Performance Improvement 1995. Adverse Events Associated With Childhood Vaccines: Evidence Bearing on Causality



An expert panel was convened to evaluate whether certain childhood vaccines cause adverse events. Vaccines against tetanus, diphtheria, measles, mumps, polio, Haemophilus influenzae type b (Hib), and hepatitis B were reviewed. By weighing the available evidence, researchers determined which adverse events can be caused by each vaccine, which cannot, and which are undetermined. The findings are being incorporated into information given to all parents and into proposals to compensate victims.


An expert assessment was sought of the scientific and medical literature on the health risks to children from the administration of vaccines or vaccine components against tetanus, diphtheria, measles, mumps, polio, Haemophilus influenzae type b, and hepatitis B.


Background Concerns about the safety and potential risks of vaccination have been raised by the media, the public, and the medical community. In response to these concerns, Congress passed the National Childhood Vaccine Injury Compensation Act of 1986 (P.L. 99-660). One component of the law requires the Department of Health and Human Services, with the help of the Institute of Medicine (IOM), to investigate the adverse effects of childhood vaccines. This mandate led to the development and publication of two evaluation reports, one of which was completed earlier and focused on adverse effects from pertussis and rubella vaccines. The second report focuses on adverse events to the following childhood vaccines: tetanus, diphtheria, measles, mumps, polio, Hib, and hepatitis B. The report was prepared by the Vaccine Safety Committee constituted by the IOM. The report did not examine risk-benefit comparisons between vaccines nor did it make recommendations about immunization schedules, vaccine purity, or vaccine production techniques.


Methods During an 18-month period, the multidisciplinary 14-member committee reviewed more than 7,000 abstracts, more than 2,000 published books and articles, and public testimony to determine whether the available scientific and medical evidence supported or rejected a causal relationship between specific vaccines and adverse health effects in children. Members of the expert panel included immunologists, pediatricians, internists, neurologists, virologists, microbiologists, epidemiologists, and public health specialists.

The reviewers used both qualitative and quantitative statistical methods in their evaluation of four types of evidence: (1) biological data; (2) individual case reports, series of case reports, and uncontrolled observational (population) studies; (3) controlled observational studies; and (4) controlled clinical trials. The adverse health effects evaluated included neurologic disorders, immunologic reactions, and death. Information from all sources of evidence was weighed and results were categorized as follows: no bearing on a causal relation, inadequate to accept or reject a causal relation, favors rejection of a causal relation, favors acceptance of a causal relation, or establishes a causal relation.


Findings The committee studied a total of 49 conditions in which childhood vaccines were suspected of leading to adverse health events; most incidents were reported in uncontrolled studies and case reports. Of the 49 cases, the evidence for 12 cases favored or established a causal relation; the evidence for 4 cases rejected a causal relation; and the evidence for the remaining 33 cases was equivocal. The cause-and-effect relationships identified by the committee are detailed in figure 2.

Figure 2

Summary of the Potential Adverse Health Effects of Certain Childhood Vaccines [a]

Evidence establishes a causal relationship between--

  • Diphtheria and tetanus toxoids and anaphylaxis (severe allergic reaction)
  • Hepatitis B vaccine and anaphylaxis
  • Measles vaccine and death from infection by the measles virus in the vaccine
  • Measles-mumps-rubella vaccine and thrombocytopenia (a blood disorder) and anaphylaxis
  • Oral polio vaccine and polio; oral polio vaccine and death from infection by the polio virus in the vaccine

Evidence favors a causal relationship between--

  • Diphtheria and tetanus toxoids and various neurologic conditions, including Guillain-Barré syndrome
  • Measles vaccine and anaphylaxis
  • Oral polio vaccine and Guillain-Barré syndrome
  • Unconjugated polysaccharide polyribosylribitol phosphate (PRP) Hib vaccine [b] and early-onset Hib disease in children 18 months or older

Evidence fails to support a causal relationship between--

  • Diphtheria and tetanus toxoids and encephalopathy (abnormal brain development), infantile spasms, and death from sudden infant death syndrome (SIDS)
  • Conjugate Hib vaccines and early-onset Hib disease

a. Based on evidence from 49 suspected cases.
b. Hib, Haemophilus influenzae type b.


The committee drew two general conclusions from these data: (1) available data were often insufficient to establish or reject causality, and (2) despite the limited data, the risk of dying or developing serious neurologic or immunologic conditions because of childhood vaccination appears to be very low.

The committee recommended active surveillance systems to follow representative samples of new vaccine recipients. It also recommended the technique of meta-analysis to combine the statistical power of future clinical and epidemiological studies of vaccines licensed or under development.


Use of Results The findings of this report have already been incorporated into proposals to revise the list of injuries presumed to have been caused by selected vaccines. This list, called the Vaccine Injury Table, identifies conditions for which automatic compensation is provided to victims and families under the National Childhood Vaccine Injury Compensation Act. The findings have already been used by the Centers for Disease Control to revise the information that practitioners are required to give parents before vaccination. Finally, changes are expected in the Food and Drug Administration's regulation of vaccine labeling.

The report also stimulated the creation of a new forum, the Vaccine Safety Forum, convened by the IOM at the request of the National Vaccine Program Office. The forum members--parents, manufacturers, government officials, and vaccine experts--are meeting periodically to discuss vaccine safety.

The report identified several research needs in assessing and quantifying the potential health risks of childhood vaccination, including (1) increased surveillance of reports of arthritis and neurologic disorders, such as demyelinating disease, following hepatitis B vaccination; (2) improved followup on reports of death and serious adverse events that may be associated with vaccination; (3) increased use of large databases to supplement other reporting systems; and (4) establishment of disease registries for rare medical conditions that may be triggered or exacerbated by vaccination.


Publication Stratton, K.R., C.J. Howe, and R.B. Johnston, Jr., eds. Adverse Effects Associated With Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: National Academy Press, 1994.


Agency sponsor: National Institutes of Health


Federal contact: Regina Rabinovich, M.D.
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Solar Building, Room 3A07
6003 Executive Boulevard
Rockville, MD 20892
(301) 496-5893 Fax: (301) 480-4528


Committee chair: Richard B. Johnson, M.D.
The March of Dimes Birth Defects Foundation, White Plains, NY

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