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Early-life environmental exposures and childhood growth: A comparison of statistical methods.

ABSTRACT: There is a growing literature that suggests environmental exposure during key developmental periods could have harmful impacts on growth and development of humans. Understanding and estimating the relationship between early-life exposure and human growth is vital to studying the adverse health impacts of environmental exposure. We compare two statistical tools, mixed-effects models with interaction terms and growth mixture models, used to measure the association between exposure and change over time within the context of non-linear growth and non-monotonic relationships between exposure and growth. We illustrate their strengths and weaknesses through a real data example and simulation study. The data example, which focuses on the relationship between phthalates and the body mass index growth of children, indicates that the conclusions from the two models can differ. The simulation study provides a broader understanding of the robustness of these models in detecting the relationships between any exposure and growth that could be observed. Data-driven growth mixture models are more robust to non-monotonic growth and stochastic relationships but at the expense of interpretability. We offer concrete modeling strategies to estimate complex relationships with growth patterns.

SUBMITTER: Heggeseth BC

PROVIDER: S-EPMC6296561 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Early-life environmental exposures and childhood growth: A comparison of statistical methods.

Heggeseth Brianna C BC Aleman Alvaro A

PloS one 20181217 12

There is a growing literature that suggests environmental exposure during key developmental periods could have harmful impacts on growth and development of humans. Understanding and estimating the relationship between early-life exposure and human growth is vital to studying the adverse health impacts of environmental exposure. We compare two statistical tools, mixed-effects models with interaction terms and growth mixture models, used to measure the association between exposure and change over ...[more]

PMID: 30557389

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Project description:BACKGROUND:Chemical and nonchemical environmental exposures are increasingly suspected to influence the development of obesity, especially during early life, but studies mostly consider single exposure groups. OBJECTIVES:Our study aimed to systematically assess the association between a wide array of early-life environmental exposures and childhood obesity, using an exposome-wide approach. METHODS:The HELIX (Human Early Life Exposome) study measured child body mass index (BMI), waist circumference, skinfold thickness, and body fat mass in 1,301 children from six European birth cohorts age 6-11 y. We estimated 77 prenatal exposures and 96 childhood exposures (cross-sectionally), including indoor and outdoor air pollutants, built environment, green spaces, tobacco smoking, and biomarkers of chemical pollutants (persistent organic pollutants, metals, phthalates, phenols, and pesticides). We used an exposure-wide association study (ExWAS) to screen all exposure-outcome associations independently and used the deletion-substitution-addition (DSA) variable selection algorithm to build a final multiexposure model. RESULTS:The prevalence of overweight and obesity combined was 28.8%. Maternal smoking was the only prenatal exposure variable associated with higher child BMI (z-score increase of 0.28, 95% confidence interval: 0.09, 0.48, for active vs. no smoking). For childhood exposures, the multiexposure model identified particulate and nitrogen dioxide air pollution inside the home, urine cotinine levels indicative of secondhand smoke exposure, and residence in more densely populated areas and in areas with fewer facilities to be associated with increased child BMI. Child blood levels of copper and cesium were associated with higher BMI, and levels of organochlorine pollutants, cobalt, and molybdenum were associated with lower BMI. Similar results were found for the other adiposity outcomes. DISCUSSION:This first comprehensive and systematic analysis of many suspected environmental obesogens strengthens evidence for an association of smoking, air pollution exposure, and characteristics of the built environment with childhood obesity risk. Cross-sectional biomarker results may suffer from reverse causality bias, whereby obesity status influenced the biomarker concentration. https://doi.org/10.1289/EHP5975.

Project description:IntroductionEarly onset and high prevalence of allergic diseases result in high individual and socio-economic burdens. Several studies provide evidence for possible effects of environmental factors on allergic diseases, but these are mainly single-exposure studies. The exposome provides a novel holistic approach by simultaneously studying a large set of exposures. The aim of the study was to evaluate the association between a broad range of prenatal and childhood environmental exposures and allergy-related outcomes in children.Material and methodsAnalyses of associations between 90 prenatal and 107 childhood exposures and allergy-related outcomes (last 12 months: rhinitis and itchy rash; ever: doctor-diagnosed eczema and food allergy) in 6-11 years old children (n = 1270) from the European Human Early-Life Exposome cohort were performed. Initially, we used an exposome-wide association study (ExWAS) considering the exposures independently, followed by a deletion-substitution-addition selection (DSA) algorithm considering all exposures simultaneously. All the exposure variables selected in the DSA were included in a final multi-exposure model using binomial general linear model (GLM).ResultsIn ExWAS, no exposures were associated with the outcomes after correction for multiple comparison. In multi-exposure models for prenatal exposures, lower distance of residence to nearest road and higher di-iso-nonyl phthalate level were associated with increased risk of rhinitis, and particulate matter absorbance (PMabs) was associated with a decreased risk. Furthermore, traffic density on nearest road was associated with increased risk of itchy rash and diethyl phthalate with a reduced risk. DSA selected no associations of childhood exposures, or between prenatal exposures and eczema or food allergy.DiscussionThis first comprehensive and systematic analysis of many environmental exposures suggests that prenatal exposure to traffic-related variables, PMabs and phthalates are associated with rhinitis and itchy rash.

Project description:BackgroundGrowing evidence exists about the fetal and environmental origins of hypertension, but mainly limited to single-exposure studies. The exposome has been proposed as a more holistic approach by studying many exposures simultaneously.ObjectivesThis study aims to evaluate the association between a wide range of prenatal and postnatal exposures and blood pressure (BP) in children.MethodsSystolic and diastolic BP were measured among 1,277 children from the European HELIX (Human Early-Life Exposome) cohort aged 6 to 11 years. Prenatal (n = 89) and postnatal (n = 128) exposures include air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals, and lifestyles. Two methods adjusted for confounders were applied: an exposome-wide association study considering the exposures independently, and the deletion-substitution-addition algorithm considering all the exposures simultaneously.ResultsDecreases in systolic BP were observed with facility density (β change for an interquartile-range increase in exposure: -1.7 mm Hg [95% confidence interval (CI): -2.5 to -0.8 mm Hg]), maternal concentrations of polychlorinated biphenyl 118 (-1.4 mm Hg [95% CI: -2.6 to -0.2 mm Hg]) and child concentrations of dichlorodiphenyldichloroethylene (DDE: -1.6 mm Hg [95% CI: -2.4 to -0.7 mm Hg]), hexachlorobenzene (-1.5 mm Hg [95% CI: -2.4 to -0.6 mm Hg]), and mono-benzyl phthalate (-0.7 mm Hg [95% CI: -1.3 to -0.1 mm Hg]), whereas increases in systolic BP were observed with outdoor temperature during pregnancy (1.6 mm Hg [95% CI: 0.2 to 2.9 mm Hg]), high fish intake during pregnancy (2.0 mm Hg [95% CI: 0.4 to 3.5 mm Hg]), maternal cotinine concentrations (1.2 mm Hg [95% CI: -0.3 to 2.8 mm Hg]), and child perfluorooctanoate concentrations (0.9 mm Hg [95% CI: 0.1 to 1.6 mm Hg]). Decreases in diastolic BP were observed with outdoor temperature at examination (-1.4 mm Hg [95% CI: -2.3 to -0.5 mm Hg]) and child DDE concentrations (-1.1 mm Hg [95% CI: -1.9 to -0.3 mm Hg]), whereas increases in diastolic BP were observed with maternal bisphenol-A concentrations (0.7 mm Hg [95% CI: 0.1 to 1.4 mm Hg]), high fish intake during pregnancy (1.2 mm Hg [95% CI: -0.2 to 2.7 mm Hg]), and child copper concentrations (0.9 mm Hg [95% CI: 0.3 to 1.6 mm Hg]).ConclusionsThis study suggests that early-life exposure to several chemicals, as well as built environment and meteorological factors, may affect BP in children.

Project description:BackgroundPersistent disparities in academic performance may result from a confluence of adverse exposures accruing disproportionately to specific subpopulations.ObjectiveOur overarching objective was to investigate how multiple exposures experienced over time affect early childhood educational outcomes. We were specifically interested in whether there were: racial/ethnic disparities in prevalence of adverse exposures; racial/ethnic disparities in associations observed between adverse exposures and early childhood educational outcomes; and interactions between exposures, suggesting that one exposure augments susceptibility to adverse effects of another exposure.MethodsWe link geocoded North Carolina birth data for non-Hispanic white (NHW) and non-Hispanic black (NHB) children to blood lead surveillance data and 4th grade end-of-grade (EOG) standardized test scores (n = 65,151). We construct a local, spatial index of racial isolation (RI) of NHB at the block group level. We fit race-stratified multi-level models of reading and mathematics EOG scores regressed on birthweight percentile for gestational age, blood lead level, maternal smoking, economic disadvantage, and RI, adjusting for maternal- and child-level covariates and median household income.ResultsThere were marked racial/ethnic disparities in prevalence of adverse exposures. Specifically, NHB children were more likely than NHW children to be economically disadvantaged (80% vs. 40%), live in block groups with the highest quintile of RI (46% vs. 5%), have higher blood lead levels (4.6 vs. 3.7 μg/dL), and lower birthweight percentile for gestational age (mean: 39th percentile vs. 51st percentile). NHB children were less likely to have mothers who reported smoking during pregnancy (11% and 22%). We observed associations between key adverse exposures and reading and math EOG scores in 4th grade. Higher birthweight percentile for gestational age was associated with higher EOG scores, while economic disadvantage, maternal smoking, and elevated blood lead levels were associated with lower EOG scores. Associations observed for NHB and NHW children were generally not statistically different from one another, with the exception of neighborhood RI. NHB children residing in block groups in the highest RI quintile had reading and math scores 1.54 (0.74, 2.34) and 1.12 (0.38, 1.87) points lower, respectively, compared to those in the lowest RI quintile; statistically significant decrements in EOG scores associated with RI were not observed for NHW children. We did not find evidence of multiplicative interactions between exposures for NHB or NHW children.DiscussionKey adverse host, environmental, and social exposures accrue disproportionately to NHB children. Decrements in test scores associated with key adverse exposures were often but not always larger for NHB children, but were not significantly different from those estimated for NHW children. While we did not observe interactive effects, NHB children on average experience more deleterious combined exposures, resulting in larger decrements to test scores compared to NHW children.

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Early-life environmental exposures and childhood growth: A comparison of statistical methods.

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Early-life environmental exposures and childhood growth: A comparison of statistical methods.

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