No evidence for measles, mumps, and rubella vaccine-associated inflammatory bowel disease or autism in a 14-year prospective study
Heikki Peltola, Annamari Patja, Pauli Leinikki, Martti Valle, Irja Davidkin, Mikho Paunio
Concern  of potential loss of confidence in measles, mumps, and rubella (MMR) vaccine has been raised by a recent paper  that suggested a causal association between this vaccine (or another environmental trigger) and a new syndrome of chronic inflammatory bowel disease and autism. Characteristically, all children described developed intestinal symptoms within days or soon after vaccination.
The National Board of Health and National Public Health Institute launched a long-term vaccination project in 1982, which aimed at the elimination of MMR diseases from Finland . All children are vaccinated twice, at age 14-18 months and 6 years; further vaccinations are carried out among recruits of the defense forces and in some schools of nursing. Only one type of live-virus vaccine (MMR or Virivac [Merck, West Point, PA, USA]) consisting of the more attenuated Enders Edmonston, Jeryl Lynn, and Wistar RA 27/3 strains for measles, mumps, and rubella, respectively, has been used since beginning of the project. Adverse events in temporal relation to MMR vaccine were reported prospectively to the Institute. A form was filled and posted to us, followed by another form with further information 2-3 weeks later. We traced those vaccinees who developed gastrointestinal symptoms or signs lasting 24 h or more at any time after MMR vaccination (apart from within the first hour). We checked hospital or health center records or interviewed the local public-health nurses.
By the end of 1996, about three million vaccine doses had been delivered by the Institute. 31 children developed gastrointestinal symptoms after vaccination (table); all except one after the first vaccine dose. Haemophilus influenzae type b conjugate vaccine was given concomitantly in four cases. 20 patients were admitted to hospital. Antibiotics were given in 11 cases, symptomatic relief in nine, and intravenous y-globulin was given to one child with Guillain Barre syndrome.
The time between the reported event and our check on their health varied from 1 year and 4 months to 15 years and 1 month. The mean interval was 9 years 3 months, the median being 10 years and 8 months.
Diarrhea, frequently with vomiting, was the most common symptom (55%, n=17), followed by gingivostomatitis (23%, n=7), vomiting only (16%, n=5), and abdominal pains (n=2). The time from MMR vaccine to onset of symptoms varied from 20 h to 15 days. Duration of symptoms was not always stated or recalled by nurses, but subsidence within a week was usual, except in a 1-year-old boy (patient 23) whose diarrhea lasted for 6 weeks. The child recovered and was healthy when checked almost 6 years later. Most symptoms and signs of the central nervous system were those one would expect in conjunction with acute gastrointestinal disease: five (16%) children had febrile seizures and two had headache. One child developed ataxia which subsided quickly. No child developed autistic spectrum disorder. Hyperornithaemic gyrate atrophy, an autosomal recessive disease, was diagnosed in one girl (patient 14) 8 years after vaccination. A boy developed H influencee and a girl meningococcal meningitis 1 day and 7 days after vaccination, respectively.
It is noteworthy that, besides gastrointestinal complaints, many children had similar symptoms and signs (fever, rash, seizure) as those in London . Presumably, some patients with symptoms or signs not far from those listed in the table were not reported to us. We do not deem this shortcoming to be of a major concern because illness in all our 31 patients was mild, and probably sometimes caused by concomitant infection .
Over a decade's effort to detect all severe adverse events associated with MMR vaccine could find no data supporting the hypothesis that it would cause pervasive developmental disorder or inflammatory bowel disease.
We thank Tapio Kurd, Olli P Heinonen, Kan Cantell, and Viena Karanko, and Irja Davidkin for their contribution. The study was partly funded by a grant by Merck Research Laboratories, West Point, PA, USA.
Helsinki University Central Hospital, Hospital for Children and Adolescents, FIN40290 Helsinki, Finland (H Peltola); National Public Health Institute, Helsinki; and Department of Public Health, University of Helsinki.
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