Probabilistic estimates of prenatal lead exposure at 195 toxic hotspots in low- and middle-income countries.

BACKGROUND: Prior estimates of pediatric lead-related disease burden in low- and middle-income countries (LMICs) used population estimates of maternal blood lead levels (BLLs). This approach may underestimate fetal BLLs by not considering potentially high prenatal lead exposure from toxic hotspots. OBJECTIVES: We developed a probabilistic approach to using the Adult Lead Methodology (ALM) to estimate fetal BLLs from prenatal exposure to lead-contaminated soil at hotspots in the Toxic Site Identification Program (TSIP). METHODS: We created distributions for each ALM parameter using published literature and extracted soil lead measurements from the TSIP database. Each iteration of the probabilistic ALM randomly selected values from the input distributions to generate a site-specific fetal BLL estimate. For each site, we ran 5000 model iterations, producing a site-specific fetal BLL distribution. RESULTS: 195 TSIP sites, in 33 LMICs, met our study inclusion criteria; an estimated 820,000 women of childbearing age are at risk for lead exposure at these sites. The predicted geometric means (GM) for site-specific fetal BLLs ranged from 3.3 µg/dL to 534 µg/dL, and 98% of sites had estimated GM fetal BLLs >5 µg/dL, the current reference level of the United States Centers for Disease Control and Prevention (CDC), while 11 sites had estimated GM fetal BLLs above the CDC chelation threshold of 45 µg/dL. DISCUSSION: The TSIP soil lead data and this probabilistic approach to the ALM show that pregnant women living near TSIP sites may have BLLs that put their fetus at risk for neurologic damage and other sequelae, underscoring the need for interventions to reduce lead exposure at toxic hotspots.

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 children's 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 (ß = 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.

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

OBJECTIVE: To evaluate the association between multisystem physiological dysfunction and depressive symptom severity in the US older adults. METHODS: We examined 2405 adults of age 60 years and older by using the data from the 2005-2008 National Health and Nutrition Examination Survey. We constructed a summary score of "physiological dysfunction," encompassing cardiovascular function, glucose regulation, liver function, and renal function. Overall depressive symptoms were obtained from the 9-item Patient Health Questionnaire depression scale, and factor analysis was used to derive affective and somatic symptom scores. We employed multiple linear regression models to estimate associations between physiological dysfunction scores and affective, somatic, and overall depressive symptoms, while adjusting for demographic, socioeconomic factors, and other potentially confounding factors. RESULTS: Greater multisystem physiological dysfunction scores were associated with an increased severity of overall, affective, and somatic depressive symptoms. These associations persisted after adjusting for all covariates: beta = 0.23 (95% confidence interval (CI) = 0.13, 0.32); beta = 0.08 (95% CI = 0.04, 0.11); beta = 0.12 (95% CI = 0.06, 0.18), respectively. CONCLUSIONS: Our results suggest that the multisystem physiological dysfunction is associated with late-life depressive symptoms. Additional longitudinal studies of links between allostatic load, psychosocial stress events throughout the life course, and late-life depressive symptoms may shed further light on this association.

Physiologic dysfunction scores and cognitive function test performance in U.S. adults.

OBJECTIVE: To investigate the relationship between a measure of cumulative physiologic dysfunction and specific domains of cognitive function. METHODS: We examined a summary score measuring physiologic dysfunction, a multisystem measure of the body's ability to effectively adapt to physical and psychological demands, in relation to cognitive function deficits in a population of 4511 adults aged 20 to 59 who participated in the Third National Health and Nutrition Examination Survey (1988-1994). Measures of cognitive function comprised three domains: working memory, visuomotor speed, and perceptual-motor speed. "Physiologic dysfunction" scores summarizing measures of cardiovascular, immunologic, kidney, and liver functions were explored. We used multiple linear regression models to estimate associations between cognitive function measures and physiologic dysfunction scores, adjusting for socioeconomic factors, test conditions, and self-reported health factors. RESULTS: We noted a dose-response relationship between physiologic dysfunction and working memory (coefficient = 0.207, 95% confidence interval = 0.066-0.348, p < .0001), which persisted after adjustment for all covariates (p = .03). We did not observe any significant relationships between dysfunction scores and visuomotor (p = .37) or perceptual-motor ability (p = .33). CONCLUSIONS: Our findings suggest that multisystem physiologic dysfunction is associated with working memory. Future longitudinal studies are needed to clarify the underlying mechanisms and explore the persistency of this association into later life. We suggest that such studies should incorporate physiologic data, neuroendocrine parameters, and a wide range of specific cognitive domains.

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.

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.

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 body's 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 hypothalamic­pituitary­adrenal 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.

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.

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 (ß = 0.27; 95% CI: 0.04, 0.50), rule-breaking behavior (ß = 0.20; 95% CI: 0.01, 0.38), aggression (ß = 0.34; 95% CI: 0.09, 0.59), and conduct problems (ß = 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 (ß = 0.15; 95% CI: 0.03, 0.28). Higher monobenzyl phthalate concentrations were associated with higher scores for oppositional behavior (ß = 0.16; 95% CI: 0.01, 0.32) and conduct problems (ß = 0.21; 95% CI: 0.06, 0.37) in boys, but with reduced anxiety scores in girls (ß = -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.

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 Organization's 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 Prevention's (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.

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 women's 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 women's 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: Women's 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.

Prenatal exposure to methylmercury and LCPUFA in relation to birth weight.

BACKGROUND: Epidemiologic studies have been inconclusive regarding the impact of coexposure to long chain polyunsaturated fatty acids (LCPUFA) and methylmercury (MeHg) from fish consumption during pregnancy on measures of fetal development. OBJECTIVES: We evaluated the association between birth weight and prenatal maternal LCPUFA status and MeHg exposure in the Republic of Seychelles. METHODS: We measured LCPUFA in maternal whole blood collected at 28 weeks of gestation and following delivery and MeHg in maternal hair obtained at delivery. There were 230 births with complete data on birth weight and covariates. Multiple linear regression models controlled for infant sex, gestational age, maternal age, smoking during pregnancy, intrapartum weight gain, prepregnancy body mass index, maternal socioeconomic status, parity, gestational diabetes, and alcohol use during pregnancy. RESULTS: The average birth weight was 3252 g (range 1654-4450) and the average gestational age was 39 weeks (range 34-41). Prenatal MeHg exposure and maternal LCPUFA status were not associated with birth weight. Infant sex and length of gestation were the only predictors, with male sex and increased gestational age consistently associated with greater birth weight. CONCLUSIONS: These findings do not support a relationship between prenatal exposure to LCPUFA and/or MeHg from fish consumption and birth weight.

Blood pressure and cognitive function: a prospective analysis among adolescents in Seychelles.

OBJECTIVE: An inverse relationship between blood pressure (BP) and cognitive function has been found in adults, but limited data are available in adolescents and young adults. We examined the prospective relation between BP and cognitive function in adolescence. METHODS: We examined the association between BP measured at the ages of 12-15 years in school surveys and cognitive endpoints measured in the Seychelles Child Development Study at ages 17 (n = 407) and 19 (n = 429) years, respectively. We evaluated multiple domains of cognition based on subtests of the Cambridge Neurological Test Automated Battery (CANTAB), the Woodcock Johnson Test of Scholastic Achievement (WJTA), the Finger Tapping test (FT) and the Kaufman Brief Intelligence Test (K-BIT). We used age, sex and height-specific z-scores of SBP, DBP and mean arterial pressure (MAP). RESULTS: Six out of the 21 cognitive endpoints tested were associated with BP. However, none of these associations were found to hold for both males and females or for different subtests within the same neurodevelopmental domain or for both SBP and DBP. Most of these associations disappeared when analyses were adjusted for selected potential confounding factors such as socio-economic status, birth weight, gestational age, BMI, alcohol consumption, blood glucose, and total n-3 and n-6 polyunsaturated fats. CONCLUSIONS: Our findings do not support a consistent association between BP and subsequent performance on tests assessing various cognitive domains in adolescents.

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.