BackgroundMany phthalates and phenols are hormonally active and are suspected to alter the course of development.ObjectiveWe investigated prenatal exposures to phthalate and phenol metabolites and their associations with body size measures of the infants at birth.MethodsWe measured 5 phenol and 10 phthalate urinary metabolites in a multiethnic cohort of 404 women in New York City during their third trimester of pregnancy and recorded size of infants at birth.ResultsMedian urinary concentrations were > 10 μg/L for 2 of 5 phenols and 6 of 10 phthalate monoester metabolites. Concentrations of low-molecular-weight phthalate monoesters (low-MWP) were approximately 5-fold greater than those of high-molecular-weight metabolites. Low-MWP metabolites had a positive association with gestational age [0.97 day gestational age per ln-biomarker; 95% confidence interval (CI), 0.07–1.9 days, multivariate adjusted] and with head circumference. Higher prenatal exposures to 2,5-dichlorophenol (2,5-DCP) predicted lower birth weight in boys (−210 g average birth weight difference between the third tertile and first tertile of 2,5-DCP; 95% CI, 71–348 g). Higher maternal benzophenone-3 (BP3) concentrations were associated with a similar decrease in birth weight among girls but with greater birth weight in boys.ConclusionsWe observed a range of phthalate and phenol exposures during pregnancy in our population, but few were associated with birth size. The association of 2,5-DCP and BP3 with reduced or increased birth weight could be important in very early or small-size births. In addition, positive associations of urinary metabolites with some outcomes may be attributable partly to unresolved confounding with maternal anthropometric factors.

BackgroundExperimental and observational studies have reported biological consequences of phthalate exposure relevant to neurodevelopment.ObjectiveOur goal was to examine the association of prenatal phthalate exposure with behavior and executive functioning at 4–9 years of age.MethodsThe Mount Sinai Children’s Environmental Health Study enrolled a multiethnic prenatal population in New York City between 1998 and 2002 (n = 404). Third-trimester maternal urines were collected and analyzed for phthalate metabolites. Children (n = 188, n = 365 visits) were assessed for cognitive and behavioral development between the ages of 4 and 9 years.ResultsIn multivariate adjusted models, increased loge concentrations of low molecular weight (LMW) phthalate metabolites were associated with poorer scores on the aggression [β = 1.24; 95% confidence interval (CI), 0.15– 2.34], conduct problems (β = 2.40; 95% CI, 1.34–3.46), attention problems (β = 1.29; 95% CI, 0.16– 2.41), and depression (β = 1.18; 95% CI, 0.11–2.24) clinical scales; and externalizing problems (β = 1.75; 95% CI, 0.61–2.88) and behavioral symptom index (β = 1.55; 95% CI, 0.39–2.71) composite scales. Increased loge concentrations of LMW phthalates were also associated with poorer scores on the global executive composite index (β = 1.23; 95% CI, 0.09–2.36) and the emotional control scale (β = 1.33; 95% CI, 0.18– 2.49).ConclusionBehavioral domains adversely associated with prenatal exposure to LMW phthalates in our study are commonly found to be affected in children clinically diagnosed with conduct or attention deficit hyperactivity disorders.

Background: Prenatal exposure to organophosphate pesticides has been shown to negatively affect child neurobehavioral development. Paraoxonase 1 (PON1) is a key enzyme in the metabolism of organophosphates.Objective: We examined the relationship between biomarkers of organophosphate exposure, PON1, and cognitive development at ages 12 and 24 months and 6–9 years.Methods: The Mount Sinai Children’s Environmental Health Study enrolled a multiethnic prenatal population in New York City between 1998 and 2002 (n = 404). Third-trimester maternal urine samples were collected and analyzed for organophosphate metabolites (n = 360). Prenatal maternal blood was analyzed for PON1 activity and genotype. Children returned for neurodevelopment assessments ages 12 months (n = 200), 24 months (n = 276), and 6–9 (n = 169) years of age.Results: Prenatal total dialkylphosphate metabolite level was associated with a decrement in mental development at 12 months among blacks and Hispanics. These associations appeared to be enhanced among children of mothers who carried the PON1 Q192R QR/RR genotype. In later childhood, increasing prenatal total dialkyl- and dimethylphosphate metabolites were associated with decrements in perceptual reasoning in the maternal PON1 Q192R QQ genotype, which imparts slow catalytic activity for chlorpyrifos oxon, with a monotonic trend consistent with greater decrements with increasing prenatal exposure.Conclusion: Our findings suggest that prenatal exposure to organophosphates is negatively associated with cognitive development, particularly perceptual reasoning, with evidence of effects beginning at 12 months and continuing through early childhood. PON1 may be an important susceptibility factor for these deleterious effects.

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 to 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 phthalate (LMW) 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.

We investigated the relationship between prenatal maternal urinary concentrations of phthalate metabolites and neonatal behavior in their 295 children enrolled in a multiethnic birth cohort between 1998 and 2002 at the Mount Sinai School of Medicine in New York City. Trained examiners administered the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) to children within 5 days of delivery. We measured metabolites of 7 phthalate esters in maternal urine that was collected between 25 and 40 weeks’ gestation. All but two phthalate metabolites were over 95% detectable. We summed metabolites on a molar basis into low and high molecular weight phthalates. We hypothesized the existence of sex-specific effects from phthalate exposure a priori given the hormonal activity of these chemicals. Overall we found few associations between individual phthalate metabolites or their molar sums and most of the BNBAS domains. However, we observed significant sex-phthalate metabolite interactions (p < 0.10) for the Orientation and Motor domains and the overall Quality of Alertness score. Among girls, there was a significant linear decline in adjusted mean Orientation score with increasing urinary concentrations of high molecular weight phthalate metabolites (B = -0.37, p = 0.02). Likewise, there was a strong linear decline in their adjusted mean Quality of Alertness score (B = -0.48, p < 0.01). In addition, boys and girls demonstrated opposite patterns of association between low and high molecular weight phthalate metabolite concentrations and Motor performance, with some indication of improved Motor performance with increasing concentration of low molecular weight phthalate metabolites among boys. This is the first study to report an association between prenatal phthalate exposure and neurological effects in humans or animals, and as such requires replication.

Objective Slight perturbations in maternal sex steroid production and metabolism may interfere with normal fetal neurodevelopment. The balance of maternal estrogens and androgens may have direct fetal effects, may influence the fetal hypothalamic-pituitary-gonadal axis or may alter local hormonal activity within the fetal brain. We investigated maternal functional polymorphisms of CYP17, CYP19 and CYP1B1, which control three major enzymatic steps in sex steroid biosynthesis and metabolism, in relation to childhood behaviors. Methods The Mount Sinai Children’s Environmental Health Study enrolled a multiethnic urban pregnancy cohort from 1998–2002 (n = 404). DNA was obtained from maternal blood (n=149) and from neonatal cord blood (n=53). At each visit, mothers completed the Behavior Assessment System for Children (BASC), a parent-reported questionnaire used to evaluate children for behavior problems. We focused on problem behaviors more commonly associated with ADHD (hyperactivity, attention problems, externalizing behaviors, conduct disorder, poor adaptability) to see if maternal genetic variants in sex steroid production and metabolism influence sexually-dimorphic behaviors in offspring. Results The more active gene variants were significantly associated with Attention Problems and poorer Adaptive Skills in male compared to female offspring. The CYP19 variant allele was also significantly associated with worse scores for boys on the Hyperactivity, Externalizing Problems Composite and Adaptive Skills Composite scales (p < 0.05). Conclusion We observed maladaptive behaviors in the male offspring of mothers who carried functional polymorphisms in the sex steroid pathway. The strongest associations were in domains commonly affected in Attention Deficit-Hyperactivity Disorder.

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