Endocrine disruptors and childhood social impairment

Department of Preventive Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
NeuroToxicology (Impact Factor: 3.38). 12/2010; 32(2):261-7. DOI: 10.1016/j.neuro.2010.12.009
Source: PubMed


Prenatal exposure to endocrine disruptors has the potential to impact early brain development. Neurodevelopmental toxicity in utero may manifest as psychosocial deficits later in childhood. This study investigates prenatal exposure to two ubiquitous endocrine disruptors, the phthalate esters and bisphenol A (BPA), and social behavior in a sample of adolescent inner-city children. Third trimester urines of women enrolled in the Mount Sinai Children's Environmental Health Study between 1998 and 2002 (n=404) were analyzed for phthalate metabolites and BPA. Mother-child pairs were asked to return for a follow-up assessment when the child was between the ages of 7 and 9 years. At this visit, mothers completed the Social Responsiveness Scale (SRS) (n=137), a quantitative scale for measuring the severity of social impairment related to Autistic Spectrum Disorders (ASD) in the general population. In adjusted general linear models increasing log-transformed low molecular weight (LMW) phthalate metabolite concentrations were associated with greater social deficits (β=1.53, 95% CI 0.25-2.8). Among the subscales, LMWP were also associated with poorer Social Cognition (β=1.40, 95% CI 0.1-2.7); Social Communication (β=1.86, 95% CI 0.5-3.2); and Social Awareness (β=1.25, 95% CI 0.1-2.4), but not for Autistic Mannerisms or Social Motivation. No significant association with BPA was found (β=1.18, 95% CI -0.75, 3.11). Prenatal phthalate exposure was associated with childhood social impairment in a multiethnic urban population. Even mild degrees of impaired social functioning in otherwise healthy individuals can have very important adverse effects over a child's lifetime. These results extend our previous finding of atypical neonatal and early childhood behaviors in relation to prenatal phthalate exposure.


Available from: Latha Soorya
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    • "There is a growing literature that suggests that early exposure to environmental contaminants, specifically those with endocrine-disrupting properties, may be associated with an increased risk of neurological disorders, such as autism. Examples include studies investigating early exposure to phthalates, polybrominated diphenyl ethers, and polychlorinated biphenyls (Larsson et al., 2009; Miodovnik et al., 2011; Mitchell et al., 2012; Testa et al., 2012; Woods et al., 2012). Although the magnitude seen in the present study is relatively small, there is evidence that large increases in neurons and glia are found in human males diagnosed with autism (Courchesne et al., 2011; Edmonson et al., 2014). "
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    ABSTRACT: Previous work has shown that exposure to bisphenol A (BPA) during early development can alter sexual differentiation of the brain in rodents, although few studies have examined effects on areas of the brain associated with cognition. The current study examined if developmental BPA exposure alters the total number of neurons and glia in the medial prefrontal cortex (mPFC) in adulthood. Pregnant Long-Evans rats were orally exposed to 0, 4, 40, or 400 μg/kg BPA in corn oil throughout pregnancy. From postnatal days 1-9, pups were given daily oral doses of oil or BPA, at doses corresponding to those given during gestation. Brains were examined in adulthood, and the volume of layers 2/3 and layers 5/6 of the mPFC were parcellated. The density of neurons and glia in these layers was quantified stereologically with the optical disector, and density was multiplied by volume for each animal. Males exposed to 400 μg/kg BPA were found to have increased numbers of neurons and glia in layers 5/6. Although there were no significant effects of BPA in layers 2/3, the pattern of increased neuron number in males exposed to 400 μg/kg BPA was similar to that seen in layers 5/6. No effects of BPA were seen in females or in males exposed to the other doses of BPA. This study indicates that males are more susceptible to the long-lasting effects of BPA on anatomy of the mPFC, an area implicated in neurological disorders.
    Neuroscience 09/2014; 279. DOI:10.1016/j.neuroscience.2014.08.038 · 3.36 Impact Factor
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    • "While the size of our study (148 mother–child pairs) did not allow for separate analyses for males and females, several studies have suggested an infant sex modified association between phthalates and developmental scores [13] [15] [16]. No sex-specific differences were observed in the association between prenatal phthalate exposure and childhood social impairment at 7–9 years of age [14]. Further analyses to examine differences in neurodevelopmental effects of phthalates between males and females seem reasonable and could be performed for the REPRO_PL cohort in the future. "
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    ABSTRACT: Background Widespread phthalate exposure has prompted investigations concerning their potential adverse health effects. The objective of this study was to evaluate the impact of pre and early postnatal phthalate exposure on child psychomotor development basing on the data from the prospective Polish Mother and Child Cohort Study (REPRO PL). Methods Phthalate exposure was determined by measuring 11 phthalate metabolites (MEP, MiBP, MnBP, 3OH-MnBP, MBzP, MEHP, 5OH-MEHP, 5oxo-MEHP, 7OH-MiNP, 7oxo-MiNP, MnOP) in the urine collected from mothers during the third trimester of pregnancy (prenatal exposure) and from their children at 24 th month of age (postnatal exposure). The analysis was performed by HPLC-MS/MS method. Child psychomotor development was assessed at the 2 nd year of age by Bayley Scales of Infant and Toddler Development. Results Child motor development was inversely associated with natural log concentrations (µg/g creatinine) of 3OH-MnBP (β=-2.3; 95% CI -4.0 to -0.6), 5OH-MEHP (β=-1.2; 95% CI -2.2 to -0.3), 5oxo-MEHP (β=-1.8; 95% CI -330 to -0.2) and DEHP metabolites (β=-2.2; 95% CI -3.60 to -0.8) and sum of high molecular weight phthalates (β=-2.5; 95% CI -4.1 to -0.9) in the urine collected from mothers during pregnancy after adjustment for variety of potential confounders. Additional adjustment for postnatal phthalate exposure did not change the results. Postnatal child exposure to phthalates was not associated with any of the measured scores of child psychomotor development. Conclusions The study findings add further support to the possibility that prenatal phthalate exposure may be detrimental to child neurodevelopment and underscore the importance of policies and public health interventions to reduce such exposure.
    Early Human Development 09/2014; 90(9):477–485. DOI:10.1016/j.earlhumdev.2014.06.006 · 1.79 Impact Factor
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    • "Thus, our results raise concern because the observed phthalate exposures may put these infants at risk. Epidemiological studies in humans have reported that phthalate exposure prenatally and in early life is associated with changes in infant sex hormones and decreased anogenital distance (AGD) (Main et al. 2006; Swan et al. 2005), allergic asthma (Bornehag and Nanberg 2010), and changes in sex-specific behavioral patterns (Miodovnik et al. 2011; Swan et al. 2010; Whyatt et al. 2012). This is corroborated by numerous animal experiments showing decreased AGD and testicular testestorone production after in utero exposure (Borch et al. 2006; Foster 2006; Howdeshell et al. 2007). "
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    ABSTRACT: Background: Some phthalates have shown antiandrogenic effects in rat offspring. Premature infants may be exposed to high amounts of specific phthalates during hospitalization, and thus are potentially at risk. Objective: We evaluated longitudinal phthalate exposure and metabolism in full-term (FT) and preterm (PT) infants. Methods: Fifty-eight FT and 67 PT (gestational age, 24.7-36.6 weeks) infants were recruited at birth and followed until 14 months (nine times). Urinary concentrations of metabolites of diethyl phthalate (DEP), dibutyl phthalate isomers (DiBP and DnBP), butylbenzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), and diisononyl phthalate (DiNP) were measured in 894 samples. Daily intake and a hazard index for antiandrogenic effects were estimated, and excretion patterns of DEHP and DiNP metabolites were analyzed. Results: Metabolites of BBzP, DiNP, and DEHP were 5-50 times higher at day 7 (D7) and month 1 (M1) in PT than in FT infants. Thereafter, metabolite concentrations were similar between the two groups. The estimated hazard index for combined DiBP, DnBP, BBzP, and DEHP exposures 7 days after birth exceeded the antiandrogenic threshold in > 80% of PT and > 30% of FT infants, and after M2, in 30% of all infants. The excretion pattern of DEHP and DiNP metabolites changed with age. Conclusion: Most PT infants and approximately one-third of healthy FT newborns were exposed to phthalates during early life at a potentially harmful level according to the European Food Safety Authority's recommended limits of daily exposure. Changes in the relative proportions of secondary phthalate metabolites over time were consistent with maturation of infant metabolic pathways during the first year of life. Further research is needed on the health effects of phthalate exposures and the influence of changes in metabolic capacity in neonates and infants.
    Environmental Health Perspectives 05/2014; 122(9). DOI:10.1289/ehp.1307569 · 7.98 Impact Factor
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