Cochrane · systematic review · CD004407

Vaccines for measles, mumps, rubella, and varicella in children

Di Pietrantonj, C, Rivetti, A, Marchione, P, et al. · Cochrane Database of Systematic Reviews · 2021 · Cochrane Library

Acute Respiratory Infections2 versionsAMSTAR 2: not assessed
SoF tableOnly the outcomes this review put in its Summary of Findings table are listed (the Cochrane Handbook caps them at about seven per comparison). Its other analyses are not shown here.
Questions
104
current version
GRADE rated
104
No studies
0
Included studies
NR
No studies 0 · 0%Ungraded 0 · 0%Very low 6 · 5.8%Low 68 · 65.4%Moderate 16 · 15.4%High 14 · 13.5%

Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.

Questions and results

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Effectiveness against measles

Population: children 9 months to 15 years old
6 questions
OutcomeEffectEvidenceStatus / GRADE
Cohort studies ‐ 1 dose
RR 0.05 [0.02, 0.13]7 studies · 12039 participantsModerate
Downgraded: risk of bias
Cohort studies ‐ 2 doses
RR 0.04 [0.01, 0.28]5 studies · 21604 participantsModerate
Downgraded: risk of bias
Cohort studies household contacts ‐ 1 dose
RR 0.19 [0.04, 0.89]3 studies · 151 participantsLow
Downgraded: risk of bias
Cohort studies household contacts ‐ 2 doses
RR 0.15 [0.03, 0.75]3 studies · 378 participantsLow
Downgraded: risk of bias
Cohort studies household contacts ‐ 3 doses
RR 0.04 [0.01, 0.23]2 studies · 151 participantsLow
Downgraded: risk of bias
Cohort studies postexposure prophylaxis
RR 0.26 [0.14, 0.5]2 studies · 283 participantsLow
Downgraded: risk of bias

Effectiveness against mumps

Population: children 9 months to 15 years old
8 questions
OutcomeEffectEvidenceStatus / GRADE
Cohort studies ‐ Jeryl Lynn strain ‐ 1 dose
RR 0.24 [0.08, 0.76]6 studies · 9915 participantsModerate
Downgraded: risk of bias
Cohort studies ‐ Jeryl Lynn strain ‐ 2 doses
RR 0.12 [0.04, 0.35]5 studies · 7792 participantsModerate
Downgraded: risk of bias
Cohort studies ‐ Jeryl Lynn strain ‐ unspecified number of doses
RR 0.23 [0.14, 0.35]4 studies · 2011 participantsLow
Downgraded: risk of bias
Cohort studies ‐ Jeryl Lynn strain ‐ household contacts
RR 0.26 [0.13, 0.49]3 studies · 1036 participantsModerate
Downgraded: risk of bias
Cohort studies ‐ Urabe strain ‐ unspecified numbers or at least 1 dose
RR 0.23 [0.12, 0.44]4 studies · 2721 participantsLow
Downgraded: risk of bias
Cohort studies ‐ Rubini strain ‐ unspecified numbers or at least 1 dose
RR 0.96 [0.55, 1.65]4 studies · 4219 participantsLow
Downgraded: risk of bias
Cohort studies ‐ mumps strain not reported or any strain
RR 0.52 [0.29, 0.94]2 studies · 769 participantsLow
Downgraded: risk of bias
Cohort studies ‐ third dose versus 2 doses
RR 0.59 [0.33, 1.05]2 studies · 5417 participantsLow
Downgraded: risk of bias

Effectiveness against rubella

Population: children 9 months to 15 years old
1 question
OutcomeEffectEvidenceStatus / GRADE
Cohort studies secondary cases ‐ any strain
RR 0.11 [0.03, 0.42]1 study · 1621 participantsModerate
Downgraded: risk of bias

Effectiveness against varicella

Population: children 9 months to 15 years old
12 questions
OutcomeEffectEvidenceStatus / GRADE
MMRV randomised controlled trial ‐ any severity ‐ 2 doses ‐
Rate ratio 0.05 [0.03, 0.08]1 study · 3022 participantsHigh
MMRV randomised controlled trial ‐ any severity ‐ 2 doses ‐
Rate ratio 0.05 [0.04, 0.06]1 study · 3023 participantsHigh
MMRV randomised controlled trial ‐ any severity ‐ 2 doses ‐
Rate ratio 0.05 [0.04, 0.06]1 study · 3023 participantsHigh
MMRV randomised controlled trial ‐ moderate/severe cases ‐ 2 doses ‐
Rate ratio 0 [0, 0.02]1 study · 3022 participantsHigh
MMRV randomised controlled trial ‐ moderate/severe cases ‐ 2 doses ‐
Rate ratio 0.01 [0, 0.02]1 study · 3023 participantsHigh
MMRV randomised controlled trial ‐ moderate/severe cases ‐ 2 doses ‐
Rate ratio 0.01 [0, 0.02]1 study · 3023 participantsHigh
MMR+V randomised controlled trial ‐ any severity ‐ 2 doses ‐
Rate ratio 0.35 [0.28, 0.43]1 study · 3006 participantsHigh
MMR+V randomised controlled trial ‐ any severity ‐ 2 doses ‐
Rate ratio 0.33 [0.29, 0.38]1 study · 3010 participantsHigh
MMR+V randomised controlled trial ‐ any severity ‐ 2 doses ‐
Rate ratio 0.33 [0.29, 0.38]1 study · 3010 participantsHigh
MMR+V randomised controlled trial ‐ moderate/severe cases ‐ 2 doses ‐
Rate ratio 0.09 [0.06, 0.14]1 study · 3006 participantsHigh
MMR+V randomised controlled trial ‐ moderate/severe cases ‐ 2 doses ‐
Rate ratio 0.1 [0.07, 0.13]1 study · 3010 participantsHigh
MMR+V randomised controlled trial ‐ moderate/severe cases ‐ 2 doses ‐
RR 0.1 [0.08, 0.14]1 study · 3010 participantsHigh

Safety: short‐term side effects (local or systemic reactions)

Population: children 9 months to 15 years old
14 questions
OutcomeEffectEvidenceStatus / GRADE
Temperature ‐ RCT/CCT axillary
RR 2.04 [1.09, 3.83]1 study · 420 participantsLow
Downgraded: risk of bias
Temperature ‐ RCT/CCT rectal
RR 0.84 [0.67, 1.06]1 study · 170 participantsLow
Downgraded: risk of bias
Temperature ‐ RCT/CCT measurement site not reported
RR 1.36 [0.83, 2.23]2 studies · 520 participantsHigh
Temperature ‐ cohort studies orally
RR 1.37 [1.04, 1.81]1 study · 334 participantsVery low
Temperature ‐ cohort studies measurement site not reported
RR 1.12 [0.84, 1.49]4 studies · 457123 participantsVery low
Rash ‐ cohort studies
RR 1.49 [0.73, 3.04]3 studies · 457261 participantsVery low
Lymphadenopathy ‐ RCT/CCT
RR 1.32 [0.52, 3.33]3 studies · 1156 participantsModerate
Lymphadenopathy ‐ cohort studies
RR 1.98 [0.19, 20.97]2 studies · 454085 participantsVery low
Coryza ‐ RCT/CCT
RR 0.45 [0.12, 1.63]2 studies · 831 participantsModerate
Downgraded: risk of bias
Coryza ‐ cohort studies
RR 1.13 [1.05, 1.2]1 study · 3176 participantsLow
Downgraded: risk of bias
URTI (rhinitis pharyngitis) ‐ RCT/CCT
RR 0.31 [0.06, 1.56]2 studies · 831 participantsLow
Downgraded: risk of bias
URTI (rhinitis pharyngitis) ‐ cohort studies
RR 1.44 [1.26, 1.64]1 study · 966 participantsVery low
Cough ‐ RCT/CCT
RR 1.99 [0.45, 8.81]2 studies · 831 participantsLow
Downgraded: risk of bias
Rash ‐ RCT/CCT
RR 2.05 [1.21, 3.48]4 studies · 1156 participantsHigh

Safety: encephalitis or encephalopathy

Population: children 9 months to 15 years old
2 questions
OutcomeEffectEvidenceStatus / GRADE
Case‐control: MMR (risk interval from 0 to 90 days)
OR 0.98 [0.64, 1.5]1 study · 452 participantsLow
Self‐controlled case series/person‐time cohort
Rate ratio 0.9 [0.5, 1.61]2 studies · 1071088 participantsLow

Safety: aseptic meningitis

Population: children 9 months to 15 years old
9 questions
OutcomeEffectEvidenceStatus / GRADE
Case‐control ‐ Jeryl Lynn ‐ risk interval 0 to 30 days
OR 0.85 [0.21, 3.41]1 study · 59 participantsLow
Case cross‐over ‐ Urabe or Hoshino
OR 4 [2.23, 7.2]2 studies · 2 participantsLow
Case cross‐over ‐ Jeryl Lynn or Rubini
OR 0.6 [0.18, 1.99]1 study · 1 participantsLow
Self‐controlled case series ‐ any strain
Rate ratio 12.4 [3.12, 49.35]1 study · 1 participantsLow
Self‐controlled case series ‐ Urabe
Rate ratio 30.71 [13.45, 70.1]3 studies · 564635 participantsLow
Self controlled case series ‐ Leningrad‐Zagreb
Rate ratio 6.4 [0.78, 52.47]1 study · 1 participantsLow
Person‐time cohort ‐ Jeryl Lynn
Rate ratio 1.3 [0.66, 2.56]1 study · 1071088 participantsLow
Case‐only ecological method ‐ Urabe
Rate ratio 9.12 [5.73, 14.52]1 study · 1054305 participantsLow
Case‐only ecological method ‐ Leningrad‐Zagreb
Rate ratio 18.56 [12.09, 28.51]3 studies · 1164964 participantsLow

Safety: seizures (febrile/afebrile)

Population: children 9 months to 15 years old
15 questions
OutcomeEffectEvidenceStatus / GRADE
Cohort studies ‐ within 1 week after MMR vaccination
Rate ratio 2.45 [2.21, 2.71]2 studies · 1451990 participantsModerate
Cohort studies ‐ between 1 and 2 weeks after MMR vaccination
Rate ratio 3.16 [2.89, 3.46]2 studies · 2147638 participantsModerate
Cohort studies ‐ > 2 weeks after MMR vaccination
Rate ratio 0.97 [0.49, 1.94]1 study · 1018998 participantsLow
Self‐controlled case series/person‐time ‐ between 1 and 2 weeks after MMR vaccination
Rate ratio 3.36 [2.65, 4.24]5 studies · 505493 participantsLow
Self‐controlled case series/person‐time ‐ > 2 weeks after MMR vaccination
Rate ratio 1.18 [0.93, 1.5]3 studies · 102099 participantsLow
Self‐controlled case series/person‐time ‐ between 1 and 2 weeks after vaccination; MMRV
Rate ratio 6.08 [4.95, 7.47]2 studies · 180480 participantsLow
Self‐controlled case series/person‐time ‐ between 1 and 2 weeks after MMR+V vaccination
Rate ratio 3.13 [2.38, 4.1]1 study · 181088 participantsLow
MMRV vs MMR+V ‐ by brand ‐ from 0 to 42 days after vaccination (Priorix‐Tetra)
RR 1.95 [0.85, 4.48]1 study · 115022 participantsLow
MMRV vs MMR+V ‐ by brand ‐ from 7 to 10 days after vaccination (Priorix‐Tetra)
RR 1.69 [0.93, 3.07]1 study · 114922 participantsLow
MMRV vs MMR+V ‐ by brand ‐ from 0 to 42 days after vaccination (ProQuad)
RR 1.3 [1.17, 1.44]4 studies · 1381609 participantsLow
MMRV vs MMR+V ‐ by brand ‐ from 7 to 10 days after vaccination (ProQuad)
RR 2.01 [1.7, 2.38]4 studies · 1381609 participantsLow
MMRV vs MMR ‐ by brand ‐ from 0 to 42 days after vaccination (Priorix‐Tetra)
RR 1.28 [1, 1.64]2 studies · 292535 participantsLow
MMRV vs MMR ‐ by brand ‐ from 7 to 10 days after vaccination (Priorix‐Tetra)
RR 2.49 [1.66, 3.74]2 studies · 292535 participantsLow
MMRV vs MMR ‐ by brand ‐ from 0 to 42 days after vaccination (ProQuad)
RR 1.6 [1.42, 1.82]3 studies · 1049831 participantsLow
MMRV vs MMR ‐ by brand ‐ from 7 to 10 days after vaccination (ProQuad)
RR 1.46 [1.32, 1.61]4 studies · 1989157 participantsLow

Safety: autistic spectrum disorders

Population: children 9 months to 15 years old
3 questions
OutcomeEffectEvidenceStatus / GRADE
Cohort studies ‐ all children, MMR
Rate ratio 0.93 [0.85, 1.01]2 studies · 1194764 participantsModerate
Cohort studies ‐ autism risk (low), MMR
Rate ratio 1 [0.89, 1.14]1 study · 93071 participantsModerate
Cohort studies ‐ autism risk (moderate/high), MMR
Rate ratio 0.8 [0.64, 0.98]1 study · 1914 participantsLow

Safety: inflammatory bowel disease

Population: children 9 months to 15 years old
3 questions
OutcomeEffectEvidenceStatus / GRADE
Case control ‐ all IBD, MMR
OR 1.42 [0.93, 2.16]3 studies · 409 participantsModerate
Case control ‐ ulcerative colitis, MMR
OR 1.35 [0.81, 2.23]2 studies · 292 participantsModerate
Case control ‐ Crohn's disease, MMR
OR 0.64 [0.42, 0.98]3 studies · 514 participantsModerate

Safety: cognitive delay ‐ developmental delay

Population: children 9 months to 15 years old
4 questions
OutcomeEffectEvidenceStatus / GRADE
Cohort study ‐ MDI‐BSID II 24th month, MMR
OR 1.35 [0.15, 12.07]1 study · 337 participantsLow
Cohort study ‐ MDI‐BSID II 36th month, MMR
OR 0.37 [0.03, 4.28]1 study · 337 participantsLow
Cohort study ‐ Raven 5th year, MMR
OR 1.22 [0.23, 6.51]1 study · 337 participantsLow
Cohort study ‐ WISC‐R verbal 6th year, MMR
OR 1.23 [0.09, 16.92]1 study · 337 participantsLow

Safety: idiopathic thrombocytopenic purpura

Population: children 9 months to 15 years old
2 questions
OutcomeEffectEvidenceStatus / GRADE
Case‐control ‐ case cross‐over ‐ case controls MMR
OR 2.8 [1.5, 5.23]2 studies · 410 participantsLow
Self‐controlled case series ‐ MMR vaccine ‐ age from 9 to 23 months
Rate ratio 4.21 [2.28, 7.78]5 studies · 3723677 participantsModerate

Safety: Henoch‐Schönlein purpura

Population: children 9 months to 15 years old
1 question
OutcomeEffectEvidenceStatus / GRADE
Case‐control ‐ MMR vaccine
OR 3.4 [1.18, 9.81]1 study · 288 participantsLow

Safety: type 1 diabetes

Population: children 9 months to 15 years old
2 questions
OutcomeEffectEvidenceStatus / GRADE
Cohort study MMR ‐ all children
Rate ratio 1.09 [0.98, 1.21]2 studies · 1666829 participantsLow
Cohort study MMR ‐ children with at least 1 sibling with type 1 diabetes
Rate ratio 0.86 [0.34, 2.16]1 study · 3848 participantsLow

Safety: asthma

Population: children 9 months to 15 years old
2 questions
OutcomeEffectEvidenceStatus / GRADE
Cohort study (rate ratio) ‐ all ages
Rate ratio 1.05 [0.8, 1.39]3 studies · 1067712 participantsLow
Downgraded: risk of bias
Cohort studies (risk ratio) ‐ all ages
RR 0.63 [0.24, 1.63]3 studies · 886 participantsLow
Downgraded: risk of bias

Safety: eczema ‐ dermatitis

Population: children 9 months to 15 years old
2 questions
OutcomeEffectEvidenceStatus / GRADE
Cohort study (rate ratio)
Rate ratio 3.5 [2.38, 5.15]1 study · 14353 participantsVery low
Cohort study (risk ratio)
RR 0.75 [0.29, 1.94]1 study · 555 participantsLow

Safety: hay fever, rhinoconjunctivitis, hypersensitivity/allergy

Population: children 9 months to 15 years old
3 questions
OutcomeEffectEvidenceStatus / GRADE
Cohort study ‐ rhinoconjunctivitis
OR 0.64 [0.19, 2.11]1 study · 489 participantsLow
Downgraded: risk of bias
Cohort study ‐ hypersensitivity/allergy
OR 0.63 [0.14, 2.77]1 study · 544 participantsLow
Downgraded: risk of bias
Case control ‐ hay fever
OR 1.16 [0.92, 1.45]0 studies · 2 participantsLow
Downgraded: risk of bias

Safety: acute leukaemia

Population: children 9 months to 15 years old
3 questions
OutcomeEffectEvidenceStatus / GRADE
Case‐control ‐ acute leukaemia
OR 0.97 [0.76, 1.24]2 studies · 941 participantsLow
Case‐control ‐ acute lymphoblastic leukaemia
OR 0.91 [0.72, 1.14]4 studies · 1375 participantsLow
Case‐control ‐ acute myeloblastic leukaemia
OR 0.56 [0.29, 1.07]1 study · 62 participantsLow

Safety: demyelinating diseases ‐ multiple sclerosis ‐ acute disseminated encephalomyelitis

Population: children 9 months to 15 years old
2 questions
OutcomeEffectEvidenceStatus / GRADE
Case‐control ‐ multiple sclerosis
OR 1.13 [0.62, 2.05]1 study · 206 participantsLow
Case‐control ‐ ADEM
OR 1.03 [0.44, 2.42]1 study · 272 participantsLow

Safety: gait disturbances

Population: children 9 months to 15 years old
3 questions
OutcomeEffectEvidenceStatus / GRADE
Self‐controlled case series (hospitalisations) ‐ hospitalisations ‐ risk period: 0 to 60 days
Rate ratio 0.46 [0.16, 1.34]1 study · 127 participantsLow
Self‐controlled case series (GP visits) ‐ GP visit ‐ risk period: 0 to 5 days
Rate ratio 1.88 [1.3, 2.72]1 study · 1398 participantsLow
Self‐controlled case series (GP visits) ‐ GP visit ‐ risk period: 6 to 60 days
Rate ratio 0.93 [0.78, 1.11]1 study · 1398 participantsLow

Safety: bacterial or viral infections, immune overload

Population: children 9 months to 15 years old
7 questions
OutcomeEffectEvidenceStatus / GRADE
Self‐controlled case series ‐ lobar pneumonia ‐ lobar pneumonia risk period (0 to 90 days)
Rate ratio 0.75 [0.64, 0.89]2 studies · 2412 participantsLow
Self‐controlled case series ‐ invasive bacterial infections ‐ invasive bacterial infections risk period (0 to 90 days)
Rate ratio 0.9 [0.71, 1.13]2 studies · 2412 participantsLow
Self‐controlled case series ‐ encephalitis meningitis ‐ encephalitis meningitis risk period (0 to 90 days)
Rate ratio 0.84 [0.2, 3.51]1 study · 2025 participantsLow
Self‐controlled case series ‐ herpes ‐ herpes risk period (0 to 90 days)
Rate ratio 1.17 [0.56, 2.46]1 study · 2025 participantsLow
Self‐controlled case series ‐ pneumonia ‐ pneumonia risk period (0 to 90 days)
Rate ratio 0.72 [0.32, 1.6]1 study · 2025 participantsLow
Self‐controlled case series ‐ varicella zoster ‐ varicella zoster risk period (0 to 90 days)
Rate ratio 0.93 [0.68, 1.27]1 study · 2025 participantsLow
Self‐controlled case series ‐ miscellaneous viral infections ‐ miscellaneous viral infections risk period (0 to 90 days)
Rate ratio 0.68 [0.43, 1.08]1 study · 2025 participantsLow