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      Prenatal Mancozeb Exposure, Excess Manganese, and Neurodevelopment at 1 Year of Age in the Infants’ Environmental Health (ISA) Study

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          Abstract

          Background:

          Although growing evidence suggests that early-life excess manganese (Mn) impairs neurodevelopment, data on the neurodevelopmental effects of mancozeb, a fungicide containing Mn, and its main metabolite ethylenethiourea (ETU) are limited.

          Objective:

          We examined whether prenatal mancozeb exposure and excess Mn were associated with neurodevelopment in 355 1-y-old infants living near banana plantations with frequent aerial mancozeb spraying in Costa Rica.

          Methods:

          We measured urinary ETU, hair Mn, and blood Mn concentrations in samples collected 1–3 times during pregnancy from mothers enrolled in the Infants’ Environmental Health (ISA) study. We then assessed neurodevelopment in their 1-y-old infants using the Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III). We estimated exposure–outcome associations using linear regression models adjusted for maternal education, parity, gestational age at birth, child age, Home Observation for Measurement of the Environment score, and location of neurodevelopmental assessment.

          Results:

          Median (P25–P75) urinary ETU, hair Mn, and blood Mn measured during pregnancy were 3.3 μ g / L (2.4–4.9; specific gravity–corrected), 1.7 μ g / g (0.9–4.1), and 24.0 μ g / L (20.3–28.0), respectively. Among girls, higher ETU was associated with lower social-emotional scores [ β per 10 -fold increase = 7.4 points (95% CI: 15.2 , 0.4)], whereas higher hair Mn was associated with lower cognitive scores [ 3.0 ( 6.1 , 0.1)]. Among boys, higher hair Mn was associated with lower social-emotional scores [ 4.6 ( 8.5 , 0.8 )]. We observed null associations for blood Mn, language, and motor outcomes.

          Conclusions:

          Our findings indicate that maternal exposure to mancozeb and excess Mn during pregnancy may have adverse and sex-specific effects on infant neurodevelopment. https://doi.org/10.1289/EHP1955

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          Most cited references 61

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          The CES-D Scale: A Self-Report Depression Scale for Research in the General Population

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            Forming inferences about some intraclass correlation coefficients.

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              Epidemiologic Evaluation of Measurement Data in the Presence of Detection Limits

              Quantitative measurements of environmental factors greatly improve the quality of epidemiologic studies but can pose challenges because of the presence of upper or lower detection limits or interfering compounds, which do not allow for precise measured values. We consider the regression of an environmental measurement (dependent variable) on several covariates (independent variables). Various strategies are commonly employed to impute values for interval-measured data, including assignment of one-half the detection limit to nondetected values or of “fill-in” values randomly selected from an appropriate distribution. On the basis of a limited simulation study, we found that the former approach can be biased unless the percentage of measurements below detection limits is small (5–10%). The fill-in approach generally produces unbiased parameter estimates but may produce biased variance estimates and thereby distort inference when 30% or more of the data are below detection limits. Truncated data methods (e.g., Tobit regression) and multiple imputation offer two unbiased approaches for analyzing measurement data with detection limits. If interest resides solely on regression parameters, then Tobit regression can be used. If individualized values for measurements below detection limits are needed for additional analysis, such as relative risk regression or graphical display, then multiple imputation produces unbiased estimates and nominal confidence intervals unless the proportion of missing data is extreme. We illustrate various approaches using measurements of pesticide residues in carpet dust in control subjects from a case–control study of non-Hodgkin lymphoma.
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                Author and article information

                Journal
                Environ Health Perspect
                Environ. Health Perspect
                EHP
                Environmental Health Perspectives
                Environmental Health Perspectives
                0091-6765
                1552-9924
                29 May 2018
                May 2018
                : 126
                : 5
                Affiliations
                [ 1 ]Central American Institute for Studies on Toxic Substances (IRET), Universidad Nacional , Heredia, Costa Rica
                [ 2 ]Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California at Berkeley , Berkeley, California, USA
                [ 3 ]Environmental Health Department, National Institute of Public Health , Mexico City, Mexico
                [ 4 ]Division of Research in Community Interventions, National Institute of Perinatology , Mexico City, Mexico
                [ 5 ]Department of Microbiology and Environmental Toxicology, University of California at Santa Cruz , Santa Cruz, California, USA
                [ 6 ]Faculty of Pharmacy, Federal University of Bahia , Bahia, Brazil
                [ 7 ]Centre for Interdisciplinary Research Centre on Health, Well-being, Society and Environment (CINBIOSE), University of Quebec in Montreal , Montreal, Quebec, Canada
                [ 8 ]Division of Occupational and Environmental Medicine, Institute of Laboratory Medicine, Lund University , Lund, Sweden
                Author notes
                Address correspondence to A.M. Mora, Central American Institute for Studies on Toxic Substances (IRET), Universidad Nacional, P.O. Box 86-3000 Heredia, Costa Rica. Telephone: 506 2277-3677. Email: ana.mora.mora@ 123456una.cr
                Article
                EHP1955
                10.1289/EHP1955
                6072008
                29847083

                EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.

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