Delayed brainstem auditory evoked potential latencies in 14-year-old children exposed to methylmercury*1 
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Katsuyuki Murata MD, DMSc, Pál Weihe MD, Esben Budtz-Jørgensen PhD, Poul J. Jørgensen MSc and Philippe Grandjean MD, DMSc, 

From the Division of Environmental Health Sciences, Akita University School of Medicine, Akita, Japan; the Department of Occupational Medicine and Public Health, Faroese Hospital System, Tórshavn, Faroe Islands; the Department of Biostatistics, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark; the Institutes of Clinical Research and Public Health, University of Southern Denmark, Odense, Denmark; and the Department of Environmental Health, Harvard University School of Public Health, Boston, Massachusetts, USA


Received 5 June 2003;  revised 11 September 2003;  accepted 28 October 2003; See related article, p 169.  Available online 30 January 2004. 

Referred to by:  Erratum
The Journal of Pediatrics, Volume 149, Issue 4, October 2006, Pages 583-584, 
Katsuyuki Murata, Pál Weihe, Esben Budtz-Jørgensen, Poul J. Jørgensen, Philippe Grandjean
 PDF (58 K)  
 

Abstract
Objective
To determine possible exposure-associated delays in auditory brainstem evoked potential latencies as an objective measure of neurobehavioral toxicity in 14-year-old children with developmental exposure to methylmercury (MeHg) from seafood.

Study design
Prospective study of a birth cohort in the Faroe Islands, where 878 of eligible children (87%) were examined at age 14 years. Latencies of brainstem evoked potential peaks I, III, and V at 20 and 40 Hz constituted the outcome variables. Mercury concentrations were determined in cord blood and maternal hair, and in the child's hair at ages 7 and 14.

Results
Latencies of peaks III and V increased by about 0.012 ms when the cord blood mercury concentration doubled. As seen at age 7 years, this effect appeared mainly within the I–III interpeak interval. Despite lower postnatal exposures, the child's hair mercury level at age 14 years was associated with prolonged III–V interpeak latencies. All benchmark dose results were similar to those obtained for dose-response relationships at age 7 years.

Conclusions
The persistence of prolonged I–III interpeak intervals indicates that some neurotoxic effects from intrauterine MeHg exposure are irreversible. A change in vulnerability to MeHg toxicity is suggested by the apparent sensitivity of the peak III–V component to recent MeHg exposure.

Author Keywords: BAEP, Brainstem auditory evoked potential; BMD, Benchmark dose; BMDL, Benchmark dose level; BMR, Benchmark response; MeHg, Methylmercury; NRC, National Research Council; PCB, Polychlorinated biphenyl

Article Outline
1. Methods
1.1. Study population and follow-up
1.2. Neurologic examination
1.3. Data analysis
2. Results
Prolonged peak III and peak V latencies at higher prenatal methylmercury exposures were caused by increased I–III intervals that were prolonged already 7 years before
Current methylmercury exposures were associated with prolonged III–V interpeak latencies
Benchmark dose results were similar to those seen at age 7 years
3. Discussion
Acknowledgements
References


 

Fig 1. Prenatal dose-effect relationship between maternal hair mercury at birth and the peak III latency of the brainstem auditory evoked potentials in 859 Faroese children at 14 years, adjusted for sex and age. The association is estimated in a generalized additive model analysis in which a smooth nonparametric curve (equivalent degrees of freedom, 3) is fitted to the data while adjusting for confounders. The broken lines indicate the point-wise 95% confidence interval for the dose-response relationship. Each vertical line above the horizontal axis represents one observation at the exposure level indicated. To convert to nmol/g, multiply mercury concentration in µg/g by 5.0. 


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Fig 2. Postnatal dose-effect relationship between the child's current hair mercury and the interpeak III-V latency of the brainstem auditory evoked potentials in 859 Faroese children at 14 years, adjusted for sex and age. The association is estimated in a generalized additive model analysis as in Figure 1, but the horizontal scales differ. The broken lines indicate the point-wise 95% confidence interval for the dose-response relationship. Each vertical line above the horizontal axis represents one observation at the exposure level indicated. To convert to nmol/g, multiply mercury concentration in µg/g by 5.0. 

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Table I. Results of developmental methylmercury exposure biomarkers for 859 birth cohort members without neurological disease examined at age 14 years*



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Table II. Mean results and regression coefficients for logarithmic transformations of mercury exposure biomarkers as predictors of latencies of brainstem auditory evoked potentials (ms) in 859 Faroese children at 14 years



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Table III. Cord blood mercury concentration (geometric mean) and peak III latency of the brainstem auditory evoked potentials measured at age 14 years (arithmetic means) in 857 Faroese cohort children in relation to the hearing threshold at 4 kHz on the right ear


P value for association (Spearman correlation coefficient) with hearing threshold:


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Corresponding author. Reprint requests: Philippe Grandjean, MD, Department of Environmental Health, Harvard School of Public Health, Landmark Center East, Room 3-110, PO Box 15967, Boston, MA 02215.

*1 Supported by the National Institute of Environmental Health Sciences (ES09797), the Danish Medical Research Council, and the Nissan Science Foundation.

The contents of this article are solely the responsibility of the authors and do not represent the official views of the National Institute of Environmental Health Sciences, the National Institutes of Health, or any other funding agency.