Disparities in Toxic Chemical Exposures and Associated Neurodevelopmental Outcomes: A Scoping Review and Systematic Evidence Map of the Epidemiological Literature.

BACKGROUND: Children are routinely exposed to chemicals known or suspected of harming brain development. Targeting Environmental Neuro-Development Risks (Project TENDR), an alliance of >50 leading scientists, health professionals, and advocates, is working to protect children from these toxic chemicals and pollutants, especially the disproportionate exposures experienced by children from families with low incomes and families of color. OBJECTIVE: This scoping review was initiated to map existing literature on disparities in neurodevelopmental outcomes for U.S. children from population groups who have been historically economically/socially marginalized and exposed to seven exemplar neurotoxicants: combustion-related air pollution (AP), lead (Pb), mercury (Hg), organophosphate pesticides (OPs), phthalates (Phth), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs). METHODS: Systematic literature searches for the seven exemplar chemicals, informed by the Population, Exposure, Comparator, Outcome (PECO) framework, were conducted through 18 November 2022, using PubMed, CINAHL Plus (EBSCO), GreenFILE (EBSCO), and Web of Science sources. We examined these studies regarding authors' conceptualization and operationalization of race, ethnicity, and other indicators of sociodemographic and socioeconomic disadvantage; whether studies presented data on exposure and outcome disparities and the patterns of those disparities; and the evidence of effect modification by or interaction with race and ethnicity. RESULTS: Two hundred twelve individual studies met the search criteria and were reviewed, resulting in 218 studies or investigations being included in this review. AP and Pb were the most commonly studied exposures. The most frequently identified neurodevelopmental outcomes were cognitive and behavioral/psychological. Approximately a third (74 studies) reported investigations of interactions or effect modification with 69% (51 of 74 studies) reporting the presence of interactions or effect modification. However, less than half of the studies presented data on disparities in the outcome or the exposure, and fewer conducted formal tests of heterogeneity. Ninety-two percent of the 165 articles that examined race and ethnicity did not provide an explanation of their constructs for these variables, creating an incomplete picture. DISCUSSION: As a whole, the studies we reviewed indicated a complex story about how racial and ethnic minority and low-income children may be disproportionately harmed by exposures to neurotoxicants, and this has implications for targeting interventions, policy change, and other necessary investments to eliminate these health disparities. We provide recommendations on improving environmental epidemiological studies on environmental health disparities. To achieve environmental justice and health equity, we recommend concomitant strategies to eradicate both neurotoxic chemical exposures and systems that perpetuate social inequities. https://doi.org/10.1289/EHP11750.

Childhood urinary organophosphate esters and cognitive abilities in a longitudinal cohort study.

The use of organophosphate esters (OPEs) as flame retardants, which has increased over the past two decades, raises concerns that OPEs may be harmful to humans, especially children. Animal studies and some human studies have reported that OPEs may adversely impact brain development, but few human studies evaluated OPE exposure during early childhood and neurodevelopmental outcomes. We aimed to fill this knowledge gap with the present study on urinary OPE metabolite concentrations at ages 1-5 years and cognitive abilities at 8 years. We used data of 223 children from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio. The point estimates for bis-2-chloroethyl-phosphate (BCEP) and bis(1,3-dichloro-2-propyl)-phosphate (BDCIPP) in association with IQ tended to be small and positive, while the point estimates for diphenyl-phosphate (DPHP) were small and negative, with 95% CIs including the null. However, we did find that socioeconomic status (SES) variables modified associations between OPEs and child IQ, with adverse OPE-IQ associations being stronger in socioeconomically disadvantaged children than in others. We identified an additional 1- to 2-point decrease in Full Scale IQ for every log-unit increase in BDCIPP, BCEP, and DPHP among those with lower maternal education, non-white race, lower income, or living in more deprived neighborhoods. We observed similar results for the Perceptual Reasoning, Verbal Comprehension, and Working Memory Index Scores. We suspect that there is residual confounding related to socioeconomic disadvantage, which was not captured with the available SES variables typically used in epidemiologic studies.

Breastfeeding and post-perinatal infant deaths in the United States, A national prospective cohort analysis.

Background: Reducing infant mortality is a major public health goal. The potential impact of breastfeeding on infant deaths is not well studied in the United States (US). Methods: We analyzed linked birth-death certificates for 3,230,500 US births that occurred in 2017, including 6,969 post-perinatal deaths from 7-364 days of age as the primary outcome, further specified as late-neonatal (7-27 days) or post-neonatal (28-364 days) deaths. The primary exposure was 'ever breastfed' obtained from birth certificates. Multiple logistic regression examined associations of ever breastfeeding with post-perinatal deaths and specific causes of deaths, controlling for maternal and infant factors. Findings: We observed an adjusted reduced odds ratio (AOR)= 0·74 with 95% confidence intervals (CI)=0·70-0·79 for the association of breastfeeding initiation with overall infant deaths (7-364 days), AOR=0·60 (0·54-0·67) for late-neonatal deaths, and AOR=0·81 (0·76-0·87) for post-neonatal deaths. In race/ethnicity-stratified analysis, significant associations of breastfeeding initiation with reduced odds of overall infant deaths were observed for Hispanics [AOR=0·64 (0·55-0·74)], non-Hispanic Whites [AOR=0·75 (0·69-0·81)], non-Hispanic Blacks [AOR=0·83 (0·75-0·91)], and non-Hispanic Asians [AOR=0·51 (0·36-0·72)]. Across racial/ethnic groups, effect sizes for late-neonatal deaths were consistently larger than those for post-neonatal deaths. Significant effects of breastfeeding initiation were observed for deaths due to infection [AOR=0·81(0·69-0·94)], Sudden Unexpected Infant Death [AOR=0·85 (0·78-0·92)], and necrotizing enterocolitis [AOR=0·67 (0·49-0·90)]. Interpretation: Breastfeeding initiation is significantly associated with reduced odds of post-perinatal infant deaths in multiple racial and ethnic groups within the US population. These findings support efforts to improve breastfeeding in infant mortality reduction initiatives.

Analysis of a non-Markov transcription model with nuclear RNA export and RNA nuclear retention.

Transcription involves gene activation, nuclear RNA export (NRE) and RNA nuclear retention (RNR). All these processes are multistep and biochemical. A multistep reaction process can create memories between reaction events, leading to non-Markovian kinetics. This raises an unsolved issue: how does molecular memory affect stochastic transcription in the case that NRE and RNR are simultaneously considered? To address this issue, we analyze a non-Markov model, which considers multistep activation, multistep NRE and multistep RNR can interpret many experimental phenomena. In order to solve this model, we introduce an effective transition rate for each reaction. These effective transition rates, which explicitly decode the effect of molecular memory, can transform the original non-Markov issue into an equivalent Markov one. Based on this technique, we derive analytical results, showing that molecular memory can significantly affect the nuclear and cytoplasmic mRNA mean and noise. In addition to the results providing insights into the role of molecular memory in gene expression, our modeling and analysis provide a paradigm for studying more complex stochastic transcription processes.

Does early life phthalate exposure mediate racial disparities in children's cognitive abilities?

Early life exposure to phthalates may be associated with reduced cognition. However, it is unknown if disproportionate exposure to phthalates contributes to racial disparities in children's intellectual abilities. Methods: We used data from 253 mother-child pairs in Cincinnati, OH (the Health Outcomes and Measures of the Environment study, 2003-2006). We measured urinary concentrations of 11 phthalate metabolites twice during pregnancy and up to six times in childhood. We evaluated children's cognitive abilities at ages 5 and 8 years. Using mediation models, we quantified covariate-adjusted direct and indirect effects of race on children's Full-Scale Intelligence Quotient (IQ) scores for individual phthalate metabolite concentrations during gestation and childhood. Results: Average IQ scores among Black children (n = 90) were 7.0 points lower (95% confidence interval [CI] = -12, -1.8) than among White children (n = 145) after adjustment for socioeconomic factors. Urinary monobenzyl phthalate and monoethyl phthalate (MEP) concentrations during gestation and childhood were higher among Black than White children. We did not observe evidence that phthalate concentrations mediated the race-IQ association, with the exception of MEP. Childhood MEP concentrations partially mediated the race-IQ association. For instance, each 10-fold increase in MEP concentrations at age 2 years contributed to a 1.9-point disparity in IQ scores between Black and White children (95% CI = -4.7, 0.7). Other phthalate metabolite concentrations during pregnancy or childhood did not mediate the race-IQ association. Conclusions: Despite observing racial disparities in exposure to some phthalates and IQ, we found little evidence that phthalates contribute to IQ disparities.

Blood lead levels mediate the relationship between social adversity and child externalizing behavior.

BACKGROUND/AIMS: The association between social adversity and externalizing behavioral problems in children is well-documented. What is much less researched are biological mechanisms that may mediate such relationships. This study examines the hypothesis that low blood lead mediates the relationship between social adversity and child externalizing behavior problems. METHODS: In this cross-sectional study, participants were 131 children aged 11-12 years (mean = 11.90) from Philadelphia, US. A venous fasting blood sample was taken and analyzed for blood lead levels. A social adversity index was calculated based on 10 total indicators derived from a psychosocial interview of the parent and official neighborhood data, while child behavior outcomes (internalizing and externalizing behavior) were assessed using both parent-report and child self-report. RESULTS: The mean blood lead level was 2.20 µg/dL. Both relatively higher blood lead levels and higher social adversity scores were associated with higher levels of parent-reported and child self-reported externalizing behaviors. Additionally, blood lead mediated the relationship between social adversity and child-reported externalizing behavior (Indirect effect: B = 0.03, 95% CI: 0.004, 0.09) and partially mediated the relationship between social adversity and parent-reported externalizing behavior (Indirect Effect: B = 0.03, 95% CI: 0.01, 0.07). CONCLUSION: To our knowledge, this study is the first to suggest that blood lead levels play a mediating role in the relationship between externalizing behavior problems and social adversity. Findings have potentially important implications for public health and environmental regulation as well as understanding biological mechanisms that link social inequality with health outcomes, especially in youth from low-income, urban areas.

Associations Between Breastfeeding Initiation and Infant Mortality in an Urban Population.

Background: Breastfeeding promotion and support are not universally accepted in the United States as a strategy to reduce infant mortality. We investigated associations between breastfeeding and infant mortality in an urban population with high infant mortality and low breastfeeding rates. Methods: A retrospective epidemiologic study linked birth-infant death data for 148,679 live births in Shelby County, Tennessee from January 2004 to December 2014. Births <500 g, deaths ≤7 days, deaths because of congenital anomalies or malignant neoplasms, and records with missing breastfeeding status were excluded. Main outcomes were infant death before the first birthday, neonatal death <28 days, and postneonatal death ≥28 days by ever or never breastfed. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for breastfeeding initiation were adjusted for maternal factors and infant factors. Results: Initiation of breastfeeding was associated with a significant reduction in total infant mortality (OR = 0.81, 95% CI = 0.68-0.97, p = 0.023). Neonatal mortality was also significantly reduced with any breastfeeding (OR = 0.49, 95% CI = 0.34-0.72, p = 0.001). Postneonatal mortality was not significantly associated with breastfeeding initiation in the overall population (OR = 0.95, 95% CI = 0.78-1.17, p = 0.65), but was significant in the nonblack population (OR = 0.63, 95% CI = 0.41-0.98, p = 0.039). An association was observed between breastfeeding initiation and infant mortality from infectious disease (OR = 0.49, 95% CI = 0.32-0.77, p = 0.002). Conclusions: In an urban area with high infant mortality and low breastfeeding rates, initiation of breastfeeding was significantly associated with reductions in overall infant mortality, neonatal mortality, and infection-related deaths. Breastfeeding promotion, protection, and support should be an integral strategy of infant mortality reduction initiatives.

The influence of interpregnancy interval on infant mortality.

BACKGROUND: In Ohio, the infant mortality rate is above the national average and the black infant mortality rate is more than twice the white infant mortality rate. Having a short interpregnancy interval has been shown to correlate with preterm birth and low birthweight, but the effect of short interpregnancy interval on infant mortality is less well established. OBJECTIVE: We sought to quantify the population impact of interpregnancy interval on the risk of infant mortality. STUDY DESIGN: This was a statewide population-based retrospective cohort study of all births (n = 1,131,070) and infant mortalities (n = 8152) using linked Ohio birth and infant death records from January 2007 through September 2014. For this study we analyzed 5 interpregnancy interval categories: 0-<6, 6-<12, 12-<24, 24-<60, and ≥60 months. The primary outcome for this study was infant mortality. During the study period, 3701 infant mortalities were linked to a live birth certificate with an interpregnancy interval available. We calculated the frequency and relative risk of infant mortality for each interval compared to a referent interval of 12-<24 months. Stratified analyses by maternal race were also performed. Adjusted risks were estimated after accounting for statistically significant and biologically plausible confounding variables. Adjusted relative risk was utilized to calculate the attributable risk percent of short interpregnancy intervals on infant mortality. RESULTS: Short interpregnancy intervals were common in Ohio during the study period. Of all multiparous births, 20.5% followed an interval of <12 months. The overall infant mortality rate during this time was 7.2 per 1000 live births (6.0 for white mothers and 13.1 for black mothers). Infant mortalities occurred more frequently for births following short intervals of 0-<6 months (9.2 per 1000) and 6-<12 months (7.1 per 1000) compared to 12-<24 months (5.6 per 1000) (P < .001 and <.001). The highest risk for infant mortality followed interpregnancy intervals of 0-<6 months (adjusted relative risk, 1.32; 95% confidence interval, 1.17-1.49) followed by interpregnancy intervals of 6-<12 months (adjusted relative risk, 1.16; 95% confidence interval, 1.04-1.30). Analysis stratified by maternal race revealed similar findings. Attributable risk calculation showed that 24.2% of infant mortalities following intervals of 0-<6 months and 14.1% with intervals of 6-<12 months are attributable to the short interpregnancy interval. By avoiding short interpregnancy intervals of ≤12 months we estimate that in the state of Ohio 31 infant mortalities (20 white and 8 black) per year could have been prevented and the infant mortality rate could have been reduced from 7.2-7.0 during this time frame. CONCLUSION: An interpregnancy interval of 12-60 months (1-5 years) between birth and conception of next pregnancy is associated with lowest risk of infant mortality. Public health initiatives and provider counseling to optimize birth spacing has the potential to significantly reduce infant mortality for both white and black mothers.

Assessment of health risk of trace metal pollution in surface soil and road dust from e-waste recycling area in China.

Informal recycling of e-waste and the resulting heavy metal pollution has become a serious burden on the ecosystem in Guiyu, China. In this investigation, we evaluated the trace metal concentration of community soil and road dust samples from 11 locations in Guiyu and 5 locations (consisting of residential areas, kindergarten/school, and farm field) in a reference area using graphite furnace atomic absorption spectrophotometer. The study spanned four seasons, 2012-2013, with a view to assess the risk associated with e-waste recycling in the study area. The concentrations of Pb, Cd, Cr, and Mn were 448.73, 0.71, 63.90, and 806.54 mg/kg in Guiyu soil and 589.74, 1.94, 69.71, and 693.74 mg/kg, in the dust, respectively. Pb and Cd values were significantly higher (P ≤ 0.05) than the reference area, and the mixed model analysis with repeated seasonal measurements revealed soil Pb and Cd levels that were 2.32 and 4.34 times, while the ratios for dust sample were 4.10 and 3.18 times higher than the reference area. Contamination factor, degree of contamination, and pollution load index indicated that all sampling points had a high level of metal contamination except farm land and kindergarten compound. The cumulative hazard index of Pb, Cd, Cr, and Mn for children in exposed area was 0.99 and 1.62 for soil and dust, respectively, suggesting non-cancer health risk potential. The significant accumulation of trace metals in the e-waste recycling area predisposes human life, especially children, to a potentially serious health risk.

Assessment of personal exposure to manganese in children living near a ferromanganese refinery.

Airborne exposure to manganese (Mn) can result in neurologic effects. Stationary air sampling is the traditional technique to assess Mn exposure for communities, yet may not accurately reflect children's personal exposure. The goal of the study was to characterize personal exposure to Mn and PM(2.5) in a cohort of children ages 7-9 years residing near a ferromanganese refinery. A subset of children living in non-smoking households ages 7-9 enrolled in the Marietta Community Actively Researching Exposure Study during March-June 2009 and 2010 were invited to participate. Blood and hair were collected and analyzed for Mn. Participants wore a PM(2.5) sampler (Personal Modular Impactor) for 48 h. TWD was based on time spent at home and school and the distance of each from the refinery. Stationary outdoor air sampling was conducted 8 km from the refinery using a Harvard-type PM(2.5) impactor. The relationship between personal Mn exposure and TWD was examined by multiple regression adjusting for stationary air Mn concentration, wind speed and direction, and precipitation. Complete personal air sampling data were collected on 38 children. TWD ranged from 4.7 km to 28.5 km with a mean distance of 11.1 (4.7 sd) km. Mn concentration in personal air samples ranged from 1.5 ng/m3 to 54.5 ng/m3 (geometric mean, 8.1 ng/m3). TWD was a significant predictor of natural log personal air Mn concentration (lnMn) with an associated decrease of 0.075 lnMn for each km TWD (p<0.05, 95% CI -0.13 to -0.01). Personal Mn exposures were positively associated with stationary air Mn levels and inversely associated with wind speed. A child's location (home and school) relative to the refinery is a significant predictor of personal Mn exposure. Wind speed is also an important contributor to personal Mn exposure.