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. 2021 Nov 22;2021(11):CD004407. doi: 10.1002/14651858.CD004407.pub5

10. Safety: short‐term side effects (local or systemic reactions) ‐ RCTs/CCTs.

Study ID and design Population
enrolled Vaccine arm
n = sample size Comparator arm
n = sample size Outcome MMR vaccine arm
events/n Other vaccine arms
events/n Comparator arm
events/n
ab‐Bloom 1975;
RCT		 Children aged
11 months to 4 years
Observation period
21 days		 MMR vaccine
Measles Schwarz
Mumps Jeryl Lynn
Rubella Cendehill
n = 183
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Temperature
above normal
sample size
n = 160
Normal temperature
rectal 99.6 °F (37.5 °C)
(163 children)
Oral 98.6 °F (37 °C)
(6 children)
Axillary 97.6 °F
(36.4 °C)
(26 children)		 Placebo
n = 40
‐‐‐‐‐‐‐‐‐‐
Temperature
sample size
n = 35		 Reactions
(a) Rash
(b) Lymphadenopathy
(c) Coryza
(d) Rhinitis
(e) Cough
(f) Other
total
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Temperature
above normal
(a) 1.5 to 2.4 °F
(b) 2.5 to 3.4 °F
(c) 3.5 to 4.4 °F
(d) 4.5 to 4.9 °F
(e) ≥ (normal + 1.5) °F		 MMR vaccine
(a) 22/183
(b) 2/183
(c) 4/183
(d) 2/183
(e) 5/183
(f) 35/183
total 70/183
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Temperature
above normal
(a) 17/160
(b) 1/160
(c) 5/160
(d) 2/160
(e) 25/160		 ‐ Placebo arm
(a) 2/40
(b) 1/40
(c) 4/40
(d) 4/40
(e) 1/40
(f) 8/40
total 20/40
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Temperature
above normal
(a) 2/35
(b) 2/35
(c) 0/35
(d) 0/35
(e) 4/35
ab‐Ceyhan 2001;
CCT		 Infants aged
38 to 40 months
Observation period
28 days		 Arm A: n = 442
(1) MV/Rouvax
Measles Schwarz
at 9 months;
and
(2) MMR/Trimovax
Measles Schwarz
Mumps Urabe AM9
Rubella Wistar RA 27/3
at 15 months
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Arm B: n = 495
(3) MMR/Trimovax
Measles Schwarz
Mumps Urabe AM9
Rubella Wistar RA 27/3
at 12 months		 No placebo arm Systemic reactions
(a) Fever
(b) Runny nose
(c) Cough
(d) Rash
(e) Diarrhoea
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Local
(f) Redness
(g) Swelling
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Total events
(x) Fever
(y) Systemic
(z) Local		 MMR vaccine
(2)15 months; (3)12 months
(a) 40/442; 55/495
(b) 7/442; 22/495
(c) 36/442; 34/495
(d) 16/442; 19/495
(e) 2/442; 5/495
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Local
(2)15 months; (3)12 months
(f) 14/442; 19/495
(g) 2/442; 3/495
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Total events
(2)15 months; (3)12 months
(x) 40/442; 55/495
(y) 61/442; 80/495
(z) 16/442; 22/495		 MV vaccine
(1) 9 months
(a) 38/442
(b) 19/442
(c) 28/442
(d) 2/442
(e) 5/442
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Local
(f) 7/442
(g) 2/442
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Total events
(x) 38/442
(y) 54/442
(z) 9/442		  
ab‐Edees 1991;
RCT		 Children aged
12 to 18 months.
Observation period
21 days		 Arm A: n = 196
MV/Rouvax
Measles Schwarz
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Arm B: n = 198
MMR/Trimovax
Measles Schwarz
Mumps Urabe AM9
Rubella Wistar RA 27/3		 No placebo arm Local symptoms 
(a) Erythema
(b) Induration
(c) Pain
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Specific systemic 
(a) Rash
(b) Parotitis
(c) Conjuntivitis
(d) Testicular swelling
(e) Arthralgia
(f) Arthritis
(g) Convulsion
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Non‐specific systemic 
(a) Fever
(b) Adenopathy
(c) Nasopharyngeal disorders
(d) Gastrointestinal disorders
(e) Restlessness
Restlessness:
used to describe a non‐specifically
unwell child; it covers terms such as irritable
miserable tearful clingy not sleeping.		 MMR vaccine (Arm B)
Local
(a) 18/198
(b) 1/198
(c) 9/198
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Specific systemic
(a) 87/198
(b) 5/198
(c) 17/198
(d) 0/198
(e) 0/198
(f) 0/198
(g) 0/198
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Non‐specific systemic
(a) 76/198
(b) 2/198
(c) 113/198
(d) 83/198
(e) 124/198		 MV vaccine (Arm A)
Local
(a) 16/196
(b) 0/196
(c) 14/196
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Specific systemic
(a) 100/196
(b) 0/196
(c) 21/196
(d) 0/196
(e) 0/196
(f) 0/196
(g) 0/196
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Non‐specific systemic
(a) 74/196
(b) 3/196
(c) 115/196
(d) 74/196
(e) 147/196		  
ab‐Lerman 1981;
RCT		 Children aged
15 months to 5 years
Observation period
42 days		 Arm(1): n = 43:
Measles (MSD)
Arm(2): n = 41:
Mumps (MSD)
Jeryl Lynn
Arm(3): n = 47:
Rubella HPV‐77:CE‐5
Arm(4): n = 142
MMR (MSD)
with Rubella HPV‐77:DE‐5
Arm(5): n = 46:
Rubella/Wistar RA27/3
Arm(6): n = 141:
MMRII (MSD)
with Rubella Wistar RA27/3		 Placebo arm
n = 42
(vaccine diluent)
1 dose
subcutaneously		 Reactions
(a) Local reaction
(b) Fever
101 to 102.9 °F
(fever 38.3 to 39.4 °C)
(c) Fever
103 to 104.9 °F
(fever 39.4 to 40.5 °C)
(d) Respiratory symptoms
(e) Rash
(f) Lymphadenopathy
(g) Sore eyes
(h) Joint symptoms		 MMR vaccine 
Arms: (4); (6)
(a) 7/142; 11/141
(b) 31/142; 35/141
(c) 11/142; 16/141
(d) 97/142; 102/141
(e) 24/142; 28/141
(f) 6/142; 11/141
(g) 24/142; 23/141
(h) 1/142; 1/141 Other vaccine arms: (1); (2); (3); (5)
(a) 1/43; 6/41; 3/47; 2/46
(b) 12/43; 6/41; 6/47; 11/46
(c) 2/43; 3/41; 3/47; 2/46
(d) 34/43; 26/41; 31/47; 31/46
(e) 5/43; 1/41; 6/47; 5/46
(f) 1/43; 2/41; 2/47; 2/46
(g) 6/43; 8/41; 8/47; 8/46
(h) 0/43; 0/41; 0/47; 0/46		 Placebo arm
(a) 3/42
(b) 10/42
(c) 0/42
(d) 31/42
(e) 4/42
(f) 0/42
(g) 4/42
(h) 0/42
ab‐Peltola 1986;
RCT		 Pairs of twins aged
(a) 14 to 18 months (first dose)
(b) 6 years (second dose)
Observation period
21 days		 MMR vaccine
Vivirac (MSD)
2 doses
n = 581		 Placebo arm
n = 581   No data available for quantitative synthesis    
ab‐Schwarz 1975;
RCT		 Children aged
10 months to 8 years
Observation period
21 days		 MMR vaccine
Measles Schwarz
Mumps Jeryl Lynn
Rubella Cendehill
n = 403		 Placebo arm
n = 205		 Temperature
(1) Axillary
(2) Rectal
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
(a) < 37.0 °C
(b) 37.0 to 37.4 °C
(c) < 37.5 °C
(d) 37.5 to 37.9 °C
(e) 38.0 to 38.4 °C
(f) 38.5 to 38.9 °C
(g) 39.0 to 39.4 °C
(h) 39.5 to 39.9 °C
(i) 40.0 to 40.4 C°
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Reactions
(s1) Rash
(s2) Lymphadenopathy
(s3) Conjunctivitis
(s4) Otitis media
(s5) Coryza
(s6) Rhinitis
(s7) Pharyngitis
(s8) Cough
(s9) Headache
(s10) Parotitis
(s11) Orchitis
(s12) Arthralgia
(s13) Paraesthesia		 MMR vaccine
(1) Temperature axillary
(a) 56/244
(b) 154/244
(c) 210/244
(d) 21/244
(e) 6/244
(f) 2/244
(g) 3/244
(h) 2/244
(i) 0/244
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
(2) Temperature rectal
(a) not reported
(b) not reported
(c) 48/142
(d) 51/142
(e) 30/142
(f) 8/142
(g) 1/142
(h) 1/142
(i) 3/142
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Reactions
(s1) 36/403
(s2) 4/403
(s3) 8/403
(s4) 4/403
(s5) 8/403
(s6) 69/403
(s7) 2/403
(s8) 7/403
(s9) 1/403
(s10) 0/403
(s11) 0/403
(s12) 1/403
(s13) 0/403		   Placebo arm
(1) Axillary temperature
(a) 32/176
(b) 132/176
(c) 164/176
(d) 9/176
(e) 2/176
(f) 1/176
(g) 0/176
(h) 0/176
(i) 0/176
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
(2) Rectal temperature
(a) Not reported
(b) Not reported
(c) 6/28
(d) 13/28
(e) 6/28
(f) 1/28
(g) 2/28
(h) 0/28
(i) 0/28
‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Reactions
(s1) 9/205
(s2) 4/205
(s3) 5/205
(s4) 1/205
(s5) 5/205
(s6) 59/205
(s7) 2/205
(s8) 1/205
(s9) 1/205
(s10) 0/205
(s11) 0/205
(s12) 0/205
(s13) 0/205
ab‐Freeman 1993;
Cluster‐RCT		 Children aged
13 to 15 months
Observation period
30 days		 MMR vaccine
MMRII (MSD)
n = 253		 No placebo arm Reactions
(a) Lymphadenopathy
(b) Nasal discharge
(c) Rash
(d) Otitis media
(e) Conjunctival abnormality
(f) Abnormal tonsils		 Reactions
(a) 57/240
(b) 15/240
(c) 11/240
(d) 8/240
(e) 8/240
(f) 2/240		    

MR: mumps‐rubella vaccine
MMR: measles, mumps, rubella vaccine
MMRV: measles, mumps, rubella, and varicella vaccine
RCT: randomised controlled trial