In an interesting study, Llop et al. (1) addressed the vulnerability of the central nervous system to mercury during early development. Their findings suggested a negative association between total cord blood mercury levels and psychomotor development at approximately 14 months of age only in girls. Although I welcome these interesting findings, I would like to raise the issue of a source of organic mercury exposure during the perinatal period, namely ethylmercury in vaccines that contain Thimerosal (Noah Technologies Corporation, San Antonio, Texas). During recruitment of mothers (in November 2003) and infants born in 2004 in the study by Llop et al., Thimerosal-containing vaccines (TCVs) were still used in some European Union countries and probably in Spain (2). Therefore, it is reasonable to assume that additional mercury exposure could have occurred, at least for some of the sampled subjects. According to Spain's vaccination schedule, some children could be exposed to TCV ethylmercury (mainly in diphtheria-tetanus-pertussis and hepatitis B vaccines); furthermore, during pregnancy, some mothers were also likely to be exposed to TCVs. Neither infant vaccines nor maternal exposure to TCVs, anti- Rho(D) immune globulin (to Rh-negative participants), or dental amalgams during pregnancy were mentioned in the otherwise assiduous study of Llop et al.

Assuming that there was a gradual discontinuation of TCVs in Spain, readers familiar with the changes occurring in vaccine type used in European Union countries during the early 2000s could benefit from a post hoc discussion of this confounding mercury source. The pertinence of this discussion is further justified by the recent reports that a subtle but significant association with psychomotor development can be shown in young children as a result of exposure to TCVs in Poland (3), Korea (4), and Brazil (5). Indeed, ecologic and epidemiologic studies in the United States, United Kingdom, and Italy (6) that addressed children's neurodevelopment associated with ethylmercury exposure in TCVs indicated collectively that “a) there is ambiguity in some studies reporting neurodevelopment outcomes that seem to depend on confounding variables; b) the risk of neurotoxicity due to low doses of Thimerosal is plausible at least for susceptible infants” (6, p. 1580). Furthermore, recent findings have shown that neurologic responses in animals (mice, rats, and rhesus monkeys) exposed to ethylmercury from the hepatitis B vaccine in the early postnatal life presented statistically significant differences when compared with controls (7); there is also strong in vitro evidence of Thimerosal neurotoxicity in small doses relevant to TCVs (7).

Ethylmercury has a shorter half-life than does methylmercury; therefore, it is unlikely that it could contribute to total mercury levels in cord blood measured by Llop et al. (1). Nevertheless, ethylmercury exposure can be ascertained from vaccination cards (3–5). Information on the association of neurodevelopment and coexposure to multiple forms of mercury is limited, and despite the current widespread use of TCVs (in most countries), it is even scarcer for specific exposure to small amounts of ethylmercury (8). Therefore, only studies like that of Llop et al. (1) can offer the opportunity to explore possible cumulative insults resulting from maternal environmental (methylmercury) exposure and additional infant ethylmercury exposure due to differential (TCV) immunization. Although I do not question the statistical model, results, or interpretation of the study by Llop et al. (1), I hope to provoke a post hoc discussion highlighting possible ethylmercury exposure during pregnancy and postnatal periods via TCVs. Without proper testing, we will never discover whether additional TCV-related mercury exposure in early life can affect neurodevelopment tests.

Acknowledgments

Conflict of interest: none declared.

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