Adjustment for seroatopy did not diminish the magnitudes of any of these associations. CONCLUSION: These findings suggest a nonallergic connection between infant nonwheeze symptoms and important consequences of urban respiratory health by school age through EIW.

Urinary polycyclic aromatic hydrocarbon metabolites among 3-year-old children from Krakow, Poland.

Polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment and can adversely affect human health. The aim of the present study is to describe the level of PAHs exposure in children living in Kraków, one of the most polluted cities in Poland, and to determine the relationship of urinary biomarkers with environmental PAHsexposure. Urinary monohydroxy metabolites (OH-PAHs) of 20 PAHs were assessed in 218 three-year old children, of which only 10 were present in nearly all the samples: monohydroxy metabolites of naphthalene, fluorene, phenantrene and pyrene. Of the metabolites analyzed, hydroxynaphthalenes were predominant and constituted almost 73% of total excreted OH-PAHs, while 1-OH-PYRene was the least abundant (2.3% of total OH-PAHs). All measured urinary OH-PAHs were statistically significantly correlated with each other (R = 0.165-0.880) but the highest correlation coefficients with other individual OH-PAHs and with total OH-PAHs were observed for 2-OH-FLUOR. Children exposed at home to environmental tobacco smoke (ETS) had higher concentrations of fluorene and pyrene urinary metabolites compared to those without ETS exposure; and those exposed to gas-based appliances used for cooking or heating water had higher levels of fluorene and phenanthrene metabolites than children not exposed. The use of coal, wood or oil for heating was associated with elevated levels of 1-OH-PYRene. Urinary PAHs metabolites only modestly reflect high molecular weight carcinogenic PAHs exposures such as those monitored in air in the present study. None of the measured PAHs metabolites was correlated with airborne PM2.5 and only two were slightly correlated with measured higher molecular mass airborne PAHs. The average concentrations of these specific metabolites in Polish children were much higher than observed in other pediatric populations living in developed countries. Our findings suggest that to capture various sources of PAHs, in addition to 1-OH-PYRene, biomonitoring of PAHs exposure should include 2-OH-NAP and 2-OH-FLUOR.

Combined effects of prenatal exposure to polycyclic aromatic hydrocarbons and material hardship on child ADHD behavior problems.

IMPORTANCE: Polycyclic aromatic hydrocarbons (PAH) are carcinogenic and neurotoxic combustion by-products commonly found in urban air. Exposure to PAH is disproportionately high in low income communities of color who also experience chronic economic stress. OBJECTIVE: In a prospective cohort study in New York City (NYC) we previously found a significant association between prenatal PAH exposure and Attention Deficit Hyperactivity Disorder (ADHD) behavior problems at age 9. Here, we have evaluated the joint effects of prenatal exposure to PAH and prenatal/childhood material hardship on ADHD behavior problems. MATERIALS AND METHODS: We enrolled nonsmoking African-American and Dominican pregnant women in New York City between 1998 and 2006 and followed their children through 9 years of age. As a biomarker of prenatal PAH exposure, PAH-DNA adducts were measured in maternal blood at delivery and were dichotomized at the limit of detection (to indicate high vs. low exposure). Maternal material hardship (lack of adequate food, housing, utilities, and clothing) was self-reported prenatally and at multiple time points through child age 9. Latent variable analysis identified four distinct patterns of hardship. ADHD behavior problems were assessed using the Conners Parent Rating Scale- Revised. Analyses adjusted for relevant covariates. RESULTS: Among 351 children in our sample, across all hardship groups, children with high prenatal PAH exposure (high adducts) generally had more symptoms of ADHD (higher scores) compared to those with low PAH exposure. The greatest difference was seen among the children with hardship persisting from pregnancy through childhood. Although the interactions between high PAH exposure and hardship experienced at either period ("persistent" hardship or "any" hardship) were not significant, we observed significant differences in the number of ADHD symptoms between children with high prenatal PAH exposure and either persistent hardship or any hardship compared to the others. These differences were most significant for combined high PAH and persistent hardship: ADHD Index (p < 0.008), DSM-IV Inattentive (p = 0.006), DSM-IV Hyperactive Impulsive problems (p = 0.033), and DSM-IV Index Total (p = 0.009). CONCLUSION: The present findings add to existing evidence that co-exposure to socioeconomic disadvantage and air pollution in early life significantly increases the risk of adverse neurodevelopmental outcomes. They suggest the need for multifaceted interventions to protect pregnant mothers and their children.

Lung function growth trajectories in non-asthmatic children aged 4-9 in relation to prenatal exposure to airborne particulate matter and polycyclic aromatic hydrocarbons - Krakow birth cohort study.

BACKGROUND: Patterns of lung function development during childhood can be helpful in understanding the pathogenesis of respiratory diseases. A variety of environmental and lifestyle factors, present from the prenatal period to adulthood, may affect or modulate lung function growth. The aim of this study was to investigate, the associations between individual growth trajectories of children's lung function during childhood and prenatal exposure to airborne fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAH), which were hypothesized to adversely affect spirometry parameters. MATERIAL AND METHODS: The study group comprised 294 non-asthmatic, full term children from the Krakow birth cohort, who underwent annual spirometry testing at the ages of 4-9 years. Individual personal air monitoring of PM2.5 and PAH were performed over 48 h in the second trimester of pregnancy. Possible confounders or modifiers such as child's gender, height, atopic status and exposure to environmental tobacco smoke (ETS) were considered. Polynomial multilevel mixed models were used to assess the growth rates of children's lung functions. RESULTS: Lung function trajectories differed significantly for boys and girls for FVC, FEV1 and FEF25-75. Girls had lower rates of increase than boys: - 20.5 (95%CI: - 32.4; - 8.6) ml/year (FVC); - 19.9 (95%CI: -30.7;-9.0) ml/year (FEV1); and - 32.5 (95%CI: - 56.9; - 8.2) ml/year (FEF25-75). Spirometry functions increased with age; however the growth rate decelerated over time. Significant lung function impairment (lower FVC and FEV1 levels) was observed from 4 to 9 years among subjects prenatally exposed to higher levels of PM2.5 as well as PAH, but not in the case of FEF25-75. No significant differences were observed in the rates of increase over time in relation to prenatal PM2.5 and PAH exposure. CONCLUSION: Our results indicate that in non-asthmatic children high prenatal exposure to airborne PM2.5 and PAH is associated with lower trajectories of FVC and FEV1, but not the rate of increase over time, suggesting that the initial effect is not diminishing in time.

DNA methylation of BDNF as a biomarker of early-life adversity.

Early-life adversity increases the risk for psychopathology in later life. The underlying mechanism(s) is unknown, but epigenetic variation represents a plausible candidate. Early-life exposures can disrupt epigenetic programming in the brain, with lasting consequences for gene expression and behavior. This evidence is primarily derived from animal studies, with limited study in humans due to inaccessibility of the target brain tissue. In humans, although there is evidence for DNA methylation changes in the peripheral blood of psychiatric patients, a fundamental question remains as to whether epigenetic markers in the blood can predict epigenetic changes occurring in the brain. We used in utero bisphenol A (BPA) exposure as a model environmental exposure shown to disrupt neurodevelopment and exert long-term effects on behavior in animals and humans. We show that prenatal BPA induces lasting DNA methylation changes in the transcriptionally relevant region of the Bdnf gene in the hippocampus and blood of BALB/c mice and that these changes are consistent with BDNF changes in the cord blood of humans exposed to high maternal BPA levels in utero. Our data suggest that BDNF DNA methylation in the blood may be used as a predictor of brain BDNF DNA methylation and gene expression as well as behavioral vulnerability induced by early-life environmental exposure. Because BDNF expression and DNA methylation are altered in several psychiatric disorders that are associated with early-life adversity, including depression, schizophrenia, bipolar disorder, and autism, BDNF DNA methylation in the blood may represent a novel biomarker for the early detection of psychopathology.

Short-term exposure to PM2.5 and vanadium and changes in asthma gene DNA methylation and lung function decrements among urban children.

BACKGROUND: Both short and long-term exposure to traffic-related air pollutants have been associated with asthma and reduced lung function. We hypothesized that short-term indoor exposure to fine particulate matter <2.5 µm (PM2.5) and vanadium (V) would be associated with altered buccal cell DNA methylation of targeted asthma genes and decreased lung function among urban children in a nested subcohort of African American and Dominican children. METHODS: Six day integrated levels of air pollutants were measured from children's homes (age 9-14; n = 163), repeated 6 months later (n = 98). Buccal samples were collected repeatedly during visits. CpG promoter loci of asthma genes (i.e., interleukin 4 (IL4), interferon gamma (IFNγ), inducible nitric oxide synthase (NOS2A), arginase 2 (ARG2)) were pyrosequenced and lung function was assessed. RESULTS: Exposure to V, but not PM2.5, was associated with lower DNA methylation of IL4 and IFNγ. In exploratory analyses, V levels were associated with lower methylation of the proinflammatory NOS2A-CpG+5099 among asthmatic overweight or obese children but not nonasthmatics. Short-term exposure to PM2.5, but not V, appeared associated with lower lung function (i.e., reduced z-scores for forced expiratory volume in one second (FEV1, FEV1/ forced vital capacity [FEV1/FVC] and forced expiratory flow at 25-75% of FVC [FEF25-75]). CONCLUSIONS: Exposure to V was associated with altered DNA methylation of allergic and proinflammatory asthma genes implicated in air pollution related asthma. However, short-term exposure to PM2.5, but not V, appeared associated with decrements in lung function among urban children.

Longitudinal effects of prenatal exposure to air pollutants on self-regulatory capacities and social competence.

BACKGROUND: We evaluated the influence of prenatal exposure to widespread urban air pollutants on the development of self-regulation and social competence in a longitudinal prospective cohort of children born to nonsmoking minority women in New York City. METHODS: Air pollutant exposure was estimated categorically by level of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in maternal blood collected at delivery, providing a biomarker of maternal exposure to PAH over a 2- to 3-month period. Deficient emotional self-regulation (DESR) was defined as moderate elevations on three specific scales of the child behavior checklist (anxious/depressed, aggressive behavior, and attention problems). We used generalized estimating equations to assess the influence of prenatal exposure to PAH on DESR in children at 3-5, 7, 9, and 11 years of age, adjusted for gender and race/ethnicity. Next, we assessed the association of prenatal exposure to PAH with social competence, as measured by the social responsiveness scale (SRS), the association of impaired self-regulation with social competence, and whether impairment in self-regulation mediated the association of prenatal exposure to PAH with social competence. RESULTS: We detected a significant interaction (at p = .05) of exposure with time, in which the developmental trajectory of self-regulatory capacity was delayed in the exposed children. Multiple linear regression revealed a positive association between presence of PAH-DNA adducts and problems with social competence (p < .04), level of dysregulation and problems with social competence (p < .0001), and evidence that self-regulation mediates the association of prenatal exposure to PAH with social competence (p < .0007). CONCLUSIONS: These data suggest that prenatal exposure to PAH produces long-lasting effects on self-regulatory capacities across early and middle childhood, and that these deficits point to emerging social problems with real-world consequences for high-risk adolescent behaviors in this minority urban cohort.

Physical activity, black carbon exposure and airway inflammation in an urban adolescent cohort.

OBJECTIVE: Regular physical activity can improve cardiopulmonary health; however, increased respiratory rates and tidal volumes during activity may increase the effective internal dose of air pollution exposure. Our objective was to investigate the impact of black carbon (BC) measured by personal sampler on the relationship between physical activity and fractional exhaled nitric oxide (FeNO), a marker of airway inflammation. We hypothesized that higher personal BC would attenuate the protective effect of physical activity on airway inflammation. METHODS: We performed a cross-sectional study nested in a birth cohort of African American and Dominican children living in the Bronx and Northern Manhattan, New York City. Children were recruited based on age (target 9-14 year olds) and presence (n=70) or absence (n=59) of current asthma. Children wore wrist mounted accelerometers for 6 days and were classified as 'active' if they had ≥60min of moderate-to-vigorous activity (MVA) each day and 'non-active' if they had <60min of MVA on any given day, based on CDC guidelines. Personal BC measured using a MicroAeth, was assessed during two 24-h periods, at the beginning and end of physical activity assessment. High BC was defined as the upper tertile of BC measured with personal sampler. FeNO measurements were sampled at the beginning and end of the of physical activity assessment. RESULTS: In multivariable linear regression models, 'active' children had 25% higher personal BC concentrations (p=0.02) and 20% lower FeNO (p=0.04) compared to 'non-active' children. Among children with high personal BC (n=33), there was no relationship between activity and FeNO (p=1.00). The significant protective relationship between activity and airway inflammation was largely driven by children with lower personal BC (n=96, p=0.04). CONCLUSIONS: Children that live in an urban environment and are physically active on a daily basis have higher personal exposure to BC. High BC offsets the protective relationship between physical activity and airway inflammation.

Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure.

Bisphenol A (BPA) is an estrogenic endocrine disruptor widely used in the production of plastics. Increasing evidence indicates that in utero BPA exposure affects sexual differentiation and behavior; however, the mechanisms underlying these effects are unknown. We hypothesized that BPA may disrupt epigenetic programming of gene expression in the brain. Here, we provide evidence that maternal exposure during pregnancy to environmentally relevant doses of BPA (2, 20, and 200 µg/kg/d) in mice induces sex-specific, dose-dependent (linear and curvilinear), and brain region-specific changes in expression of genes encoding estrogen receptors (ERs; ERα and ERß) and estrogen-related receptor-γ in juvenile offspring. Concomitantly, BPA altered mRNA levels of epigenetic regulators DNA methyltransferase (DNMT) 1 and DNMT3A in the juvenile cortex and hypothalamus, paralleling changes in estrogen-related receptors. Importantly, changes in ERα and DNMT expression in the cortex (males) and hypothalamus (females) were associated with DNA methylation changes in the ERα gene. BPA exposure induced persistent, largely sex-specific effects on social and anxiety-like behavior, leading to disruption of sexually dimorphic behaviors. Although postnatal maternal care was altered in mothers treated with BPA during pregnancy, the effects of in utero BPA were not found to be mediated by maternal care. However, our data suggest that increased maternal care may partially attenuate the effects of in utero BPA on DNA methylation. Overall, we demonstrate that low-dose prenatal BPA exposure induces lasting epigenetic disruption in the brain that possibly underlie enduring effects of BPA on brain function and behavior, especially regarding sexually dimorphic phenotypes.

Gestational weight gain and obesity, adiposity and body size in African-American and Dominican children in the Bronx and Northern Manhattan.

Gestational weight gain (GWG) is potentially modifiable and is associated with infant size and body composition; however, long-term effects on childhood obesity have not been reported among multi-ethnic urban populations. We examined the association between GWG and child anthropometric measures and body composition at 7 years [waist circumference (WC), body mass index z-score (BMIZ), obesity (BMIZ ≥95%ile) and bioelectrical impedance analysis estimates of percentage body fat (%fat)] in African-American and Dominican dyads (n = 323) in the Columbia Center for Children's Environmental Health prospective birth cohort study from 1998 to 2013. Linear and logistic regression evaluated associations between excessive GWG [>Institute of Medicine (IOM) 2009 guidelines] and outcomes, adjusting for pre-pregnancy BMI and covariates. Pre-pregnancy BMI (mean ± standard deviation, all such values) and total GWG were 25.8 ± 6.2 kg m(-2) (45% overweight/obese) and 16.4 ± 7.9 kg (64% > IOM guidelines), respectively. Excessive GWG was associated with higher BMIZ {0.44 [95% confidence interval (CI): 0.2, 0.7], P < 0.001}, WC [ß: 2.9 cm (95% CI: 1.1, 4.6), P = 0.002], %fat at 7 years [ß: 2.2% (95% CI: 1.0, 3.5), P = 0.001)] and obesity [odds ratio: 2.93 (95% CI: 1.5, 5.8), P = 0.002]. Pre-pregnancy BMI was positively associated with child size, adiposity and obesity (all P < 0.05). Excessive GWG was highly prevalent and was associated with child obesity, greater percentage body fat and abdominal adiposity. Strategies to support healthy GWG are warranted to promote healthy growth and prevent childhood obesity.

Depressed height gain of children associated with intrauterine exposure to polycyclic aromatic hydrocarbons (PAH) and heavy metals: the cohort prospective study.

Fetal exposure to environmental toxicants may program the development of children and have long-lasting health impacts. The study tested the hypothesis that depressed height gain in childhood is associated with prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAH) and heavy metals (lead and mercury). The study sample comprised 379 children born to non-smoking mothers among whom a total of 2011 height measurements were carried out over the 9-year follow-up period. Prenatal airborne PAH exposure was assessed by personal air monitoring of the mother in the second trimester of pregnancy and heavy metals were measured in cord blood. At the age of 3 residential air monitoring was done to evaluate the level of airborne PAH, and at the age 5 the levels of heavy metals were measured in capillary blood. The effect estimates of prenatal PAH exposure on height growth over the follow-up were adjusted in the General Estimated Equation (GEE) models for a wide set of relevant covariates. Prenatal exposure to airborne PAH showed a significant negative association with height growth, which was significantly decreased by 1.1cm at PAH level above 34.7 ng/m(3) (coeff.=-1.07, p=0.040). While prenatal lead exposure was not significantly associated with height restriction, the effect of mercury was inversely related to cord blood mercury concentration above 1.2 µg/L (coeff.=-1.21, p=0.020), The observed negative impact of prenatal PAH exposure on height gain in childhood was mainly mediated by shorter birth length related to maternal PAH exposure during pregnancy. The height gain deficit associated with prenatal mercury exposure was not seen at birth, but the height growth was significantly slower at later age.

Prenatal polycyclic aromatic hydrocarbon (PAH) exposure, antioxidant levels and behavioral development of children ages 6-9.

PURPOSE: Prenatal polycyclic aromatic hydrocarbon (PAH) exposure has been shown to increase DNA adduct levels and to affect neurodevelopment. Micronutrients may modify the adverse effect of PAH on neurodevelopment. Thus, we examined if micronutrient concentrations modified the association between PAH exposure and neurodevelopmental outcomes. METHODS: 151 children from a birth cohort who had micronutrient concentrations measured in cord blood and completed the Child Behavioral Checklist (CBCL), between the ages of 6 and 9 years, were evaluated. Prenatal airborne PAH exposure was measured by personal air monitoring. The betas and 95% CI for the associations of antioxidant concentrations and PAH exposure with each of the outcomes of CBCL raw score and dichotomized standardized T-score (based on clinical cutpoints) were estimated, respectively, by multivariable poisson and logistic models. RESULTS: Children below the median for alpha-tocopherol and gamma-tocopherol concentrations, compared to those above, were more likely to have thought problems, aggressive behavior and externalizing problems (p<0.05). Lower carotenoid concentration was associated with more thought problems (MVß=0.60, p<0.001) and externalizing problems (MVß=0.13, p<0.05) for the same contrast. No statistically significant associations were observed between retinol concentrations and neurodevelopmental symptoms. Overall, no consistent patterns were observed when we examined the interaction between antioxidants (e.g., alpha-tocopherol) and PAH in relation to CBCL symptoms (e.g., internalizing and externalizing problems, p<0.05). CONCLUSIONS: Lower alpha-tocopherol, gamma-tocopherol and carotenoid levels may adversely affect healthy neurodevelopment, even after accounting for PAH exposure. Future research to confirm these findings are warranted given the importance of identifying modifiable factors for reducing harmful PAH effects.

Repeatedly high polycyclic aromatic hydrocarbon exposure and cockroach sensitization among inner-city children.

BACKGROUND: Exposures to traffic-related air pollutants including polycyclic aromatic hydrocarbons (PAH) have been associated with the development and exacerbation of asthma. However, there is limited evidence on whether these pollutants are associated with the development of cockroach sensitization, a strong risk factor for urban asthma. We hypothesized that repeatedly high PAH exposure during childhood would be associated with increased risk of new cockroach sensitization. METHODS: As part of the research being conducted by the Columbia Center for Children's Environmental Health (CCCEH) birth cohort study in New York, a spot urine sample was collected from children at age 5 years (2003-2008) and again at age 9-10 years (2008-2012; n=248) and analyzed for 10 PAH metabolites. Repeatedly high PAH (High-High) exposure was defined as measures above median for age 5 PAH metabolites at both time points. Child blood samples at age 5 and 9 years were analyzed for total, anti-cockroach, mouse, dust mite, cat and dog IgE. Relative risks (RR) were estimated with multivariable modified Poisson regression. RESULTS: Individual PAH metabolite levels, except for 1-naphthol (1-OH-NAP), increased by 10-60% from age 5 to age 9-10. The prevalence of cockroach sensitization increased from 17.6% (33/188) at age 5 to 33.0% (62/188) at 9 years (p=0.001). After controlling for potential covariates including cockroach sensitization at age 5 in regression analyses, positive associations were found between repeatedly high exposure (High-High) to 1-OH-NAP, 3-hydroxyphenanthrene (3-OH-PHEN), or 1-hydroxypyrene (1-OH-PYR) and cockroach sensitization at age 9 (p-values<0.05). Compared to Low-Low exposure, the relative risk (RR) [95% CI] with repeatedly high exposure was 1.83 [1.06-3.17] for 1-OH-NAP, 1.54 [1.06-2.23] for 3-OH-PHEN, and 1.59 [1.04-2.43] for 1-OH-PYR. CONCLUSIONS: Repeatedly high levels of urinary PAH metabolites during childhood may increase likelihood of sensitization to cockroach allergen in urban inner-city children at age 9 years.

Bisphenol A exposure and behavioral problems among inner city children at 7-9 years of age.

BACKGROUND: Bisphenol A (BPA) is a ubiquitous endocrine disrupting compound. Several experimental and epidemiological studies suggest that gestational BPA exposure can lead to neurodevelopmental and behavioral problems in early-life, but results have been inconsistent. We previously reported that prenatal BPA exposure may affect child behavior and differently among boys and girls at ages 3-5 years. OBJECTIVES: We investigated the association of prenatal and early childhood BPA exposure with behavioral outcomes in 7-9 year old minority children and hypothesized that we would observe the same sex-specific pattern observed at earlier ages. METHODS: African-American and Dominican women enrolled in an inner-city prospective cohort study and their children were followed from mother's pregnancy through children's age 7-9 years. Women during the third trimester of pregnancy and children at ages 3 and 5 years provided spot urine samples. BPA exposure was categorized by tertiles of BPA urinary concentrations. The Child Behavioral Checklist (CBCL) was administered at ages 7 and 9 to assess multiple child behavior domains. Associations between behavior and prenatal (maternal) BPA concentrations and behavior and postnatal (child) BPA concentration were assessed via Poisson regression in models stratified by sex. These models accounted for potential confounders including prenatal or postnatal urinary BPA concentrations, child age at CBCL assessment, ethnicity, gestational age, maternal intelligence, maternal education and demoralization, quality of child's home environment, prenatal environmental tobacco smoke exposure, and prenatal mono-n-butyl phthalate concentration. RESULTS: The direction of the associations differed between boys and girls. Among boys (n=115), high prenatal BPA concentration (upper tertile vs. lower two tertiles) was associated with increased internalizing (ß=0.41, p<0.0001) and externalizing composite scores (ß=0.40, p<0.0001) and with their corresponding individual syndrome scales. There was a general decrease in scores among girls that was significant for the internalizing composite score (ß=-0.17, p=0.04) (n=135). After accounting for possible selection bias, the results remained consistent for boys. Conversely, high postnatal BPA concentration was associated with increased behaviors on both the internalizing composite (ß=0.30, p=0.0002) and externalizing composite scores (ß=0.33, p<0.0001) and individual subscores in girls but fewer symptoms in boys. These results remained significant in girls after accounting for selection bias. CONCLUSION: These results suggest BPA exposure may affect childhood behavioral outcomes in a sex-specific manner and differently depending on timing of exposure.

Brain anomalies in children exposed prenatally to a common organophosphate pesticide.

Prenatal exposure to chlorpyrifos (CPF), an organophosphate insecticide, is associated with neurobehavioral deficits in humans and animal models. We investigated associations between CPF exposure and brain morphology using magnetic resonance imaging in 40 children, 5.9-11.2 y, selected from a nonclinical, representative community-based cohort. Twenty high-exposure children (upper tertile of CPF concentrations in umbilical cord blood) were compared with 20 low-exposure children on cortical surface features; all participants had minimal prenatal exposure to environmental tobacco smoke and polycyclic aromatic hydrocarbons. High CPF exposure was associated with enlargement of superior temporal, posterior middle temporal, and inferior postcentral gyri bilaterally, and enlarged superior frontal gyrus, gyrus rectus, cuneus, and precuneus along the mesial wall of the right hemisphere. Group differences were derived from exposure effects on underlying white matter. A significant exposure × IQ interaction was derived from CPF disruption of normal IQ associations with surface measures in low-exposure children. In preliminary analyses, high-exposure children did not show expected sex differences in the right inferior parietal lobule and superior marginal gyrus, and displayed reversal of sex differences in the right mesial superior frontal gyrus, consistent with disruption by CPF of normal behavioral sexual dimorphisms reported in animal models. High-exposure children also showed frontal and parietal cortical thinning, and an inverse dose-response relationship between CPF and cortical thickness. This study reports significant associations of prenatal exposure to a widely used environmental neurotoxicant, at standard use levels, with structural changes in the developing human brain.

Association of recent exposure to ambient metals on fractional exhaled nitric oxide in 9-11 year old inner-city children.

Exposure to ambient metals in urban environments has been associated with wheeze, and emergency room visits and hospitalizations due to respiratory illness. However, the effect of ambient metals exposure on airway inflammation, and how these associations may be modified by seroatopy, has not been determined. Fractional exhaled nitric oxide (FENO) is a reliable proxy marker of airway inflammation. We hypothesized that recent ambient concentrations of Ni, V, Zn and Fe would be associated differentially with proximal and distal fractions of exhaled NO, and that these associations would be modified by seroatopy. As part of the Columbia Center for Children's Environmental Health (CCCEH) birth cohort study, 9-11 year old children (n=192) were evaluated. Ambient measures of Ni, V, Zn and Fe were obtained from a local central monitoring site and averaged over 9 days based on three 24h measures every third day. Fractional exhaled nitric oxide (FENO) samples were obtained at constant flows of 50 (FENO50), 83 and 100mL/s, and used to determine surrogate measures for proximal (JNO) and alveolar (Calv) inflammation. Seroatopy was determined by specific IgE at age 7. Data were analyzed using multivariable linear regression. Ambient V and Fe concentrations were associated positively with FENO50 (p=0.018, p=0.027). Ambient Fe was associated positively with JNO (p=0.017). Ambient Ni and V concentrations were associated positively with Calv (p=0.004, p=0.018, respectively). A stronger association of Ni concentrations with Calv was observed among the children with seroatopy. These results suggest that ambient metals are associated differentially with different fractions of FENO production, and this relationship may be modified by seroatopy.

Polycyclic aromatic hydrocarbon exposure, obesity and childhood asthma in an urban cohort.

BACKGROUND: Exposure to traffic-related air pollutants, including polycyclic aromatic hydrocarbons (PAHs) from traffic emissions and other combustion sources, and childhood obesity, have been implicated as risk factors for developing asthma. However, the interaction between these two on asthma among young urban children has not been studied previously. METHODS: Exposure to early childhood PAHs was measured by two week residential indoor monitoring at age 5-6 years in the Columbia Center for Children's Environmental Health birth cohort (n=311). Semivolatile [e.g., methylphenanthrenes] and nonvolatile [e.g., benzo(a)pyrene] PAHs were monitored. Obesity at age 5 was defined as a body mass index (BMI) greater than or equal to the 95th percentile of the year 2000 age- and sex-specific growth charts (Center for Disease Control). Current asthma and recent wheeze at ages 5 and 7 were determined by validated questionnaires. Data were analyzed using a modified Poisson regression in generalized estimating equations (GEE) to estimate relative risks (RR), after adjusting for potential covariates. RESULTS: Neither PAH concentrations or obesity had a main effect on asthma or recent wheeze. In models stratified by presence/absence of obesity, a significant positive association was observed between an interquartile range (IQR) increase in natural log-transformed 1-methylphenanthrene (RR [95% CI]: 2.62 [1.17-5.88] with IQRln=0.76), and 9-methylphenanthrene (2.92 [1.09-7.82] with IQRln=0.73) concentrations and asthma in obese children (n=63). No association in non-obese (n=248) children was observed at age 5 (Pinteraction<0.03). Similar associations were observed for 3-methylphenanthrene, 9-methylphenanthrene, and 3,6-dimethylphenanthrene at age 7. CONCLUSIONS: Obese young children may be more likely to develop asthma in association with greater exposure to PAHs, and methylphenanthrenes in particular, than non-obese children.