The results show a strong relationship between child age at the administration of the first MMR and autism incidence exclusively for African American boys which could indicate a role of the vaccine in the etiology of autism within this population group. This particular analysis was not completed in the original Destefano et al. [14] (CDC) study. Although the previous study considered MMR timing and African Americans in general, no statistically significant effect was observed. This is in contrast to our result for African Americans in general, because the CDC study limited the total African American cohort to include only those individuals who possessed a valid State of Georgia birth certificate which decreased the statistical power of their analysis. Although a statistically significant relationship between first MMR age and autism incidence was seen in the general (all races) population within the earlier Destefano et al. [14] study, the coauthors interpreted this result as an artifact of “healthcare seeking behavior” citing that autistic children would receive their vaccines earlier in order to enroll in State of Georgia early intervention programs. However, it is highly unlikely that this type of behavior would be seen exclusively in African American males and thus, alternative hypotheses must be explored, including the possibility that the MMR vaccine may be causally linked to autism in African American males.

It should be noted that a recent publication has shown that the prevalence of autism in African Americans is nearly 25% higher than that of whites [15]. This value was obtained when CDC data were appropriately analyzed based on socioeconomic status. This could be due to issues regarding vitamin D status with African Americans as it has been estimated that vitamin D sufficiency among whites is between 30-60% but is only 5-10% among African Americans [16]. Patrick et al. [17] have very recently proposed a mechanism for the link between vitamin D status and autism via selective production of serotonin in the brain. Disruption of the serotonergic system is a very consistent observation with autism [18] as serotonin promotes prosocial behavior and proper assessment of emotional social cues [19].

Vitamin D has a multitude of other physiological functions in vivo. Vitamin D receptor has been found in many different tissues including the small intestine, colon, osteoblasts, activated T and B lymphocytes, islet cells and most organs in the body [20]. Vitamin D has also been implicated in many important physiological processing including modulation of activated T and B lymphocyte function [21, 22] and prevention of inflammatory bowel disease [23]. Lower vitamin D status African American females are more susceptible to lupus [24]. Also, Epstein-Barr Virus antibody titers are significantly higher in African American youth as compared to compared to white youth [25] which may be a consequence of vitamin D insufficiency. Also, childhood adversity, which could be more prevalent in African American boys, can have lasting immune consequences [26].

Gallagher et al. [27] have reported previously regarding the Hepatitis B vaccine and autism in neonates, specifically within the 1997 to 2002 time period when this vaccine series still contained thimerosal. Regarding non-whites they specifically stated in the abstract, “Non-white boys bore greater risk” of receiving an autism diagnosis if they received the Hep B as neonates. The data reported in this paper show a statistically significant risk ratio of 5.53 (p = 0.019) for black boys as opposed to white boys who had a risk of 1.87 (p = 0.171) which was not statistically significant, when looking at autism in those infants that received their first Hep B vaccine during the first month of life.

A strength of the current study is that the MADDSP data were collected independently of the design used in the analysis. These data were collected as part of the diagnoses individuals received as part of their participation in special education program and as such, the healthcare providers in no way were thinking about the potential association between vaccine exposures and potential health outcomes. Also the current study controlled for a possible association between low birth weight individuals and autism as in the final analysis on the African American cohort, all children of birthweight less than 2500 grams were eliminated from the cohort. Although low birthweight (LBW) has been shown to be associated with an increased risk of autism [28], insufficient information existed within the study population to assess the effect of LBW on autism incidence or any interaction between LBW and MMR timing.

The weaknesses of the current study include the age groups selected for autism cases and controls within the original data set. The average age to receive an autism diagnosis has been reported (using the CDC’s Vaccine Safety Datalink) as between 3.7 [29] and 4.2 years of age [30]. However, the CDC’s dataset included controls as young as 3 years of age who could have been “too young” to receive an autism diagnosis. Accordingly, there is a greater than 50% probability that some of the controls could have later received an autism diagnoses, thus skewing the analysis to the null (“no effect”) hypothesis. However, when the analysis was recompleted using controls that were six years of age or older, very similar results were obtained (data not shown). Also, information on the timing of other infant vaccines was not released by the CDC and thus it was impossible to control this factor in the current analysis. In addition, socioeconomic factors were not assessed in the current analysis. Thus, any differences in “healthcare seeking behavior” among individuals vaccinated ontime versus late could not be assessed.