Prenatal Exposure to Tetrachloroethylene-Contaminated Drinking Water and the Risk of Congenital Anomalies: A Retrospective Cohort Study

BACKGROUND: Prior animal and human studies of prenatal exposure to solvents including tetrachloroethylene (PCE) have shown increases in the risk of certain congenital anomalies among exposed offspring. OBJECTIVES: This retrospective cohort study examined whether PCE contamination of public drinking water supplies in Massachusetts influenced the occurrence of congenital anomalies among children whose mothers were exposed around the time of conception. METHODS: The study included 1,658 children whose mothers were exposed to PCE-contaminated drinking water and a comparable group of 2,999 children of unexposed mothers. Mothers completed a self-administered questionnaire to gather information on all of their prior births, including the presence of anomalies, residential histories and confounding variables. PCE exposure was estimated using EPANET water distribution system modeling software that incorporated a fate and transport model. RESULTS: Children whose mothers had high exposure levels around the time of conception had an increased risk of congenital anomalies. The adjusted odds ratio of all anomalies combined among children with prenatal exposure in the uppermost quartile was 1.5 (95% CI: 0.9, 2.5). No meaningful increases in the risk were seen for lower exposure levels. Increases were also observed in the risk of neural tube defects (OR: 3.5, 95% CI: 0.8, 14.0) and oral clefts (OR 3.2, 95% CI: 0.7, 15.0) among offspring with any prenatal exposure. CONCLUSION: The results of this study suggest that the risk of certain congenital anomalies is increased among the offspring of women who were exposed to PCE-contaminated drinking water around the time of conception. Because these results are limited by the small number of children with congenital anomalies that were based on maternal reports, a follow-up investigation should be conducted with a larger number of affected children who are identified by independent records.National Institute of Environmental Health (5 P42 ES007381); National Institutes of Healt

Spatial analysis of learning and developmental disorders in upper Cape Cod, Massachusetts using generalized additive models

The spatial variability of three indicators of learning and developmental disability (LDD) was assessed for Cape Cod, Massachusetts. Maternal reports of receiving special education services, attention deficit hyperactivity disorder, and educational attainment were available for a birth cohort from 1969-1983. Using generalized additive models and residential history, maps of the odds of LDD were produced that also controlled for known risk factors. While results were not statistically significant, they suggest that children living in certain parts of Cape Cod were more likely to have a LDD. The spatial variation may be due to variation in the physical and social environment

Long-term Neurotoxic Effects of Early-life Exposure to Tetrachloroethylene-contaminated Drinking Water

Background: Tetrachloroethene (PCE) is a common environmental and occupational contaminant and an acknowledged neurotoxicant. From 1968 through 1983, widespread contamination of public drinking water supplies with PCE occurred in the Cape Cod region of Massachusetts. The source of the contamination was a vinyl liner applied to the inner surface of water distributionpipes. Objectives: A retrospective cohort study (the Cape Cod Health Study) was undertaken to examine possible health consequences of early-life exposure to PCE-contaminated drinking water. This review describes the study methods and findings regarding the effects of prenatal and childhood exposure on neurologic outcomes during early adulthood, including vision, neuropsychological functioning, brain structure, risky behaviors, and mental illness. The review also describes the strengths and challenges of conducting population-based epidemiologic research in this unique setting. Methods: Participants were identified by cross-matching birth certificates and water system data. Information on health outcomes and confounding variables was collected from self-administered surveys (n = 1689), neuropsychological tests (n = 63), vision examinations (n = 63), and magnetic resonance imaging (n = 42). Early-life exposure to PCE was estimated using a leaching and transport model. The data analysis compared the occurrence of each health outcome among individuals with prenatal and early childhood PCE exposure to unexposed individuals while considering the effect of confounding variables. Findings: The study found evidence that early-life exposure to PCE-contaminated drinking water has long-term neurotoxic effects. The strongest associations were seen with illicit drug use, bipolar disorder, and post-traumatic stress disorder. Key strengths of the study were availability of historical data on affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little confounding. Challenges arose mainly from the historical nature of the exposure assessments. Conclusions: The Cape Cod Health Study demonstrates how scientists can take advantage of unique “natural experiments” to learn about the health effects of environmental pollution. This body of work has improved our understanding of the long-term health effects of early-life exposure to this common environmental contaminant and will help risk assessors and policymakers ensure that drinking water supplies in the United States are safe for vulnerable populations

Andrographolide Attenuates Gut-Brain-Axis Associated Pathology in Gulf War Illness by Modulating Bacteriome-Virome Associated Inflammation and Microglia-Neuron Proinflammatory Crosstalk

Gulf War Illness (GWI) is a chronic multi-symptomatic illness that is associated with fatigue, pain, cognitive deficits, and gastrointestinal disturbances and presents a significant challenge to treat in clinics. Our previous studies show a role of an altered Gut-Brain axis pathology in disease development and symptom persistence in GWI. The present study utilizes a mouse model of GWI to study the role of a labdane diterpenoid andrographolide (AG) to attenuate the Gut-Brain axis-linked pathology. Results showed that AG treatment in mice (100 mg/kg) via oral gavage restored bacteriome alterations, significantly increased probiotic bacteria , , and , the genera that are known to aid in preserving gut and immune health. AG also corrected an altered virome with significant decreases in virome families and known to be associated with gastrointestinal pathology. AG treatment significantly restored tight junction proteins that correlated well with decreased intestinal proinflammatory mediators IL-1β and IL-6 release. AG treatment could restore Claudin-5 levels, crucial for maintaining the BBB integrity. Notably, AG could decrease microglial activation and increase neurotrophic factor BDNF, the key to neurogenesis. Mechanistically, microglial conditioned medium generated from IL-6 stimulation with or without AG in a concentration similar to circulating levels found in the GWI mouse model and co-incubated with neuronal cells in vitro, decreased Tau phosphorylation and neuronal apoptosis. In conclusion, we show that AG treatment mitigated the Gut-Brain-Axis associated pathology in GWI and may be considered as a potential therapeutic avenue for the much-needed bench to bedside strategies in GWI

Occurrence of mental illness following prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>While many studies of adults with solvent exposure have shown increased risks of anxiety and depressive disorders, there is little information on the impact of prenatal and early childhood exposure on the subsequent risk of mental illness. This retrospective cohort study examined whether early life exposure to tetrachloroethylene (PCE)-contaminated drinking water influenced the occurrence of depression, bipolar disorder, post-traumatic stress disorder, and schizophrenia among adults from Cape Cod, Massachusetts.</p> <p>Methods</p> <p>A total of 1,512 subjects born between 1969 and 1983 were studied, including 831 subjects with both prenatal and early childhood PCE exposure and 547 unexposed subjects. Participants completed questionnaires to gather information on mental illnesses, demographic and medical characteristics, other sources of solvent exposure, and residences from birth through 1990. PCE exposure originating from the vinyl-liner of water distribution pipes was assessed using water distribution system modeling software that incorporated a leaching and transport algorithm.</p> <p>Results</p> <p>No meaningful increases in risk ratios (RR) for depression were observed among subjects with prenatal and early childhood exposure (RR: 1.1, 95% CI: 0.9-1.4). However, subjects with prenatal and early childhood exposure had a 1.8-fold increased risk of bipolar disorder (N = 36 exposed cases, 95% CI: 0.9-1.4), a 1.5-fold increased risk post-traumatic stress disorder (N = 47 exposed cases, 95% CI: 0.9-2.5), and a 2.1-fold increased risk of schizophrenia (N = 3 exposed cases, 95% CI: 0.2-20.0). Further increases in the risk ratio were observed for bipolar disorder (N = 18 exposed cases, RR; 2.7, 95% CI: 1.3-5.6) and post-traumatic stress disorder (N = 18 exposed cases, RR: 1.7, 95% CI: 0.9-3.2) among subjects with the highest exposure levels.</p> <p>Conclusions</p> <p>The results of this study provide evidence against an impact of early life exposure to PCE on the risk of depression. In contrast, the results provide support for an impact of early life exposure on the risk of bipolar disorder and post-traumatic stress disorder. The number of schizophrenia cases was too small to draw reliable conclusions. These findings should be confirmed in investigations of other similarly exposed populations.</p

Childhood Fish Consumption and Learning and Behavioral Disorders

Fish is a major source of nutrients critical for brain development during early life. The importance of childhood fish consumption is supported by several studies reporting associations of n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation with better behavior and school performance. However, fish may have a different effect than n-3 PUFA alone due to the neurotoxic effects of methylmercury, a frequent contaminant. We investigated associations of childhood fish consumption with learning and behavioral disorders in birth cohort study of the neurotoxic effects of early life exposure to solvent-contaminated drinking water. Childhood (age 7–12 years) fish consumption and learning and behavioral problems were reported in self-administered questionnaires (age 23–41 at questionnaire completion). Fish consumption was not meaningfully associated with repeating a grade, tutoring, attending summer school, special class placement, or low educational attainment. However, participants who ate fish several times a week had an elevated odds of Attention Deficit Disorder/Attention Deficit Hyperactivity Disorder (odds ratio: 5.2; 95% confidence interval: 1.5–18) compared to participants who did not eat fish. While these findings generally support the safety of the observed level of fish consumption, the absence of a beneficial effect may be attributed to insufficient fish intake or the choice of relatively low n-3 PUFA fish