A review of: Montiel-Nava, C., Pena, J.A. (2008). Epidemiological findings of pervasive developmental disorders in a Venezuelan study. Autism, 12(2), 191-202. DOI: 10.1177/1362361307086663

I decided to write a brief review of this article for two reasons. First, I often hear questions about how the rate of autism in the US, Canada, and the UK compare to that found in other countries. The answer to this question is relevant, although not as illuminating as most would like, to the major scientific debates regarding the perceived increase in rate in autism during the last two decades and the role of specific environmental factors in the development of autism. The second reason is more personal. Once upon a time, when Michael Jackson was on top of the charts, I called Venezuela my home.

The authors examined the rates of autism in a large metropolitan area of Venezuela, a country of 26,000,000 people with a large youth population (33% under the age of 14). In the first step of the study, the authors reviewed local medical records to identify children with a diagnosis of ASDs. The authors found 610 current cases in children between 3-9 years of age. Then, the authors independently confirmed the diagnosis in about 70% of the sample (N=430). The remaining children did not meet standard DSM-IV criteria or there was insufficient information to achieve an adequate diagnosis. This resulted in a prevalence rate of 1.7 per 1,000. Although this is much lower than reports in the US and other industrialized countries, the authors stated that unlike some previous reports, their methods provided rates for documented (identified) cases and did not include estimations of children that may be affected but have not yet been identified. In addition, the authors used only administrative sources for case identification (medical records) instead of large scale direct community assessments. Reliance on only administrative sources has been shown to provide lower prevalence rates. In summary, the rates of autism in Venezuela appear to be much lower than in other industrialized countries. However, the specific methods used in this study may have affected the results; in addition to the more common explanations, such as more limited access to specialized services, limited awareness about autism in the population, and higher stigma associated with these disorders, all of which limit service-utilization in developing countries.

A final note: I was informed by two Venezuelan MDs that thimerosal was still routinely used in vaccines in Venezuela. However, I sent a request for clarification to the pediatricians’ organization in Venezuela and a governmental health official, since I was not able to confirm this information from any reliable online source.

Title: Mercury Levels in Newborns and Infants After Receipt of Thimerosal-Containing Vaccines
Authors: Michael E. Pichichero, MDa, Angela Gentile, MDb, Norberto Giglio, MDb, Veronica Umido, MDb, Thomas Clarkson, PhDc, Elsa Cernichiari, MSc, Grazyna Zareba, PhDc, Carlos Gotelli, PhDd, Mariano Gotelli, PhDd, Lihan Yan, MSe and John Treanor, MDa
Source: PEDIATRICS Vol. 121 No. 2 February 2008, pp. e208-e214

The famous Thimerosal study from the American Academy of Pediatrics journal finally was released this morning. This short review could not possibly do justice to the major controversy about mercury and autism, so I will limit the commentary to the results of THIS STUDY ONLY. Given that Thimerosal is commonly used in vaccines in other countries outside of the US and Europe, the researchers teamed with a research group in Argentina to examine how infants and toddlers process Thimerosal when injected as part of their standard vaccination procedures. The researchers examined newborns, 2 month old babies, and 6 month old babies. The infants received a birth dosage of BCG and HBV vaccines that contained 32.5 ug of mercury (ethyl mercury). The 2-months-olds received the first dosage of diphtheria-tetanus-whole-cell pertusis and Hib, the first dosage of polio, and the second dosage of HBV, providing a total of about 40-50 ug of mercury. Finally the 6-month-olds received the additional dosage of diphtheria-tetanus-whole-cell pertusis, Hib, and HBV for a total mercury intake also between 40-50 ug. Then the researchers examined mercury levels in the blood, stool, and urine 1, 3, 5, 11, 21, and 30 days after the vaccinations. The 1/2 life of mercury was found to be 3.7 days in new born, 2 days for 2-month olds, and 2.2 days for 6-months olds. Blood mercury levels returned to baseline by day 11 after the vaccination. The 1/2 life refers to the time it takes for the drug to reach 1/2 of its original value (max in the first cycle). Why is this significant? Because part of the argument against the use of Thimerosal in vaccines was based on the effect of Methylmercury in adults. Methylmercury has a 1/2 life of about 50 Days with studies reporting as long as 180 days! This long 1/2 life of Methylmercury means that the person is exposed to levels of mercury for extended periods of times (weeks), which has many potential side effects. The argument made by the authors of this study is that the 1/2 life of Ethyl Mercury as found in children is only about 3 days, significantly reducing the exposure to mercury in these babies. Now, the authors correctly state that this study does not address the “toxicity” of thimerosal, so it could be argued that exposure to ethyl mercury even for a short period of time (3-4 days)could be enough to cause maturational changes in the brain leading to permanent impairments.

Title: Continuing Increases in Autism Reported
to California’s Developmental Services System
Authors: Robert Schechter, MD, MSc; Judith K. Grether, PhD
Source: Arch Gen Psychiatry. 2008;65(1):19-24

While we wait for the release of the new Academy of Pediatrics study on Thimerosal (see last blog entry), I thought this recent article from the Archives of General Psychiatry was worth reviewing, especially given the current controversy regarding ABC “Eli Stone” episode. This study was simple and elegant. It follows a straightforward logic. If the use of Thimerosal in vaccines has a causal role in the development of autism, the elimination of Thimerosal in vaccines should result in a drop in the rates of autism, or at the very least, a pause in the accelerated increase of these rates. To test this hypothesis the authors reviewed the rates of autism in the State of California from 1995 to 2007. The found a consistent increase in rates during these 11 years without any indication of a slowdown or a drop in autism rates. One particular finding is worth mentioning. The rates of autism in 3 to 5 year old kids increased from 3 to 4.1 per 1000 live births from 2004 to 2007, which represented a higher increase than those observed for all other developmental disabilities. This is of major importance because during this same period all but trace amounts of Thimerosal had been eliminated from vaccines in the State of California. If the link between Thimerosal and autism were “causal” and strong, the rates of autism during the 2004-2007 year should have dropped. Instead these rates increased. Now, although strong, this is far from conclusive evidence, since people could argue that rates continued to increase because of vaccinated babies moving to California or that such trace amounts of Thimerosal were enough to continue the increase in autism. But this last hypothesis will likely be answered by the Pediatrics article due to come out next week.

UPDATE: I found an interesting post at Autism in New Brunswick about a University of Kentucky professor’s (Dr. Boyd Haley) skepticism of this research based on the idea that mercury exposure continued after thimerosal was supposedly removed from vaccines in California (see the press story here). The difficulty with Dr. Haley’s argument is that I can’t find any reliable data showing that the levels of mercury in vaccines continued to be higher than trace amounts after Thimerosal was taken out of vaccines. At least I can’t find any published studies in scientific journals of such effect. It is difficult to believe that after Thimerosal was removed there was not a reduction in mercury exposure. Arguing that mercury exposure remained stable implies that either Thimerosal was not actually removed, that the new non-Thimerosal vaccines were so delayed to reach Drs offices as to not affect the overall mercury exposure, or that somehow these children continued to be exposed to mercury through a difference source. Otherwise, the most rational conclusion is to assume that mercury exposure was significantly reduced after Thimerosal was pulled from the market and therefore a parallel reduction in new cases with autism is expected. Sadly this didn’t happen.