Higher Glycemic Index and Glycemic Load Diet Is Associated with Slower Disease Progression in Amyotrophic Lateral Sclerosis.

OBJECTIVE: High-caloric diets may slow the progression of amyotrophic lateral sclerosis; however, key macronutrients have not been identified. We examined whether dietary macronutrients are associated with the rate of progression and length of survival among the prospective cohort study participants. METHODS: Participants with a confirmed diagnosis of sporadic amyotrophic lateral sclerosis enrolled in the Multicenter Cohort Study of Oxidative Stress were included (n = 304). We evaluated baseline macronutrient intake assessed by food frequency questionnaire in relation to change in revised amyotrophic lateral sclerosis functional rating scale total-score, and tracheostomy-free survival using linear regression and Cox proportional hazard models. Baseline age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised amyotrophic lateral sclerosis functional rating scale total-score, and forced vital capacity were included as covariates. RESULTS: Baseline higher glycemic index and load were associated with less decline of revised amyotrophic lateral sclerosis functional rating scale total score at 3-month follow-up (ß = -0.13, 95% CI -0.2, -0.01, p = 0.03) and (ß = -0.01, 95% CI -0.03, -0.0007, p = 0.04), respectively. Glycemic index second-quartile, third-quartile, and fourth-quartile groups were associated with less decline at 3 months by 1.9 (95% CI -3.3, -0.5, p = 0.008), 2.0 (95% CI -3.3, -0.6, p = 0.006), and 1.6 (95% CI -3.0, -0.2, p = 0.03) points compared with the first-quartile group; the glycemic load fourth-quartile group had 1.4 points less decline compared with the first-quartile group (95% CI -2.8, 0.1, p = 0.07). Higher glycemic index was associated with a trend toward longer tracheostomy-free survival (HR 0.97, 95% CI 0.93, 1.00, p = 0.07). INTERPRETATION: Higher dietary glycemic index and load are associated with slower disease progression in amyotrophic lateral sclerosis. ANN NEUROL 2024;95:217-229.

Mixed metals exposure and cognitive function in Bangladeshi adolescents.

BACKGROUND: Over 57 million people in Bangladesh have been chronically exposed to arsenic-contaminated drinking water. They also face environmental exposure to elevated levels of cadmium (Cd), manganese (Mn), and lead (Pb), all of which have been previously observed in environmental and biological samples for this population. These metals have been linked to adverse neurocognitive outcomes in adults and children, though their effects on adolescents are not yet fully characterized. Additionally, previous studies have linked selenium (Se) to protective effects against the toxicity of these other metals. OBJECTIVES: To examine the associations between mixed metals exposure and cognitive function in Bangladeshi adolescents. METHODS: The Metals, Arsenic, & Nutrition in Adolescents study (MANAs) is a cross-sectional study of 572 Bangladeshi adolescents aged 14-16 years, whose parents were enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Biosamples were collected from these adolescents for measurement of whole blood metalloid/metal levels of As, Cd, Mn, Pb, and Se. Participants also completed an abbreviated version of The Cambridge Neuropsychological Test Automated Battery (CANTAB), a cognitive function test designed to measure performance across several aspects of executive function. Linear regression was used to examine associations for each metal while controlling for the other metals. Bayesian Kernel Machine Regression (BKMR) assessed the overall mixture effect in addition to confirming the effects of individual metal components observed via linear regression. RESULTS: Linear regression revealed negative associations for Spatial Working Memory and both As and Mn (As B=-2.40, Mn B=-5.31, p < 0.05). We also observed negative associations between Cd and Spatial Recognition Memory (B=-2.77, p < 0.05), and Pb and Delayed Match to Sample, a measure of visual recognition and memory (B=-3.67, p < 0.05). Finally, we saw a positive association for Se and Spatial Span Length (B=0.92, p < 0.05). BKMR results were largely consistent with the regression analysis, showing meaningful associations for individual metals and CANTAB subtests, but no overall mixture effect. Via BKMR, we observed negative associations between Pb and Delayed Match to Sample, and Cd and Spatial Recognition Memory; this analysis also showed positive associations for Se and the Planning, Reaction Time, and Spatial Span subtests. BKMR posterior inclusion probability consistently reported that Se, the only component of the mixture to show a positive association with cognition, was the most important member of the mixture. CONCLUSIONS: Overall, we found Se to be positively associated with cognition, while Mn and As were linked to poorer working memory, and Cd and Pb were associated with poorer visual recognition and memory. Our observations are consistent with previous reports on the effects of these metal exposures in adults and children. Our findings also suggest agreement between linear regression and BKMR methods for analyzing metal mixture exposures. Additional studies are needed to evaluate the impact of mixed metals exposure on adverse health and poorer cognition later in life for those exposed during adolescence. Findings also suggest that metal exposure mitigation efforts aimed at adolescents might influence lifelong cognitive outcomes in regions where environmental exposure to metals is endemic.

Association of Birth During the COVID-19 Pandemic With Neurodevelopmental Status at 6 Months in Infants With and Without In Utero Exposure to Maternal SARS-CoV-2 Infection.

Importance: Associations between in utero exposure to maternal SARS-CoV-2 infection and neurodevelopment are speculated, but currently unknown. Objective: To examine the associations between maternal SARS-CoV-2 infection during pregnancy, being born during the COVID-19 pandemic regardless of maternal SARS-CoV-2 status, and neurodevelopment at age 6 months. Design, Setting, and Participants: A cohort of infants exposed to maternal SARS-CoV-2 infection during pregnancy and unexposed controls was enrolled in the COVID-19 Mother Baby Outcomes Initiative at Columbia University Irving Medical Center in New York City. All women who delivered at Columbia University Irving Medical Center with a SARS-CoV-2 infection during pregnancy were approached. Women with unexposed infants were approached based on similar gestational age at birth, date of birth, sex, and mode of delivery. Neurodevelopment was assessed using the Ages & Stages Questionnaire, 3rd Edition (ASQ-3) at age 6 months. A historical cohort of infants born before the pandemic who had completed the 6-month ASQ-3 were included in secondary analyses. Exposures: Maternal SARS-CoV-2 infection during pregnancy and birth during the COVID-19 pandemic. Main Outcomes and Measures: Outcomes were scores on the 5 ASQ-3 subdomains, with the hypothesis that maternal SARS-CoV-2 infection during pregnancy would be associated with decrements in social and motor development at age 6 months. Results: Of 1706 women approached, 596 enrolled; 385 women were invited to a 6-month assessment, of whom 272 (70.6%) completed the ASQ-3. Data were available for 255 infants enrolled in the COVID-19 Mother Baby Outcomes Initiative (114 in utero exposed, 141 unexposed to SARS-CoV-2; median maternal age at delivery, 32.0 [IQR, 19.0-45.0] years). Data were also available from a historical cohort of 62 infants born before the pandemic. In utero exposure to maternal SARS-CoV-2 infection was not associated with significant differences on any ASQ-3 subdomain, regardless of infection timing or severity. However, compared with the historical cohort, infants born during the pandemic had significantly lower scores on gross motor (mean difference, -5.63; 95% CI, -8.75 to -2.51; F1,267 = 12.63; P<.005), fine motor (mean difference, -6.61; 95% CI, -10.00 to -3.21; F1,267 = 14.71; P < .005), and personal-social (mean difference, -3.71; 95% CI, -6.61 to -0.82; F1,267 = 6.37; P<.05) subdomains in fully adjusted models. Conclusions and Relevance: In this study, birth during the pandemic, but not in utero exposure to maternal SARS-CoV-2 infection, was associated with differences in neurodevelopment at age 6 months. These early findings support the need for long-term monitoring of children born during the COVID-19 pandemic.

Associations of prenatal exposure to mixtures of organochlorine pesticides and smoking and drinking behaviors in adolescence.

It is important to identify the factors that influence the prevalence of disinhibitory behaviors, as tobacco and alcohol use in adolescence is a strong predictor of continued use and substance abuse into adulthood. Organochlorine pesticides (OCPs) are persistent organic pollutants that pose a potential risk to the developing fetus and offspring long-term health. We examined associations between prenatal exposure OCPs and their metabolites (i.e., p,p'-DDT, p,p'-DDE, o,p'-DDT, oxychlordane, and hexachlorobenzene (HCB)), both as a mixture and single compounds, and alcohol consumption and smoking at adolescence in a sample (n = 554) from the Child Health and Development Studies prospective birth cohort. Bayesian Kernel Machine Regression demonstrated a trend of higher risk of alcohol use and smoking with higher quartile mixture levels. Single-component analysis showed increased odds of smoking and drinking with increases in lipid-adjusted p,p'-DDE serum levels (aOR = 2.06, 95% CI 0.99-4.31, p = 0.05, per natural log unit increase). We found significant effect modification in these associations by sex with higher p,p'-DDT serum levels (aOR = 0.26, 95% CI 0.09-0.076, p = 0.01, per natural log unit increase) was associated with lower odds of smoking and drinking in female adolescents, while higher p,p'-DDE serum levels (aOR = 2.98, 95% CI 1.04-8.51, p = 0.04, per natural log unit increase) was associated with higher odds of the outcomes. Results of the mutually adjusted model were not significant for male adolescents. Further research to understand reasons for these sex-differences are warranted.

Case-control study in ALS using the National ALS Registry: lead and agricultural chemicals are potential risk factors.

Objective: To identify occupational risk factors for ALS using well-characterized participants with ALS (P-ALS), sibling controls (S-controls), and matched population controls (P-controls) within the National ALS Registry. We also compared oxidative stress (OS) biomarkers between groups. Methods: P-ALS were recruited over 4 years. Demographic, socioeconomic, and medical data were ascertained from medical records and structured interviews. P-ALS were followed prospectively for 2 years or until death, whichever came sooner. S-controls and age-, sex-, race/ethnicity-, and residential location-matched P-controls were recruited over 3 years. Occupational exposure to lead and agricultural chemicals (ACs) were assigned by an occupational hygienist, blinded to case status. OS biomarkers in urine were measured. Results: P-ALS (mean age 62.8 years; 63% males) resided across the United States. Demographic and socioeconomic variables did not differ among P-ALS, S-controls, and P-controls. P-ALS were more likely to report occupations with exposure to lead (adjusted OR (aOR)=2.3, 95% CI 1.1, 4.6) and ACs (aOR = 2.4, 95% CI 1.2, 4.6) compared to pooled controls. Among those with occupations with exposure to both lead and ACs, aOR was 7.2 (95% CI 2.0, 26.1). Urinary 8-oxo-dG was significantly elevated among P-ALS (11.07 ± 5.42 ng/mL) compared to S-controls, P-controls, or pooled controls (pooled 7.43 ± 5.42 ng/mL; p < 0.0001) but was not associated with occupational exposure to either lead or ACs. Conclusions: Findings reveal increased risk of ALS diagnosis among those with occupational exposure to lead and ACs and increased OS biomarkers among cases compared to controls. OS may be an important pathogenic mechanism in ALS.

What are the determinants of childhood infections in India's peri-urban slums? A case study of eight cities.

BACKGROUND: Respiratory Tract Infections (RTIs) and Gastro-Intestinal (GI) infections are the leading causes of child mortality and morbidity. This study investigates the associations between the individual, household and slum-level determinants of children's health and vulnerability to RTIs and GI infections in peri-urban slums in India; an area of research interest at the Childhood Infections and Pollution Consortium. METHODS: The 2015-16 Indian National Family Health Survey was used for data analysis on children aged 0-5 years. NFHS-4 includes data on slums in eight Indian cities, including Delhi, Meerut, Kolkata, Indore, Mumbai, Nagpur, Hyderabad, Chennai. The outcome variables, having fever and cough (FeCo) and diarrhoea in the last two weeks, were used to define the phenotype of infections; for this analysis fever and cough were measures of RTIs and diarrhoea was used to measure GI infections. Exposures considered in this study include variables at the individual, household and slum level and were all informed by existing literature. Multilevel models were used to estimate the association between exposures and outcomes variables; a prior of Cauchy distribution with a scale of 2.5 was selected when building the multilevel logistic models. RESULTS: The total sample size of the number of children included in the analysis was n = 1,424. Data was imputed to account for missingness, and the original and imputed sample showing similar distributions. Results showed that diarrhoea and FeCo were both found to be more present in younger children than older children by a few months. In fixed effects, the odds of developing FeCo were higher if the mother perceives the child was born smaller than average (AOR 4.41, 1.13-17.17, P<0.05) at individual level. On the other hand, the odds of the diarrhoea outcome were lower if the child was older (AOR 0.97, 0.96-0.98, P<0.05) at individual level, and household's water source was public tap or standpipe (AOR 0.54, 0.31-0.96, P<0.05) at household level. CONCLUSION: The determinants of health, both social and related to health care, at all levels demonstrated linkages to child morbidity in RTIs and GI infections. The empirical evidence highlights the need for contextualised ideas at each level, including one health approach when designing interventions to improve child health.

Prenatal exposure to air pollution is associated with childhood inhibitory control and adolescent academic achievement.

BACKGROUND: Prenatal air pollution exposure is associated with reductions in self-regulation and academic achievement. Self-regulation has been separately linked with academic achievement. Understudied, however, are the contributions of pollution exposure to inhibitory control, a facet of self-regulation, and whether pollution-related inhibitory control deficits are associated with impairment in academic achievement. METHODS: Participants were recruited from a prospective birth cohort. Measures of prenatal airborne polycyclic aromatic hydrocarbons (PAH) during the third trimester of pregnancy, inhibitory control (NEPSY Inhibition) at mean age = 10.4 years, and Woodcock-Johnson Tests of Achievement-III at mean age = 13.7 were available for N = 200 participants. Multiple linear regression examined sex-dependent and sex independent associations among prenatal PAH, childhood inhibitory control, and academic achievement during adolescence, and whether childhood inhibitory control mediated associations between prenatal PAH and academic achievement during adolescence, controlling for ethnicity, maternal country of birth, language of prenatal interview, maternal marital status, maternal years of education, material hardship, quality of home caregiving environment, and early life stress. RESULTS: Across all participants, higher prenatal PAH was significantly associated with worse spelling skills (WJ-III Spelling, ß = -0.16, 95%Confidence Interval [CI]: 0.30, -0.02, p = .02). Trend level associations between higher prenatal PAH and worse reading comprehension (WJ-III Passage Comprehension, ß = -0.13, 95%CI: 0.28, 0.01, p = .07) and math skills (WJ-III Broad Math, ß = -0.11, 95%CI: 0.25, 0.03, p = .11) were detected. Across all participants, higher PAH was significantly associated with worse inhibitory control (ß = -0.15, 95%CI: 0.29,-0.01 p = .03). Better inhibitory control was significantly associated with better reading comprehension (WJ-III Passage Comprehension, ß = 0.22, 95%CI: 0.09, 0.36, p < .002) and math skills (WJ-III Broad Math Index, ß = 0.32, 95%CI: 0.19, 0.45, p < .001), and trend level associations with better spelling skills (WJ-III Spelling, ß = 0.12, 95%CI: 0.02, 0.26, p = .10). Inhibitory control significantly mediated PAH-related achievement effects for Passage Comprehension (ß = -0.61, 95%CI: 1.49, -0.01) and Broad Math Index (ß = -1.09, 95%CI: 2.36, -0.03). CONCLUSIONS: Higher prenatal PAH exposure and lower childhood inhibitory control were associated with worse spelling, passage comprehension, and math in adolescence. Notably, childhood inhibitory control mediated PAH exposure-related effects on achievement in adolescents. Identifying these potential exposure-related phenotypes of learning problems may promote interventions that target inhibitory control deficits rather than content specific deficits.

History of vigorous leisure-time physical activity and early onset amyotrophic lateral sclerosis (ALS), data from the national ALS registry: 2010-2018.

Background: Previous research has suggested that vigorous physical activity (VPA) during adolescence and early adulthood is associated with ALS. The National ALS Registry (Registry) collects physical activity data from persons with ALS. Objective: To examine the association between vigorous VPA and early onset ALS, defined as a diagnosis before age 60, among patients enrolled in the Registry. VPA was defined as engaging in dynamic exercise for at least 10 minutes in a session that caused heavy sweating or large increases in breathing or heart rate. Methods: A cross-sectional study was conducted of 5463 ALS patients with VPA history and 956 ALS patients who never engaged in VPA. Patient characteristics were collected via online surveys in the following areas: demographic, lifetime VPA history, and initial onset of symptoms. General linear modeling was used to estimate mean age of diagnosis and to compute 95% confidence intervals. Results: Patients who reported engaging in VPA at least moderately (three times a week) during early adulthood were more likely to have an ALS diagnosis earlier compared to patients who did not (p < 0.0001). After controlling for year of birth, statistically significant associations between those reporting VPA at age 15-24 and 25-34 and diagnosis of ALS earlier (p = 0.0009, p = 0.0144 respectively). Conclusion: Patients with ALS who had a history of VPA before age 35, were significantly more likely to be diagnosed with ALS before age 60 compared to patients with ALS who never engaged vigorously. More research is needed in the relationship between VPA and early onset ALS.

Prenatal and early childhood exposure to phthalates and childhood behavior at age 7 years.

BACKGROUND: Emerging evidence suggests that phthalate exposure may be associated with behavior problems in children and that these associations may be sex specific. METHODS: In a follow up study of 411 inner-city minority mothers and their children, mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), monethyl phthalate (MEP) and four di-2-ethylhexyl phthalate metabolites (DEHP) were quantified in maternal urine samples collected during the third trimester and in child urine samples at ages 3 and 5 years. The Conners' Parent Rating Scale-Revised: Long Form (CPRS) and Child Behavior Checklist (CBCL) were administered to the mothers to assess children's behavior problems at 7 years of age. The analysis included children with available measures of CBCL, CPRS and phthalates measured in maternal urine. We performed both Quasi-Poisson regression and a mixture analysis using Weighted Quantile Sum(WQS) regression to assess the risk for CPRS scores and for internalizing and externalizing behaviors (from the CBCL) following intra-uterine exposure to the phthalate metabolites for boys and girls separately. RESULTS: Among boys, increases in in anxious-shy behaviors were associated with prenatal exposure to MBzP (Mean Ratio [MR] = 1.20, 95%CI 1.05-1.36) and MiBP (Mean Ratio (MR) = 1.22, 95%CI 1.02-1.47). Among girls, increases in perfectionism were associated with MBzP (MR = 1.15, 95%CI 1.01-1.30). In both boys and girls, increases in psychosomatic problems were associated with MiBP (MR = 1.28, 95%CI 1.02-1.60), and MnBP (MR = 1.28, 95%CI 1.02-1.59), respectively. Among girls, decreased hyperactivity was associated with two DEHP metabolites, mono(2-ethyl-5-oxohexyl) phthalate (MR = 0.83, 95%CI 0.71-0.98) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MR = 0.85, 95%CI 0.72-0.99). Using weighted Quantile Sum logistic regression, no associations were found between the Weighted Quantile Sum (WQS) of phthalate metabolites and CPRS scores or externalizing and internalizing behaviors. Nonetheless, when the analysis was performed separately for DEHP and non-DEHP metabolites significant associations were found between the WQS of DEHP metabolites and social problems in boys (OR = 2.15, 95%CI 1.13-4.06, p-value = 0.02) anxious-shy problems in girls (OR = 2.19, 95%CI 1.15-4.16, p = 0.02), and emotional lability problems in all children (OR = 0.61, 95%CI 0.38-0.97, p = 0.04). MEHP and MEOHP were the most highly weighted DEHP metabolites in WQS mixture. The analysis performed with CBCL scale corroborated these associations. CONCLUSION: Concentration of non-DEHP metabolites was associated with anxious-shy behaviors among boys. DEHP phthalate metabolites were associated with decreased hyperactivity and impulsivity among girls on CPRS scores. These findings lend further support to the adverse associations between prenatal phthalate exposure and childhood outcomes, and clearly suggest that such associations are sex and mixture specific.

Plasma creatinine and oxidative stress biomarkers in amyotrophic lateral sclerosis.

Objective: To determine the associations between plasma creatinine (PCr), plasma uric acid (PUA), and urinary oxidative stress (OS) biomarkers with the ALSFRS-R at baseline and survival in a large epidemiological cohort study (ALS COSMOS) with a well-phenotyped patient population (N = 355).Methods: Fasting plasma and first void urine samples were obtained. PCr, PUA, urinary 8-oxo-deoxy guanosine (8-oxodG), and 15-F2t-isoprostane (IsoP) were analyzed at baseline, near the midpoint of follow-up, and at the final blood draw (before death or withdrawal from study). We estimated associations between these biomarkers and the ALSFRS-R at baseline and survival.Results: At baseline, PCr correlated with ALSFRS-R (Spearman r = 0.30), percent (%) FVC (r = 0.20), PUA (r = 0.37), and 8-oxodG (r = -0.13, all p < 0.05). Baseline PCr significantly predicted survival (adjusted hazard ratio 0.28, p < 0.001). Time to death from baseline was shortest for those in the lowest two PCr quartiles relative to the highest two quartiles. PCr and ALSFRS-R values were significantly correlated at all three time points (baseline: r = 0.29, midpoint: r = 0.23, final: r = 0.38, all p < 0.001). PCr and PUA significantly declined over time, whereas OS biomarkers significantly increased over time.Conclusions: To date, PCr predicted survival the best, compared to PUA, 8-oxodG, and IsoP. Although PCr represents the degree of muscle mass, it may also represent complex biochemical changes in ALS. Because the field has no reliable prognostic biomarkers, the importance of PCr warrants further investigation through clinical studies in ALS.

Prepregnancy obesity is associated with lower psychomotor development scores in boys at age 3 in a low-income, minority birth cohort.

Whether maternal obesity and gestational weight gain (GWG) are associated with early-childhood development in low-income, urban, minority populations, and whether effects differ by child sex remain unknown. This study examined the impact of prepregnancy BMI and GWG on early childhood neurodevelopment in the Columbia Center for Children's Environmental Health Mothers and Newborns study. Maternal prepregnancy weight was obtained by self-report, and GWG was assessed from participant medical charts. At child age 3 years, the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Intelligence were completed. Sex-stratified linear regression models assessed associations between prepregnancy BMI and pregnancy weight gain z-scores with child PDI and MDI scores, adjusting for covariates. Of 382 women, 48.2% were normal weight before pregnancy, 24.1% overweight, 23.0% obese, and 4.7% underweight. At 3 years, mean scores on the PDI and MDI were higher among girls compared to boys (PDI: 102.3 vs. 97.2, P = 0.0002; MDI: 92.8 vs. 88.3, P = 0.0001). In covariate-adjusted models, maternal obesity was markedly associated with lower PDI scores in boys [b = -7.81, 95% CI: (-13.08, -2.55), P = 0.004], but not girls. Maternal BMI was not associated with MDI in girls or boys, and GWG was not associated with PDI or MDI among either sex (all-P > 0.05). We found that prepregnancy obesity was associated with lower PDI scores at 3 years in boys, but not girls. The mechanisms underlying this sex-specific association remain unclear, but due to elevated obesity exposure in urban populations, further investigation is warranted.

Perinatal phthalates exposure decreases fine-motor functions in 11-year-old girls: Results from weighted Quantile sum regression.

INTRODUCTION: Phthalates are a group of high production chemicals, generally used as plasticizers and odor enhancers. Phthalates cross the blood-placenta barrier and are associated with deficits in cognitive functions and behavior problems in offspring. We previously reported sex-specific associations with motor function when phthalates are considered singly. Because exposure to phthalates usually occurs as mixtures, here we assess these associations between a mixture of phthalates and motor function at age 11 years. METHODS: Data come from the prospective cohort study of mothers and offspring who participated in the Columbia Center for Children's Environmental Health birth cohort (CCCEH). Seven phthalate metabolites were measured in maternal spot urine obtained during the third trimester and motor function was evaluated using the short form of the Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition (BOT-2) at the age of 11 years. We used Weighted Quartile Sum (WQS) regression models to examine the effect of phthalate metabolites in males and females separately. The models were adjusted for child age in months, child BMI, maternal race (African-American vs. Dominican), prenatal alcohol consumption, maternal demoralization score, HOME score, and urine specific gravity. In a secondary analysis we used linear regression models to examine the association between the sum of molar concentrations of both DEHP and non-DEHP metabolites, and outcomes of gross and fine motor functions. RESULTS: 209 mother-child pairs were eligible for this analysis. A significant decrease in fine-motor functions was observed among females, but not among males, following exposure to high levels of weighted quartile sum of seven phthalate metabolites (Covariates-adjusted coefficient estimate B = -2.7, 95% Confidence Interval [CI] -4.64 to -0.75, p = 0.01 for females [n = 116] and B = -1.63, 95%CI -3.94 to 0.69, p = 0.16 for males [n = 93]). The most highly weighted phthalate metabolites, associated with fine-motor functions among females, were MBP, MBZP, and MIBP, all non-DEHP phthalates. No significant associations were found between the weighted quartile sum of seven phthalate metabolites and gross-motor functions at the age of 11 years for males (B = -0.81, 95%CI -1.17 to 1.96, p = 0.23). With the molar sum of four non-DEHP phthalates as main predictor of linear regression models, we found significant decrease in gross and fine motor functions among females prenatally exposed to non-DEHP phthalates B = -0.98, 95%CI -1.98 to 0.03, p = 0.05 and B = -0.85, 95%CI -1.49 to -0.20, p = 0.01, respectively). CONCLUSIONS: Phthalate exposure during pregnancy was associated with decreased motor functions among 11-year-old girls.

Body mass index across the life course: emergence of race-by-sex disparities in early childhood.

PURPOSE: The purpose of this study was to assess when in the life-course race-by-sex disparities in body mass index (BMI) emerge. METHODS: Child Health and Development Studies participants, from whom height and weight data were collected at ages 5, 9-11, and 15-17 years, were followed up at the age of 50 years for anthropometric outcomes. Follow-up was completed for 605 subjects, 460 of whom were assessed for height and weight at the age of 50 years, had at least one available childhood BMI measure, and self-identified as either non-Hispanic black or non-Hispanic white. Linear regression analyses were conducted to determine whether interactions existed between race (black vs. white) and sex for predicting BMI at ages 5, 9-11, 15-17, and 50 years. RESULTS: At age 5 years, BMI was independent of sex for both blacks and whites, but by the age of 9-11 years, BMI was sex-dependent in blacks, with higher BMI observed among black females. This sex dependence for BMI among blacks persisted at ages 15-17 years and age 50 years. The race-by-sex interaction was significant at ages 9-11, 15-17, and 50 years (P for interaction = 0.001, 0.002, and 0.01, respectively). CONCLUSIONS: Race-by-sex disparities in body size were observed by the age of 9-11 years and persisted until the age of 50 years.

A preliminary study on prenatal polybrominated diphenyl ether serum concentrations and intrinsic functional network organization and executive functioning in childhood.

BACKGROUND: The prenatal period is a period of vulnerability during which neurotoxic exposures exert persistent changes in brain development and behavior. Polybrominated diphenyl ethers (PBDEs), used as flame retardants in commercial products, are known to be developmental neurotoxicants. PBDEs were phased out of use in the United States a decade ago, but exposure remains widespread due to their release from existing products and biopersistence. Despite consistent animal and epidemiological evidence of developmental neurotoxicity, the neural substrates linking prenatal PBDE serum concentrations to impaired neurodevelopment are poorly understood. METHODS: In the present study, we used resting state functional magnetic resonance imaging (fMRI) to examine associations between prenatal PBDE concentrations measured in maternal serum and intrinsic functional network organization (i.e., global and local efficiency; estimated using a graph-theoretical approach) in 5-year-old children (n = 34). We explored whether PBDE serum concentrations were associated with executive functioning (EF) assessed using a parent-report questionnaire (BRIEF-P) (n = 106) and whether changes in intrinsic functional network organization linked the association between prenatal PBDE serum concentrations and EF problems. RESULTS: Children with higher prenatal PBDE serum concentrations showed: (a) increased global efficiency of brain areas involved in visual attention (e.g., inferior occipital gyrus) (ß's = .01, FDR-corrected p's ≤ .05); (b) more reported EF problems (ß's = .001, FDR-corrected p's ≤ .05). Higher global efficiency of brain areas involved in visual attention was associated with more EF problems (ß's = .01, FDR-corrected p's < .05). CONCLUSIONS: Intrinsic functional network organization of visual attention brain areas linked prenatal PBDE concentrations to EF problems in childhood. Visual attention may contribute to the development of higher-order cognitive functions, such as EF, which could be explored in future studies.

Pre- and Postnatal Polybrominated Diphenyl Ether Concentrations in Relation to Thyroid Parameters Measured During Early Childhood.

Background: Penta-brominated diphenyl ethers (PentaBDEs) are endocrine-disrupting chemicals that structurally resemble thyroid hormones and were widely used as flame retardants in household consumer products from 1975 to 2004. Polybrominated diphenyl ethers (PBDEs) cross the placenta, and evidence suggests that for many children, body burdens may peak during the toddler years. This study aimed to understand the impact of exposure timing by examining both pre- and postnatal exposure to BDE-47, the predominant penta-brominated diphenyl ether congener detected in humans, in relation to thyroid hormone parameters measured during early childhood. Methods: The Columbia Center for Children's Environmental Health Mothers and Newborns Study is a prospective birth cohort of African American and Dominican maternal-child pairs. Pregnant women were recruited from two prenatal clinics in Northern Manhattan and the South Bronx between 1998 and 2006. Participants included 158 children with (i) plasma PBDE concentrations measured at birth and in the toddler years (age 2-3 years), and (ii) serum thyroid parameters measured at three and/or five years of age. Outcomes included concentrations of serum thyrotropin, free thyroxine, and total thyroxine. Results: Children with high exposure to BDE-47 during the prenatal period (-17% [confidence interval -29 to -2]) or toddler age (-19% [confidence interval -31 to -5]) had significantly lower geometric mean thyrotropin levels compared to children with low BDE-47 exposure throughout early life. Associations with thyroxine were also inverse; however, they did not reach statistical significance at the p = 0.05 level. Sex-stratified models suggest associations with postnatal exposure may be stronger among boys compared to girls. Conclusions: The thyroid regulatory system may be sensitive to BDE-47 during pre- and postnatal periods.

Longitudinal Screening Detects Cognitive Stability and Behavioral Deterioration in ALS Patients.

Objective: To evaluate longitudinal cognitive/behavioral change over 12 months in participants enrolled in the ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS). Methods: We analyzed data from 294 ALS participants, 134 of whom were studied serially. Change over time was evaluated controlling for age, sex, symptom duration, education, race, and ethnicity. Using multiple regression, we evaluated associations among decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores, forced vital capacity (FVC), and cognitive/behavioral changes. Change in cognitive/behavioral subgroups was assessed using one-way analyses of covariance. Results: Participants with follow-up data had fewer baseline behavior problems compared to patients without follow-up data. We found significant worsening of behavior (ALS Cognitive Behavioral Screen (ALS CBS) behavioral scale, p < 0.001; Frontal Behavioral Inventory-ALS (FBI-ALS) disinhibition subscale, p = 0.044). Item analysis suggested change in frustration tolerance, insight, mental rigidity, and interests (p < 0.05). Changes in ALSFRS-R correlated with the ALS CBS. Worsening disinhibition (FBI-ALS) did not correlate with ALSFRS-R, FVC, or disease duration. Conclusion: We did not detect cognitive change. Behavioral change was detected, and increased disinhibition was found among patients with abnormal baseline behavioral scores. Disinhibition changes did not correlate with disease duration or progression. Baseline behavioral problems were associated with advanced, rapidly progressive disease and study attrition.

Transient, Isolated Head Tremor in "Unaffected" Individuals: Is Essential Tremor an Even More Prevalent Disease Than We Suppose?

Background: Mild and transient head tremor may sometimes be observed in otherwise tremor-free relatives of essential tremor (ET) cases, although its prevalence is unclear. A diagnostic question is whether this transient, isolated head tremor, often observed as no more than a wobble, is an early manifestation of ET or whether it is a normal finding. A direct comparison with controls is needed. Methods: Two hundred and forty-one first-degree relatives of ET cases (FD-ET) and 77 spousal controls (Co) were enrolled in a study of ET. Each underwent a detailed evaluation that included a tremor history and videotaped neurological examination. None of the enrollees reported tremor, had a prior diagnosis of ET, or had significant tremor on screening spirals. All videotaped examinations were initially reviewed by a movement disorder neurologist blinded to subject type, and among those with head tremor on examination, co-reviewed by two additional movement disorders neurologists. Results: Twenty-six (10.8, 95% Confidence interval [CI] = 7.5-15.3%) of 241 FD-ET vs. 2 (2.6, 95% CI = 0.7-9.0%) of 77 Co had isolated, transient head tremor (odds ratio = 4.54, 95% CI = 1.05-19.57, p = 0.04). No enrollee had significant upper extremity tremor and none met inclusion criteria for ET based on the presence of upper extremity tremor. With one exception, head tremor occurred during or after phonation. It was always transient (generally a single back and forth wobble) and rare (observed briefly on one or two occasions during the videotaped examination) and had a faster frequency, lower amplitude and a different quality than voluntary head shaking. Conclusion: The basis for the observed isolated head tremor is unknown, but it could be an early feature of ET in ET families.Indeed, one-in-ten otherwise unaffected first-degree relatives of ET cases exhibited such tremor. To a far lesser extent it was also observed in "unaffected" controls. In both, it is likely a sign of early, emerging, undiagnosed ET, although follow-up studies are needed to confirm this. If it were ET, it would indicate that the prevalence of ET may be considerably higher than previously suspected.

Caffeine Consumption in First-Degree Relatives of Essential Tremor Cases: Evidence of Dietary Modification Before Disease Onset.

BACKGROUND: Caffeine can exacerbate tremor. Reducing caffeine intake or switching to decaffeinated beverages can lessen tremor. Unaffected relatives of essential tremor (ET) cases often have mild, subclinical tremor. One question is whether the coffee and tea consumption pattern in these individuals differs from that of controls (Co). METHODS: We ascertained the patterns of coffee and tea intake using a structured questionnaire, and compared the use in unaffected first-degree relatives of ET cases (FD-ET) to the use in age-matched Co. Three measures of relative caffeinated coffee + tea to decaffeinated coffee + tea were constructed. Caffeine index 1 = (cups of caffeinated coffee + tea) - (cups of decaffeinated coffee + tea) consumed on the day of evaluation. Caffeine index 2 = (cups of caffeinated coffee + tea) - (cups of decaffeinated coffee + tea) consumed in a typical month. The percentage of coffee and tea that was caffeinated in a typical month was also calculated. RESULTS: There were 263 individuals (190 FD-ET, 73 Co). Caffeine index 1 in FD-ET was less than 1-half that of Co (p = 0.001). Caffeine index 2 was similarly lower in FD-ET than Co (p = 0.027). The percentage of coffee and tea that was caffeinated in a typical month was also significantly lower in FD-ET than Co (p = 0.018). CONCLUSION: The balance of caffeinated to decaffeinated beverages is different in FD-ET than Co. These data raise several intriguing questions. Among these is whether relatives of ET cases modify their caffeine consumption before disease onset.

Prepregnancy overweight and obesity are associated with impaired child neurodevelopment.

The authors examined the relationship of prepregnancy body mass index (BMI) and gestational weight gain (GWG) with child neurodevelopment. Mother-child dyads were a subgroup (n = 2,084) of the Child Health and Development Studies from the Oakland, California, area enrolled during pregnancy from 1959 to 1966 and followed at child age 9 years. Linear regression was used to examine associations between prepregnancy BMI, GWG, and standardized Peabody Picture Vocabulary Test and Raven Progressive Matrices scores and to evaluate effect modification of GWG by prepregnancy BMI. Before pregnancy, 77% of women were normal weight, 8% were underweight, 11% were overweight, and 3% were obese. Associations between GWG and child outcomes did not vary by prepregnancy BMI, suggesting no evidence for interaction. In multivariable models, compared to normal prepregnancy BMI, prepregnancy overweight and obesity were associated with lower Peabody scores (b: -1.29; 95% CI [-2.6, -0.04] and b: -2.7; 95% CI [-5.0, -0.32], respectively). GWG was not associated with child Peabody score [b: -0.03 (95% CI: -0.13, 0.07)]. Maternal BMI and GWG were not associated with child Raven score (all P >0.05). Maternal prepregnancy overweight and obesity were associated with lower scores for verbal recognition in mid-childhood. These results contribute to evidence linking maternal BMI with child neurodevelopment. Future research should examine the role of higher prepregnancy BMI values and the pattern of pregnancy weight gain in child cognitive outcomes.

Arsenic exposures alter clinical indicators of anemia in a male population of smokers and non-smokers in Bangladesh.

Drinking water arsenic (WAs) exposure has been linked to a number of detrimental health outcomes including anemia, primarily among pregnant women. Little is known about the effects of arsenic (As) on hematological disorders among men. We have examined the role of As exposure on hematological indicators of anemia in a group of men exposed to a wide range of As in their drinking water. We conducted a cross-sectional investigation among 119 healthy men in the Health Effects of As Longitudinal Study (HEALS) cohort, in rural Bangladesh. The participants are part of an ongoing study focused on evaluating the influence of As and smoking on immune function. Samples were collected at recruitment and analyzed for water As, urinary As (UAs) and UAs metabolites to assess As exposure. Blood samples were also collected at recruitment and assayed immediately for hematological parameters. We found that increased WAs levels were associated with decreased red blood cell counts [ß=-0.13, p<0.0001] as well as hematocrit packed cell volumes [ß=-0.68, p=0.008] following adjustment for age, smoking, body mass index and polycyclic aromatic hydrocarbon-DNA adducts. Other measures of As exposure (UAs and its metabolites) demonstrated similar associations. Slightly stronger effects were observed among smokers. We also observed an effect of As on hemoglobin among smokers in relation to UAs [ß=-0.54, p<0.05]. Our analysis revealed effects of As exposure on hematological indicators of anemia in a group of healthy male smokers and non-smokers.