Relation of Prenatal Methylmercury Exposure from Environmental Sources to Childhood IQ

Background

Although prenatal methylmercury exposure has been linked to poorer intellectual function in several studies, data from two major prospective, longitudinal studies yielded contradictory results. Associations with cognitive deficits were reported in a Faroe Islands cohort, but few were found in a study in the Seychelles Islands. It has been suggested that co-exposure to another contaminant, polychlorinated biphenyls (PCBs), may be responsible for the positive findings in the former study and that co-exposure to nutrients in methylmercury-contaminated fish may have obscured and/or protected against adverse effects in the latter.

Objectives

We aimed to determine the degree to which co-exposure to PCBs may account for the adverse effects of methylmercury and the degree to which co-exposure to docosahexaenoic acid (DHA) may obscure these effects in a sample of Inuit children in Arctic Québec.

Methods

IQ was estimated in 282 school-age children from whom umbilical cord blood samples had been obtained and analyzed for mercury and other environmental exposures.

Results

Prenatal mercury exposure was related to poorer estimated IQ after adjustment for potential confounding variables. The entry of DHA into the model significantly strengthened the association with mercury, supporting the hypothesis that beneficial effects from DHA intake can obscure adverse effects of mercury exposure. Children with cord mercury ≥ 7.5 μg/L were four times as likely to have an IQ score < 80, the clinical cut-off for borderline intellectual disability. Co-exposure to PCBs did not alter the association of mercury with IQ.

Conclusions

To our knowledge, this is the first study to document an association of prenatal mercury exposure with poorer performance on a school-age assessment of IQ, a measure whose relevance for occupational success in adulthood is well established. This association was seen at levels in the range within which many U.S. children of Asian-American background are exposed.

Citation

Jacobson JL, Muckle G, Ayotte P, Dewailly É, Jacobson SW. 2015. Relation of prenatal methylmercury exposure from environmental sources to childhood IQ. Environ Health Perspect 123:827–833; http://dx.doi.org/10.1289/ehp.1408554     

Disparities in Water and Sewer Services in North Carolina: An Analysis of the Decision-Making Process

Objectives. We examined the factors that affect access to municipal water and sewer service for unincorporated communities relying on wells and septic tanks.Methods. Using a multisite case study design, we conducted in-depth, semistructured interviews with 25 key informants from 3 unincorporated communities in Hoke, New Hanover, and Transylvania counties, North Carolina, July through September 2013. Interviewees included elected officials, health officials, utility providers, and community members. We coded the interviews in ATLAS.ti to identify common themes.Results. Financing for water and sewer service emerged as the predominant factor that influenced decisions to extend these services. Improved health emerged as a minor factor, suggesting that local officials may not place a high emphasis on the health benefits of extending public water and sewer services. Awareness of failed septic systems in communities can prompt city officials to extend sewer service to these areas; however, failed systems are often underreported.Conclusions. Understanding the health costs and benefits of water and sewer extension and integrating these findings into the local decision-making process may help address disparities in access to municipal services.In July 2010, the United Nations General Assembly passed Resolution 64/292, recognizing the human right to clean drinking water and safe sanitation.1 The resolution called on all member states to ensure equitable access to water and sanitation. Although piped water and sewer services have been heralded as among the greatest public health achievements in 20th-century US history,2 communities across the country are still fighting for equal access to this basic right. These communities rely on self-supplied, on-site wells and septic systems that serve 1 or several households and are therefore unregulated by the US Safe Drinking Water Act (Pub. L. 93-523, 88 Stat. 1660 [1974]). Previous US studies have shown that populations relying on self-supplied water and sewer systems face excess health and economic risks in comparison with populations with access to community water and sewer service. For example, whereas waterborne disease outbreaks have declined in community water systems since monitoring began in 1971, waterborne disease outbreaks for self-supplied wells have increased owing to weak standards and poor monitoring of these systems.3 Also, increased septic tank density in neighborhoods has been associated with greater risks of both bacterial and viral diarrheal illness.4 In addition to health concerns, well and septic system users cite stench, decreased property value, and high repair costs as adverse effects of relying on self-supplied systems.5Despite the potential health and societal costs, 26% of North Carolinians rely on self-supplied water systems and 49% on septic systems, compared with national estimates of 14% and 24%, respectively.6,7 Although many of these people reside in rural areas where homes are widely dispersed and piped water and sewer services are impractical, some live in small, densely populated communities bordering cities and towns with centralized services.8–12 Despite their proximity, these unincorporated communities lack not only water and sewer service but often also city fire and police protection, municipal voting rights, and trash collection.5 These disparities in public services may, in turn, contribute to disparities in public health and safety.Understanding the factors influencing decisions to extend water and sewer service to underserved communities can provide insight into how to overcome service disparities and improve overall service quality. Little is known about how the major stakeholders and the social, political, and physical environment affect the local decision-making processes of water and sewer extension. We sought to close this knowledge gap and identify the barriers and avenues to water and sewer service extension through a series of in-depth, semistructured interviews with key informants from 3 North Carolina communities.     

Glutamine Improves Innate Immunity and Prevents Bacterial Enteroinvasion During Parenteral Nutrition

Background: Patients receiving parenteral nutrition (PN) are at increased risk of infectious complications compared with enteral feeding, which is in part explained by impaired mucosal immune function during PN. Adding glutamine (GLN) to PN has improved outcome in some clinical patient groups. Although GLN improves acquired mucosal immunity, its effect on innate mucosal immunity (defensins, mucus, lysozymes) has not been investigated. Methods: Forty‐eight hours following venous cannulation, male Institute of Cancer Research mice were randomized to chow (n = 10), PN (n = 12), or PN + GLN (n = 13) for 5 days. Small intestine tissue and luminal fluid were collected for mucin 2 (MUC2), lysozyme, cryptdin 4 analysis, and luminal interleukin (IL)–4, IL‐10, and IL‐13 level measurement. Tissue was also harvested for ex vivo intestinal segment culture to assess tissue susceptibility to enteroinvasive Escherichia coli. Results: In both luminal and tissue samples, PN reduced MUC2 and lysozyme (P < .0001, respectively) compared with chow, whereas GLN addition increased MUC2 and lysozyme (luminal, P < .05; tissue, P < .0001, respectively) compared with PN alone. PN significantly suppressed cryptdin 4 expression, while GLN supplementation significantly enhanced expression. IL‐4, IL‐10, and IL‐13 decreased significantly with PN compared with chow, whereas GLN significantly increased these cytokines compared with PN. Functionally, bacterial invasion increased with PN compared with chow (P < .05), while GLN significantly decreased enteroinvasion to chow levels (P < .05). Conclusions: GLN‐supplemented PN improves innate immunity and resistance to bacterial mucosal invasion lost with PN alone. This work confirms a clinical rationale for providing glutamine for the protection of the intestinal mucosa.     

A balanced hazard ratio for risk group evaluation from survival data

Common clinical studies assess the quality of prognostic factors, such as gene expression signatures, clinical variables or environmental factors, and cluster patients into various risk groups. Typical examples include cancer clinical trials where patients are clustered into high or low risk groups. Whenever applied to survival data analysis, such groups are intended to represent patients with similar survival odds and to select the most appropriate therapy accordingly. The relevance of such risk groups, and of the related prognostic factors, is typically assessed through the computation of a hazard ratio. We first stress three limitations of assessing risk groups through the hazard ratio: (1) it may promote the definition of arbitrarily unbalanced risk groups; (2) an apparently optimal group hazard ratio can be largely inconsistent with the p‐value commonly associated to it; and (3) some marginal changes between risk group proportions may lead to highly different hazard ratio values. Those issues could lead to inappropriate comparisons between various prognostic factors. Next, we propose the balanced hazard ratio to solve those issues. This new performance metric keeps an intuitive interpretation and is as simple to compute. We also show how the balanced hazard ratio leads to a natural cut‐off choice to define risk groups from continuous risk scores. The proposed methodology is validated through controlled experiments for which a prescribed cut‐off value is defined by design. Further results are also reported on several cancer prognosis studies, and the proposed methodology could be applied more generally to assess the quality of any prognostic markers. Copyright © 2015 John Wiley & Sons, Ltd.     

Pathway‐Based Association Study of Multiple Candidate Genes and Multiple Traits Using Structural Equation Models

There is increasing interest in the joint analysis of multiple genetic variants from multiple genes and multiple correlated quantitative traits in association studies. The classical approach involves testing univariate associations between genotypes and phenotypes and correcting for multiple testing that results in loss of power to detect associations. In this paper, we propose modeling complex relationships between genetic variants in candidate genes and measured correlated traits using structural equation models (SEM), taking advantage of prior knowledge on clinical and genetic pathways. We adopt generalized structured component analysis (GSCA) as an approach to SEM and develop a single association test between multiple genetic variants in a gene and a set of correlated traits, taking into account all available data from other genes and other traits. The performance of this test is investigated by simulations. We apply the proposed method to the Quebec Child and Adolescent Health and Social Survey (1999) data to investigate genetic associations with cardiovascular disease‐related traits.     

Early‐onset hypoparathyroidism and chronic keratitis revealing APECED

Early diagnosis of potentially life‐threatening autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy (APECED) is crucial, but is often delayed due to the clinical heterogeneity of the disorder. Even in the absence of the classic disease triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical insufficiency, a diagnosis of APECED should be considered in children who have hypoparathyroidism and chronic keratitis, with a past medical history showing a mild and transient Candida infection.     

Determination of the renal concentration capacity following intravenous administration of dDAVP in healthy humans

The synthetic AVP analogue 1-desamino-8-d-arginine-vasopressin (dDAVP) is used for treatment of polyuric disorders. Lack of commercially available assays limits the usefulness of dDAVP as a diagnostic tool in the assessment of renal concentrating capacity. We aimed to develop a specific radioimmunoassay (RIA) for determination of plasma dDAVP (pdDAVP) in order to investigate the relationship between pdDAVP levels and urine osmolality (Uosm). Further, we aimed to determine the onset, duration, and maximum concentrating capacity following intravenous (i.v.) bolus dDAVP injection. The dDAVP assay was based on a well-established RIA for measurements of AVP. Fourteen healthy subjects (aged 15–18 years) participated. Blood and urine samples were collected prior to and after i.v. bolus of 0.03?µg/kg dDAVP. Diuresis and Uosm was measured for nine hours following dDAVP administration. PdDAVP and Uosm were analyzed.We established a specific RIA for the measurement of pdDAVP. All subjects reached maximal pdDAVP concentration (C_max) 30 minutes following infusion, and a rise in Uosm after 60 minutes. Maximal Uosm varied between subjects, with no direct correlation to the achieved pdDAVP levels. We found no significant intra-individual variation between two dDAVP infusions and the effect was reproducible in terms of C_max and maximal Uosm. We characterized the relationship between pdDAVP and Uosm after dDAVP bolus injection in healthy adolescents using our dDAVP assay. Maximal Uosm achieved correlated with the baseline Uosm levels and seemed unrelated to achieved pdDAVP levels. The urine concentrating response was maintained at least eight hours.