Roni W. Kobrosly

Prenatal phthalate exposures and neurobehavioral development scores in boys and girls at 6-10 years of age.

Background: There is concern over potential neurobehavioral effects of prenatal phthalate exposures, but available data are inconsistent. Objectives: We examined associations between prenatal urinary concentrations of phthalate metabolites and neurobehavioral scores among children. Methods: We measured phthalate metabolite concentrations in urine samples from 153 pregnant participants in the Study for Future Families, a multicenter cohort study. Mothers completed the Child Behavior Checklist when the children were 6–10 years of age. We estimated overall and sex-specific associations between phthalate concentrations and behavior using adjusted multiple regression interaction models. Results: In boys, concentrations of monoisobutyl phthalate were associated with higher scores for inattention (β = 0.27; 95% CI: 0.04, 0.50), rule-breaking behavior (β = 0.20; 95% CI: 0.01, 0.38), aggression (β = 0.34; 95% CI: 0.09, 0.59), and conduct problems (β = 0.39; 95% CI: 0.20, 0.58), whereas the molar sum of di(2-ethylhexyl) phthalate metabolites was associated with higher scores for somatic problems (β = 0.15; 95% CI: 0.03, 0.28). Higher monobenzyl phthalate concentrations were associated with higher scores for oppositional behavior (β = 0.16; 95% CI: 0.01, 0.32) and conduct problems (β = 0.21; 95% CI: 0.06, 0.37) in boys, but with reduced anxiety scores in girls (β = –0.20; 95% CI: –0.39, –0.01). In general, the associations reported above were close to the null among girls. Model coefficients represent the difference in the square root–transformed outcome score associated with a 1-unit increase in log-transformed metabolites. Conclusions: Our results suggest associations between exposure to certain phthalates in late pregnancy and behavioral problems in boys. Given the few studies on this topic and methodological and population differences among studies, additional research is warranted. Citation: Kobrosly RW, Evans S, Miodovnik A, Barrett ES, Thurston SW, Calafat AM, Swan SH. 2014. Prenatal phthalate exposures and neurobehavioral development scores in boys and girls at 6–10 years of age. Environ Health Perspect 122:521–528; http://dx.doi.org/10.1289/ehp.1307063

Prenatal bisphenol A exposure and maternally reported behavior in boys and girls.

Prenatal exposure to gonadal hormones plays a major role in the normal development of the male and female brain and sexually dimorphic behaviors. Hormone-dependent differences in brain structure and function suggest that exposure to exogenous endocrine disrupting chemicals may be associated with sex-specific alterations in behavior. Bisphenol A (BPA) is an environmental chemical that has been shown to alter estrogen, androgen, and thyroid hormone signaling pathways. Epidemiological and experimental studies suggest associations between prenatal exposure to BPA and child behavior, however data are inconsistent, and few studies have examined school age children. We examined BPA concentration in spot urine samples from women at mean 27 weeks of pregnancy in relation to child behavior assessed at age 6-10 years using the parent-completed Child Behavior Checklist (CBCL). We report associations between maternal BPA urinary concentrations and several CBCL scores in 153 children (77 boys and 76 girls). We observed a significant interaction between maternal urinary BPA and sex for several behaviors (externalizing, aggression, Anxiety Disorder, Oppositional/Defiant Disorder and Conduct Disorder traits), but no significant associations between BPA and scores on any CBCL scales. However in analyses restricted to children of mothers with detectable prenatal urinary BPA (n=125), BPA was associated with moderately increased internalizing and externalizing behaviors, withdrawn/depressed behavior, somatic problems, and Oppositional/Defiant Disorder traits in boys. In addition we observed a significant interaction between BPA and sex for several behaviors (externalizing, withdrawn/depressed, rule-breaking, Oppositional/Defiant Disorder traits, and Conduct Disorder traits). These results suggest that prenatal exposure to BPA may be related to increased behavior problems in school age boys, but not girls.

Socioeconomic factors and phthalate metabolite concentrations among United States women of reproductive age.

INTRODUCTION Relatively little is known about the socioeconomic correlates of phthalate metabolite urine concentrations among the general population, exposures of increasing public health concern, particularly for women of reproductive age. METHODS We pooled data from the 2001-2008 cycles of the National Health and Nutrition Examination Survey to examine the associations between phthalate metabolite concentrations (including the molar sum of four di-2-ethylhexyl phthalate (DEHP) metabolites, the molar sum of two dibutyl phthalate (DBP) metabolites, and metabolites of benzylbutyl phthalate (BzBP) and diethyl phthalate (DEP)) with socioeconomic indicators (including ethnicity, education, income, and food security status) among women 20 to 39 years age. We also derived a socioeconomic status summary measure using factor analysis and investigated its associations with metabolite concentrations. RESULTS In fully adjusted models, the lowest quartile of overall socioeconomic status was associated with 1.83 (95% CI=1.54-2.17) times the concentrations of mono-benzyl phthalate (MBzP), and 0.72 (95% CI=0.54-0.98) times the concentrations of (molar sum) DEHP metabolites compared with the highest quartile of overall socioeconomic status. This latter association was driven primarily by educational attainment. All Non-White ethnicities combined had 1.24 (95% CI=1.09-1.40) times the concentrations of (molar sum) DBP metabolites, 1.32 (95% CI=1.12-1.56) times the mono-ethyl phthalate (MEP) concentrations, and 0.82 (95% CI=0.71-0.96) the concentrations of MBzP of Non-Hispanic Whites. CONCLUSIONS Biomarkers of phthalate exposure vary with socioeconomic factors in women of reproductive age in the United States. Given the public health concern surrounding phthalate exposure, more research is needed to elucidate the reasons for these differences.

Associations between immunologic, inflammatory, and oxidative stress markers with severity of depressive symptoms: an analysis of the 2005-2006 National Health and Nutrition Examination Survey.

Previous studies have demonstrated increased levels of serum markers of systemic inflammation and immune system function among individuals with depressive symptoms. Despite these observations, the biological mechanisms behind this association remain elusive. The objective of the present analysis was to examine the individual and joint associations of white blood cell counts, platelet counts, and C-reactive protein with depression severity and to determine whether oxidative stress might mediate these associations. We conducted an analysis of 3867 subjects from the 2005-2006 National Health and Nutritional Examination Survey. Ordinal logistic regression was used to assess associations between three levels of depression symptom severity (as measured by the nine-item Patient Health Questionnaire) and serum C-reactive protein, white blood cell counts, platelet counts, and four surrogate markers of oxidative stress. Covariates included sex, age, smoking status, physical activity, education, poverty to income ratio, as well as medication use and medical conditions influencing inflammation levels. In separate models, the risk of moderate to severe depression was significantly greater in the highest quartiles of CRP (OR=1.84. 95 percent confidence interval (CI)=1.35-2.52), WBC (OR=1.70, CI=1.31-2.19), and platelet counts (OR=1.41, CI=1.13-1.76) after adjusting for basic sociodemographic and behavioral factors. After additional adjustment for medication use and oxidative stress surrogate measures, the highest quartile of WBC counts remained associated with depression (OR=1.60, CI=1.23-2.09). Adjustment for oxidative stress measures did not substantially affect estimated associations of inflammation/immunologic markers. In summary, we observed significantly elevated white blood cell counts among subjects with moderate and severe depression, and oxidative stress and a medical history of inflammatory diseases do not appear to mediate this association. Although limited through its use of cross-sectional data, this is the first analysis to simultaneously consider immunologic and oxidative stress markers. Further research is needed to identify the biological basis for this persistent association.

Environmental health attitudes and behaviors: findings from a large pregnancy cohort study

OBJECTIVE Environmental chemicals are widely found in food and personal care products and may have adverse effects on fetal development. Our aim was to examine womens attitudes about these chemicals and ask whether they try to limit their exposure during pregnancy. STUDY DESIGN A multi-center cohort of women in the first trimester of pregnancy completed questionnaires including items on attitudes and behaviors related to environmental chemicals. Multivariable logistic regression models were used to examine: (1) whether sociodemographic variables predict environmental health attitudes and behaviors; and (2) whether womens attitudes about environmental chemicals affect their lifestyle behaviors, particularly diet and personal care product use. RESULTS Of the 894 subjects, approximately 60% strongly agreed that environmental chemicals are dangerous and 25% strongly felt they were impossible to avoid. Adjusting for covariates, educated women were more likely to believe that environmental chemicals are dangerous (OR 1.74, 95% CI 1.13, 2.66), and that belief, in turn, was associated with a number of healthy behaviors including choosing organic foods, foods in safe plastics, and chemical-free personal care products, and limiting fast food intake. Younger women were more likely to believe that environmental chemicals are impossible to avoid (OR 1.04, 95% CI 1.00, 1.08). CONCLUSIONS Womens attitudes about environmental chemicals may impact their choices during pregnancy. Overcoming a lack of concern about environmental chemicals, particularly among certain sociodemographic groups, is important for the success of clinical or public health prevention measures.

Choline status and neurodevelopmental outcomes at 5 years of age in the Seychelles Child Development Nutrition Study

Choline is an essential nutrient that is found in many food sources and plays a critical role in the development of the central nervous system. Animal studies have shown that choline status pre- and postnatally can have long-lasting effects on attention and memory; however, effects in human subjects have not been well studied. The aim of the present study was to examine the association between plasma concentrations of free choline and its related metabolites in children and their neurodevelopment in the Seychelles Child Development Nutrition Study, an ongoing longitudinal study assessing the development of children born to mothers with high fish consumption during pregnancy. Plasma concentrations of free choline, betaine, dimethylglycine (DMG), methionine and homocysteine and specific measures of neurodevelopment were measured in 210 children aged 5 years. The childrens plasma free choline concentration (9·17 (sd 2·09) μmol/l) was moderately, but significantly, correlated with betaine (r 0·24; P= 0·0006), DMG (r 0·15; P= 0·03), methionine (r 0·24; P= 0·0005) and homocysteine (r 0·19; P= 0·006) concentrations. Adjusted multiple linear regression revealed that betaine concentrations were positively associated with Preschool Language Scale – total language scores (β = 0·066; P= 0·04), but no other associations were evident. We found no indication that free choline concentration or its metabolites, within the normal physiological range, are associated with neurodevelopmental outcomes in children at 5 years of age. As there is considerable animal evidence suggesting that choline status during development is associated with cognitive outcome, the issue deserves further study in other cohorts.

Blood Lead Levels in Mexico and Pediatric Burden of Disease Implications

BACKGROUND Although there has been success in reducing lead exposure with the phase-out of leaded gasoline, exposure to lead in Mexico continues to threaten the health of millions, much of which is from lead-based glazes used in pottery that leaches into food. OBJECTIVES An extensive historical review and analysis of available data on blood lead levels in Mexican populations was conducted. We used a calculated geometric mean to evaluate the effect of lead on the pediatric burden of disease. METHODS An extensive bibliographic search identified 83 published articles from 1978 to 2010 with blood lead level (BLL) data in Mexican populations representing 150 data points from more than 50,000 study participants. Values from these publications were categorized into various groupings. We then calculated the incidence of disease and disability-adjusted life-years resulting from these BLLs using the World Health Organizations burden of disease spreadsheets for mild mental retardation. RESULTS Reviewing all relevant studies, the geometric means of Mexican BLLs in urban and rural areas were found to be 8.85 and 22.24 ug/dL, respectively. Since the phase-out of leaded gasoline, the mean in urban areas was found to be 5.36 ug/dL and the average in rural areas is expected to be much higher. The U.S. Centers for Disease Control and Preventions (CDC) upper limit of blood lead in children under the age of 6 years is 5 ug/dL and the current U.S. average is 1.2 ug/dL. Our results indicate that more than 15% of the population will experience a decrement of more than 5 IQ points from lead exposure. The analysis also leads us to believe that lead is responsible for 820,000 disability-adjusted life-years for lead-induced mild mental retardation for children aged 0 to 4 years. CONCLUSION Lead continues to threaten the health of millions and remains a significant cause of disability in Mexico. Additional interventions in reducing or managing lead-based ceramic glazes are necessary to protect the public health.

Depressive symptoms are associated with allostatic load among community-dwelling older adults

The allostatic load model has been used to quantify the physiological costs of the bodys response to repeated stressful demands and may provide a useful, integrative perspective on the various correlates of late-life depressive symptoms. We interviewed 125 Rochester, NY adults, ranging in age from 67 to 94 years. We employed an allostatic load score as a measure of multisystem dysfunction in hypothalamic–pituitary–adrenal axis function, immune function, anabolic activity, and cardiovascular activity. Overall, affective, and somatic depressive symptom scores were computed using the 20-item Center for Epidemiologic Studies Depression Scale. Multiple linear regression models were used to estimate associations between allostatic load scores and affective, somatic, and overall depressive symptoms. Among our sample of mean age 76.1 years, the one-week prevalence of clinically significant depressive symptoms was 12.8%. In models adjusting for demographic, socioeconomic, and health-related factors, higher allostatic load scores were associated with elevated scores for overall, affective, and somatic depressive symptoms: beta = 1.21 (95% CI = 0.38, 2.05); beta = 0.14 (95% CI = 0.040, 0.24); beta = 0.60 (95% CI = 0.23, 0.97), respectively. Our results suggest that allostatic load measure is associated with late-life depressive symptoms. This association appears to be of clinical significance, as the magnitude of the effect size was comparable (but opposite in direction) to that of antidepressant use. Future research should examine the inter-relationships of allostatic load, psychological stress, and late-life depressive symptoms.

Socioeconomic Position and Cognitive Function in the Seychelles: A Life Course Analysis

Objective: Poorer socioeconomic conditions early in life have been linked with memory, attention and learning deficits in adulthood, as well as with specific areas of educational achievement. It remains unclear, however, whether these distal associations are mediated by more current socioeconomic factors. In this study, we sought to confirm the relation between early-life socioeconomic position (SEP) and adult cognitive function, and to examine potential mediation by contemporaneous SEP. Methods: Data from 463 young adults from the Main Cohort of the Seychelles Child Development Study were analyzed using subtests of the Cambridge Neurological Test Automated Battery and the Woodcock Johnson Test of Scholastic Achievement in relation to maternal Hollingshead Social Status Index scores at study enrollment (infancy), follow-up at 107 months, and follow-up at 17 years. Results: Findings include evidence of a link between infant-period SEP and 17-year memory, which was not mediated by childhood and 17-year SEP. Verbal and mathematical achievement at 17 years was associated with SEP at all points in the life course. Conclusions: SEP at different points during the young-adult life course may affect different cognitive domains later in life, which may provide targets for societal investment in ensuring adequate family resources throughout childhood and adolescence.

Multisystem physiological dysfunction is associated with depressive symptoms in a population-based sample of older adults.

To evaluate the association between multisystem physiological dysfunction and depressive symptom severity in the US older adults.