The combined measles, mumps, and rubella vaccines and the total number of vaccines are not associated with development of autism spectrum disorder: The first case-control study in Asia.

A paper from researchers in Japan studies the questions of whether vaccines cause autism. In this study, The combined measles, mumps, and rubella vaccines and the total number of vaccines are not associated with development of autism spectrum disorder: The first case-control study in Asia, the authors use a case-control method. The study is moderate in size, 189 autistics and 224 controls.

OBJECTIVE: The aim of this study was to investigate the relationship between autism spectrum disorder (ASD) and general vaccinations, including measles-mumps-rubella (MMR) vaccine, in Japanese subjects, a population with high genetic homogeneity.

PATIENTS AND METHODS: A case-control study was performed. Cases (n=189) were diagnosed with ASD, while controls (n=224) were volunteers from general schools, matched by sex and birth year to cases. Vaccination history and prenatal, perinatal, and neonatal factors from the Maternal and Child Health handbook, which was part of each subject’s file, were examined. To determine the relationship between potential risk factors and ASD, crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated, and the differences in mean values of the quantitative variables between cases and controls were analyzed using an unpaired t-test. Moreover, MMR vaccination and the effect of the number of vaccine injections were investigated using a conditional multiple regression model.

RESULTS: For MMR vaccination, the OR was 1.04 (95% CI, 0.65-1.68), and no significant differences were found for the other vaccines. For all of the prenatal, perinatal and neonatal factors, there were no significant differences between cases and controls. Furthermore, regarding the presence of ASD, MMR vaccination and the number of vaccine injections had ORs of 1.10 (95% CI, 0.64-1.90) and 1.10 (95% CI, 0.95-1.26), respectively, in the conditional multiple regression model; no significant differences were found.

CONCLUSIONS: In this study, there were not any convincing evidences that MMR vaccination and increasing the number of vaccine injections were associated with an increased risk of ASD in a genetically homogeneous population. Therefore, these findings indicate that there is no basis for avoiding vaccination out of concern for ASD.

The authors confirm multiple previous studies that the MMR vaccine does not increase the reisk of autism. They also present results that the number of vaccine injections also does not increase the risk of autism.

The authors also find that the number of injections is does not increase the risk of autism.

The MMR vaccine was used in Japan from 1984 to 1993, and the study includes children born from April 1984 to April 1992. Controls were selected according to these criteria:

One to two controls were selected for each case, matched by sex and year of birth and recruited as volunteers from general schools in the Kanto area, the same area where YPDC patients reside. Consent for participation in the present study was obtained from the parents (or legal guardians) of the students. Students who had previously been recognized as having developmental problems and were already receiving care were excluded, as were those whose records in the MCH handbook were missing or illegible and those with a history of vaccination in another country.

The team had a pool of 354 autistics to work from in this geographic region and time period. They were unable to obtain controls for all of these 354, so 189 autistics were randomly selected as cases.

Among the patients who initially consulted the clinic between April 1997 and March 2011, 1875 cases of ASD were identified. Of these, 89 cases were excluded because the MCH handbook was missing or the vaccination record in the handbook could not be read, and 3 were excluded because they had received MMR vaccination overseas. Of the remaining 1783 cases, 1429 were born before March 1984 or after May 1992, leaving 354 cases (males: n = 286, 80.8%) born between April 1984 and April 1992, the possible time period for MMR vaccination. The ASD group consisted of 280 subjects with Autistic disorder (79.1%), 27 subjects with Asperger disorder (7.6%), and 47 subjects with Pervasive developmental disorder not otherwise specified (13.3%).

MMR was not universally given in Japan during this time, and here are the vaccination rates for the cases and controls:

The vaccination rates in cases and controls were as follows: MMR, 24.9% of cases and 24.1% of controls; Measles, 66.7% and 62.9%; Mumps, 58.2% and 49.1%; Rubella, 57.1% and 53.6%; DPT, 97.9% and 97.8%; Polio, 97.4% and 98.7%; B-encephalitis, 88.4% and 92.0%, and BCG 96.3% and 97.3% (Table 1). The mean times of each vaccine injection in cases and controls were as follows: DPT, 3.8 times of cases and 3.7 times of controls; Polio, 1.9 times and 2.0 times; B-encephalitis, 1.7 times and 1.8 times (Table 2).

The authors note that this is the fourth case-control study on autism and the MMR, but that those studies relied upon more genetically heterogeneous populations:

The three previous case–control studies focused on the relationship between ASD and MMR. Specifically, the investigation of DeStefano et al. was based on the Metropolitan Atlanta Developmental Disabilities Surveillance Program [31]; Smeeth et al. used data from the UK General Practice Research Database [32]; and DeWilde et al. examined the association using the UK Doctors’ Independent Network Database [33].

As a side result, the authors tested whether maternal hypertension was associated with autism. They found an odds ratio of 2.4, but that this result was not statistically significant. This is in contrast to a recent study from the U.C. Davis MIND Institute.

Here is table 1 from the study, giving the odds ratios for MMR and other vaccines (click to enlarge):

Criticisms will include: the moderate size of the group, the selection criteria, the fact that the controls were volunteers and might therefore have some selection bias, the fact that not enough controls were recruited to include all the autistics, and the fact that most children who did not get the MMR received the measles, mumps and/or rubella vaccines as individual vaccines, the fact that vaccine uptake is high in Japan, the lack of a “vaccinated vs. unvaccinated” structure to the study and more.

Taken alone, yes, this would not be convincing evidence that the MMR vaccine doesn’t increase the risk of autism. This doesn’t mean this isn’t a good study. Further, it is well worth noting that this study does *not*stand alone. Multiple studies have shown that the MMR does not increase the risk of autism.

Also worth noting is that by looking at the total number of injections, this study in essence considers the question of whether “too many too soon” is a cause of autism. Based on these results, within the limitations of the study, the answer is no.