Prenatal exposure to chlorpyrifos (CPF), an organophosphorus insecticide, has long been associated with delayed neurocognitive development and most recently with decrements in working memory at age 7. In the current paper, we expanded the previous work on CPF to investigate how additional biological and social environmental factors might create or explain differential neurodevelopmental susceptibility, focusing on main and moderating effects of the quality of the home environment (HOME) and child sex. We evaluate how the quality of the home environment (specifically, parental nurturance and environmental stimulation) and child sex interact with the adverse effects of prenatal CPF exposure on working memory at child age 7 years. We did not observe a remediating effect of a high quality home environment (either parental nurturance or environmental stimulation) on the adverse effects of prenatal CPF exposure on working memory. However, we detected a borderline significant interaction between prenatal exposure to CPF and child sex (B (95% CI) for interaction term = −1.714 (−3.753 to 0.326)) suggesting males experience a greater decrement in working memory than females following prenatal CPF exposure. In addition, we detected a borderline interaction between parental nurturance and child sex (B (95% CI) for interaction term = 1.490 (−0.518 to 3.499)) suggesting that, in terms of working memory, males benefit more from a nurturing environment than females. To our knowledge, this is the first investigation into factors that may inform an intervention strategy to reduce or reverse the cognitive deficits resulting from prenatal CPF exposure.
chlorpyrifos; neurodevelopment; working memory; HOME inventory; sex-specific
Exercise-induced wheeze (EIW) may identify a distinct population among asthmatics and give insight into asthma morbidity etiology. The prevalence of pediatric asthma and associated urgent medical visits varies greatly by neighborhood in New York City and is highest in low-income neighborhoods. Although increased asthma severity might contribute to the disparities in urgent medical visits, when controlling for health insurance coverage, we previously observed no differences in clinical measures of severity between asthmatic children living in neighborhoods with lower (3%–9%) versus higher (11%–19%) asthma prevalence. Among these asthmatics, we hypothesized that EIW would be associated with urgent medical visits and a child’s neighborhood asthma prevalence.
Families of 7- to 8-year-old children were recruited into a case-control study of asthma through an employer-based health insurance provider. Among the asthmatics (n = 195), prevalence ratios (PRs) for EIW were estimated. Final models included children with valid measures of lung function, seroatopy, and waist circumference (n = 140).
EIW was associated with urgent medical visits for asthma (PR, 2.29; P = .021), independent of frequent wheeze symptoms. In contrast to frequent wheeze, EIW was not associated with seroatopy or exhaled NO, suggesting a distinct mechanism. EIW prevalence among asthmatics increased with increasing neighborhood asthma prevalence (PR, 1.09; P = .012), after adjustment for race, ethnicity, maternal asthma, environmental tobacco smoke, household income, and neighborhood income.
EIW may contribute to the disparities in urgent medical visits for asthma between high- and low-income neighborhoods. Physicians caring for asthmatics should consider EIW an indicator of risk for urgent medical visits.
asthma; allergy; exercise; emergency department; exercise-induced bronchoconstriction
Despite data associating exposure to traffic-related polycyclic aromatic hydrocarbons (PAH) in asthma, mechanistic support has been limited. We hypothesized that both prenatal and early postnatal exposure to PAH would increase airway hyperreactivity (AHR) and that the resulting AHR may be insensitive to treatment with a β2AR agonist drug, procaterol. Further, we hypothesized that these exposures would be associated with altered β2AR gene expression and DNA methylation in mouse lungs. Mice were exposed prenatally or postnatally to a nebulized PAH mixture versus negative control aerosol 5 days a week. Double knockout β2AR mice were exposed postnatally only. Prenatal exposure to PAH was associated with reduced β2AR gene expression among nonsensitized mice offspring, but not increases in DNA methylation or AHR. Postnatal exposure to PAH was borderline associated with increased AHR among sensitized wildtype, but not knockout mice. In the first study that delivers PAH aerosols to mice in a relatively physiological manner, small effects on AHR and β2AR gene expression, but not β2AR agonist drug activity, were observed. If confirmed, the results may suggest that exposure to PAH, common ambient urban pollutants, affects β2AR function, although the impact on the efficacy of β2AR agonist drugs used in treating asthma remains uncertain.
Previously we reported that airborne concentrations of cis-permethrin, but not trans-permethrin, measured during pregnancy in an inner city pediatric cohort was associated with cough by age 5. However, the effect of subsequent exposures to both permethrins during early childhood, and to piperonyl butoxide (PBO, a synergist for residential pyrethroid insecticides) remains to be elucidated. We hypothesized that prenatal and age 5-6 year measures of PBO and permethrins would be associated with cough at age 5-6 years in this cohort. Further, we explored the associations between these pesticides measures and wheeze, asthma, seroatopy, and fractional exhaled nitric oxide (FeNO).
PBO and permethrins were measured in personal air during the third trimester of pregnancy and indoor residential air at age 5-6 years (n=224). Health outcome questionnaires were administered to the mothers of 5-6 years old children. Indoor allergen specific and total immunoglobulin (Ig) E production was measured from sera collected at age 5, and FeNO was measured at 5-6 years. The hypotheses were tested using regression models adjusting for common confounders.
Noninfectious cough was reported among 14% of children at age 5-6 years. Measures of prenatal PBO, but not age 5-6 year PBO or permethrins, increased the odds of cough [OR (95% CI): 1.27 (1.09-1.48), p<0.01; n=217]. No significant associations were found for other measured health outcomes.
Prenatal PBO exposure was associated with childhood cough. It is unclear whether the observed effect is due mainly to PBO itself or residential pyrethroids of which PBO is an indicator.
prenatal pesticide exposure; cough; piperonyl butoxide; permethrin
Rationale: Phthalates are used widely in consumer products. Exposure to several phthalates has been associated with respiratory symptoms and decreased lung function. Associations between children’s phthalate exposures and fractional exhaled nitric oxide (FeNO), a biomarker of airway inflammation, have not been examined.
Objectives: We hypothesized that urinary concentrations of four phthalate metabolites would be positively associated with FeNO and that these associations would be stronger among children with seroatopy or wheeze.
Methods: In an urban ongoing birth cohort, 244 children had phthalate metabolites determined in urine collected on the same day as FeNO measurement. Repeated sampling gathered 313 observations between ages 4.9 and 9.1 years. Seroatopy was assessed by specific IgE. Wheeze in the past year was assessed by validated questionnaire. Regression models used generalized estimating equations.
Measurements and Main Results: Log-unit increases in urinary concentrations of metabolites of diethyl phthalate (DEP) and butylbenzyl phthalate (BBzP) were associated with a 6.6% (95% confidence interval [CI] 0.5–13.1%) and 8.7% (95% CI, 1.9–16.0%) increase in FeNO, respectively, adjusting for other phthalate metabolites and potential covariates/confounders. There was no association between concentrations of metabolites of di(2-ethylhexyl) phthalate or di-n-butyl phthalate and FeNO. There was no significant interaction by seroatopy. The BBzP metabolite association was significantly stronger among children who wheeze (P = 0.016).
Conclusions: Independent associations between exposures to DEP and BBzP and FeNO in a cohort of inner-city children were observed. These results suggest that these two ubiquitous phthalates, previously shown to have substantial contributions from inhalation, are positively associated with airway inflammation in children.
airway inflammation; asthma; diethyl phthalate; butylbenzyl phthalate; fractional exhaled nitric oxide
Our primary purpose was to assess sex-specific fetal growth reduction in newborns exposed prenatally to fine particulate matter. Only women 18–35 years of age, who claimed to be non-smokers, with singleton pregnancies, without illicit drug use and HIV infection, free from chronic diseases were eligible for the study. A total of 481 enrolled pregnant women who gave birth between 37 and 43 weeks of gestation were included in the study. Prenatal personal exposure to fine particles over 48 h during the second trimester was measured using personal monitors. To evaluate the relationship between the level of PM2.5 measured over 48 h in the second trimester of pregnancy with those in the first and the third trimesters, a series of repeated measurements in each trimester was carried out in a random subsample of 85 pregnant women. We assessed the effect of PM2.5 exposure on the birth outcomes (weight, length and head circumference at birth) by multivariable regression models, controlling for potential confounders (maternal education, gestational age, parity, maternal height and prepregnancy weight, sex of infant, prenatal environmental tobacco smoke, and season of birth). Birth outcomes were associated positively with gestational age, parity, maternal height and prepregnancy weight, but negatively with the level of prenatal PM2.5 exposure. Overall average increase in gestational period of prenatal exposure to fine particles by about 30 μg/m3, i.e., from 25th percentile (23.4 μg/m3) to 75th percentile (53.1 μg/m3) brought about an average birth weight deficit of 97.2 g (95% CI: −201, 6.6) and length at birth of 0.7cm (95% CI: −1.36, −0.04). The corresponding exposure lead to birth weight deficit in male newborns of 189 g (95% CI: −34.2, −343) in comparison to 17 g in female newborns; the deficit of length at birth in male infants amounted to 1.1 cm (95% CI: −0.11, −2.04). We found a significant interrelationship between self-reported ETS and PM2.5, however, none of the models showed a significant interaction of both variables. The joint effect of various levels of PM2.5 and ETS on birth outcomes showed the significant deficit only for the categories of exposure with higher component of PM2.5. Concluding, the results of the study suggest that observed deficits in birth outcomes are rather attributable to prenatal PM2.5 exposure and not to environmental tobacco smoke. The study also provided evidence that male fetuses are more sensitive to prenatal PM2.5 exposure and this should persuade policy makers to consider birth outcomes by gender separately while setting air pollution guidelines.
Cohort study; Prenatal exposure; Air pollutants; Fine particles; Gender; Fetal growth deficits
While exposures to urban fine particulate matter (PM2.5) and soot-black carbon (soot-BC) have been associated with asthma exacerbations, there is limited evidence on whether these pollutants are associated with the new development of asthma or allergy among young inner city children. We hypothesized that childhood exposure to PM2.5 and the soot-BC component would be associated with the report of new wheeze and development of seroatopy in an inner city birth cohort.
As part of the research being conducted by the Columbia Center of Children’s Environmental Health (CCCEH) birth cohort study in New York City, two-week integrated residential monitoring of PM2.5, soot-BC (based on a multi-wavelength integrating sphere method), and modified absorption coefficient (Abs*; based on the smoke stain reflectometer) was conducted between October 2005 and May 2011 for 408 children at age 5–6 years old. Residential monitoring was repeated 6 months later (n=262) to capture seasonal variability. New wheeze was identified through the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires during up to 3 years of follow-up and compared to a reference group that reported never wheeze, remitted wheeze, or persistent wheeze. Specific immunoglobulin (Ig) E against cockroach, mouse, cat, and dust mite and total IgE levels were measured in sera at ages 5 and 7 years.
PM2.5, soot-BC, and Abs* measured at the first visit were correlated moderately with those at the second visit (Pearson r > 0.44). Using logistic regression models, a positive association between PM2.5 and new wheeze was found with adjusted odds ratio [95% confidence intervals] of 1.51 [1.05–2.16] per interquartile range (IQR). Positive but nonsignificant association was found between the development of new wheeze and soot-BC and (OR 1.40 [0.96–2.05]), and Abs* (OR 1.57 [0.91–2.68]); Significantly positive associations were found between air pollutant measurements and new wheeze when restricting to those participants with repeat home indoor measurements 6 months apart. Associations between pollutants and IgE levels were not detected.
Our findings suggest that childhood exposure to indoor air pollution, much of which penetrated readily from outdoor sources, may contribute to the development of wheeze symptoms among children age 5 to 7 years.
indoor air pollution; long-term exposure; PM2.5; black carbon; wheeze; asthma; young children
Impaired fetal development is associated with a number of adult chronic diseases and it is believed that these associations arise as a result of the phenomenon of “epigenetic programming”, which involves persisting changes in structure and function of various body organs caused by ambient factors during critical and vulnerable periods of early development. The main goal of the study was to assess the association between lung function in early childhood and prenatal exposure to fine particulate matter (PM2.5 ), which represents a wide range of chemical compounds potentially hazardous for fetal development. Among pregnant women recruited prenatally to the study personal measurements of PM2.5 was performed over 48 hours in the second trimester of pregnancy. After delivery, infants were followed over five years and the interviewers visited participants at their homes to record children’s respiratory symptoms every three months in the child’s first two years of life and every 6 months later. In the fifth year of the follow-up, children were invited for standard lung function testing and quantified by FVC, FEV1 and FEV05 levels. Material consisted of 176 children of nonsmoking mothers, who performed at least two acceptable spirometry measurements. Multivariable linear regression model showed a significant deficit of FVC at the highest quartile of PM2.5 exposure (beta coefficient = − 91.9 , P = 0.008), after adjustment for covariates (age, gender, birth weight, height and wheezing). Also FEV1 level in children was inversely correlated with prenatal exposure to PM2.5, and the average FEV1 deficit amounted to 87.7 ml (P = 0.008) at the higher level of exposure. Although the effect of PM2.5 exposure on FEV05 was proportionally weaker (−72.7, P = 0.026) it was significant as well. The lung function level was inversely and significantly associated with the wheezing recorded over the follow-up. The findings showed that significant lung function deficits in early childhood is associated with prenatal exposure to fine particulate matter, which may affect fetal lung growth.
prenatal exposure; air pollution; birth cohort; lung function; preschool children
DNA methylation changes have been implicated in many common chronic diseases leading to the hypothesis that environmental and age-related DNA methylation changes within individuals are involved in disease etiology. Few studies have examined DNA methylation changes within an individual over time and all of these studies have been conducted in adults. Here, we aim to characterize how global DNA methylation changes from birth to age three within a longitudinal birth cohort study and to determine whether there are consistent predictors of DNA methylation levels measured three years apart. We measured global DNA methylation in the same children at birth (cord blood) and again at three years of age among 165 children, using an immunoassay. We found that on average, DNA methylation was significantly higher in blood at age 3-years than in cord blood (p<0.01). However, for any individual child, the difference was less than would be expected by chance. We found that pre-pregnancy BMI was negatively predictive of both cord and three-year DNA methylation, even after statistical adjustment to account for the correlation between cord blood and three-year DNA methylation. The biologic implications of small changes in global DNA methylation are unknown. However, the observation that global DNA methylation levels persist within an individual from birth to age three supports the belief that factors that influence global DNA methylation, including pre-pregnancy BMI, may confer long-term effects.
The main goal of the study was to assess the effect of exclusive breastfeeding on the neurodevelopment of children over a seven-year follow-up period and to test the hypothesis that the observed cognitive gain in breastfed children in the first years of life is a strong predictor of their cognitive development trajectory, which may be continued in later life.
The analysis is based on data from the seven-year follow-up of 468 term babies (>36 weeks of gestation) born to non-smoking mothers participating in an ongoing prospective cohort study. The cognitive function of children was assessed by psychometric tests performed 5 times at regular intervals from infancy through the preschool age. The study included valid neurodevelopmental assessment of the children – 443 participants were evaluated least twice, 425 – three times and 307 five times in the follow-up period. The association between the cognitive achievements of preschool age children and exclusive breastfeeding of various duration was performed using the GEE (General Estimation Equation) longitudinal model, adjusted for major confounders such as maternal education, gender, parity, and weight gain in pregnancy.
Children breastfed exclusively for up to 3 months had IQs that were on average 2.1 points higher compared to the others (95%CI: 0.24 – 3.9); children breastfed for 4 – 6 months scored higher by 2.6 points (95%CI: 0.87 – 4.27); and the benefit for children breastfed even longer (>6 months) increased by 3.8 points (95%CI: 2.11 – 5.45). Other predictors were maternal education, gender of the child, having an older sibling, and weight gain during pregnancy.
The results of the study support the WHO expert recommendations on exclusive breastfeeding for six months; moreover, they provide evidence that even a shorter duration of exclusive breastfeeding in early infancy produces beneficial effects on the cognitive development of children. The breastfeeding-related IQ gain observed already at the age of 1 was sustained through preschool age and the difference in terms of IQ score between breastfed children and the reference group (mixed breastfeeding) held constant over the whole preschool period.
breastfeeding; cognitive function in early childhood; prospective birth cohort study
In a birth cohort study, we have assessed the dose-response relationship between individual measurements of prenatal airborne PAH exposure and specific PAH-DNA adducts in cord blood adjusted for maternal blood adducts and season of birth. The study uses data from an earlier established birth cohort of children in Krakow. The final analysis included 362 pregnant women who gave birth to term babies and had complete data on personal exposure in the second trimester of pregnancy to eight airborne polycyclic aromatic hydrocarbons (PAH) including benzo[a]pyrene (B[a]P), as well as DNA adducts, both in maternal and cord blood.
The relation between cord blood PAH-DNA adducts and airborne prenatal PAH exposure was non-linear. While cord blood PAH-DNA adducts were significantly associated with the B[a]P exposure categorized by tertiles (nonparametric trend z = 3.50, p < 0.001), the relationship between B[a]P and maternal blood adducts was insignificant (z = 1.63, p = 0.103). Based on the multivariable linear regression model we estimated the effect of the prenatal airborne B[a]P on the level of cord blood adducts. In total, 14.8% of cord blood adducts variance was attributed to the level of maternal adducts and 3% to a higher prenatal B[a] exposure above 5.70 ng/m3. The calculated fetal/maternal blood adducts ratio (FMR) linearly increased with the B[a]P exposure (z = 1.99, p = 0.047) and was highest at B[a]P concentrations exceeding 5.70 ng/m3.
In conclusion, the results support other findings that transplacental exposure to B[a[P from maternal inhalation produces DNA damage in the developing fetus. It also confirms the heightened fetal susceptibility to prenatal PAH exposure that should be a matter of public health concern particularly in the highly polluted areas because DNA adducts represent a pro-carcinogenic alteration in DNA The continuation of this birth cohort study will assess the possible health effects of fetal DNA damage on health of children and help in establishing new protective guidelines for newborns.
prenatal exposure; polycyclic aromatic hydrocarbons; biomarkers of exposure; PAH-DNA adducts; birth cohort study
This summary provides a synopsis of talks included in a symposium entitled “Current Needs and Future Directions of Occupational Safety and Heath in a Globalized World”. The purpose of the symposium was to (1) highlight national and international agencies with occupational health related activities; (2) address electronic (e-)waste issues in developing countries where exposures are secondary to the handling and scavenging of scrap; and (3) discuss the effects of hazardous materials, such as polycyclic aromatic hydrocarbon (PAH) and tobacco smoke on child intelligence quotient (IQ) in developing countries.
The primary purpose of this study was to assess the relationship between very low-level of prenatal lead exposure measured in the cord blood (<5 µg/dL) and possible gender-specific cognitive deficits in the course of the first three years of life. The accumulated lead dose in infants over the pregnancy period was measured by the cord blood lead level (BLL) and cognitive deficits were assessed by the Bayley Mental Development Index (MDI). The study sample consisted of 457 children born to non-smoking women living in the inner city and the outlying residential areas of Krakow. The relationship between prenatal lead exposure and MDI scores measured at 12, 24 and 36 months of age and adjusted to a set of important covariates (gender of child, maternal education, parity, breastfeeding, prenatal and postnatal environmental tobacco smoke) was evaluated with linear multivariate regression, and the Generalized Estimating Equations (GEE) longitudinal panel model. The median of lead level in cord blood was 1.21 µg/dL with the range of values from 0.44 to 4.60 µg/dL. Neither prenatal BLL (dichotomized by median) nor other covariates affected MDI score at 12 months of age. Subsequent testing of children at 24 months of age showed a borderline significant inverse association of lead exposure and mental function (beta coeff. = −2.42, 95%CI: −4.90 to 0.03), but the interaction term (BLL × male gender) was not significant. At 36 months, prenatal lead exposure was inversely and significantly associated with cognitive function in boys (Spearman correlation coefficient = −0.239, p=0.0007) but not girls (r = − 0.058, p = 0.432) and the interaction between BLL and male gender was significant (beta coeff. = − 4.46; 95%CI: −8.28 to −0.63). Adjusted estimates of MDI deficit in boys at 36 months confirmed very strong negative impact of prenatal lead exposure (BLL>1.67µg/dL) compared with the lowest quartile of exposure (beta coeff. = −6.2, p = 0.002), but the effect in girls was insignificant (beta coeff = −0.74, p = 0.720). The average deficit of cognitive function in the total sample over the first three years of life (GEE model) associated with higher prenatal lead exposure was also significant (beta coefficient = − 3.00; 95%CI: −5.22 to −0.70). Beside prenatal lead exposure, presence of older siblings at home and prenatal environmental tobacco smoke had a negative impact on MDI score. Better maternal education showed a strong beneficial effect on the cognitive development of children. Conclusion: The study suggests that there might be no threshold for lead toxicity in children and provides evidence that 3-year old boys are more susceptible than girls to prenatal very low lead exposure. The results of the study should persuade policy makers to consider gender-related susceptibility to lead and possibly to other toxic hazards in setting environmental protection guidelines. To determine whether the cognitive deficit documented in this study persists to older ages, the follow-up of the children over the next several years is to be carried out.
prenatal lead exposure; cognitive function; early childhood; prospective birth cohort study
Early life exposure to ambient polycyclic aromatic hydrocarbons (PAHs) can result in developmental delay. The negative health effects of PAHs have been well-documented but the cost of developmental delay due to PAH exposure has not been studied. The Columbia Center for Children’s Environmental Health previously has reported the significant effect of prenatal exposure to ambient PAHs on delayed mental development at three years, using the Bayley Scales in a cohort of low-income women and children in New York City (NYC). Here we have used the cohort results to estimate the annual costs of preschool special education services for low-income NYC children with developmental delay due to PAH exposure using the Environmentally Attributable Fraction method. The estimated cost of PAH-exposure-related services is over $13.7 million per year for Medicaid births in NYC. This high cost supports policies to reduce level of PAHs in NYC air.
PAH; developmental delay; costs
Physical activity; anti-oxidant
Exposure to naphthalene, an IARC-classified possible carcinogen and polycyclic aromatic hydrocarbon (PAH), is widespread, though resulting health effects are poorly understood. Metabolites of naphthalene, 1- and 2-naphthol, are measurable in urine and are biomarkers of personal exposure. Chromosomal aberrations (CAs), including translocations, are established markers of cancer risk and a bio-dosimeter of clastogenic exposures. Although prenatal (maternal) PAH exposure predicts CAs in cord blood, few studies have examined CAs in school-age children and none has examined their association with metabolites of specific PAHs.
Using Whole Chromosome Paint Fluorescent in Situ Hybridization, we documented CAs including translocations, in 113 five year old urban minority children and examined their association with concurrent concentrations of PAH metabolites measured in urine.
We report that in lymphocytes, the occurrence and frequency of CAs including translocations are associated with levels of urinary 1- and 2-naphthol. When doubling the levels of urinary naphthols, gender-adjusted Odds Ratio (OR) for CAs are 1.63 (95%CI: 1.21, 2.19) and 1.44 (95%CI: 1.02, 2.04) for 1-and 2-naphthol respectively; and for translocations: OR=1.55 (95%CI: 1.11-2.17) and 1.92 (95%CI: 1.20-3.08) for 1- and 2-naphthol respectively.
Our results demonstrate that markers of exposure to naphthalene in children are associated with translocations in a dose related manner, and that naphthalene may be a clastogen.
Indoor exposure to elevated levels of naphthalene is prevalent in large regions of the world. This study is the first to present an association between a marker of naphthalene exposure and a pre-carcinogenic effect in humans.
Naphthalene; Chromosomal aberrations; Polycyclic aromatic hydrocarbons; Cohort study; Postnatal
The purpose of the study was to check the hypothesis that early wheezing as reported by mothers would be associated with reduced lung function in 4-year-olds. Study participants were recruited prenatally, as part of a prospective cohort study on the respiratory health of young children exposed to various ambient air pollutants. After delivery, infants were followed over four years and the interviewers visited participants at their home to record respiratory symptoms every three months in the child’s first two years of life and every 6 months in the third and fourth years. In the fourth year of follow-up, children were invited for standard lung function testing by spirometry quantified by FVC, FEV1 and FEV05 levels. Out of 258 children attending spirometry testing 139 performed at least two acceptable exhalation efforts. Cohort children with acceptable spirometric measurements did not differ with respect to wheezing experience and exposure characteristics from those without. The study shows that episodic wheeze was reported in 28.1% of 4-year-olds, 6.5% had transient wheeze and 4.3% had recurrent wheeze. There was an increased frequency of wheezing symptoms and their duration in transient and recurrent wheezers. Adjusted multivariable regression models for gender and height showed that children who reported more than 2 episodes of wheezing at any point over the follow-up had FVC values lower by 120.5 mL (p = 0.016) and FEV1 values lower by 98.3 mL (p = 0.034) compared to those who did not report any wheezing; children experiencing more than 10 wheezing days by age 4 showed FVC deficit of 87.4 mL (p = 0.034) and FEV1 values of 65.7 mL (p = 0.066) The ratios of FEV1/FVC% and FEV05/FVC% were neither associated with wheezing episodes nor wheezing days. In recurrent wheezers lung function decrement amounted to 207 mL of FVC, 175 mL of FEV1 and 104 mL of FEV05. In conclusion, our findings show that wheezing experience during early postnatal life may be associated with lung function deficit of restrictive character in preschool children and detailed history of wheeze in early postnatal life, even though not physician-confirmed, may help define the high risk group of children for poor lung function testing.
Differential exposure to combustion by-products and allergens may partially explain the marked disparity in asthma prevalence (3%–18%) among New York City neighborhoods. Subclinical changes in airway inflammation can be measured by fractional exhaled nitric oxide (FeNO). FeNO could be used to test independent effects of these environmental exposures on airway inflammation. Seven and eight year-old children from neighborhoods with lower (range 3–9%, n=119) and higher (range 11–18%, n=121) asthma prevalence participated in an asthma case-control study. During home visits, FeNO was measured, and samples of bed dust (allergens) and air (black carbon) were collected. Neighborhood built-environment characteristics were assessed for the 500m surrounding participants’ homes. Airborne black carbon concentrations in homes correlated with neighborhood asthma prevalence (P<0.001) and neighborhood densities of truck routes (P<0.001) and buildings burning residual oil (P<0.001). FeNO concentrations were higher among asthmatics with compared to asthmatics without frequent wheeze (≥4 times/year) (P=0.002). FeNO concentrations correlated with domestic black carbon among children without seroatopy (P=0.012) and with dust mite allergen among children with seroatopy (P=0.020). The association between airborne black carbon in homes and both neighborhood asthma prevalence and FeNO suggest that further public health interventions on truck emissions standards and residual oil use are warranted.
Asthma; air pollution; airway inflammation; FeNO; residual oil
Bulky DNA adducts are markers of exposure to genotoxic aromatic compounds, which reflect an individual’s ability to metabolically activate carcinogens and to repair DNA damage. Polycyclic aromatic hydrocarbons (PAH) represent a major class of carcinogens that are capable of forming such adducts. Factors that have been reported to be related to DNA adduct levels include smoking, diet, body mass index (BMI), genetic polymorphisms, the season of collection of biologic material, and air pollutants.
We pooled eleven studies (3,600 subjects) in which bulky DNA adducts were measured in human white blood cells with similar 32P-postlabelling techniques and for which a similar set of variables was available, including individual data on age, gender, ethnicity, batch, smoking habits, BMI, season of blood collection and a limited set of gene variants.
Lowest DNA adduct levels were observed in the spring (median 0.50 adducts per 108 nucleotides), followed by summer (0.64), autumn (0.70) and winter (0.85) (p=0.006). The same pattern emerged in multivariate analysis, but only among never smokers (p=0.02). Adduct levels were significantly lower (p=0.001) in Northern Europe (the Netherlands, Denmark) (mean 0.60, median 0.40) than in Southern Europe (Italy, Spain, France, Greece) (mean 0.79, median 0.60).
In this large pooled analysis, we have found only weak associations between bulky DNA adducts and exposure variables. Seasonality (with higher adducts levels in winter) and air pollution may partly explain some of the inter-area differences (North vs South Europe), but most inter-area and inter-individual variation in adduct levels still remain unexplained.
Our study describes the largest pooled analysis of bulky DNA adducts so far, showing that inter-individual variation is still largely unexplained, though seasonality appears to play a role.
DNA adducts; air pollution; seasonality
The main goal of the study was to determine the relationship between prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) measured by PAH-DNA adducts in umbilical cord blood and early wheeze. The level of PAH-DNA adducts in the cord blood is assumed to reflect the cumulative dose of PAHs absorbed by the fetus over the prenatal period. The effect of prenatal PAH exposure on respiratory health measured by the incidence rate ratio (IRR) for the number of wheezing days in the subsequent four year follow-up was adjusted for potential confounding factors such as personal prenatal exposure to fine particulate matter (PM2.5), environmental tobacco smoke (ETS), gender of child, maternal characteristics (age, education and atopy), parity, and mold/dampness in the home. The study sample includes 339 newborns of non-smoking mothers 18-35 years of age and free from chronic diseases, who were recruited from ambulatory prenatal clinics in the first or second trimester of pregnancy. The number of wheezing days during the first two years of life was positively associated with prenatal level of PAH-DNA adducts (IRR = 1.69, 95%CI = 1.52 – 1.88), prenatal particulate matter (PM2.5) level dichotomized by the median (IRR = 1.38; 95%CI: 1.25 – 1.51), maternal atopy (IRR = 1.43; 95%CI: 1.29 – 1.58), moldy/damp house (IRR = 1.43; 95%CI: 1.27 – 1.61). The level of maternal education and maternal age at delivery were inversely associated with the IRRs for wheeze. The significant association between frequency of wheeze and the level of prenatal environmental hazards (PAHs and PM2.5) was not observed at ages 3 or 4 years. Although the frequency of wheezing at ages 3 or 4 years was no longer associated with prenatal exposure to PAHs and PM2.5, its occurrence depended on the presence of wheezing in the first two years of life, which nearly tripled the risk of wheezing in later life. In conclusion, the findings may suggest that driving force for early wheezing (<24 months of age) are different to those leading to later onset of wheeze. As we reported no synergistic effects between prenatal PAH (measured by PAH-DNA adducts) and PM2.5 exposures on early wheeze, this suggests the two exposures may exert independent effects via different biological mechanism on wheeze.
prenatal exposure to polycyclic aromatic hydrocarbons; biomarkers of exposure; DNA adducts; early wheeze; 4-year olds; birth cohort study
The main purpose of the study was to answer the question whether young children without clinical diagnosis of asthma but experiencing early wheezing disorders and therefore being at high risk of developing asthma may have cognitive deficits. In the ongoing birth cohort study wheezing symptoms were recorded postpartum over two first years of age and subsequently cognitive status of children at the age of 3 years was assessed with the Bayley Mental Development Index (MDI). In the statistical analysis a wide range of modifying and confounding factors (maternal education, gender of children, prenatal exposure to lead and environmental tobacco smoke (ETS) were considered to assess the independent effect of early wheezing phenotypes on cognitive development of children. The MDI score correlated inversely with the number of wheezing days recorded over 24 months (r = −0.13, p=0.007), lead cord blood concentration (r = − 0.12, p = − 0.02), number of siblings (r = − 0.17, p = 0.0006) and the number of cigarettes smoked daily by other household members at home over the pregnancy period (r = − 0.18, p = 0.0002). While the children who experienced wheezing over the first year of age showed deficit of 2 MDI scores (beta coeff. = −2.31, 95%CI: −4.63 to 0.02), those with persistent wheezing had the score deficit of 4 points (beta coeff. = − 4.41, 95%CI: −8.27 to −0.55).
To our knowledge, it is the first report in the literature showing that early wheezing is associated the cognitive deficit in a community-recruited very young children. Observed cognitive deficit in early wheezers may be caused by RSV infections or can be related to lower lung function attributed to persistent wheezing, which reducing oxygen supply would affect rapidly developing brain.
cognitive development; children; wheezing phenotypes; birth cohort study
There are concerns that prenatal exposure to endocrine-disrupting chemicals increases children’s risk of obesity. African-American and Hispanic children born in the Bronx or Northern Manhattan, New York (1998–2006), whose mothers underwent personal air monitoring for polycyclic aromatic hydrocarbon (PAH) exposure during pregnancy, were followed up to ages 5 (n = 422) and 7 (n = 341) years. At age 5 years, 21% of the children were obese, as were 25% of those followed to age 7 years. After adjustment for child’s sex, age at measurement, ethnicity, and birth weight and maternal receipt of public assistance and prepregnancy obesity, higher prenatal PAH exposures were significantly associated with higher childhood body size. In adjusted analyses, compared with children of mothers in the lowest tertile of PAH exposure, children of mothers in the highest exposure tertile had a 0.39-unit higher body mass index z score (95% confidence interval (CI): 0.08, 0.70) and a relative risk of 1.79 (95% CI: 1.09, 2.96) for obesity at age 5 years, and they had a 0.30-unit higher body mass index z score (95% CI: 0.01, 0.59), a 1.93-unit higher percentage of body fat (95% CI: 0.33, 3.54), and a relative risk of 2.26 (95% CI: 1.28, 4.00) for obesity at age 7 years. The data indicate that prenatal exposure to PAHs is associated with obesity in childhood.
cohort studies; environment; obesity; pediatrics; polycyclic hydrocarbons, aromatic
We previously reported an association between prenatal exposure to airborne PAH and lower birth weight, birth length and head circumference. The main goal of the present analysis was to assess the possible impact of co-exposure to PAH-containing of barbecued meat consumed during pregnancy on birth outcomes.
The birth cohort consisted of 432 pregnant women who gave birth at term (>36 weeks of gestation). Only non-smoking women with singleton pregnancies, 18-35 years of age, and who were free from chronic diseases such as diabetes and hypertension were included in the study. Detailed information on diet over pregnancy was collected through interviews and the measurement of exposure to airborne PAHs was carried out by personal air monitoring during the second trimester of pregnancy. The effect of barbecued meat consumption on birth outcomes (birthweight, length and head circumference at birth) was adjusted in multiple linear regression models for potential confounding factors such as prenatal exposure to airborne PAHs, child’s sex, gestational age, parity, size of mother (maternal prepregnancy weight, weight gain in pregnancy) and prenatal environmental tobacco smoke (ETS).
The multivariable regression model showed a significant deficit in birthweight associated with barbecued meat consumption in pregnancy (coeff = −106.0 g; 95%CI: −293.3, −35.8); The effect of exposure to airborne PAHs was about the same magnitude order (coeff. = −164.6 g; 95%CI: −172.3, − 34.7). Combined effect of both sources of exposure amounted to birth weight deficit of 214.3 g (95%CI: −419.0, − 9.6). Regression models performed for birth length and head circumference showed similar trends but the estimated effects were of borderline significance level. As the intake of barbecued meat did not affect the duration of pregnancy, the reduced birthweight could not have been mediated by shortened gestation period.
In conclusion, the study results provided epidemiologic evidence that prenatal PAH exposure from diet including grilled meat might be hazardous for fetal development.
barbecued meat; pregnancy; birth weight; birth cohort study
Background: Urban landscape elements, particularly trees, have the potential to affect airflow, air quality, and production of aeroallergens. Several large-scale urban tree planting projects have sought to promote respiratory health, yet evidence linking tree cover to human health is limited.
Objectives: We sought to investigate the association of tree canopy cover with subsequent development of childhood asthma, wheeze, rhinitis, and allergic sensitization.
Methods: Birth cohort study data were linked to detailed geographic information systems data characterizing 2001 tree canopy coverage based on LiDAR (light detection and ranging) and multispectral imagery within 0.25 km of the prenatal address. A total of 549 Dominican or African-American children born in 1998–2006 had outcome data assessed by validated questionnaire or based on IgE antibody response to specific allergens, including a tree pollen mix.
Results: Tree canopy coverage did not significantly predict outcomes at 5 years of age, but was positively associated with asthma and allergic sensitization at 7 years. Adjusted risk ratios (RRs) per standard deviation of tree canopy coverage were 1.17 for asthma (95% CI: 1.02, 1.33), 1.20 for any specific allergic sensitization (95% CI: 1.05, 1.37), and 1.43 for tree pollen allergic sensitization (95% CI: 1.19, 1.72).
Conclusions: Results did not support the hypothesized protective association of urban tree canopy coverage with asthma or allergy-related outcomes. Tree canopy cover near the prenatal address was associated with higher prevalence of allergic sensitization to tree pollen. Information was not available on sensitization to specific tree species or individual pollen exposures, and results may not be generalizable to other populations or geographic areas.
aeroallergen; allergic sensitivity; asthma; built environment; childhood disease; environmental agents; epidemiology; pollen; urban life
It has been suggested that children with larger brains tend to perform better on IQ tests or cognitive function tests. Prenatal head growth and head growth in infancy are two crucial periods for subsequent intelligence. Studies have shown that environmental exposure to air pollutants during pregnancy is associated with fetal growth reduction, developmental delay, and reduced IQ. Meanwhile, genetic polymorphisms may modify the effect of environment on head growth. However, studies on gene–environment or gene–gene interactions on growth trajectories have been quite limited partly due to the difficulty to quantitatively measure interactions on growth trajectories. Moreover, it is known that assessing the significance of gene–environment or gene–gene interactions on cross-sectional outcomes empirically using the permutation procedures may bring substantial errors in the tests. We proposed a score that quantitatively measures interactions on growth trajectories and developed an algorithm with a parametric bootstrap procedure to empirically assess the significance of the interactions on growth trajectories under the likelihood framework. We also derived a Wald statistic to test for interactions on growth trajectories and compared it to the proposed parametric bootstrap procedure. Through extensive simulation studies, we demonstrated the feasibility and power of the proposed testing procedures. We applied our method to a real dataset with head circumference measures from birth to age 7 on a cohort currently being conducted by the Columbia Center for Children's Environmental Health (CCCEH) in Krakow, Poland, and identified several significant gene–environment interactions on head circumference growth trajectories.
gene–environment interactions; growth curves; Wald test; parametric bootstrap