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      Prenatal Exposure to Phthalates and Neurodevelopment in the CHAMACOS Cohort

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          Abstract

          Background:

          Previous studies suggest that prenatal exposure to phthalates, ubiquitous synthetic chemicals, may adversely affect neurodevelopment. However, data are limited on how phthalates affect cognition, executive function, and behavioral function into adolescence.

          Objective:

          We aimed to investigate associations of prenatal phthalate exposure with neurodevelopment in childhood and adolescence in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study.

          Methods:

          We examined associations between maternal urinary phthalate metabolite concentrations measured twice during pregnancy and a range of neurodevelopmental outcomes from ages 7 through 16 y in the CHAMACOS birth cohort ( n = 334 ). We used age-specific linear regression models and generalized estimating equation models to assess longitudinal effects and examined differences by sex.

          Results:

          Phthalate metabolites were detected in 88%–100% of samples, depending on the metabolite. Associations of phthalates with neurodevelopmental outcomes were largely null with some noteworthy patterns. Higher prenatal concentrations of metabolites of low-molecular weight phthalates ( Σ LMW ) were associated with more self-reported hyperactivity [ β = 0.8 , 95% confidence interval (CI): 0.1, 1.4 per 2-fold increase in Σ LMW phthalates], attention problems ( β = 1.5 , 95% CI: 0.7, 2.2), and anxiety ( β = 0.9 , 95% CI: 0.0, 1.8) at age 16. We observed sex-specific differences for the sums of high-molecular-weight and di(2-ethylhexyl) metabolites and cognitive outcomes (e.g., β for Full-Scale IQ for boys = 1.9 , 95% CI: 4.1 , 0.3 and 1.7 , 95% CI: 3.8 , 0.3, respectively; β for girls = 1.8 , 95% CI: 0.1, 3.4 and 1.6, 95% CI: 0.0, 3.2, respectively; p -int = 0.01 for both).

          Conclusion:

          We found predominantly null associations of prenatal phthalates with neurodevelopment in CHAMACOS, and weak associations of Σ LMW phthalates with internalizing and externalizing behaviors in adolescence. No previous studies have examined associations of prenatal phthalate exposure with neurodevelopment into adolescence, an important time for manifestations of effects. https://doi.org/10.1289/EHP5165

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          Most cited references55

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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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            Is Open Access

            The Role of Puberty in the Developing Adolescent Brain

            Adolescence refers to the period of physical and psychological development between childhood and adulthood. The beginning of adolescence is loosely anchored to the onset of puberty, which brings dramatic alterations in hormone levels and a number of consequent physical changes. Puberty onset is also associated with profound changes in drives, motivations, psychology, and social life; these changes continue throughout adolescence. There is an increasing number of neuroimaging studies looking at the development of the brain, both structurally and functionally, during adolescence. Almost all of these studies have defined development by chronological age, which shows a strong—but not unitary—correlation with pubertal stage. Very few neuroimaging studies have associated brain development with pubertal stage, and yet there is tentative evidence to suggest that puberty might play an important role in some aspects of brain and cognitive development. In this paper we describe this research, and we suggest that, in the future, developmental neuroimaging studies of adolescence should consider the role of puberty. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc.
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              Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000.

              We measured the urinary monoester metabolites of seven commonly used phthalates in approximately 2,540 samples collected from participants of the National Health and Nutrition Examination Survey (NHANES), 1999-2000, who were greater than or equal to 6 years of age. We found detectable levels of metabolites monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono-(2-ethylhexyl) phthalate (MEHP) in > 75% of the samples, suggesting widespread exposure in the United States to diethyl phthalate, dibutyl phthalate or diisobutylphthalate, benzylbutyl phthalate, and di-(2-ethylhexyl) phthalate, respectively. We infrequently detected monoisononyl phthalate, mono-cyclohexyl phthalate, and mono-n-octyl phthalate, suggesting that human exposures to di-isononyl phthalate, dioctylphthalate, and dicyclohexyl phthalate, respectively, are lower than those listed above, or the pathways, routes of exposure, or pharmacokinetic factors such as absorption, distribution, metabolism, and elimination are different. Non-Hispanic blacks had significantly higher concentrations of MEP than did Mexican Americans and non-Hispanic whites. Compared with adolescents and adults, children had significantly higher levels of MBP, MBzP, and MEHP but had significantly lower concentrations of MEP. Females had significantly higher concentrations of MEP and MBzP than did males, but similar MEHP levels. Of particular interest, females of all ages had significantly higher concentrations of the reproductive toxicant MBP than did males of all ages; however, women of reproductive age (i.e., 20-39 years of age) had concentrations similar to adolescent girls and women 40 years of age. These population data on exposure to phthalates will serve an important role in public health by helping to set research priorities and by establishing a nationally representative baseline of exposure with which population levels can be compared.
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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
                25 October 2019
                October 2019
                : 127
                : 10
                : 107010
                Affiliations
                [1 ]Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California at Berkeley , Berkeley, California, USA
                [2 ]Central American Institute for Studies on Toxic Substances (IRET), Universidad Nacional , Heredia, Costa Rica
                [3 ]Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, Georgia, USA
                Author notes
                Address correspondence to Sharon K. Sagiv, Center for Environmental Research and Children’s Health (CERCH), School of Public Health, University of California at Berkeley, 1995 University Ave., Suite 265, Berkeley, CA 94704, USA
                Article
                EHP5165
                10.1289/EHP5165
                6867166
                31652105
                839c7d20-c4e4-473d-8e94-f3868a1d3010

                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.

                History
                : 08 February 2019
                : 24 September 2019
                : 02 October 2019
                Categories
                Research

                Public health
                Public health

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