Environmental factors, here taken to include pollutants, lifestyle factors and behaviours, can play an important role in serious, chronic pathologies with large societal and economic costs, including ...respiratory disease. However, measurement of the environmental component in epidemiological studies has traditionally relied on much more uncertain and incomplete assessments than measurement of the genome. The 'exposome' has therefore been proposed as a new paradigm to encompass the totality of human environmental (meaning all non-genetic) exposures from conception onwards, complementing the genome. Evidently, there are large challenges in developing the exposome concept into a workable approach for epidemiological research. These include: (1) the accurate and reliable measurement of many exposures in the external environment, (2) the measurement of a wide range of biological responses in the internal environment, and (3) addressing the dynamic, life course nature of the exposome. New tools and technologies that can be applied to address these challenges include exposure biomarker technologies, geographical mapping and remote sensing technologies, smartphone applications and personal exposure sensors, and high-throughput molecular 'omics' techniques. Prospective, population-based cohort studies have recently started to implement these methods using the exposome framework. The exposome thus offers a new and exciting paradigm for improvement and integration of currently scattered and uncertain data on the environmental component in disease aetiology. This should lead to a better understanding of the role of environmental risk factors in respiratory disease and other chronic pathologies, and ultimately to better primary prevention strategies.
In recent years, many new studies have evaluated associations between environmental pollutants and child health. This review aims to provide a broad summary of this literature, comparing the state of ...epidemiological evidence for the effects of a wide range of environmental contaminants (air pollutants, heavy metals, organochlorine compounds, perfluoroalkyl substances, polybrominated diphenyl ethers, pesticides, phthalates and bisphenol A) on child health outcomes. The review addresses effects on foetal growth and prematurity, neurodevelopment, respiratory and immune health, and childhood growth and obesity.
Findings of recent prospective studies and meta-analyses have corroborated previous good evidence, often at lower exposure levels, for effects on foetal growth of air pollution and polychlorinated biphenyls (PCBs), for neurotoxic effects of lead, methylmercury, PCBs and organophosphate pesticides, and for respiratory health effects of air pollution. Moderate evidence has emerged for a potential role of environmental pollutants in attention deficit hyperactivity disorder and autism (lead, PCBs, air pollution), respiratory and immune health (dichlorodiphenyldichloroethylene – DDE – and PCBs), and obesity (DDE). In addition, there is now moderate evidence that certain chemicals of relatively recent concern may be associated with adverse child health outcomes, specifically perfluorooctanoate and foetal growth, and polybrominated diphenyl ethers and neurodevelopment. For other chemicals of recent concern, such as phthalates and bisphenol A, the literature is characterised by large inconsistencies preventing strong conclusions.
In conclusion, since most of the recent literature evaluates common exposures in the general population, and not particularly high exposure situations, this accumulating body of evidence suggests that the unborn and young child require more protection than is currently provided. Large, coordinated research efforts are needed to improve understanding of long-term effects of complex chemical mixtures.
Background There is growing concern that prenatal exposure to bisphenol A (BPA) and phthalates, which are widely used in consumer products, might affect susceptibility to infections and the ...development of allergy and asthma in children, but there are currently very few prospective studies. Objective We sought to evaluate whether prenatal exposure to BPA and phthalates increases the risk of respiratory and allergic outcomes in children at various ages from birth to 7 years. Methods We measured BPA and metabolites of high-molecular-weight phthalates, 4 di-(2-ethylhexyl) phthalate (DEHP) metabolites (Σ4 DEHP) and mono-benzyl phthalate (MBzP), and 3 low-molecular-weight phthalate (LMWP) metabolites (Σ3 LMWP) in urine samples collected during the first and third trimesters in pregnant women participating in the Infancia y Medio Ambiente–Sabadell birth cohort study. The occurrence of chest infections, bronchitis, wheeze, and eczema in children was assessed at ages 6 and 14 months and 4 and 7 years through questionnaires given to the mothers. Atopy (specific IgE measurement) and asthma (questionnaire) were assessed at ages 4 and 7 years, respectively. Results The relative risks (RRs) of wheeze (RR, 1.20; 95% CI, 1.03-1.40; P = .02), chest infections (RR, 1.15; 95% CI, 1.00-1.32; P = .05), and bronchitis (RR, 1.18; 95% CI, 1.01-1.37; P = .04) at any age increased for each doubling in concentration of maternal urinary BPA. Σ4 DEHP metabolites were associated with the same outcomes (wheeze: RR, 1.25; 95% CI, 1.04-1.50, P = .02; chest infections: RR, 1.15; 95% CI, 0.97-1.35; P = .11; bronchitis: RR, 1.20; 95% CI, 1.01-1.43; P = .04). MBzP was associated with higher risk of wheeze (RR, 1.15; 95% CI, 1.00-1.33; P = .05). The risk of asthma at age 7 years was also increased with increasing prenatal BPA, Σ4 DEHP, and MBzP exposure. There were no other exposure-outcome associations. Conclusions Prenatal exposure to BPA and high-molecular-weight phthalates might increase the risk of asthma symptoms and respiratory tract infections throughout childhood.
The exposome constitutes a promising framework to improve understanding of the effects of environmental exposures on health by explicitly considering multiple testing and avoiding selective ...reporting. However, exposome studies are challenged by the simultaneous consideration of many correlated exposures.
We compared the performances of linear regression-based statistical methods in assessing exposome-health associations.
In a simulation study, we generated 237 exposure covariates with a realistic correlation structure and with a health outcome linearly related to 0 to 25 of these covariates. Statistical methods were compared primarily in terms of false discovery proportion (FDP) and sensitivity.
On average over all simulation settings, the elastic net and sparse partial least-squares regression showed a sensitivity of 76% and an FDP of 44%; Graphical Unit Evolutionary Stochastic Search (GUESS) and the deletion/substitution/addition (DSA) algorithm revealed a sensitivity of 81% and an FDP of 34%. The environment-wide association study (EWAS) underperformed these methods in terms of FDP (average FDP, 86%) despite a higher sensitivity. Performances decreased considerably when assuming an exposome exposure matrix with high levels of correlation between covariates.
Correlation between exposures is a challenge for exposome research, and the statistical methods investigated in this study were limited in their ability to efficiently differentiate true predictors from correlated covariates in a realistic exposome context. Although GUESS and DSA provided a marginally better balance between sensitivity and FDP, they did not outperform the other multivariate methods across all scenarios and properties examined, and computational complexity and flexibility should also be considered when choosing between these methods. Citation: Agier L, Portengen L, Chadeau-Hyam M, Basagaña X, Giorgis-Allemand L, Siroux V, Robinson O, Vlaanderen J, González JR, Nieuwenhuijsen MJ, Vineis P, Vrijheid M, Slama R, Vermeulen R. 2016. A systematic comparison of linear regression-based statistical methods to assess exposome-health associations. Environ Health Perspect 124:1848-1856; http://dx.doi.org/10.1289/EHP172.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Prenatal exposure to endocrine-disrupting chemicals (EDCs) may induce weight gain and obesity in children, but the obesogenic effects of mixtures have not been studied.
We evaluated the associations ...between pre- and perinatal biomarker concentrations of 27 EDCs and child weight status at 7 years of age.
In pregnant women enrolled in a Spanish birth cohort study between 2004 and 2006, we measured the concentrations of 10 phthalate metabolites, bisphenol A, cadmium, arsenic, and lead in two maternal pregnancy urine samples; 6 organochlorine compounds in maternal pregnancy serum; mercury in cord blood; and 6 polybrominated diphenyl ether congeners in colostrum. Among 470 children at 7 years, body mass index (BMI) z-scores were calculated, and overweight was defined as BMI > 85th percentile. We estimated associations with EDCs in single-pollutant models and applied principal-component analysis (PCA) on the 27 pollutant concentrations.
In single-pollutant models, HCB (hexachlorobenzene), βHCH (β-hexachlorocyclohexane), and polychlorinated biphenyl (PCB) congeners 138 and 180 were associated with increased child BMI z-scores; and HCB, βHCH, PCB-138, and DDE (dichlorodiphenyldichloroethylene) with overweight risk. PCA generated four factors that accounted for 43.4% of the total variance. The organochlorine factor was positively associated with BMI z-scores and with overweight (adjusted RR, tertile 3 vs. 1: 2.59; 95% CI: 1.19, 5.63), and these associations were robust to adjustment for other EDCs. Exposure in the second tertile of the phthalate factor was inversely associated with overweight.
Prenatal exposure to organochlorines was positively associated with overweight at age 7 years in our study population. Other EDCs exposures did not confound this association.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Ambient air pollution may increase the risk of overweight and obesity in children. However, available evidence is still scarce and has mainly focused on ambient air pollution exposure occurring at ...home without considering the school environment. The aim of this study is to assess whether exposure to ambient air pollution at home and school is associated with overweight and obesity in primary school children.
We studied 2660 children aged 7–10 years during 2012 in Barcelona. Child weight and height were measured and age- and sex-specific z-scores for body mass index (zBMI) were calculated using the WHO growth reference 2007. Overweight and obesity were defined using the same reference. Land use regression models were used to estimate levels of nitrogen dioxide (NO2), particulate matter <2.5 μm (PM2.5), <10 μm (PM10) and coarse (PMcoarse) at home. Outdoor levels of NO2, PM2.5, elemental carbon (EC), and ultrafine particles (UFP) were measured in the schoolyard. Multilevel mixed linear and ordered logistic models were used to assess the association between ambient air pollution (continuous per interquartile range (IQR) increase and categorical with tertile cutoffs) and zBMI (continuous and ordinal: normal, overweight, obese), after adjusting for socio-demographic characteristics.
An IQR increase in PM10-home (5.6 μg/m3) was associated with a 10% increase in the odds of being overweight or obese (odds ratio (OR) = 1.10; 95% CI = 1.00, 1.22). Children exposed to the highest tertile of UFP-school (>27,346 particles/cm3) had a 30% higher odds of being overweight or obese (OR = 1.30; 95%CI = 1.03, 1.64) compared to the lowest tertile of UFP exposure. We also observed that exposure to NO2, PM2.5 or EC at schools was associated with higher odds of overweight or obese at medium compared to low levels of exposure. Home and school exposures did not show any significant associations with zBMI (except PM2.5-school comparing tertile 2 vs tertile 1) but were similar in direction.
This study suggests that exposure to ambient air pollution, especially at school, is associated with childhood risk for overweight and obesity. A cautious interpretation is warranted because associations were not always linear and because school and home air pollution measurements were not directly comparable.
•Ambient air pollution was evaluated at home and schools in 2660 children.•Most children were exposed to air pollution levels above the WHO recommended levels.•Exposure to air pollution at schools increased the risk of overweight and obesity.
Objective: We systematically reviewed epidemiologic studies on ambient air pollution and congenital anomalies and conducted meta-analyses for a number of air pollutant—anomaly combinations. Data ...sources and extraction: From bibliographic searches we extracted 10 original epidemiologic studies that examined the association between congenital anomaly risk and concentrations of air pollutants. Meta-analyses were conducted if at least four studies published risk estimates for the same pollutant and anomaly group. Summary risk estimates were calculated for a) risk at high versus low exposure level in each study and b) risk per unit increase in continuous pollutant concentration. Data synthesis: Each individual study reported statistically significantly increased risks for some combinations of air pollutants and congenital anomalies, among many combinations tested. In meta-analyses, nitrogen dioxide (NO₂) and sulfur dioxide (SO₂) exposures were related to increases in risk of coarctation of the aorta odds ratio (OR) per 10 ppb NO₂= 1.17; 95% confidence interval (CI), 1.00-1.36; OR per 1 ppb SO, = 1.07; 95% CI, 1.01-1.13 and tetralogy of Fallot (OR per 10 ppb NO₂ = 1.20; 95% CI, 1.02-1.42; OR per 1 ppb SO?₂ = 1.03; 95% CI, 1.01-1.05), and PM₁₀ (paniculate matter ≤ 10 μrn) exposure was related to an increased risk of atrial septal defects (OR per 10 μg/m³ = 1.14; 95% CI, 1.01-1.28). Meta-analyses found no statistically significant increase in risk of other cardiac anomalies and oral clefts. Conclusions: We found some evidence for an effect of ambient air pollutants on congenital cardiac anomaly risk. Improvements in the areas of exposure assessment, outcome harmonization, assessment of other congenital anomalies, and mechanistic knowledge are needed to advance this field.
Human evidence on the effects of early life phthalate exposure on obesity and cardiovascular disease risks, reported by experimental studies, is limited to a few cross-sectional studies.
We evaluated ...the associations between prenatal phthalate exposure and childhood growth and blood pressure in a Spanish birth cohort study.
We assessed exposure using the average of two phthalate metabolite spot-urine concentrations collected from the mothers in the first and third pregnancy trimesters (creatinine-adjusted, n = 391). Study outcomes were the difference in age- and sex-specific z-scores for weight between birth and 6 months of age; and repeated age- and sex-specific z-scores for body mass index (BMI) at 1, 4, and 7 years; waist-to-height ratio at 4 and 7 years; and age- and height-specific z-scores for systolic and diastolic blood pressure at 4 and 7 years.
The sum of five high-molecular-weight phthalate metabolites (ΣHMWPm) was associated with lower weight z-score difference between birth and 6 months (β per doubling of exposure = -0.41; 95% CI: -0.75, -0.06) and BMI z-scores at later ages in boys (β = -0.28; 95% CI: -0.60, 0.03) and with higher weight z-score difference (β = 0.24; 95% CI: -0.16, 0.65) and BMI z-scores in girls (β = 0.30; 95% CI: -0.04, 0.64) (p for sex interaction = 0.01 and 0.05, respectively). The sum of three low-molecular-weight phthalates (ΣLMWPm) was not significantly associated with any of the growth outcomes. ΣHMWPm and ΣLMWPm were associated with lower systolic blood pressure z-scores in girls but not in boys.
This study suggests that prenatal phthalate exposure may be associated with postnatal growth and blood pressure in a sex-specific manner. Inconsistencies with previous cross-sectional findings highlight the necessity for evaluating phthalate health effects in prospective studies.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Exposure to perfluoroalkyl substances (PFASs) may increase risk for metabolic diseases; however, epidemiologic evidence is lacking at the present time. Pregnancy is a period of enhanced tissue ...plasticity for the fetus and the mother and may be a critical window of PFAS exposure susceptibility.
We evaluated the associations between PFAS exposures and metabolic outcomes in pregnant women.
We analyzed 1,240 pregnant women from the Spanish INMA Environment and Childhood Project (INfancia y Medio Ambiente) birth cohort study (recruitment period: 2003-2008) with measured first pregnancy trimester plasma concentrations of four PFASs (in nanograms/milliliter). We used logistic regression models to estimate associations of PFASs (log
-transformed and categorized into quartiles) with impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM), and we used linear regression models to estimate associations with first-trimester serum levels of triglycerides, total cholesterol, and C-reactive protein (CRP).
Perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were positively associated with IGT (137 cases) OR per log
-unit increase=1.99 (95% CI: 1.06, 3.78) and OR=1.65 ( 95% CI: 0.99, 2.76), respectively. PFOS and PFHxS associations with GDM (53 cases) were in a similar direction, but less precise. PFOS and perfluorononanoate (PFNA) were negatively associated with triglyceride levels percent median change per log
-unit increase=-5.86% (95% CI: -9.91%, -1.63%) and percent median change per log
-unit increase=-4.75% (95% CI: -8.16%, -0.61%, respectively, whereas perfluorooctanoate (PFOA) was positively associated with total cholesterol percent median change per log
-unit increase=1.26% (95% CI: 0.01%, 2.54%). PFASs were not associated with CRP in the subset of the population with available data (
=640).
Although further confirmation is required, the findings from this study suggest that PFAS exposures during pregnancy may influence lipid metabolism and glucose tolerance and thus may impact the health of the mother and her child. https://doi.org/10.1289/EHP1062.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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