Correspondence
Early Thimerosal Exposure and Neuropsychological Outcomes
N Engl J Med 2008; 358:93-94January 3, 2008
- Article
To the Editor:
Thompson et al. (Sept. 27 issue)1 report the results of a study investigating the neuropsychological outcomes of early exposure to thimerosal. As a dissenting member of the panel of external consultants for this study, I object to the authors' conclusion that there is no causal association between thimerosal and children's brain function. The sample comprised children who were least likely to exhibit neuropsychological impairments. Specifically, children with congenital problems, those from multiple births, those of low birth weight, and those not living with their biological mother were excluded. The sample was skewed toward higher socioeconomic status and maternal education — factors that are associated with lower rates of neurobehavioral problems and higher intervention rates and that were not measured. The sampling frame included only children enrolled from birth in the health maintenance organization (HMO) and still enrolled after 7 to 10 years, excluding children in higher-mobility families, who tend to have lower academic and behavioral function.2 Children with neurobehavioral problems may have been less likely to remain with the HMO. Only 30% of families selected for recruitment participated, a low rate for scientific research. Among the families selected for recruitment, 26% refused to participate. Another 28% “could not be located,” which included families that did not respond to multiple recruitment attempts (internal documentation from the study contractor, Abt Associates) — another form of refusal.
2 ReferencesSallie Bernard, B.A.
SafeMinds, Aspen, CO 81611
sbernard@safeminds.org 1
Thompson WW ,Price C ,Goodson B , et al. Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years. N Engl J Med 2007;357:1281-1292
Full Text | Web of Science | Medline2
Rumberger RW. Student mobility and academic achievement. In: Child & adolescent development. MentalHelp.net. January 23, 2003. (Accessed December 12, 2007, at http://mentalhelp.net/poc/view_doc.php?type=doc&id=2084&cn=28.)
To the Editor:
Recently, I summarized several nutritional factors that are likely to play a large role in modulating the toxicity of the various forms of mercury.1 These factors include plasma thiol levels, zinc and selenium status, and dietary fiber intake, and they have been shown in various studies to be important as regulating factors in both the biological transport and the distribution of the different forms of mercury and therefore as mediators of mercury toxicity. In addition, several genes have been identified that are also thought to affect the toxicity of mercury. These genes are currently known to include the CPOX4 polymorphism2,3 and the BDNF gene.4 The CPOX4 polymorphism is known to lead to an atypical toxicologic response to mercury from dental amalgam in up to 15% of the population.2,3 Each of these nutritional and genetic factors represents a confounding variable of unpredictable magnitude that may have affected the results of the study by Thompson et al.
4 ReferencesJames P.K. Rooney, B.Sc.
Royal College of Surgeons in Ireland, Dublin 2, Ireland
jrooney@rcsi.ie 1
Rooney JPK . The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury. Toxicology 2007;234:145-156
CrossRef | Web of Science | Medline2
Woods JS ,Echeverria D ,Heyer NJ ,Simmonds PL ,Wilkerson J ,Farin FM . The association between genetic polymorphisms of coproporphyrinogen oxidase and an atypical porphyrinogenic response to mercury exposure in humans. Toxicol Appl Pharmacol 2005;206:113-120
CrossRef | Web of Science | Medline3
Echeverria D ,Woods JS ,Heyer NJ , et al. The association between a genetic polymorphism of coproporphyrinogen oxidase, dental mercury exposure and neurobehavioral response in humans. Neurotoxicol Teratol 2006;28:39-48
CrossRef | Web of Science | Medline4
Echeverria D ,Woods JS ,Heyer NJ , et al. Chronic low-level mercury exposure, BDNF polymorphism, and associations with cognitive and motor function. Neurotoxicol Teratol 2005;27:781-796
CrossRef | Web of Science | Medline
Author/Editor Response
Bernard raises several points that we wish to address. First, children with low birth weight or serious congenital conditions or conditions developing in infancy that are known to be associated with an increased probability of neurodevelopmental problems were excluded from the study. It would have been difficult to distinguish the possible added influence of thimerosal exposure on neuropsychological deficits among such children. To do so, a larger study with a different design would be required.
Second, our sample was probably skewed toward higher socioeconomic status because participating families were members of HMOs in which coverage was provided by employers. In the study population, thimerosal exposure was associated with both maternal education and maternal IQ. We therefore controlled for socioeconomic factors, maternal education, and maternal IQ in the statistical analyses.
Third, our study was less likely to include highly mobile families because the participants had to have been enrolled in the same HMO during the first year of life and during the time of testing 7 to 10 years later. These criteria ensured that we had all immunization records during the first year of life, as well as access to the participants' medical records during the time of testing. This enhanced the internal validity of our study but makes the results less generalizable to highly mobile families.
Finally, the 30% participation rate may have resulted in some unmeasured biases. Participation in the study required a substantial time commitment from mothers and their children. Although the 30% participation rate was relatively low, it was higher than we estimated when we planned the study. More discussion regarding participation and other issues can be found in the study technical reports, available on the Web site of the Centers for Disease Control and Prevention.1,2
Although nutrition and genetics play an important role in neurodevelopmental outcomes, we believe that the factors pointed out by Mr. Rooney were unlikely to confound the results of our study because they are unlikely to be correlated with thimerosal exposure.
2 ReferencesWilliam W. Thompson, Ph.D.
Centers for Disease Control and Prevention, Atlanta, GA 30333
wct2@cdc.gov Cris Price, Sc.M.
Abt Associates, Bethesda, MD 20814Frank DeStefano, M.D., M.P.H.
RTI International, Atlanta, GA 303411
Price C, Goodson B, Stewart G. Infant environmental exposure to thimerosal and neuropsychological outcomes at ages 7 to 10 years. Technical report. Vol. I. Bethesda, MD: Abt, 2007.
2
Idem. Infant environmental exposure to thimerosal and neuropsychological outcomes at ages 7 to 10 years. Technical report. Vol. II. Bethesda, MD: Abt, 2007.
- Citing Articles (3)
Citing Articles
1
Anna Kata. (2011) Anti-vaccine activists, Web 2.0, and the postmodern paradigm – An overview of tactics and tropes used online by the anti-vaccination movement. Vaccine
CrossRef2
J. P. Barile, G. P. Kuperminc, E. S. Weintraub, J. W. Mink, W. W. Thompson. (2011) Thimerosal Exposure in Early Life and Neuropsychological Outcomes 7-10 Years Later. Journal of Pediatric Psychology
CrossRef3
Wesley Sattler, Kevin Yurkerwich, Gerard Parkin. (2009) Molecular structures of protonated and mercurated derivatives of thimerosal. Dalton Transactions:22, 4327
CrossRef
