TABLE 1

Results: Safety of Vaccines Used for Routine Immunization of Children

VaccineConclusions and Strength of Evidence2011 IOM FindingsNew Findings
DTaPModerate: no association with type 1 diabetesEvidence “favors rejection” of a causal relationship between vaccines containing diphtheria toxoid, tetanus toxoid, and acellular pertussis antigens and type 1 diabetes.No additional studies met inclusion criteria.
Hepatitis A vaccineModerate: purpuraNot covered.In a large postlicensure study of >1.8 million vaccine recipients, purpura was associated with vaccination against hepatitis A in children aged 7–17 y. These results were based on 1 or 2 cases per vaccine type/age group. According to the authors, most cases were mild and acute.
Hepatitis B vaccineInsufficient: food allergyAlthough no epidemiologic studies were identified by the IOM, mechanistic evidence “favored acceptance” of a causal relationship between the vaccine and anaphylaxis in yeast-sensitive individuals.Hepatitis B vaccine in the first 6 mo of life was associated with elevated total immunoglobulin E in a postlicensure study of children with a family history of food allergy but not with clinical allergy.
Moderate: no association with MSA 2002 IOM report “favors rejection” of a causal relationship with MS onset or exacerbation.
Hib vaccineModerate: no association with serious AEs in short termNot covered.No serious AEs were associated in 3 high-quality clinical trials.
IPVInsufficient: food allergyNot covered.One postlicensure study reported association between polio vaccine in newborns and sensitivity to food allergens.
Influenza vaccines (live attenuated and inactivated)Moderate: mild gastrointestinal disorders, febrile seizuresEvidence was “inadequate to accept or reject” a causal relationship with any AEs investigated.We identified 1 trial of seasonal influenza vaccine (including a strain of H1N1) and 1 cohort comparison study of 2009 monovalent H1N1 vaccine published after the IOM search dates; the studies found no evidence of an association of the vaccines with any AEs.
Low: Influenza-like symptomsBoth seasonal influenza vaccines and monovalent H1N1 vaccine (administered only in 2009 season) were associated with mild gastrointestinal disorders, such as vomiting and diarrhea, in children in the short term in 2 large postlicensure studies. One of these studies found that younger vaccinated children (aged 5–8 y) were more likely to experience these symptoms than older vaccinated children (aged 9–17 y). (Children aged <5 y were not included in that study).
Both live and inactivated seasonal influenza vaccines were associated with influenza-like symptoms in children in the short term in 1 new study.
A large US postlicensure study of children aged <5 y found TIV associated with febrile seizures. Risk was increased if PCV13 was administered concomitantly.
MMRHigh: no association with autism spectrum disordersEvidence “convincingly supports” causal relationships anaphylaxis in allergic children and febrile seizures.Five new postmarketing studies were identified. Vaccination was associated with thrombocytopenic purpura in the short term in 3; it was not studied in the other 2. In 1 study, MMR vaccination was associated with increased emergency department visits within 2 wk; this is indirect support of the IOM’s findings that MMR vaccine is associated with febrile seizures.
High: anaphylaxis in children with allergies, febrile seizuresEvidence “favors acceptance” of a causal relationship between MMR and transient arthralgiaA new case-control study found MMR vaccine was unrelated to autism.
Moderate: transient arthralgiaEvidence “favors rejection” of a causal relationship between MMR and autism.
Moderate: thrombocytopenic purpura
Meningococcal vaccines (MCV4, MPSV)Moderate: anaphylaxis in children with allergiesEvidence “convincingly supports” a causal relationship with anaphylaxis allergic children.Two new trials of quadrivalent meningococcal conjugate vaccines found no association with any AEs assessed.
PCV13Moderate: febrile seizuresNot covered.The US VSD found an association with febrile seizures. Estimated rate for 16-mo-old patients is 13.7 cases per 100 000 doses for PCV13 without concomitant TIV and 44.9 per 100 000 doses for concomitant TIV and PCV13.
Rotavirus vaccines: RotaTeq and RotarixModerate: IntussusceptionNot covered.In 31 clinical trials, there was no association between either of the current vaccines (RotaTeq and Rotarix) and any serious AEs, including intussusception, in the long or short term.
A high-quality Australian epidemiologic study found RotaTeq associated with intussusception 1–21 d after the first of 3 required doses in infants 1–3 mo of age. Two case–control studies conducted in Latin America found an association of Rotarix with intussusception in children after the first of 2 required doses. Although 1 US epidemiologic study found no association, a recent analysis of the US PRISM program found both RotaTeq and Rotarix associated with intussusception in the short term. Estimated rate was 1.1–1.5 cases per 100 000 doses of RotaTeq and 5.1 cases per 100 000 doses of Rotarix.
Varicella vaccineHigh: anaphylaxis; disseminated Oka VZV without other organ involvement; disseminated Oka VZV with subsequent infection resulting in pneumonia, meningitis, or hepatitis in individuals with demonstrated immunodeficiencies; vaccine strain viral reactivation without other organ involvement; vaccine strain viral reactivation with subsequent infection resulting in meningitis or encephalitis.Evidence “convincingly supports” causal relationships between varicella virus vaccine and the following: disseminated Oka VZV without other organ involvement; disseminated Oka VZV with subsequent infection resulting in pneumonia, meningitis, or hepatitis in individuals with demonstrated immunodeficiencies; vaccine strain viral reactivation without other organ involvement; vaccine strain viral reactivation with subsequent infection resulting in meningitis or encephalitis; and anaphylaxis.In a large postlicensure study of >1.8 million vaccine recipients, purpura was associated with vaccination against varicella in children aged 11–17. These results were based on 1 or 2 cases per vaccine type/age group. According to the authors most cases were mild and acute.
Moderate: purpura
MiscellaneousHigh: no association of childhood leukemia with MMR, DTaP, Td, Hib, hepatitis B, and polio vaccinesNot applicable.Four large epidemiologic studies conducted analyses to assess which, if any, of the following vaccines might be associated with childhood leukemia: MMR, DTaP, Td, Hib, hepatitis B, and polio vaccine. No association was found for any vaccine.
  • EPC, Evidence-based Practice Center; MS, multiple sclerosis; MCV, meningococcal conjugate vaccine; MPSV, meningococcal polysaccharide vaccine; PCV, pneumococcal conjugate vaccine; VZV, varicella-zoster virus.