An overview of the Be Well Home Health Navigator Program to reduce contaminants in well water: Design and methods.

BACKGROUND: The Be Well Home Health Navigator Program is a prospective, randomized controlled trial (RCT) implemented to compare a community health navigator program to usual care program to reduce contaminants in drinking water. DESIGN AND SETTING: This 4-year two-armed RCT will involve well owners in Oregon that have private drinking water wells that contain arsenic, nitrate, or lead above maximum contaminant levels. INTERVENTION: The intervention leverages the trusted relationship between Cooperative Extension Service (CES) Community Educators and rural well owners to educate, assist and motivate to make decisions and set actionable steps to mitigate water contamination. In this study, CES will serve as home health navigators to deliver: 1) individualized feedback, 2) positive reinforcement, 3) teach-back moments, 4) decision-making skills, 5) navigation to resources, 6) self-management, and 7) repeated contact for shaping and maintenance of behaviors. Usual care includes information only with no access to individual meetings with CES. MEASURABLE OUTCOMES: Pre-specified primary outcomes include 1) adoption of treatment to reduce exposure to arsenic, nitrate, or lead in water which may include switching to bottled water and 2) engagement with well stewardship behaviors assessed at baseline, and post-6 and 12 months follow-up. Water quality will be measured at baseline and 12-month through household water tests. Secondary outcomes include increased health literacy scores and risk perception assessed at baseline and 6-month surveys. IMPLICATIONS: The results will demonstrate the efficacy of a domestic well water safety program to disseminate to other CES organizations. TRIAL REGISTRATION NUMBER: NCT05395663.

Organophosphate ester flame retardants and plasticizers in house dust and mental health outcomes among Canadian mothers: A nested prospective cohort study in CHILD.

Organophosphate ester flame retardants and plasticizers (OPEs) are common exposures in modern built environments. Toxicological models report that some OPEs reduce dopamine and serotonin in the brain. Deficiencies in these neurotransmitters are associated with anxiety and depression. We hypothesized that exposure to higher concentrations of OPEs in house dust would be associated with a greater risk of depression and stress in mothers across the prenatal and postpartum periods. We conducted a nested prospective cohort study using data collected on mothers (n = 718) in the CHILD Cohort Study, a longitudinal multi-city Canadian birth cohort (2008-2012). OPEs were measured in house dust sampled at 3-4 months postpartum. Maternal depression and stress were measured at 18 and 36 weeks gestation and 6 months and 1 year postpartum using the Centre for Epidemiologic Studies for Depression Scale (CES-D) and Perceived Stress Scale (PSS). We used linear mixed models to examine the association between a summed Z-Score OPE index and continuous depression and stress scores. In adjusted models, one standard deviation increase in the OPE Z-score index was associated with a 0.07-point (95% CI: 0.01, 0.13) increase in PSS score. OPEs were not associated with log-transformed CES-D (ß: 0.63%, 95% CI: -0.18%, 1.46%). The effect of OPEs on PSS score was strongest at 36 weeks gestation and weakest at 1 year postpartum. We observed small increases in maternal perceived stress levels, but not depression, with increasing OPEs measured in house dust during the prenatal and early postpartum period in this cohort of Canadian women. Given the prevalence of prenatal and postpartum anxiety and the ubiquity of OPE exposures, additional research is warranted to understand if these chemicals affect maternal mental health.

Correction: Effects of chronic exposure to arsenic on the fecal carriage of antibiotic-resistant Escherichia coli among people in rural Bangladesh.

[This corrects the article DOI: 10.1371/journal.ppat.1010952.].

Effects of chronic exposure to arsenic on the fecal carriage of antibiotic-resistant Escherichia coli among people in rural Bangladesh.

Antibiotic resistance is a leading cause of hospitalization and death worldwide. Heavy metals such as arsenic have been shown to drive co-selection of antibiotic resistance, suggesting arsenic-contaminated drinking water is a risk factor for antibiotic resistance carriage. This study aimed to determine the prevalence and abundance of antibiotic-resistant Escherichia coli (AR-Ec) among people and drinking water in high (Hajiganj, >100 µg/L) and low arsenic-contaminated (Matlab, <20 µg/L) areas in Bangladesh. Drinking water and stool from mothers and their children (<1 year) were collected from 50 households per area. AR-Ec was detected via selective culture plating and isolates were tested for antibiotic resistance, arsenic resistance, and diarrheagenic genes by PCR. Whole-genome sequencing (WGS) analysis was done for 30 E. coli isolates from 10 households. Prevalence of AR-Ec was significantly higher in water in Hajiganj (48%) compared to water in Matlab (22%, p <0.05) and among children in Hajiganj (94%) compared to children in Matlab (76%, p <0.05), but not among mothers. A significantly higher proportion of E. coli isolates from Hajiganj were multidrug-resistant (83%) compared to isolates from Matlab (71%, p <0.05). Co-resistance to arsenic and multiple antibiotics (MAR index >0.2) was observed in a higher proportion of water (78%) and child stool (100%) isolates in Hajiganj than in water (57%) and children (89%) in Matlab (p <0.05). The odds of arsenic-resistant bacteria being resistant to third-generation cephalosporin antibiotics were higher compared to arsenic-sensitive bacteria (odds ratios, OR 1.2-7.0, p <0.01). WGS-based phylogenetic analysis of E. coli isolates did not reveal any clustering based on arsenic exposure and no significant difference in resistome was found among the isolates between the two areas. The positive association detected between arsenic exposure and antibiotic resistance carriage among children in arsenic-affected areas in Bangladesh is an important public health concern that warrants redoubling efforts to reduce arsenic exposure.

Testing the Limit: Evaluating Drinking Water Arsenic Regulatory Levels Based on Adverse Pregnancy Outcomes in Bangladesh.

(1) Background: Arsenic (As) is a common drinking water contaminant that is regulated as a carcinogen. Yet, As is a systemic toxicant and there is considerable epidemiological data showing As adversely impacts reproductive health. This study used data from a birth cohort in Bangladesh (2008−2011) to examine associations between drinking water As levels and reproductive outcomes. (2) Methods: Pregnant individuals (n = 1597) were enrolled at <16 weeks gestation and drinking water As was measured. Participants with live births (n = 1130) were propensity score matched to participants who experienced miscarriage (n = 132), stillbirth (n = 72), preterm birth (n = 243), and neonatal mortality (n = 20). Logistic regression was used to examine drinking water As recommendations of 50, 10, 5, 2.5, and 1 µg/L on the odds of adverse birth outcomes. (3) Results: The odds of miscarriage were higher for pregnant women exposed to drinking water ≥2.5 versus <2.5 µg As/L [adjusted odds ratio (OR) 1.90, 95% Confidence Interval (CI): 1.07−3.38)]. (4) Conclusions: These preliminary findings suggest a potential threshold where the odds of miscarriage increases when drinking water As is above 2.5 µg/L. This concentration is below the World Health Organizations and Bangladesh's drinking water recommendations and supports the re-evaluation of drinking water regulations.

A prospective study of arsenic and manganese exposures and maternal blood pressure during gestation.

BACKGROUND: Pregnancy is a sensitive time for maternal cardiovascular functioning and exposures to arsenic or manganese may adversely affect blood pressure (BP). OBJECTIVES: This study examined the associations between arsenic and manganese exposures and maternal BP measured during pregnancy. Effect modification by pre-pregnancy body mass index (BMI) was evaluated. METHODS: Pregnant women (N = 1522) were recruited for a prospective cohort study in Bangladesh (2008-2011). Exposure to arsenic and manganese was measured in drinking water at <16 weeks gestation and toenails at one-month postpartum. Systolic and diastolic BP were measured monthly. Linear mixed models estimated mean BP and differences in mean BP over gestation for arsenic or manganese exposures and adjusted for covariates. RESULTS: Arsenic levels had an increasing dose-response association with maternal BP after 25 weeks gestation. Effect modification was observed for BMI. Participants with lower BMI (<23 kg/m2) exposed to 50 µg/L arsenic had 2.83 mmHg (95% CI:1.74-3.92) greater mean systolic and 1.96 mmHg (95% CI: 1.02-2.91 mmHg) diastolic BP compared to those exposed to ≤ 1 µg/L arsenic at 40 weeks gestation. Participants with higher BMI (≥23 kg/m2) showed a greater mean systolic BP of 5.72 mmHg (95% CI: 3.18-8.27 mmHg) and diastolic BP change of 6.09 mmHg (95% CI: 4.02-8.16 mmHg) at 40 weeks gestation when exposed to 50 µg/L compared to ≤ 1 µg/L arsenic. Participants with lower BMI exposed to drinking water manganese in the 2nd quartile (181-573 µg/L) had 1.04 mmHg higher mean diastolic BP (95% CI: 0.01-2.07 mmHg) at 40 weeks gestation compared to those in the 1st quartile (0.5-180 µg/L). CONCLUSION: Arsenic exposures during pregnancy were consistently associated with increased average maternal systolic and diastolic BP. The effect of manganese on BP was less consistent.

Household use of crop residues and fuelwood for cooking and newborn birth size in rural Bangladesh.

OBJECTIVES: We aimed to investigate the association between type of cooking biomass fuels (crop residues vs fuelwood) and newborn birth outcomes in Bangladeshi children. METHODS: In this birth cohort study, pregnant women who were 18 years or older with ultrasound confirmed singleton pregnancy of ≤16 weeks of gestation were enrolled from two Bangladesh clinics between January 2008 and June 2011. Exposure to cooking biomass fuels during pregnancy was assessed by an administered questionnaire. The newborn size metrics were measured at the time of delivery. We used multiple linear regression and logistic regression to assess the associations between the type of cooking biomass fuels and birth outcomes after adjusting for covariates. RESULTS: A total of 1137 participants were using biomass fuels, including crop residues (30.3%) and fuelwood (69.7%), respectively, for cooking. After adjusting for covariates, the use of crop residues for cooking was associated with a 0.13 SD decrease in birth length (95% CI 0.25 to -0.01), a 0.14 SD decrease in head circumference (95% CI -0.27 to -0.02), and increased risk of low birth weight (LBW, OR 1.52, 95% CI 1.07 to 2.15) compared with the use of fuelwood. CONCLUSION: The use of crop residues for cooking was associated with reduced birth size and increased risk for LBW in Bangladeshi children, implying that the use of crop residues during pregnancy may have a detrimental effect on fetal growth.

Developing a Short Assessment of Environmental Health Literacy (SA-EHL).

Environmental health literacy (EHL) is defined as the understanding of how the environment can impact human health, yet there are few tools to quantify EHL. We adapted the Short Assessment of Health Literacy (SAHL) to create the Short Assessment of Environmental Health Literacy (SA-EHL). Using the Amazon mTurk platform, users (n = 864) completed the 18-item SAHL and the 17-item SA-EHL. The SA-EHL was originally tested with 30 items; 13 items were removed because they were outside the acceptable difficulty parameters (DIFF: -0.4-4.0) or because of limited variance (>90% correct or incorrect), resulting in the final 17 items. Overall, participants scored highly on the SAHL, with 89.9% exhibiting high literacy. In contrast, the majority had low EHL (<1.0% high literacy, 99.2% low literacy) measured by the SA-EHL. The two scales were not correlated with each other (R2 = 0.013) as measured via linear regression and dichotomous variables. Scores on the SAHL and the SA-EHL were positively correlated with education. The SAHL was positively correlated with age, gender and marital status, whereas the SA-EHL was not. The SA-EHL can be used to gauge EHL for communities, and the results used to improve interventions and research translation materials.

Associations between residential proximity to oil and gas extraction and hypertensive conditions during pregnancy: a difference-in-differences analysis in Texas, 1996-2009.

BACKGROUND: Oil and gas extraction produces air pollutants that are associated with increased risks of hypertension. To date, no study has examined residential proximity to oil and gas extraction and hypertensive conditions during pregnancy. This study quantifies associations between residential proximity to oil and gas development on gestational hypertension and eclampsia. METHODS: We utilized a population-based retrospective birth cohort in Texas (1996-2009), where mothers reside <10 km from an active or future drilling site (n = 2 845 144.) Using full-address data, we linked each maternal residence at delivery to assign exposure and evaluate this exposure with respect to gestational hypertension and eclampsia. In a difference-in-differences framework, we model the interaction between maternal health before (unexposed) or after (exposed) the start of drilling activity (exposed) and residential proximity near (0-1, >1-2 or >2-3 km) or far (≥3-10 km) from an active or future drilling site. RESULTS: Among pregnant women residing 0-1 km from an active oil or gas extraction site, we estimate 5% increased odds of gestational hypertension [95% confidence interval (CI): 1.00, 1.10] and 26% increased odds of eclampsia (95% CI: 1.05, 1.51) in adjusted models. This association dissipates in the 1- to 3-km buffer zones. In restricted models, we find elevated odds ratios among maternal ages ≤35 years at delivery, maternal non-Hispanic White race, ≥30 lbs gained during pregnancy, nulliparous mothers and maternal educational attainment beyond high school. CONCLUSIONS: Living within 1 km of an oil or gas extraction site during pregnancy is associated with increased odds of hypertensive conditions during pregnancy.

Associations between Residential Proximity to Oil and Gas Drilling and Term Birth Weight and Small-for-Gestational-Age Infants in Texas: A Difference-in-Differences Analysis.

BACKGROUND: Oil and natural gas extraction may produce environmental pollution at levels that affect reproductive health of nearby populations. Available studies have primarily focused on unconventional gas drilling and have not accounted for local population changes that can coincide with drilling activity. OBJECTIVE: Our study sought to examine associations between residential proximity to oil and gas drilling and adverse term birth outcomes using a difference-in-differences study design. METHODS: We created a retrospective population-based term birth cohort in Texas between 1996 and 2009 composed of mother-infant dyads (n=2,598,025) living <10km from an oil or gas site. We implemented a difference-in-differences approach to estimate associations between drilling activities and infant health: term birth weight and term small for gestational age (SGA). Using linear and logistic regression, we modeled interactions between births before (unexposed) or during (exposed) drilling activity and residential proximity near (0-1, 1-2, or 2-3km) or far (3-10km) from an active or future drilling site, adjusting for individual- and neighborhood-level characteristics. RESULTS: The adjusted mean difference in term birth weight for mothers living 0-1 vs. 3-10km from a current or future drilling site was -7.3g [95% confidence interval (CI): -11.6, -3.0] for births during active vs. future drilling. The corresponding adjusted odds ratio for SGA was 1.02 (95% CI: 0.98, 1.06). Negative associations with term birth weight were observed for the 1-2 and 2-3km near groups, and no consistent differences were identified by type of drilling activity. Larger, though imprecise, adverse associations were found for infants born to Hispanic women, women with the lowest educational attainment, and women living in cities. CONCLUSIONS: Residing near oil and gas drilling sites during pregnancy was associated with a small reduction in term birth weight but not SGA, with some evidence of environmental injustices. Additional work is needed to investigate specific drilling-related exposures that might explain these associations. https://doi.org/10.1289/EHP7678.

Umbilical Cord Blood Metal Mixtures and Birth Size in Bangladeshi Children.

BACKGROUND: Studies have evaluated environmental exposure to toxic metals such as arsenic (As), cadmium (Cd), manganese (Mn), or lead (Pb) on birth size; however, information on potential effects of exposures to metal mixtures is limited. OBJECTIVES: We assessed the association between metal mixtures (As, Cd, Mn, Pb) in umbilical cord blood and neonate size in Bangladeshi children. METHODS: In this birth cohort study, pregnant women who were ≥18 years of age with an ultrasound-confirmed singleton pregnancy of ≤16wk gestation were recruited from two Bangladesh clinics between 2008 and 2011. Neonate size metrics were measured at the time of delivery. Metals in cord blood were measured using inductively coupled plasma mass spectrometry. We employed multivariable linear regression and Bayesian kernel machine regression (BKMR) to estimate associations of individual metals and metal mixtures with birth size parameters. RESULTS: Data from 1,088 participants was assessed. We found a significant negative association between metal mixture and birth length and head circumference when all metal concentrations were above the 60th and 55th percentiles, respectively, compared with the median. An interquartile range (IQR) increase in log Cd concentration {log[Cd (in micrograms per deciliter)] IQR=2.51} was associated with a 0.13-standard deviation (SD) decrease in mean birth length (95% CI: -0.25, -0.02) and a 0.17-SD decrease in mean head circumference (95% CI: -0.28, -0.05), based on linear regression models adjusted for covariates and the other metals. An IQR increase in log Mn concentration {log[Mn (in micrograms per deciliter)] IQR=0.69} was associated with a 0.07-SD decrease in mean birth weight (95% CI: -0.15, 0.002). DISCUSSION: Metal mixtures in cord blood were associated with reduced birth size in Bangladeshi children. Results from linear regression models adjusted and the BKMR mixtures analyses suggest adverse effects of Cd and Mn, as individual metal exposures, on birth size outcomes. https://doi.org/10.1289/EHP7502.

Trends in urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) in the non-smoking U.S. population, NHANES 2001-2014.

BACKGROUND: Recent studies indicate airborne PAH levels have decreased in the U.S., but it is unclear if this has resulted in PAH exposure changes in the U.S. OBJECTIVE: Examine temporal trends in urinary metabolites of Naphthalene, Fluorene, Phenanthrene, and Pyrene in U.S. non-smokers, 6+ years old. METHODS: We used biomonitoring data from the National Health and Nutrition Examination Survey (NHANES) program, 2001-2014, (N = 11,053) using survey weighted linear regression. Models were adjusted for age, sex, race/ethnicity, creatinine, BMI, income, diet, and seasonality. Stratified models evaluated the effect of age, sex, and race/ethnicity on trends. RESULTS: Between 2001 and 2014, Naphthalene exposure increased 36% (p < 0.01); Pyrene exposure increased 106% (p < 0.01); Fluorene and Phenanthrene exposure decreased 55% (p < 0.01), and 37% (p < 0.01), respectively. Naphthalene was the most abundant urinary PAH, 20-fold higher than Fluorene and Phenanthrene, and over 50-fold higher than Pyrene compared to reference groups, effect modification was observed by age (Naphthalene, Pyrene), sex (Fluorene, Pyrene), and race/ethnicity (Naphthalene, Fluorene, Phenanthrene, Pyrene). SIGNIFICANCE: This study shows exposure to Naphthalene and Pyrene increased, while exposure to Fluorene and Phenanthrene decreased among the non-smoking U.S. general population between 2001 and 2014, suggesting environmental sources of PAHs have changed over the time period.

Urinary polycyclic aromatic hydrocarbons concentrations and hepatitis B antibody serology in the United States (NHANES, 2003-2014).

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that are hepatotoxic and immunotoxic. PAH exposure may modulate hepatitis B immunology. OBJECTIVE: We used data from 6 cycles of the National Health and Nutrition Examination Survey (2003-2014) to evaluate the associations between urinary PAH metabolites and hepatitis B serology. METHODS: This analysis included individuals who self-reported receiving ≥3 doses of hepatitis B vaccine and urinary PAH metabolites (i.e. 1-napthol, 2-napthol, 3-fluorene, 2-fluorene, 1-phenanthrene, 1-pyrene, and total PAH [sum of all metabolites]). Separate logistic regression models assessed the association between hepatitis B vaccination status (i.e. individuals who were immune due to vaccination or susceptible) and tertiles of urinary PAH. Models were adjusted for age, gender, race/ethnicity, survey cycle, family income to poverty ratio, BMI, country of birth, serum cotinine, and urinary creatinine. RESULTS: Among participants who reported receiving ≥3 doses of vaccine and had no antibodies indicating a history of hepatitis B infection and/or current hepatitis B infection, dose-response relationships were observed where individuals with the lowest odds of serology indicating a response to the hepatitis B vaccine (i.e., anti-HBs+, anti-HBc-, and HBsAg-) were in the highest tertile of 2-Napthol (adjusted Odds Ratio [aOR]: 0.70, 95% confidence interval [CI]: 0.54, 0.91), 3-Napthol (aOR: 0.68, 95% CI: 0.53, 0.87), 2-Fluorene (aOR: 0.61, 95% CI: 0.54, 0.86), 1-Phenanthrene (aOR: 0.79, 95% CI: 0.65, 0.97), 1-Pyrene (aOR): 0.68, 95% CI: 0.55, 0.83), and total PAH (aOR: 0.73, 95% CI: 0.56, 0.95) had the compared to the lowest tertile. CONCLUSION: This cross-sectional study supports a hypothesis that PAH exposures experienced by the general US population may modulate hepatitis B vaccine induced immunity. Given the ubiquity of PAH exposures in the US, additional research is warranted to explore the effects of chronic PAH exposures on hepatitis B related humoral immunity.

Assessing the effectiveness of vehicle emission regulations on improving perinatal health: a population-based accountability study.

BACKGROUND: Since the 1990s, extensive regulations to reduce traffic-related air pollution (TRAP) have been implemented, yet the effectiveness of these regulations has not been assessed with respect to improving infant health. In this study, we evaluate how infant health risks associated with maternal residences near highways during pregnancy have changed over time. METHODS: We created a population-based retrospective birth cohort with geocoded residential addresses in Texan metropolitan areas from 1996 through 2009 (n = 2 259 411). We compared term birthweight (37-42 weeks of gestation) among maternal residences <300 m from a highway (high TRAP exposure) (n = 394 346) and 500-3500 m from a highway (comparison group) (n = 1 865 065). We implemented linear regressions to evaluate interactions between high TRAP exposure and birth year, adjusting for demographics, socioeconomic status and neighbourhood context. In addition, we used propensity score matching to further reduce residual confounding. RESULTS: From 1996 to 2009, outdoor NO2 decreased by 51.3%, based on regulatory monitoring data in Texas. Among pregnant women who resided in the high TRAP zone during pregnancy, interaction terms between residential location and birth year show that birthweight increased by 1.1 g [95% confidence interval CI): 0.7, 1.5) in unadjusted models and 0.3 g (95% CI: 0.0, 0.6) in matched models. Time-stratified models also show decreasing impacts of living in high TRAP areas on birthweight when comparing infants born in 1996-97 with 2008-09. Sensitivity analyses with alternative exposure and control groups show consistent results. CONCLUSIONS: Infant health risks associated with maternal residence near highways have reduced over time, paralleling regulatory measures to improve exhaust pipe emissions.

A prospective cohort study of in utero and early childhood arsenic exposure and infectious disease in 4- to 5-year-old Bangladeshi children.

BACKGROUND: Previous research found that infants who were exposed to high levels of arsenic in utero had an increased risk of infectious disease in the first year of life. This prospective study examined the association between arsenic exposures during gestation, and respiratory, diarrheal, and febrile morbidity in children 4-5 years of age. METHODS: A cohort of pregnant women was recruited in 2008-2011 in Bangladesh. Their children (N = 989) were followed, and household drinking water samples were collected during pregnancy, toddlerhood (12-40 months of age), and childhood (4-5 years of age). We actively surveyed mothers every 2 weeks regarding their children's infectious diseases symptoms from 4 to 5 years of age. Poisson regression models were used to estimate the association between arsenic exposure and respiratory and febrile illness. RESULTS: Median drinking water arsenic was 4.6, 8.8, and 4.2 µg/L in pregnancy, toddlerhood, and childhood, respectively. We observed 0.01, 1.2, and 1.0 cases per 100 person-days of diarrhea, respiratory, and febrile illness, respectively. The incident rate ratios (IRRs) for each doubling of drinking water arsenic during pregnancy were 1.10 (95% confidence interval [CI] = 1.00, 1.22) and 0.93 (95% CI = 0.82, 1.05) for respiratory and febrile illness, respectively, after adjusting for covariates. The association between arsenic exposure measured during toddlerhood and childhood was attenuated and not significantly associated with either outcome. Diarrheal disease was too infrequent to assess. CONCLUSIONS: Drinking water arsenic exposure during pregnancy was associated with a higher risk of acute respiratory infections in children 4-5 years old in Bangladesh.

Evaluating the effects between metal mixtures and serum vaccine antibody concentrations in children: a prospective birth cohort study.

BACKGROUND: Many populations are exposed to arsenic, lead, and manganese. These metals influence immune function. We evaluated the association between exposure to single and multiple metals, including arsenic, lead, and manganese, to humoral immunity as measured by antibody concentrations to diphtheria and tetanus toxoid among vaccinated Bangladeshi children. Additionally, we examined if this association was potentially mediated by nutritional status. METHODS: Antibody concentrations to diphtheria and tetanus were measured in children's serum at age 5 (n = 502). Household drinking water was sampled to quantify arsenic (W-As) and manganese (W-Mn), whereas lead was measured in blood (B-Pb). Exposure samples were taken during pregnancy, toddlerhood, and early childhood. Multiple linear regression models (MLRs) with single or combined metal predictors were used to determine the association with antibody outcomes. MLR results were transformed to units of percent change in outcome per doubling of exposure to improve interpretability. Structural equation models (SEMs) were used to further assess exposure to metal mixtures. SEMs regressed a latent exposure variable (Metals), informed by all measured metal variables (W-As, W-Mn, and B-Pb), on a latent outcome variable (Antibody), informed by measured antibody variables (diphtheria and tetanus). Weight-for-age z-score (WFA) at age 5 was evaluated as a mediator. RESULTS: Diphtheria antibody was negatively associated with W-As during pregnancy in MLR, but associations were attenuated after adjusting for W-Mn and B-Pb (- 2.9% change in diphtheria antibody per doubling in W-As, 95% confidence interval [CI]: - 7%, 1.5%). Conversely, pregnancy levels of B-Pb were positively associated with tetanus antibody, even after adjusting for W-As and W-Mn (13.3%, 95% CI: 1.7%, 26.3%). Overall, null associations were observed between W-Mn and antibody outcomes. Analysis by SEMs showed that the latent Metals mixture was significantly associated with the latent Antibody outcome (ß = - 0.16, 95% CI: - 0.26, - 0.05), but the Metals variable was characterized by positive and negative loadings of W-As and B-Pb, respectively. Sex-stratified MLR and SEM analyses showed W-As and B-Pb associations were exclusive to females. Mediation by WFA was null, indicating Metals only had direct effects on Antibody. CONCLUSIONS: We observed significant modulation of vaccine antibody concentrations among children with pregnancy and early life exposures to drinking water arsenic and blood lead. We found distinct differences by child sex, as only females were susceptible to metal-related modulations in antibody levels. Weight-for-age, a nutritional status proxy, did not mediate the association between the metal mixture and vaccine antibody.

Cord blood DNA methylation of DNMT3A mediates the association between in utero arsenic exposure and birth outcomes: Results from a prospective birth cohort in Bangladesh.

BACKGROUND: Fetal epigenetic programming plays a critical role in development. DNA methyltransferase 3 alpha (DNMT3A), which is involved in de novo DNA methylation (DNAm), is a prime candidate gene as a mediator between prenatal exposures and birth outcomes. We evaluated the relationships between in utero arsenic (As) exposure, birth outcomes, and DNMT3A DNAm. METHODS: In a prospective Bangladeshi birth cohort, cord blood DNAm of three DNMT3A CpGs was measured using bisulfite pyrosequencing. Maternal toenail As concentrations at birth were measured to estimate in utero exposure. Among vaginal births (N = 413), structural equation models (SEMs) were used to evaluate relationships between DNMT3A methylation, log2 (toenail As), birth weight, and gestational age. RESULTS: In an adjusted SEM including birth weight and gestational age, maternal toenail As levels were associated with DNMT3A DNAm (B = 0.40; 95% CI: 0.15, 0.66) and gestational age (B = -0.19 weeks; 95% CI: 0.36, -0.03). DNMT3A DNAm was associated with gestational age (B = -0.10 weeks; 95% CI: 0.16, -0.04) and birth weight (B = -11.0 g; 95% CI: 21.5, 0.4). There was an indirect effect of As on gestational age mediated through DNMT3A DNAm (B = -0.04; 95% CI: 0.08, -0.01), and there were indirect effects of maternal toenail As levels on birth weight through pathways including gestational age (B = -14.4 g; 95% CI: 29.2, -1.9), DNMT3A DNAm and gestational age (B = -3.1 g; 95% CI: 6.6, -0.8), and maternal weight gain and gestational age (B = -5.1 g; 95% CI: 9.6, -1.5). The total effect of a doubling in maternal toenail As concentration is a decrease in gestational age of 2.1 days (95% CI: 0.9, 3.3) and a decrease in birth weight of 29 g (95% CI: 14, 46). CONCLUSIONS: DNMT3A plays a critical role in fetal epigenetic programming. In utero arsenic exposure was associated with greater methylation of CpGs in DNMT3A which partially mediated associations between prenatal As exposure and birth outcomes. Additional studies are needed to verify this finding.

A passive sampling model to predict PAHs in butter clams (Saxidomus giganteus), a traditional food source for Native American tribes of the Salish Sea Region.

Native Americans face disproportionate exposures to environmental pollution through traditional subsistence practices including shellfish harvesting. In this study, the collection of butter clams (Saxidomus giganteus) was spatially and temporally paired with deployment of sediment pore water passive samplers at 20 locations in the Puget Sound region of the Salish Sea in the Pacific Northwest, USA, within adjudicated usual and accustomed tribal fishing grounds and stations. Clams and passive samplers were analyzed for 62 individual PAHs. A linear regression model was constructed to predict PAH concentrations in the edible fraction of butter clams from the freely dissolved fraction (Cfree) in porewater. PAH concentrations can be predicted within a factor of 1.9 ±â€¯0.2 on average from the freely dissolved PAH concentration in porewater using the following equation: PAHClam=4.1±0.1×PAHporewater This model offers a simplified, cost effective, and low impact approach to assess contaminant levels in butter clams which are an important traditional food.

Arsenic Drinking Water Violations Decreased across the United States Following Revision of the Maximum Contaminant Level.

Arsenic poses a threat to public health due to widespread environmental prevalence and known carcinogenic effects. In 2001, the US EPA published the Final Arsenic Rule (FAR) for public drinking water, reducing the maximum contaminant level (MCL) from 50 to 10 µg/L. We investigated impacts of the FAR on drinking water violations temporally and geographically using the Safe Drinking Water Information System. Violations exceeding the MCL and the population served by violating systems were analyzed across the conterminous US from 2006 (onset of FAR enforcement) to 2017. The percentage of public water system violations declined from 1.3% in 2008 to 0.55% in 2017 (p < 0.001, slope = -0.070), and the population served decreased by over 1 million (p < 0.001, slope = -106 886). Geographical analysis demonstrated higher mean violations and populations served in certain counties rather than evenly distributed across states. The decline in violations is likely due to the adoption of documented and undocumented treatment methods and possibly from reduced environmental releases. Considering other studies that have shown decreased urinary arsenic levels in the population served by public water systems since the new standard, it may be inferred that the FAR is facilitating the reduction of arsenic exposure in the US.