Letter to the Editor

Journal of Exposure Science and Environmental Epidemiology (2012) 22, 425–426; doi:10.1038/jes.2012.48

Prenatal exposure to neurotoxicants and neurodevelopment in Mexican neonates

James P K Rooney1 and José G Dórea2

  1. 1Centre for Synthesis and Chemical Biology, Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin, Ireland
  2. 2Faculty of Health Sciences, Universidade de Brasilia, Brasilia, DF, Brazil

Correspondence: James P.K. Rooney, E-mail: jrooney@rcsi.ie

Bahena-Medina et al.1 evaluated “abnormal reflexes with the Brazelton Scale (NBAS), neurological soft signs with the Graham–Rosenblith Scale, as well as mental and psychomotor development by the Bayley Scales of Infant Development” at 1 month of age in Mexican infants. This interesting work showed that neonatal neurological functions were not associated with DDE exposure. The authors acknowledge that exposure to DDE in the neonatal stage is not conclusive. We posit that many confounders during fetal and neonatal stage could interfere with results. In this regard, they (understandably) considered only constitutional risk factors associated with neurodevelopment. In Mexico, like in many other non-industrialized countries, Thimerosal-containing vaccines (TCV) are used during pregnancy and at birth.2 Therefore, ethylmercury (etHg) is a potential cumulative neurotoxicant that needs to be taken into account in such studies.

Bahena-Medina et al.1 adjusted their data for breast-feeding and found no significant effect on children's mental development or psychomotor development index. It is important to emphasize that when neurodevelopmental studies are properly adjusted for exposure to TCV-Hg in early immunization (especially hepatitis B) there are indications that subtle neurological effects can be demonstrated.3, 4 Studies on the association between postnatal low doses of mercury exposure and neurotoxicity are limited; the scientific literature is even scarcer for the specific exposure to etHg derived from TCV, which are used in many countries, including single-dose flask of hepatitis B also used in Mexico.5

There has been an increase in the number of vaccines given to infants and, with the exception of some industrialized countries, children worldwide are immunized with several TCV's. Following the National Immunization Program (NIP) of Mexico, the amount of etHg from routine immunizations against hepatitis B (one birth dose), and maternal immunizations during pregnancy could be estimated. Therefore, it seems that Mexican infants are postnatally exposed to varied etHg concentrations (depending on the vaccine) in tandem with doses varying as a function of the infant's weight at time of vaccination. Mexican women may take tetanus toxoid (TT) vaccines2 as well as other vaccines such as seasonal influenza; we could also be informed of the possibility of other vaccines being given during pregnancy or other products such as anti-RhoD immune globulins that could contain Thimerosal.

As reviewed recently, there are significant questions remaining to be answered with regard to (a) the single-dose toxicity of low-dose Thimerosal, and (b) the potential for accumulation of mercury in the brain, post-exposure to etHg — particularly in the neonatal and prenatal setting.6, 7 Therefore, we suggest that TCVs as sources of prenatal and postnatal etHg exposure represent a potentially important confounder in studies investigating the developmental neurotoxicity of other substances, such as DDE, in the prenatal and postnatal exposure time-frames.

In low-dose exposure to neurotoxicants, accounting for confounders is difficult owing to (a) the difficulty in quantifying minute exposures, (b) the unknown, but potentially exquisite sensitivity of the developing fetus to single-point exposures, which may vary with gestation, and (c) the potential for bioaccumulation/synergy of toxins. However, through vaccination records, we are provided unique opportunity among toxins to account for this confounder through statistical modeling when looking at other developmental neurotoxins. Generally, it is unlikely that controlling for a second potential neurotoxin (i.e. etHg) as a confounder, where there has been no effect found by the first neurotoxin (i.e. DDE), would unmask an effect by the first agent. However, this is dependent on the relative distributions among the cohort of the two risk factors in question, and may not hold true in all cases. In this context, the study of Bahena-Medina et al.1 could include etHg exposure through vaccination as a confounder in their models — both to help clarify their own results and as a guide to improve interpretation of such studies in the future. The essential role of vaccines in preventing serious illness is not in question;6 yet, in the particular case of vaccine preservatives, the exoneration/caution related to neurological effects can be aided by such analyses.



  1. Bahena-Medina L.A., Torres-Sánchez L., Schnaas L., Cebrián M.E., Chávez C.H., and Osorio-Valencia E., et al. Neonatal neurodevelopment and prenatal exposure to dichlorodiphenyldichloroethylene (DDE): a cohort study in Mexico. J Expo Sci Environ Epidemiol 2011: 21: 609–614. | Article | PubMed |
  2. WHO. Immunization Profile—the Republic of Mexico 2010: http://www.who.int/vaccines/gl
    ; updated 3 October 2011, accessed 6 December 2011.
  3. Jedrychowski W. Reply to the correspondence letter by M.D. Majewska: Krakow's children and cognitive function: can the study by Jedrychowski et al. show us the bigger picture? Eur J Pediatr 2012: 171(2): 407. | Article |
  4. Lee B.E., and H.a. EH Response to commentary “Co-exposure and confounders during neurodevelopment: We need them in the bigger picture of secondhand smoke exposure during pregnancy”. Environ Res 2012: 112: 235. | Article | PubMed |
  5. Guzmán-Mar J.L., Hinojosa-Reyes L., Serra A.M., Hernández-Ramírez A., and Cerdà V. Applicability of multisyringe chromatography coupled to cold-vapor atomic fluorescence spectrometry for mercury speciation analysis. Anal Chim Acta 2011: 708: 11–18. | Article | PubMed |
  6. Dorea J.G. Integrating experimental (in vitro and in vivo) neurotoxicity studies of low-dose Thimerosal relevant to vaccines. Neurochem Res 2011: 36: 927–938. | Article | PubMed |
  7. Rooney J.P.K. Mercury levels in newborns and infants after receipt of Thimerosal-containing vaccines. Pediatrics 2008: 122: 902–903. | Article | PubMed |