Pierce Kuhnell

Manganese Exposure and Neurocognitive Outcomes in Rural School-Age Children: The Communities Actively Researching Exposure Study (Ohio, USA)

Background Manganese (Mn) plays a vital role in brain growth and development, yet excessive exposure can result in neurotoxicity. Marietta, Ohio, is home to the nation’s longest-operating ferromanganese refinery, and community concern about exposure led to the development of the research study. Objectives Our overall goal was to address the community’s primary research question: “Does Mn affect cognitive development of children?” We evaluated the relationships between Mn exposure as measured by blood and hair Mn, along with other neurotoxicants including blood lead (Pb) and serum cotinine, and child cognition. Methods Children 7–9 years of age were enrolled (n = 404) in the Communities Actively Researching Exposure Study (CARES) from Marietta and Cambridge, Ohio, and their surrounding communities from October 2008 through March 2013. Blood and hair were analyzed for Mn and Pb, and serum was analyzed for cotinine. We used penalized splines to assess potential nonlinear associations between biological measures and IQ subscale scores, followed by multivariable regression models with categorical variables based on quartiles of the distribution for biological measures with nonlinear associations and continuous variables for biological measures with linear associations. Results Geometric mean blood (n = 327) and hair Mn (n = 370) concentrations were 9.67 ± 1.27 μg/L and 416.51 ± 2.44 ng/g, respectively. After adjusting for potential confounders, both low and high blood and hair Mn concentrations were associated with lower Full Scale IQ and subscale scores, with significant negative associations between the highest quartile and middle two quartiles of blood Mn (β –3.51; 95% CI: –6.64, –0.38) and hair Mn (β –3.66; 95% CI: –6.9, –0.43%) and Full Scale IQ. Conclusions Both low and high Mn concentrations in blood and hair were negatively associated with child IQ scores. Serum cotinine was negatively associated with child cognitive function. Citation Haynes EN, Sucharew H, Kuhnell P, Alden J, Barnas M, Wright RO, Parsons PJ, Aldous KM, Praamsma ML, Beidler C, Dietrich KN. 2015. Manganese exposure and neurocognitive outcomes in rural school-age children: the Communities Actively Researching Exposure Study (Ohio, USA). Environ Health Perspect 123:1066–1071; http://dx.doi.org/10.1289/ehp.1408993

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 childrens 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 childs 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.

Childhood exposure to manganese and postural instability in children living near a ferromanganese refinery in southeastern Ohio

Airborne manganese (Mn) exposure can result in neurotoxicity and postural instability in occupationally exposed workers, yet few studies have explored the association ambient exposure to Mn in children and postural stability. The goal of this study was to determine the association between Mn and lead (Pb) exposure, as measured by blood Pb, blood and hair Mn and time weighted distance (TWD) from a ferromanganese refinery, and postural stability in children. A subset of children ages 7-9 years enrolled in the Marietta Community Actively Researching Exposure Study (CARES) were invited to participate. Postural balance was conducted on 55 children residing in Marietta, Ohio and the surrounding area. Samples of blood were collected and analyzed for Mn and Pb, and samples of hair were analyzed for Mn. Neuromotor performance was assessed using postural balance testing with a computer force platform system. Pearson correlations were calculated to identify key covariates. Associations between postural balance testing conditions and Mn and Pb exposure were estimated with linear regression analyses adjusting for gender, age, parent IQ, and parent age. Mean blood Mn was 10 μg/L (SEM=0.36), mean blood Pb was 0.85 μg/dL (SEM=0.05), and mean hair Mn was 0.76 μg/g (SEM=0.16). Mean residential distance from the refinery was 11.5 km (SEM=0.46). All three measures of Mn exposure were significantly associated with poor postural balance. In addition, low-level blood Pb was also negatively associated with balance outcomes. We conclude that Mn exposure and low-level blood Pb are significantly associated with poor postural balance.

Community Engagement and Data Disclosure in Environmental Health Research.

Summary: Federal funding agencies increasingly support stakeholder participation in environmental health studies, and yet there is very little published research on engagement of community members in the development of data disclosure (DD) strategies. The Ohio Environmental Protection Agency reported airborne manganese (Mn) concentrations in East Liverpool, Ohio, 30 times higher than the reference concentration, which led to an academic–community research partnership to address community concern about Mn exposure, particularly among children. Children and their families were recruited to participate in a pilot study. Samples of blood and hair were collected from the children and analyzed for metals. DD mechanisms were developed using an iterative approach between community and academic partners. Individual DD letters were mailed to each participating family, and a community meeting was held. A post-meeting survey was administered to gauge community perception of the DD strategies. The purpose of this article is to demonstrate the effectiveness of engaging community partners in the conduct of environmental health research and in the development of DD strategies for individuals and the community at large. Scientists should include community partners in the development of DD strategies to enhance translation of the research findings and support the right of study participants to know their individual results.

Publication Track Records as a Metric of Clinical Research Training Effectiveness

Clinical research training programs exist across the country, but no quantitative studies have been performed to evaluate the effectiveness of these programs. The goal of this study was to evaluate the success of the clinical research training program at the University of Cincinnati by comparing the publication histories of pediatric fellows who graduated from the clinical and translational research Master of Science (MS) degree programs between 1995 and 2011 with fellows who did not pursue an MS degree. Among 296 pediatric fellows, 44 of 54 graduates (81%) published at least 1 first‐authored paper, as compared with 149 of 242 (62%) fellows who did not obtain an MS degree (P < 0.01). In multivariable analysis, 3–4 years after program completion, MS graduates published more papers overall (R2 = 0.10) and more first‐authored papers than did non‐MS graduates (R2 = 0.04). These findings suggest that graduate training in clinical and translational research is related to an increase in research productivity as assessed by publication rates.

NIH Grant Awards as a Metric of Clinical and Translational Research Training Effectiveness

The number of clinical research training programs has increased over the past 5–10 years, but few studies have quantitatively evaluated the effectiveness of these programs. The goal of this study was to evaluate the clinical and translational research training program at the University of Cincinnati by comparing the number of National Institutes of Health grants awarded to pediatric fellows who graduated from the MS degree program between 1995 and 2013 versus fellows who did not pursue an MS degree. Among 394 pediatric fellows, 16 of 81 (20%) MS alumni were awarded at least one NIH grant, as compared with 28 of 313 (9%) fellows who did not obtain an MS degree (p < 0.02). In multivariable analysis, MS alumni were more than three times as likely to have received at least one grant than were non‐MS fellows (OR = 3.5, 95% CI [1.7–7.2]; C‐statistic = 0.71) and MS alumni were more likely to obtain at least one K‐series (OR = 4.1, 95% CI [1.6–10.2]; C‐statistic = 0.74), M‐series (OR = 11.8, 95% CI [3.4–41.4]; C‐statistic = 0.81), or R‐series (OR = 10.1, 95% CI [2.4–42.8]; C‐statistic = 0.74) grant than were non‐MS fellows. These findings suggest that graduate training in clinical and translational research prepares graduates for the highly competitive field of clinical and translational research.

Postdischarge Nurse Home Visits and Reuse: The Hospital to Home Outcomes (H2O) Trial

Through a randomized controlled trial, we use this study to examine the effects of a single home nurse visit after standard pediatric discharge. BACKGROUND: Hospital discharge is stressful for children and families. Poor transitional care is linked to unplanned health care reuse. We evaluated the effects of a pediatric transition intervention, specifically a single nurse home visit, on postdischarge outcomes in a randomized controlled trial. METHODS: We randomly assigned 1500 children hospitalized on hospital medicine, neurology services, or neurosurgery services to receive either a single postdischarge nurse-led home visit or no visit. We excluded children discharged with skilled home nursing services. Primary outcomes included 30-day unplanned, urgent health care reuse (composite measure of unplanned readmission, emergency department, or urgent care visit). Secondary outcomes, measured at 14 days, included postdischarge parental coping, number of days until parent-reported return to normal routine, and number of “red flags” or clinical warning signs a parent or caregiver could recall. RESULTS: The 30-day reuse rate was 17.8% in the intervention group and 14.0% in the control group. In the intention-to-treat analysis, children randomly assigned to the intervention group had higher odds of 30-day health care use (odds ratio: 1.33; 95% confidence interval: 1.003–1.76). In the per protocol analysis, there were no differences in 30-day health care use (odds ratio: 1.14; confidence interval: 0.84–1.55). Postdischarge coping scores and number of days until returning to a normal routine were similar between groups. Parents in the intervention group recalled more red flags at 14 days (mean: 1.9 vs 1.6; P < .01). CONCLUSIONS: Children randomly assigned to the intervention had higher rates of 30-day postdischarge unplanned health care reuse. Parents in the intervention group recalled more clinical warning signs 2 weeks after discharge.

Development and Evaluation of a Manganese and Iron Food Frequency Questionnaire for Pediatrics

Manganese (Mn) is an essential nutrient, but overexposure can lead to neurotoxicity. Given the essentiality of Mn in the diet, particularly during children’s growth and development, it is imperative to quantify dietary Mn intake in populations that may be exposed to industrial sources of Mn. Dietary absorption of Mn is inversely associated with iron (Fe) stores, yet there is currently no food frequency questionnaire (FFQ) to assess dietary Mn and Fe intake. The study objective was to develop and evaluate the validity of a FFQ to measure dietary Mn and Fe intake in pediatrics by comparing the estimated intakes of Mn and Fe with biomarkers: Mn in blood and hair and Fe in serum. This study utilized a subset of the Communities Actively Researching Exposure Study (CARES) population residing in Guernsey County, Ohio. Dietary Mn was not correlated with either blood or hair Mn; however, dietary Mn and serum ferritin were significantly correlated, with a correlation coefficient of 0.51, p < 0.01. Moreover, dietary Fe and serum ferritin were also significantly correlated, with a correlation coefficient of 0.51, p < 0.01. This FFQ is a valid measurement tool for Fe intake as measured by serum ferritin; however, Mn intake did not correlate with either blood or hair Mn.

Impact of air manganese on child neurodevelopment in East Liverpool, Ohio

HighlightsAir manganese levels in East Liverpool, Ohio exceeded EPA reference levels for a decade.An academic‐community partnership was essential for the conduct of the study.IQ scores for children aged 7–9 were negatively associated with manganese levels in hair. Background: East Liverpool, Ohio, the site of a hazardous waste incinerator and a manganese (Mn) processor, has had air Mn concentrations exceeding United States Environmental Protection Agency reference levels for over a decade. Save Our County, Inc., a community organization, was formed to address community environmental health concerns related to local industry. Researchers from the University of Cincinnati partnered with Save Our County to determine if air Mn had an impact on the neurocognitive function of children in the community. Methods: Children 7–9 years of age from East Liverpool and its surrounding communities, were enrolled (N = 106) in the Communities Actively Researching Exposure Study from between March 2013–June 2014. Blood and hair were analyzed for Mn and lead, and serum was analyzed for cotinine. We used linear regression to assess associations between biological measures and IQ subscale scores. Results: Geometric mean blood lead (n = 67), blood Mn (n = 66), hair Mn (n = 98), and serum cotinine (n = 69) concentrations were 1.13 ± 1.96 &mgr;g/dL, 10.06 ± 1.30 &mgr;g/L, and 360.22 ± 2.17 ng/g, 0.76 ± 6.12 &mgr;g/L respectively. After adjusting for potential confounders, hair Mn was negatively associated with Full Scale IQ. Conclusions: Hair Mn was negatively associated with child IQ scores. Community partners were instrumental in the conception and implementation of this study.

Assessment of Nonalcoholic Fatty Liver Disease Progression in Children Using Magnetic Resonance Imaging

Objective To assess liver disease progression using paired magnetic resonance imaging (MRI) measurements of liver fat fraction (FF) and stiffness. Study design Retrospective cohort study including patients with nonalcoholic fatty liver disease who had undergone repeat MRI studies. Descriptive statistics were used, as well as Pearson or Spearman correlation when appropriate. Mixed model analyses were used to determine relationships between liver FF/stiffness and predictor variables. Results Sixty‐five patients (80% non‐Hispanic, mean age 14 ± 3 years) were included. Time from first to last MRI was 27 ± 14 months. Over time, body mass index z score remained stable, and there were no significant differences in mean serum aminotransferases, insulin, glucose, triglycerides, low‐density lipoprotein, and high‐density lipoprotein (HDL) levels. However, the proportion of patients with alanine aminotransferase (ALT) < 50 U/L increased. MRI FF and stiffness decreased in 29% and 20% of patients, respectively, and increased in 25% and 22% of patients, respectively. There was a weak positive correlation between FF change and ALT change (r = 0.41, P = .053) and a moderate negative correlation between change in FF and change in serum HDL levels (r = ‐0.58, P = .004). After adjusting for HDL, increase in serum insulin was the only variable predictive of increase in FF (P = .061). There was no correlation between change in liver stiffness and change in ALT (r = .02, P = .910). Conclusions MRI‐determined hepatic FF and stiffness improved in a minority of patients overtime. ALT levels were not reflective of the change in FF or stiffness. MRI‐based imaging is complementary in the assessment of NAFLD progression.