Early-life exposure to environmental toxicants can have detrimental effects on children’s neurodevelopment. In the current study, we employed a causal modeling framework to examine the direct effect of specific maternal prenatal exposures on infants’ neurodevelopment in the context of co-occurring metals. Maternal metal exposure and select micronutrients’ concentrations were assessed using samples collected at the time of delivery from mothers living across Navajo Nation with community exposure to metal mixtures originating from abandoned uranium mines. Infants’ development across five domains was measured at ages 10 to 13 months using the Ages and Stages Questionnaire Inventory (ASQ:I), an early developmental screener. After adjusting for effects of other confounding metals and demographic variables, prenatal exposure to lead, arsenic, antimony, barium, copper, and molybdenum predicted deficits in at least one of the ASQ:I domain scores. Strontium, tungsten, and thallium were positively associated with several aspects of infants’ development. Mothers with lower socioeconomic status (SES) had higher lead, cesium, and thallium exposures compared to mothers from high SES backgrounds. These mothers also had infants with lower scores across various developmental domains. The current study has many strengths including its focus on neurodevelopmental outcomes during infancy, an understudied developmental period, and the use of a novel analytical method to control for the effects of co-occurring metals while examining the effect of each metal on neurodevelopmental outcomes. Yet, future examination of how the effects of prenatal exposure on neurodevelopmental outcomes unfold over time while considering all potential interactions among metals and micronutrients is warranted.

Purpose of Review Zinc is an essential micronutrient with a myriad of key roles in human health. This review summarizes mechanistic data supporting the protective effects of zinc on metal toxicity and discusses the framework for an interventional clinical trial of zinc supplementation within a metal exposed Native American community. Recent Findings Many metals have common underlying mechanisms of toxicity that contribute to adverse human health effects. Studies demonstrate that multiple aspects of metal toxicity can be attributed to disruption of essential zinc-dependent functions. Multiple lines of evidence suggest that zinc may confer protection against metal toxicity in human populations with mixed-metal exposures. Thinking Zinc is a mechanism-informed intervention study of zinc supplementation to test the potential benefits of zinc while maintaining a culturally responsive research approach. Summary The current knowledge of diverse metal and zinc interactions, coupled with strong mechanistic evidence for zinc benefits in the context of toxic metal exposures, supports the hypothesis that zinc supplementation may mitigate the impact of toxic metals exposures in populations with chronic mixed metal exposures and in populations with low zinc status.

Many tribal populations are characterized by health disparities, including higher rates of infection, metabolic syndrome, and cancer—all of which are mediated by the immune system. Members of the Navajo Nation have suffered chronic low-level exposure to metal mixtures from uranium mine wastes for decades. We suspect that such metal and metalloid exposures lead to adverse health effects via their modulation of immune system function. We examined the relationships between nine key metal and metalloid exposures (in blood and urine) with 11 circulating biomarkers (cytokines and CRP in serum) in 231 pregnant Navajo women participating in the Navajo Birth Cohort Study. Biomonitored levels of uranium and arsenic species were considerably higher in participants than NHANES averages. Each biomarker was associated with a unique set of exposures, and arsenic species were generally immunosuppressive (decreased cellular and humoral stimulating cytokines). Overall, our results suggest that environmental metal and metalloid exposures modulate immune status in pregnant Navajo women, which may impact long-term health outcomes in mothers and their children.

Background: The financial hardships and social isolation experienced during the COVID-19 pandemic have been found to adversely affect children’s developmental outcomes. While many studies thus far have focused on school-aged children and the pandemic-related impacts on their academic skills and behavior problems, relatively less is known about pandemic hardships and associations with children’s development during their early years. Using a racially and economically diverse sample, we examined whether hardships experienced during the pandemic were associated with children’s development with a particular focus on communication and socioemotional development. Methods: Participants from eight cohorts of the Environmental influences on Child Health Outcomes program provided data on pandemic-related financial and social hardships as well as child developmental outcomes. Financial hardship was defined as at least one parent experiencing job loss or change, and social hardship was defined as families’ quarantining from household members or extended family and friends. The development of children under 4 was assessed longitudinally, before and during the pandemic (N = 684), using the Ages and Stages Questionnaire (ASQ). The Generalized Estimating Equations, which accounted for within-child correlation, were used for analysis. Results: Families from minority backgrounds and low socioeconomic status disproportionately experienced pandemic-related hardships. Male children had higher odds of experiencing negative changes in communication and personal social skills from pre- to during-pandemic visits (ORs ranged between 2.24 and 3.03 in analysis with binary ASQ outcomes and ranged from −0.34–0.36 in analyses with ASQ z-scores, ps = 0.000). Pandemic-related hardships in the social and financial areas did not explain within-individual changes in children’s developmental outcomes. Conclusion: Negative developmental changes from pre- to during-pandemic were found in boys, yet we did not find any associations between increased experience of pandemic-related hardships and children’s development. E how pandemic hardships affect development using a larger sample size and with longer follow-up is warranted.

Background/Aims: Despite a sophisticated understanding of the hematopoietic developmental program at the transcriptional level, our understanding of the role of E3 ubiquitin ligases remains underdeveloped. The E3 ubiquitin ligase, GRAIL (RNF128), is expressed in the bone marrow, but its role is as yet undefined. In this study, we evaluate the effect of GRAIL expression during hematopoietic differentiation in vitro and in vivo. Methods: Retroviral transduction of hematopoietic multipotent progenitor cells was used for methylcellulose colony assays and bone marrow reconstitution. Results: Enforced expression of GRAIL in colony assays demonstrated skewing of hematopoietic lineage development toward granulocytic/monocytic cells. Bone marrow reconstitution experiments with progenitor cells expressing biologically varied levels of GRAIL demonstrated diminished erythropoiesis and megakaryopoiesis if GRAIL (endogenous or forced) is maintained throughout hematopoiesis. Conclusion: These data highlight a role for GRAIL during hematopoiesis and emphasize the importance of studying posttranslational effects to complement our current understanding of the transcriptional regulation of hematopoiesis.