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In the United States, adolescent obesity is a growing epidemic associated with maladaptive executive functioning. Likewise, data link the microbiome to obesity. Emerging microbiome research has demonstrated an interconnection between the gut microbiome and the brain, indicating a bidirectional communication system within the gut–microbiome–brain axis in the pathophysiology of obesity. This narrative review identifies and summarizes relevant research connecting adolescent obesity as it relates to three core domains of executive functioning and the contribution of the gut microbiome in the relationship between obesity and executive functions in adolescence. The review suggests that (1) the interconnection between obesity, executive function, and the gut microbiome is a bidirectional connection, and (2) the gut microbiome may mediate the neurobiological pathways between obesity and executive function deficits. The findings of this review provide valuable insights into obesity-associated executive function deficits and elucidate the possible mediation role of the gut microbiome. • Adolescent obesity is bidirectionally linked to three domains of executive function. • The gut-microbiome-brain-axis provides links between obesity and executive function. • A feedback loop exists among obesity, the gut microbiome, and executive function. [ABSTRACT FROM AUTHOR]

The perinatal period is a window of susceptibility for later life disease. Recent epigenetic findings are beginning to increase our understanding of the molecular mechanisms that may contribute to the programming of obesity. This review summarizes recent evidence that supports the role of epigenetically mediated early life programming in the later onset of obesity. Establishing such links between environmental exposures and modifiable molecular changes ultimately holds promise to inform interventional efforts toward alleviating the environmentally mediated onset of obesity. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Superfund Research Program (SRP) is an academically based, multidisciplinary, translational research program that for 25 years has sought scientific solutions to health and environmental problems associated with hazardous waste sites. SRP is coordinated by the National Institute of Environmental Health Sciences (NIEHS). It supports multi-project grants, undergraduate and postdoctoral training programs, individual research grants, and Small Business Innovation Research (SBIR) and Technology Transfer Research (STTR) grants. RESULTS: SRP has had many successes: discovery of arsenic's toxicity to the developing human central nervous system; documentation of benzene toxicity to hematologic progenitor cells in human bone marrow; development of novel analytic techniques such as the luciferase expression assay and laser fragmentation fluorescence spectroscopy; demonstration that PCBs can cause developmental neurotoxicity at low levels and alter the genomic characteristics of sentinel animals; elucidation of the neurodevelopmental toxicity of organophosphate insecticides; documentation of links between antimicrobial agents and alterations in hormone response; discovery of biological mechanisms through which environmental chemicals may contribute to obesity, atherosclerosis, diabetes, and cancer; tracking the health and environmental effects of the attacks on the World Trade Center and Hurricane Katrina; and development of novel biological and engineering techniques to facilitate more efficient and lower-cost remediation of hazardous waste sites. CONCLUSION: SRP must continue to address the legacy of hazardous waste in the United States, respond to new issues caused by rapid advances in technology, and train the next generation of leaders in environmental health science while recognizing that most of the world's worst toxic hot spots are now located in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Recent advances in estimating fine particle (PM2.5) ambient concentrations use daily satellite measurements of aerosol optical depth (AOD) for spatially and temporally resolved exposure estimates. Mexico City is a dense megacity that differs from other previously modeled regions in several ways: it has bright land surfaces, a distinctive climatological cycle, and an elevated semi-enclosed air basin with a unique planetary boundary layer dynamic. We extend our previous satellite methodology to the Mexico City area, a region with higher PM2.5 than most U.S. and European urban areas. Using a novel 1 km resolution AOD product from the MODIS instrument, we constructed daily predictions across the greater Mexico City area for 2004-2014. We calibrated the association of AOD to PM2.5 daily using municipal ground monitors, land use, and meteorological features. Predictions used spatial and temporal smoothing to estimate AOD when satellite data were missing. Our model performed well, resulting in an out-of-sample cross-validation R² of 0.724. Cross-validated root-mean-squared prediction error (RMSPE) of the model was 5.55 μg/m³. This novel model reconstructs long- and short-term spatially resolved exposure to PM2.5 for epidemiological studies in Mexico City. [ABSTRACT FROM AUTHOR]

Purpose Maternal lead exposure is associated with poor birth outcomes in populations with moderate to high blood levels. However, no studies have looked at exposure levels commonly experienced by US women. Methods We evaluated the relationship between maternal red blood cell (RBC) lead levels in midpregnancy and birth outcomes in 949 mother–child pairs in a prebirth cohort. We used multiple linear regression and logistic regression, adjusted for potential confounders including maternal age, race, prepregnancy body mass index, and smoking to relate maternal lead to infant birth size and risk for preterm birth (<37 weeks). Results Mean RBC lead level was 1.2 μg/dL (range, 0.0–5.0). Mean (standard deviation) birthweight was 3505 (520) g, birthweight for gestational age z-score 0.22 (0.93), and length of gestation 39.5 (1.7) weeks. Mothers in the highest versus lowest lead quartile did not have higher odds (OR, 1.85; 95% confidence interval [CI], 0.79–4.34) of preterm delivery; after stratifying by child sex, there was an association among males (OR, 5.51; 95% CI, 1.21–25.15) but not females (OR, 0.82; 95% CI, 0.24–2.85). Maternal RBC lead was not associated with any continuous outcomes in combined or sex-stratified analyses. Conclusions Maternal lead exposure, even at very low levels, may adversely affect some childbirth outcomes, particularly preterm birth among males. [ABSTRACT FROM AUTHOR]

ObjectiveTo assess sociodemographic correlates of micronutrient intakes from food and dietary supplements in an urban, ethnically diverse sample of pregnant women in the USA.DesignCross-sectional analyses of data collected using a validated semi-quantitative FFQ. Associations between racial, ethnic and sociodemographic factors and micronutrient intakes were examined using logistic regression controlling for pre-pregnancy BMI, maternal age and smoking status.SettingPrenatal clinics, Boston, MA, USA.SubjectsAnalyses included pregnant women (n 274) in the PRogramming of Intergenerational Stress Mechanisms (PRISM) study, an urban longitudinal cohort designed to examine how stress influences respiratory health in children when controlling for other environmental exposures (chemical stressors, nutrition).ResultsHigh frequencies of vitamin E (52 %), Mg (38 %), Fe (57 %) and vitamin D (77 %) inadequacies as well as suboptimal intakes of choline (95 %) and K (99 %) were observed. Factors associated with multiple antioxidant inadequacies included being Hispanic or African American, lower education and self-reported economic-related food insecurity. Hispanics had a higher prevalence of multiple methyl-nutrient inadequacies compared with African Americans; both had suboptimal betaine intakes and higher odds for vitamin B6 and Fe inadequacies compared with Caucasians. Nearly all women (98 %) reported Na intakes above the tolerable upper limit; excessive intakes of Mg (35 %), folate (37 %) and niacin (38 %) were also observed. Women reporting excessive intakes of these nutrients were more likely Caucasian or Hispanic, more highly educated, US-born and did not report food insecurity.ConclusionsRacial/ethnic and other sociodemographic factors should be considered when tailoring periconceptional dietary interventions for urban ethnic women in the USA. [ABSTRACT FROM AUTHOR]

Endocrine disrupting chemicals that are structurally similar to steroid or amine hormones have the potential to mimic endocrine endpoints at the receptor level. However, more recently, epigenetic-induced alteration in gene expression has emerged as an alternative way in which environmental compounds may exert endocrine effects. We review concepts related to environmental epigenetics and relevance for endocrinology through three broad examples: 1) effect of early-life nutritional exposures on future obesity and insulin resistance, 2) effect of lifetime environmental exposures such as ionizing radiation on endocrine cancer risk, and 3) potential for compounds previously classified as endocrine disrupting to additionally or alternatively exert effects through epigenetic mechanisms. The field of environmental epigenetics is still nascent, and additional studies are needed to confirm and reinforce data derived from animal models and preliminary human studies. Current evidence suggests that environmental exposures may significantly impact expression of endocrine-related genes and thereby affect clinical endocrine outcomes. [ABSTRACT FROM AUTHOR]

Background: Arsenic, cadmium, mercury, and lead are associated with cardiovascular disease in epidemiologic research. These associations may be mediated by direct effects of the metals on blood pressure (BP) elevation. Manganese is associated with cardiovascular dysfunction and hypotension in occupational cohorts. Objectives: We hypothesized that chronic arsenic, cadmium, mercury, and lead exposures elevate BP and that manganese lowers BP. Methods: We conducted a cross-sectional analysis of associations between toenail metals and BP among older men from the Normative Aging Study (n = 639), using linear regression and adjusting for potential confounders. Results: An interquartile range increase in toenail arsenic was associated with higher systolic BP [0.93 mmHg; 95% confidence interval (CI): 0.25, 1.62] and pulse pressure (0.76 mmHg; 95% CI: 0.22, 1.30). Positive associations between arsenic and BP and negative associations between manganese and BP were strengthened in models adjusted for other toenail metals. Conclusions: Our findings suggest associations between BP and arsenic and manganese. This may be of public health importance because of prevalence of both metal exposure and cardiovascular disease. Results should be interpreted cautiously given potential limitations of toenails as biomarkers of metal exposure. [ABSTRACT FROM AUTHOR]

Objective: To find the best lead exposure assessment marker for children. Methods: We recruited 11 children, calculated a cumulative blood lead index (CBLI) for the children, measured their concurrent BLL, assessed their development, and measured their bone lead level. Results: Nine of 11 children had clinically significant neurodevelopment problems. CBLI and current blood lead level, but not the peak lead level, were significantly or marginally negatively associated with the full-scale IQ score. Conclusion: Lead exposure at younger age significantly impacts a child's later neurodevelopment. CBLI may be a better predictor of neurodevelopment than are current or peak blood lead levels. [ABSTRACT FROM AUTHOR]

Background: DNA methylation is an epigenetic mark that regulates gene expression. Changes in DNA methylation within white blood cells may result from cumulative exposure to environmental metals such as lead. Bone lead, a marker of cumulative exposure, may therefore better predict DNA methylation than does blood lead. Objective: In this study we compared associations between lead biomarkers and DNA methylation. Methods: We measured global methylation in participants of the Normative Aging Study (all men) who had archived DNA samples. We measured patella and tibia lead levels by K-X-Ray fluorescence and blood lead by atomic absorption spectrophotometry. DNA samples from blood were used to determine global methylation averages within CpG islands of long interspersed nuclear elements-1 (LINE-1) and Alu retrotransposons. A mixed-effects model using repeated measures of Alu or LINE-1 as the dependent variable and blood/bone lead (tibia or patella in separate models) as the primary exposure marker was fit to the data. Results: Overall mean global methylation (± SD) was 26.3 ± 1.0 as measured by Alu and 76.8 ± 1.9 as measured by LINE-1. In the mixed-effects model, patella lead levels were inversely associated with LINE-1 (β = -0.25; p < 0.01) but not Alu (β = -0.03; p = 0.4). Tibia lead and blood lead did not predict global methylation for either Alu or LINE-1. Conclusion: Patella lead levels predicted reduced global DNA methylation within LINE-1 elements. The association between lead exposure and LINE-1 DNA methylation may have implications for the mechanisms of action of lead on health outcomes, and also suggests that changes in DNA methylation may represent a biomarker of past lead exposure. [ABSTRACT FROM AUTHOR]

High-level arsenic exposure is consistently associated with QT prolongation, a risk factor for arrhythmia and sudden cardiac death. Arsenic may act on QT by increasing cardiac calcium currents. The authors hypothesized that low-level arsenic exposure would be associated with QT duration and that this effect would be stronger among persons not using calcium channel blockers. They performed a cross-sectional analysis in elderly men from the Normative Aging Study to analyze associations between toenail arsenic and QT and heart rate-corrected QT (QTc) durations and to examine effect modification by calcium channel blocker use, using linear regression and adjusting for potential confounders. Participants were examined in Boston, Massachusetts, between 2000 and 2002 or in 2006. An interquartile range increase in arsenic concentration was associated with a 3.8-millisecond increase in QT (95% confidence interval: 0.82, 6.8) and a 2.5-millisecond increase in QTc (95% confidence interval: 0.11, 4.9). There was no evidence of effect modification by medication use for either QT (P = 0.93) or QTc (P = 0.58). The authors observed positive associations between a biomarker of arsenic exposure and QT duration but found no evidence of effect modification by calcium channel blocker use, possibly because of modest power. [ABSTRACT FROM PUBLISHER]

Metals are ubiquitous and play a critical role in neurobiology. Transition metals are important because they alter the redox state of the physical environment. Biologically, transition metals catalyze redox reactions that are critical to cellular respiration, chemical detoxification, metabolism, and even neurotransmitter synthesis. Many metals are both nutrients and neurotoxicants, such as iron, zinc, copper, and manganese. Other metals, such as lead and cadmium, are metabolized similarly to these metals, particularly iron. Iron metabolism and genes that regulate iron metabolism may be the key to understanding metal toxicity. Finally, recent evidence demonstrates that early life exposures may program later life and adult disease phenotypes via processes of epigenetics. Parallel work in metals demonstrates that epigenetics may be a critical pathway by which metals produce health effects. [ABSTRACT FROM AUTHOR]

Presents questions and answers related to phthalates in food and medical devices. Environmental toxicity of phthalates; Health effects of phthalates exposure; Link between phthalate exposure and asthma and allergy.

OBJECTIVES. We aimed to determine the correlation between end-tidal carbon dioxide levels and serum bicarbonate concentrations among patients with gastroenteritis, to compare the end-tidal carbon dioxide with other clinical parameters that might also be associated with the degree of acidosis, and to examine the relationship between end-tidal carbon dioxide levels and return visits. METHODS. Our prospective sample included patients presenting to the emergency department with a chief complaint of vomiting and/or diarrhea. The association between end-tidal carbon dioxides and serum bicarbonate concentrations was determined with simple linear-regression analysis. Receiver operating characteristic curves were computed to determine the predictive ability of the end-tidal carbon dioxide to detect metabolic acidosis. RESULTS. One hundred thirty of 146 subjects who were approached were included in the final analysis. For those for whom laboratory studies were performed, the mean serum bicarbonate concentration was 17.3 ± 4.3 mmol/L and the mean end-tidal carbon dioxide level was 34.2 ± 5.2 mm Hg. End-tidal carbon dioxide levels and serum bicarbonate concentrations were correlated linearly in bivariate analysis. Receiver operating characteristic curves were calculated for end-tidal carbon dioxide as a predictor of serum bicarbonate concentrations of ≤13, ≤15, and ≤ 17 mmol/L, with areas under the curves of 0.94, 0.95, and 0.90, respectively. The relationship between end-tidal carbon dioxide levels and serum bicarbonate concentrations was independent of other potential predictors of acidosis in multivariable analysis. The mean end-tidal carbon dioxide level for patients who required an unanticipated return visit (33.0 + 4.0 mm Hg) was lower than the level for those who did not seek reevaluation (36.6 + 3.6 mm Hg). CONCLUSIONS. End-tidal carbon dioxide levels were correlated with serum bicarbonate concentrations among children with vomiting and diarrhea, independent of other clinical parameters. Capnography offers an objective noninvasive measure of the severity of acidosis among patients with gastroenteritis. [ABSTRACT FROM AUTHOR]

Abstract: A pilot study was conducted to explore the potential associations between hair metal levels and the neuropsychological function and behavior of school-aged children. Thirty-two children, 11–13 years old, were administered a battery of tests that assessed general intelligence, visual-motor skills, receptive language, verbal memory, nonverbal problem-solving, and behavior problems. Parents and teachers rated the children''s attention, executive functions, and behavior problems. The concentrations of manganese (Mn), arsenic (As), and cadmium (Cd) were measured in hair samples provided by 31 of the children. The mean hair metal levels were: Mn, 471.5 parts per billion (ppb); As, 17.8ppb; Cd, 57.7ppb. Children''s general intelligence scores, particularly verbal IQ scores, were significantly related, inversely, to hair Mn and As levels, as were scores on tests of memory for stories and a word list. In some cases, a significant Mn-by-As interaction was found. It appeared that it was the low scores of children for whom both Mn and As levels were above the median values in the sample that were responsible for the main effects observed for each metal. No other significant relationships were found. These results suggest the need to study further the neuropsychological correlates of developmental exposure to Mn and As, particularly as a mixture. [Copyright &y& Elsevier]

Fish and other seafood may contain organic mercury but also beneficial nutrients such as n-3 polyunsaturated fatty acids. We endeavored to study whether maternal fish consumption during pregnancy harms or benefits fetal brain development. We examined associations of maternal fish intake during pregnancy and maternal hair mercury at delivery with infant cognition among 135 mother-infant pairs in Project Viva, a prospective U.S. pregnancy and child cohort study. We assessed infant cognition by the percent novelty preference on visual recognition memory (VRM) testing at 6 months of age. Mothers consumed an average of 1.2 fish servings per week during the second trimester. Mean maternal hair mercury was 0.55 ppm, with 10% of samples > 1.2 ppm. Mean VRM score was 59.8 (range, 10.9-92.5). After adjusting for participant characteristics using linear regression, higher fish intake was associated with higher infant cognition. This association strengthened after adjustment for hair mercury level: For each additional weekly fish serving, offspring VRM score was 4.0 points higher [95% confidence interval (CI), 1.3 to 6.7]. However, an increase of 1 ppm in mercury was associated with a decrement in VRM score of 7.5 (95% CI, -13.7 to -1.2) points. VRM scores were highest among infants of women who consumed > 2 weekly fish servings but had mercury levels ≤ 1.2 ppm. Higher fish consumption in pregnancy was associated with better infant cognition, but higher mercury levels were associated with lower cognition. Women should continue to eat fish during pregnancy but choose varieties with lower mercury contamination. [ABSTRACT FROM AUTHOR]

Because body iron burden is inversely associated with lead absorption, genes associated with hemochromatosis may modify body lead burden. Our objective was to determine whether the C282Y and/or H63D hemochromatosis gene (HFE) is associated with body lead burden. Patella and tibia lead levels were measured by K X-ray fluorescence in subjects from the Normative Aging Study. DNA samples were genotyped for C282Y and H63D using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). A series of multivariate linear regression models were constructed with bone or blood lead as dependent variables; age, smoking, and education as independent variables; and C282Y or H63D as independent risk factors and/or effect modifiers. Of 730 subjects, 94 (13%) carried the C282Y variant and 183 (25%) carried the H63D variant. In the crude analysis, mean tibia, patella, and blood lead levels were consistently lower in carriers of either HFE varistor compared with levels in subjects with wild-type genotypes. In multivariate analyses that adjusted for age, smoking, and education, having an HFE variant allele was an independent predictor of significantly lower patella lead levels (p < 0.05). These data suggest that HFE variants have altered kinetics of lead accumulation after exposure. Among elderly men, subjects with HFE variants had lower patella lead levels. These effects may be mediated by alterations in lead toxicokinetics via iron metabolic pathways regulated by the HFE gene product and body iron stores. [ABSTRACT FROM AUTHOR]

Objective. The purpose of this study was to examine the association between iron deficiency and low level lead poisoning. Methods: Data were collected in urban primary care clinic from 3650 children aged 9 to 48 months. Iron deficiency was defined as a red cell mean Cropuscular volume (MCV) of less than 70 fL and a red cell distribution width (RDW) of more than 14.5 in children younger than 2 years, and an MCV of' less than 73 fL and RDW of more than 14.5 in those 2 years or older. Results. After adjustment for age, hemoglobin concentration, and insurance status, the odds ratios for iron deficiency predicting blood lead levels greater than or equal to 5 μg/dL and greater than or equal 10μg/dL were 1.63 (95% confidence interval [CI] = 1.29, 2.04) and 1.44 (95% CI = 1.004, 2.05). Conclusions. Iron deficiency is significantly associated with low-level lead poisoning in children aged 9 to 48 months. [ABSTRACT FROM AUTHOR]

Focuses on the toxic effects of an acetaminophen overdose in a patient with glucose-6-phosphate dehydrogenase deficiency. Development of a Coomb's negative hemolytic anemia; Hemoglobin presentation; Recommendation for observing patients with the disease poisoned by acetaminophen for subsequent drug-induced hemolysis.

Presents information on a drug experimentation of baclofen overdose in a group of teenagers. Information on the muscle relaxant drug; Details on the drug experimentation; Discussion concerning the experiment conducted.

Determines pediatric emergency medicine fellows' level of preparedness to respond to battered mothers and assesses obstacles and attitudinal barriers to their effective response. Training background of respondents; Didactic training on woman battering during PEM Fellowship; Potential obstacles to identifying and reporting suspected battering of a child's mother.

We applied a novel hierarchical Bayesian weighted quantile sum (HBWQS) regression to combine data across 3 study sites to examine associations between prenatal exposure to metals and cognitive functioning in childhood. Data from 326 mother-child dyads enrolled in an ongoing cohort study, the Programming of Intergenerational Stress Mechanisms (PRISM) Study, based in New York, New York (recruitment in 2013–2020) and Boston, Massachusetts (recruitment 2011–2013), and the First Thousand Days of Life (FTDL) cohort study (recruitment 2012–2019), based in northern Virginia, were used. Arsenic, cadmium, manganese, lead, and antimony were measured in urine collected during pregnancy. Cognitive functioning was assessed in children aged 3–11 years using the National Institutes of Health Toolbox Cognition Battery. The HBWQS regression showed a negative association between the urinary metal mixture and the Cognition Early Childhood Composite Score in the PRISM New York City (β = −3.67, 95% credible interval (CrI): −7.61, −0.01) and FTDL (β = −3.76, 95% CrI: −7.66, −0.24) samples, with a similar trend in the PRISM Boston sample (β = −3.24, 95% CrI: −6.77, 0.144). We did not detect these associations in traditionally pooled models. HBWQS regression allowed us to account for site heterogeneity and detect associations between prenatal metal-mixture exposure and cognitive outcomes in childhood. Given the ubiquity of metals exposure, interventions aimed at reducing prenatal exposure may improve cognitive outcomes in children. This article is part of a Special Collection on Environmental Epidemiology. [ABSTRACT FROM AUTHOR]

Objectives. To examine whether a previously reported association between airborne lead exposure and children's cognitive function replicates across a geographically diverse sample of the United States. Methods. Residential addresses of children (< 5 years) were spatially joined to the Risk-Screening Environmental Indicators model of relative airborne lead toxicity. Cognitive outcomes for children younger than 8 years were available for 1629 children with IQ data and 1476 with measures of executive function (EF; inhibitory control, cognitive flexibility). We used generalized linear models using generalized estimating equations to examine the associations of lead, scaled by interquartile range (IQR), accounting for individual- and area-level confounders. Results. An IQR increase in airborne lead was associated with a 0.74-point lower mean IQ score (b = −0.74; 95% confidence interval = −1.00, −0.48). The association between lead and EF was nonlinear and was modeled with a knot at the 97.5th percentile of lead in our sample. Lead was significantly associated with lower mean inhibitory control but not with cognitive flexibility. This effect was stronger among males for both IQ and inhibitory control. Conclusions. Early-life exposure to airborne lead is associated with lower cognitive functioning. (Am J Public Health. 2024;114(3):309–318. https://doi.org/10.2105/AJPH.2023.307519) [ABSTRACT FROM AUTHOR]

Background: Stunting is an indicator of poor linear growth in children and is an important public health problem in many countries. Both nutritional deficits and toxic exposures can contribute to lower height-for-age Z-score (HAZ) and stunting (HAZ < -2). Objectives: In a community-based cross-sectional sample of 97 healthy children ages 6–59 months in Kampala, Uganda, we examined whether exposure to Pb, As, Cd, Se, or Zn were associated with HAZ individually or as a mixture. Methods: Blood samples were analyzed for a mixture of metals, which represent both toxins and essential nutrients. The association between HAZ and metal exposure was tested using multivariable linear regression and Weighted Quantile Sum (WQS) regression, which uses mixtures of correlated exposures as a predictor. Results: There were 22 stunted children in the sample, mean HAZ was -0.74 (SD = 1.84). Linear regression showed that Pb (β = -0.80, p = 0.021) and Se (β = 1.92, p = 0.005) were significantly associated with HAZ. The WQS models separated toxic elements with a presumed negative effect on HAZ (Pb, As, Cd) from essential nutrients with presumed positive effect on HAZ (Se and Zn). The toxic mixture was significantly associated with lower HAZ (β = -0.47, p = 0.03), with 62% of the effect from Pb. The nutrient WQS index did not reach statistical significance (β = -0.47, p = 0.16). Discussion: Higher blood lead and lower blood selenium level were both associated with lower HAZ. The significant associations by linear regression were reinforced by the WQS models, although not all associations reached statistical significance. These findings suggest that healthy children in this neighborhood of Kampala, Uganda, who have a high burden of toxic exposures, may experience detrimental health effects associated with these exposures in an environment where exposure sources are not well characterized. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exposure to environmental metals has been consistently associated with attention and behavioral deficits in children, and these associations may be modified by coexposure to other metals or iron (Fe) status. However, few studies have investigated Fe status as a modifier of a metal mixture, particularly with respect to attention-related behaviors. METHODS: We used cross-sectional data from the Public Health Impact of Metals Exposure study, which included 707 adolescents (10–14 years of age) from Brescia, Italy. Manganese, chromium, and copper were quantified in hair samples, and lead was quantified in whole blood, using inductively coupled plasma mass spectrometry. Concentrations of Fe status markers (ferritin, hemoglobin, transferrin) were measured using immunoassays or luminescence assays. Attention-related behaviors were assessed using the Conners Rating Scales Self-Report Scale–Long Form, Parent Rating Scales Revised–Short Form, and Teacher Rating Scales Revised–Short Form. We employed Bayesian kernel machine regression to examine associations of the metal mixture with these outcomes and evaluate Fe status as a modifier. RESULTS: Higher concentrations of the metals and ferritin were jointly associated with worse self-reported attention-related behaviors: metals and ferritin set to their 90th percentiles were associated with 3.0% [&#946= 0.03; 95% credible interval (CrI): -0.01, 0.06], 4.1% (&#946= 0.04; 95% CrI: 0.00, 0.08), and 4.1% (β= 0.04; 95% CrI: 0.00, 0.08) higher T-scores for self-reported attention deficit/hyperactivity disorder (ADHD) index, inattention, and hyperactivity, respectively, compared with when metals and ferritin were set to their 50th percentiles. These associations were driven by hair manganese, which exhibited nonlinear associations with all self-reported scales. There was no evidence that Fe status modified the neurotoxicity of the metal mixture. The metal mixture was not materially associated with any parent-reported or teacher-reported scale. CONCLUSIONS: The overall metal mixture, driven by manganese, was adversely associated with self-reported attention-related behavior. These findings suggest that exposure to multiple environmental metals impacts adolescent neurodevelopment, which has significant public health implications. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exposure to environmental metals has been consistently associated with attention and behavioral deficits in children, and these associations may be modified by coexposure to other metals or iron (Fe) status. However, few studies have investigated Fe status as a modifier of a metal mixture, particularly with respect to attention-related behaviors. METHODS: We used cross-sectional data from the Public Health Impact of Metals Exposure study, which included 707 adolescents (10–14 years of age) from Brescia, Italy. Manganese, chromium, and copper were quantified in hair samples, and lead was quantified in whole blood, using inductively coupled plasma mass spectrometry. Concentrations of Fe status markers (ferritin, hemoglobin, transferrin) were measured using immunoassays or luminescence assays. Attention-related behaviors were assessed using the Conners Rating Scales Self-Report Scale–Long Form, Parent Rating Scales Revised–Short Form, and Teacher Rating Scales Revised–Short Form. We employed Bayesian kernel machine regression to examine associations of the metal mixture with these outcomes and evaluate Fe status as a modifier. RESULTS: Higher concentrations of the metals and ferritin were jointly associated with worse self-reported attention-related behaviors: metals and ferritin set to their 90th percentiles were associated with 3.0% [&#946= 0.03; 95% credible interval (CrI): -0.01, 0.06], 4.1% (&#946= 0.04; 95% CrI: 0.00, 0.08), and 4.1% (β= 0.04; 95% CrI: 0.00, 0.08) higher T-scores for self-reported attention deficit/hyperactivity disorder (ADHD) index, inattention, and hyperactivity, respectively, compared with when metals and ferritin were set to their 50th percentiles. These associations were driven by hair manganese, which exhibited nonlinear associations with all self-reported scales. There was no evidence that Fe status modified the neurotoxicity of the metal mixture. The metal mixture was not materially associated with any parent-reported or teacher-reported scale. CONCLUSIONS: The overall metal mixture, driven by manganese, was adversely associated with self-reported attention-related behavior. These findings suggest that exposure to multiple environmental metals impacts adolescent neurodevelopment, which has significant public health implications. [ABSTRACT FROM AUTHOR]

In‐utero exposures interact in complex ways that influence neurodevelopment. Animal research demonstrates that fetal sex moderates the impact of joint exposure to metals and prenatal stress measures, including cortisol, on offspring socioemotional outcomes. Further research is needed in humans. We evaluated the joint association of prenatal exposures to a metal mixture and cortisol with infant negative affectivity, considering sex differences. Analyses included 226 (29% White, Non‐Hispanic) mother‐infant pairs with data on exposures and negative affectivity assessed using the Infant Behavior Questionnaire‐Revised in 6‐month‐olds. Results showed that girls whose mothers had higher cortisol had significantly higher scores of Fear and Sadness with greater exposure to the mixture. Examining higher‐order interactions may better elucidate the effects of prenatal exposure to metals and cortisol on socioemotional functioning. [ABSTRACT FROM AUTHOR]

Background: Gestational exposure to ambient air pollution has been associated with adverse health outcomes for mothers and newborns. The placenta is a central regulator of the in utero environment that orchestrates development and postnatal life via fetal programming. Ambient air pollution contaminants can reach the placenta and have been shown to alter bulk placental tissue DNA methylation patterns. Yet the effect of air pollution on placental cell-type composition has not been examined. We aimed to investigate whether the exposure to ambient air pollution during gestation is associated with placental cell types inferred from DNA methylation profiles. Methods: We leveraged data from 226 mother–infant pairs in the Programming of Intergenerational Stress Mechanisms (PRISM) longitudinal cohort in the Northeastern US. Daily concentrations of fine particulate matter (PM2.5) at 1 km spatial resolution were estimated from a spatiotemporal model developed with satellite data and linked to womens' addresses during pregnancy and infants' date of birth. The proportions of six cell types [syncytiotrophoblasts, trophoblasts, stromal, endothelial, Hofbauer and nucleated red blood cells (nRBCs)] were derived from placental tissue 450K DNA methylation array. We applied compositional regression to examine overall changes in placenta cell-type composition related to PM2.5 average by pregnancy trimester. We also investigated the association between PM2.5 and individual cell types using beta regression. All analyses were performed in the overall sample and stratified by infant sex adjusted for covariates. Results: In male infants, first trimester (T1) PM2.5 was associated with changes in placental cell composition (p = 0.03), driven by a decrease [per one PM2.5 interquartile range (IQR)] of 0.037 in the syncytiotrophoblasts proportion (95% confidence interval (CI) [− 0.066, − 0.012]), accompanied by an increase in trophoblasts of 0.033 (95% CI: [0.009, 0.064]). In females, second and third trimester PM2.5 were associated with overall changes in placental cell-type composition (T2: p = 0.040; T3: p = 0.049), with a decrease in the nRBC proportion. Individual cell-type analysis with beta regression showed similar results with an additional association found for third trimester PM2.5 and stromal cells in females (decrease of 0.054, p = 0.024). Conclusion: Gestational exposure to air pollution was associated with placenta cell composition. Further research is needed to corroborate these findings and evaluate their role in PM2.5-related impact in the placenta and consequent fetal programming. [ABSTRACT FROM AUTHOR]

• Maternal antenatal atopy is associated with ADHD-related behaviors among children. • Girls may be more sensitive to antenatal maternal atopy compared to boys. • Antenatal maternal atopy may contribute to the incidence of clinically significant ADHD. • Mechanisms may involve maternal immune activation during fetal neurodevelopment. Identifying modifiable risk factors for neuropsychological correlates of attention deficit hyperactivity disorder (ADHD) in early childhood can inform prevention strategies. Prenatal inflammatory states, such as maternal asthma and other atopic disorders, have been increasingly linked to enhanced risk for neurobehavioral disorders in children, with some studies suggesting sex-specific effects. To assess the association between maternal active asthma and/or atopy in the antenatal period and child symptoms of ADHD during mid-childhood and, given the male-bias in ADHD prevalence, to examine modifying effects of child sex. The study sample includes 250 maternal-child pairs enrolled in the Boston-based Asthma Coalition on Community, Environment and Social Stress (ACCESS) pregnancy cohort. We defined antenatal active atopy based on maternal report of current asthma, allergic rhinitis or atopic dermatitis during and/or in the year before pregnancy. When children were approximately 6 years old, mothers completed a battery of standardized child behavior rating scales designed for evaluating symptoms of ADHD. We used multivariable quantile regression to assess the relations between maternal antenatal atopy and symptoms of ADHD among children. In adjusted models, maternal atopy was significantly associated with greater risk for ADHD behaviors, as indicated by scores on the Conners' Parent Rating Scale-Revised ADHD index (β = 3.32, 95% CI: 0.33, 6.32). In sex-stratified models this association was stronger among girls (5.96, 95% CI = 0.95, 10.96) compared to boys (−2.14, 95% CI = −5.75, 1.45, p-interaction = 0.01). Among girls, we observed a similar finding for the Behavior Assessment System for Children 2nd Edition Parent Rating Scale Attention Problems subscale (β = 7.77, 95% CI = 1.57, 13.97). Results from other outcome subscales were similar in magnitude and direction, however, associations did not reach statistical significance at the p = 0.05 level. Maternal antenatal active atopy may be a risk factor for the development of ADHD-like symptoms, especially among girls. [ABSTRACT FROM AUTHOR]

BACKGROUND: The developing fetal brain is sensitive to many environmental exposures. However, the independent and joint effects of prenatal exposure to metals and micronutrients on child cognition are not well understood. OBJECTIVES: Our aim was to evaluate associations of first-trimester (~10 wk) maternal erythrocyte concentrations of mixtures of nonessential and essential metals and micronutrients with early (~3 y) and mid-childhood (~8 y) cognitive test scores in Project Viva, a prebirth cohort in Boston, Massachusetts, USA. METHODS: We measured concentrations of five essential metals (Cu, Mg, Mn, Se, Zn) and two micronutrients (vitamin B12 and folate), together termed the “nutrient mixture,” as well as six nonessential metals (As, Ba, Cd, Cs, Hg, Pb), together termed the “neurotoxic mixture,” in first-trimester (~10 wk) maternal erythrocytes (metals) or plasma (micronutrients). We assessed visual-motor function and receptive vocabulary in early childhood (~3 y), and visual-motor function, visual memory, and fluid and crystallized intelligence in mid-childhood (~8 y). We employed adjusted quantile g-computation and linear regression to estimate mixture and individual component associations, respectively. RESULTS: Analyses included 900 mother–child pairs (74% college graduates; 52% male children). In mixture analyses, a quartile increase in the nutrient mixture was associated with a mean difference in early childhood receptive vocabulary score of 1.58 points [95% confidence interval (CI): 0.06, 3.10], driven by Zn and Se. A quartile increase in the neurotoxic mixture was associated with a mean difference in mid-childhood visual-motor score of -3.01 points (95% CI: -5.55, -0.47), driven by Ba and Cs. Linear regressions supported quantile g-computation findings for mixture component contributions. DISCUSSION: Maternal circulating concentrations of several essential (Zn and Se) and nonessential (Ba and Cs) metals were associated with some domains of child cognition. In this folate-replete cohort, first-trimester circulating concentrations of known neurotoxic metals, such as Pb, were not associated with child cognition. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the editorial article "Mercury and Health" by M. McNutt in the September 27, 2013 issue which discusses the developmental toxicity of mercury and the potential impacts of toxic chemicals on the health of children.

In this work, we propose the use of molecular emission of calcium fluoride (CaF) by laser induced breakdown spectroscopy (LIBS) to obtain quantitative fluoride distribution images of teeth. LIBS has proved to be an efficient technique to detect low amounts of fluoride in solids, and human teeth have the advantage being a matrix rich in calcium. We used new calibration material from sintered hydroxyapatite pellets doped with fluoride to determine the optimized LIBS conditions of argon flow at 1 L min−1 and using the green emission bands of CaF in 530 nm, and obtained a calibration curve between 0 and 400 μg g−1, and LOD of 18 μg g−1. This methodology was applied within a rat model of fluoride exposure and showed increasing tooth-fluoride with increased exposure dose. To demonstrate applicability of this method in human teeth, we quantified fluoride distribution in teeth from three children from non-fluorinated and fluorinated water regions. Samples from children living in fluoridated water regions showed higher fluoride concentrations in dentine formed after birth, compared to a child from a non-fluoridated region. Teeth have been used as biomarkers for environmental exposure and this new method opens the opportunity in epidemiology research to study critical windows of early life exposure to fluoride as well. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental condition diagnosed in approximately 2% of children. Reliance on the emergence of clinically observable behavioral patterns only delays the mean age of diagnosis to approximately 4 years. However, neural pathways critical to language and social functions develop during infancy, and current diagnostic protocols miss the age when therapy would be most effective. We developed non-invasive ASD biomarkers using mass spectrometry analyses of elemental metabolism in single hair strands, coupled with machine learning. We undertook a national prospective study in Japan, where hair samples were collected at 1 month and clinical diagnosis was undertaken at 4 years. Next, we analyzed a national sample of Swedish twins and, in our third study, participants from a specialist ASD center in the US. In a blinded analysis, a predictive algorithm detected ASD risk as early as 1 month with 96.4% sensitivity, 75.4% specificity, and 81.4% accuracy (n = 486; 175 cases). These findings emphasize that the dynamics in elemental metabolism are systemically dysregulated in autism, and these signatures can be detected and leveraged in hair samples to predict the emergence of ASD as early as 1 month of age. [ABSTRACT FROM AUTHOR]

Evidence suggests that prenatal per- and polyfluoroalkyl substances (PFAS) and metals, two classes of chemicals found ubiquitously in human populations, influence immune system development and response. We evaluated whether first trimester blood PFAS and metals were associated with antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion. We measured six PFAS, as well as six nonessential and four essential metals, in first trimester blood from participants in the longitudinal pre-birth Project Viva cohort, recruited between 1999 and 2000 in eastern Massachusetts. We measured antigen- or mitogen-stimulated cord blood mononuclear cell proliferation responses (n = 269–314) and cytokine secretion (n = 217–302). We used covariate-adjusted least absolute shrinkage and selection operator (LASSO) for variable selection and multivariable regression to estimate associations with the immune markers. Each ng/mL of MeFOSAA was associated with a 3.6% (1.4, 5.8) higher lymphocyte proliferation response after stimulation with egg antigen, as well as 0.8 (0.7, 1.0) reduced odds of having IFN-γ detected in response to dust mite. Each ng/g increment of cesium was associated with 27.8% (−45.1, −4.9) lower IL-10 levels in response to dust mite. Each ng/g increment of mercury was associated with 12.0% (1.3, 23.8) higher IL-13 levels in response to mitogen PHA. Each ng/g increment of selenium and zinc was associated with 0.2% (0.01, 0.4) and 0.01% (0.002, 0.02) higher TNF-α in response to mitogen PHA, respectively. Prenatal metals and PFAS influence cord blood lymphocyte proliferation and cytokine secretion in ways that may increase risk for atopic disease in childhood. • Prenatal selenium and zinc associated with higher cord blood TNF-α in response to PHA. • Cesium is associated with lower IL-10 levels in response to dust mite. • Mercury is associated with higher IL-13 levels in response to PHA. • MeFOSAA is associated with higher lymphocyte proliferation after egg allergen stimulation. • Immune markers may be disease pathway biomarkers for risk of childhood atopic disease. [ABSTRACT FROM AUTHOR]

The burden of pediatric asthma and other allergic diseases is not evenly distributed among United States populations. To determine whether urinary biomarkers are associated with asthma morbidity, and if associations vary by child race, ethnicity and sex. This study includes n = 152 children with physician-diagnosed asthma who participated in the School Inner-City Asthma Intervention Study (SICAS-2). Metabolites of phenol, paraben, polycyclic aromatic hydrocarbons, and phthalate analytes were analyzed from urine samples collected at baseline. Asthma symptom days over the past 2 weeks were dichotomized to no asthma symptom days or any asthma symptom days. Cross-sectional regression models were adjusted for age, sex, number of colds, household income, prescription control, race and ethnicity, body mass index (BMI) percentile, and smoke exposure. Weighted quantile sum regression was used to analyze each chemical class and a total mixture effect, controlling for the same covariates. Analyses were conducted with the assistance of the National Institute of Environmental Health Sciences Children's Health Exposure Analysis Resource (CHEAR). Participants were mostly Hispanic/Latino and low income with an average age of 7.83 years and the average maximum asthma symptom days over the past two weeks of 2.13 (standard deviation: 3.56). The maximum concentrations indicate extreme values for several chemicals, including bisphenol-3, 2,5-dichlorophenol, propyl and methyl parabens, triclosan, methyl paraben and cotinine. We found a significant interaction effect and differing contributions of analytes for children with allergen sensitivity versus those that did not. For stratified analyses assessing effect modification by child race and ethnicity, weighted quantile sum interaction models showed reduced odds of asthma symptoms to a greater magnitude in children of other races and ethnicities compared to Black, Non-Hispanic children. Preliminary analyses of the association between environmental chemical exposure and asthma symptoms among inner-city children revealed an inverse association, which may be due to personal care and medication use and can be understood further in future analyses. Beneficial effects were detected for most of the chemicals. [ABSTRACT FROM AUTHOR]

Environmental pollution has been linked to obesogenic tendencies. Using environmental-related posts from Twitter (now known as X) from U.S. counties, we aim to uncover the association between Twitter linguistic data and U.S. county-level obesity rates. Analyzing nearly 300 thousand tweets from January 2020 to December 2020 across 207 U.S. counties, using an innovative Differential Language Analysis technique and drawing county-level obesity data from the 2020 Food Environment Atlas to identify distinct linguistic features in Twitter relating to environmental-related posts correlated with socioeconomic status (SES) index indicators, obesity rates, and obesity rates controlled for SES index indicators. We also employed predictive modeling to estimate Twitter language's predictive capacity for obesity rates. Results revealed a negative correlation between environmental-related tweets and obesity rates, both before and after adjusting for SES. Contrarily, non-environmental-related tweets showed a positive association with higher county-level obesity rates, indicating that individuals living in counties with lower obesity rates tend to tweet environmental-related language more frequently than those living in counties with higher obesity rates. The findings suggest that linguistic patterns and expressions employed in discussing environmental-related themes on Twitter can offer unique insights into the prevailing cross-sectional patterns of obesity rates. Although Twitter users are a subset of the general population, incorporating environmental-related tweets and county-level obesity rates and using a novel language analysis technique make this study unique. Our results indicated that Twitter users engaging in more active dialog about environmental concerns might exhibit healthier lifestyle practices, contributing to reduced obesity rates. [ABSTRACT FROM AUTHOR]

Background: Woman's weight changes during pregnancy and postpartum contribute to obesity and health outcomes later in life. This study aimed to identify and characterize weight change trajectories from pregnancy to one year postpartum among adult women.Methods: We used data from an ongoing cohort of healthy adult women (n = 819) with singleton pregnancies from 2007 - 2011. Sociodemographic data, pre-pregnancy body weight, and sedentary and breastfeeding practices were collected using questionaries applied by trained professionals. We applied a group-based trajectory modeling to distinguish weight change measured in the second and third trimesters of pregnancy and at one month, six, and 12 months postpartum. Multinomial regression models were run to characterize each trajectory.Results: We identified six weight change trajectories with the main difference in the patterns followed after one month of delivery. One in three women (36.7%) was classified in some of the three postpartum weight gain trajectories and regained weight from the second trimester of the first year postpartum. Women who followed some of these trajectories were more likely to have higher age, obesity before pregnancy, < 10 years of schooling, and partner, compared with women (10.7%, n = 87) in a postpartum sustained-fast-lost-weight trajectory (p < 0.05).Conclusions: Women with obesity before pregnancy have higher odds of regaining gestational weight after delivery without reaching their pre-pregnancy weight. The first six months postpartum are crucial to establishing obesity prevention strategies. Further research is needed to evaluate the effect of the interventions that prevent substantial weight gain through reproductive years in high-risk women. [ABSTRACT FROM AUTHOR]

Epidemiologists often study the associations between a set of exposures and multiple biologically relevant outcomes. However, the frequently used scale-and-context-dependent regression coefficients may not offer meaningful comparisons and could further complicate the interpretation if these outcomes do not have similar units. Additionally, when scaling up a hypothesis-driven study based on preliminary data, knowing how large to make the sample size is a major uncertainty for epidemiologists. Conventional p-value-based sample size calculations emphasize precision and might lead to a large sample size for small- to moderate-effect sizes. This asymmetry between precision and utility is costly and might lead to the detection of irrelevant effects. Here, we introduce the " δ -score" concept, by modifying Cohen's f 2 . δ -score is scale independent and circumvents the challenges of regression coefficients. Further, under a new hypothesis testing framework, it quantifies the maximum Cohen's f 2 with certain optimal properties. We also introduced "Sufficient sample size", which is the minimum sample size required to attain a δ -score. Finally, we used data on adults from a 2017–2018 U.S. National Health and Nutrition Examination Survey to demonstrate how the δ -score and sufficient sample size reduced the asymmetry between precision and utility by finding associations between mixtures of per-and polyfluoroalkyl substances and metals with serum high-density and low-density lipoprotein cholesterol. [ABSTRACT FROM AUTHOR]

Epidemiological studies often call for analytical methods that use a small biospecimen volume to quantify trace level exposures to environmental chemical mixtures. Currently, as many as 150 polar metabolites of environmental chemicals have been found in urine. Therefore, we developed a multi-class method for quantitation of biomarkers in urine. A single sample preparation followed by three LC injections was optimized in a proof-of-approach for a multi-class method. The assay was validated to quantify 50 biomarkers of exposure in urine, belonging to 7 chemical classes and 16 sub-classes. The classes represent metabolites of 12 personal care and consumer product chemicals (PCPs), 5 polycyclic aromatic hydrocarbons (PAHs), 5 organophosphate flame retardants (OPFRs), 18 pesticides, 5 volatile organic compounds (VOCs), 4 tobacco alkaloids, and 1 drug of abuse. Human urine (0.2 mL) was spiked with isotope-labeled internal standards, enzymatically deconjugated, extracted by solid-phase extraction, and analyzed using high-performance liquid chromatography-tandem mass spectrometry. The methanol eluate from the cleanup was split in half and the first half analyzed for PCPs, PAH, and OPFR on a Betasil C18 column; and pesticides and VOC on a Hypersil Gold AQ column. The second half was analyzed for tobacco smoke metabolites and a drug of abuse on a Synergi Polar RP column. Limits of detection ranged from 0.01 to 1.0 ng/mL of urine, with the majority ≤0.5 ng/mL (42/50). Analytical precision, estimated as relative standard deviation of intra- and inter-batch uncertainty, variabilities, was <20%. Extraction recoveries ranged from 83 to 109%. Results from the optimized multi-class method were qualified in formal international proficiency testing programs. Further method customization options were explored and method expansion was demonstrated by inclusion of up to 101 analytes of endo- and exogenous chemicals. This exposome-scale assay is being used for population studies with savings of assay costs and biospecimens, providing both quantitative results and the discovery of unexpected exposures. [ABSTRACT FROM AUTHOR]

Gene-environment and nutrition-environment studies often involve testing of high-dimensional interactions between two sets of variables, each having potentially complex nonlinear main effects on an outcome. Construction of a valid and powerful hypothesis test for such an interaction is challenging, due to the difficulty in constructing an efficient and unbiased estimator for the complex, nonlinear main effects. In this work, we address this problem by proposing a cross-validated ensemble of kernels (CVEK) that learns the space of appropriate functions for the main effects using a cross-validated ensemble approach. With a carefully chosen library of base kernels, CVEK flexibly estimates the form of the main-effect functions from the data, and encourages test power by guarding against over-fitting under the alternative. The method is motivated by a study on the interaction between metal exposures in utero and maternal nutrition on children's neurodevelopment in rural Bangladesh. The proposed tests identified evidence of an interaction between minerals and vitamins intake and arsenic and manganese exposures. Results suggest that the detrimental effects of these metals are most pronounced at low intake levels of the nutrients, suggesting nutritional interventions in pregnant women could mitigate the adverse impacts of in utero metal exposures on the children's neurodevelopment. for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement. [ABSTRACT FROM AUTHOR]

Background Childhood blood pressure (BP) is an important determinant of adult cardiovascular disease. Prenatal exposure to methylmercury through maternal fish consumption has been reported to increase the BP of children years later. Methods Mother–child pairs were enrolled from Project Viva, a prospective cohort study in Massachusetts. From second trimester maternal blood samples, we measured erythrocyte mercury concentration. Systolic BP in children, measured up to 5 times per visit in early and mid-childhood (median ages 3.2 and 7.7 years), was the primary outcome. We used mixed-effect regression models to account for variation in the number of BP measurements and to average effects over both time points. Results Among 1103 mother–child pairs, mean (SD) second trimester total erythrocyte mercury concentration was 4.0 (3.9) ng/g among mothers whose children were assessed in early childhood and 4.0 (4.0) ng/g for children assessed in mid-childhood. Mean (SD) offspring systolic BP was 92.1 (10.4) mm Hg in early childhood and 94.3 (8.4) mm Hg in mid-childhood. After adjusting for mother and infant characteristics, mean second trimester blood mercury concentration was not associated with child systolic BP (regression coefficient, 0.1 mm Hg; 95% CI, −1.3 to 1.5 for quartile 4 vs. quartile 1) at either time period. Further adjusting for second trimester maternal fish consumption, as well as docosahexaenoic acid and eicosapentaenoic acid consumption, did not substantially change the estimates. Conclusions The results of this study demonstrate an absence of association between childhood blood pressure and low-level mercury exposure typical of the general US population. [ABSTRACT FROM AUTHOR]

Early life phthalates exposure has been associated with adverse respiratory outcomes. However, evidence linking prenatal phthalates exposure and childhood lung function has been inconclusive. Additionally, few studies have examined phthalates exposure as a mixture and explored sexually dimorphic associations. We aimed to investigate sex-specific associations of prenatal phthalates mixtures with childhood lung function using the PROGRESS cohort in Mexico (N = 476). Prenatal phthalate concentrations were measured in maternal urine collected during the 2nd and 3rd trimesters. Children's lung function was evaluated at ages 8–13 years. Individual associations were assessed using multivariable linear regression, and mixture associations were modeled using repeated holdout WQS regression and hierarchical BKMR; data was stratified by sex to explore sex-specific associations. We identified significant interactions between 2nd trimester phthalates mixture and sex on FEV 1 and FVC z-scores. Higher 2nd trimester phthalate concentrations were associated with higher FEV 1 (β = 0.054, 95 %CI: 0.005, 0.104) and FVC z-scores (β = 0.074, 95 % CI: 0.024, 0.124) in females and with lower measures in males (FEV 1 , β = −0.017, 95 %CI: −0.066, 0.026; FVC, β = −0.014, 95 %CI: −0.065, 0.030). This study indicates that prenatal exposure to phthalates is related to childhood lung function in a sex-specific manner. [Display omitted] • Prenatal phthalate mixture associated with childhood lung function in a sex-specific manner. • 2nd trimester phthalate mixture linked to higher FEV 1 and FVC z-scores in females. • 2nd trimester phthalate mixture associated with lower FEV 1 and FVC z-scores in males. • Repeated holdout WQS and BKMR used to assess phthalate mixture effects on lung function. [ABSTRACT FROM AUTHOR]

Externalizing disorders, such as attention-deficit/hyperactivity disorder (ADHD), account for the majority of the child/adolescent referrals to mental health services and increase risk for later-life psychopathology. Although the expression of externalizing disorders is more common among males, few studies have addressed how sex modifies associations between metal exposure and adolescent externalizing symptoms. This study aimed to examine sex-specific associations between co-exposure to multiple metals and externalizing symptoms in adolescence and young adulthood. Among 150 adolescents and young adults (55% female, ages: 15–25 years) enrolled in the Public Health Impact of Metals Exposure (PHIME) study in Brescia, Italy, we measured five metals (manganese (Mn), lead (Pb), copper (Cu), chromium (Cr), nickel (Ni)) in four biological matrices (blood, urine, hair, and saliva). Externalizing symptoms were assessed using the Achenbach System of Empirically Based Assessment (ASEBA) Youth Self-Report (YSR) or Adult Self Report (ASR). Using generalized weighted quantile sum (WQS) regression, we investigated the moderating effect of sex (i.e., assigned at birth) on associations between the joint effect of exposure to the metal mixture and externalizing symptoms, adjusting for age and socioeconomic status. We observed that metal mixture exposure was differentially associated with aggressive behavior in males compared to females (β = −0.058, 95% CI [-0.126, −0.009]). In males, exposure was significantly associated with more externalizing problems, and aggressive and intrusive behaviors, driven by Pb, Cu and Cr. In females, exposure was not significantly associated with any externalizing symptoms. These findings suggest that the effect of metal exposure on externalizing symptoms differs in magnitude between the sexes, with males being more vulnerable to increased externalizing symptoms following metal exposure. Furthermore, our findings support the hypothesis that sex-specific vulnerabilities to mixed metal exposure during adolescence/young adulthood may play a role in sex disparities observed in mental health disorders, particularly those characterized by externalizing symptoms. • Sex specific associations between metal exposure and adolescent externalizing symptoms are understudied. • We examined sex-specific associations between a metal mixture and adolescent/young adult externalizing symptoms. • Adolescent/young adult metal mixture exposure is associated with higher externalizing symptoms in males, notfemales. • Pb, Cr, and Cu contributed most to associations between metals and externalizing symptoms. [ABSTRACT FROM AUTHOR]

Greater understanding of the pathways through which an environmental mixture operates is important to design effective interventions. We present new methodology to estimate natural direct and indirect effects and controlled direct effects of a complex mixture exposure on an outcome through a mediator variable. We implement Bayesian Kernel Machine Regression (BKMR) to allow for all possible interactions and nonlinear effects of (1) the co‐exposures on the mediator, (2) the co‐exposures and mediator on the outcome, and (3) selected covariates on the mediator and/or outcome. From the posterior predictive distributions of the mediator and outcome, we simulate counterfactuals to obtain posterior samples, estimates, and credible intervals of the mediation effects. Our simulation study demonstrates that when the exposure‐mediator and exposure‐mediator‐outcome relationships are complex, BKMR‐Causal Mediation Analysis performs better than current mediation methods. We applied our methodology to quantify the contribution of birth length as a mediator between in utero co‐exposure to arsenic, manganese, and lead, and children's neurodevelopmental scores, in a prospective birth cohort in Bangladesh. Among younger children, we found a negative (adverse) association between the metal mixture and neurodevelopment. We also found evidence that birth length mediates the effect of exposure to the metal mixture on neurodevelopment for younger children. If birth length were fixed to its 75th percentile value, the harmful effect of the metal mixture on neurodevelopment is attenuated, suggesting nutritional interventions to help increase fetal growth, and thus birth length, could potentially block the harmful effect of the metal mixture on neurodevelopment. [ABSTRACT FROM AUTHOR]

• Prenatal fine particulate matter (PM 2.5) exposure may increase placental mutational load. • PM 2.5 -related mutations may accumulate in genes coding for NADH dehydrogenase and subunits of ATP synthase. • Participants of African ancestry may represent an at-risk population. Prenatal ambient particulate matter (PM 2.5) exposure impacts infant development and alters placental mitochondrial DNA abundance. We investigated whether the timing of PM 2.5 exposure predicts placental mitochondrial mutational load using NextGen sequencing in 283 multi-ethnic mother-infant dyads. We observed increased PM 2.5 exposure, particularly during mid- to late-pregnancy and among genes coding for NADH dehydrogenase and subunits of ATP synthase, was associated with a greater amount of nonsynonymous mutations. The strongest associations were observed for participants of African ancestry. Further work is needed to tease out the role of mitochondrial genetics and its impact on offspring development and emerging disease disparities. [ABSTRACT FROM AUTHOR]