Supplementary Table 1. Pooled analyses of incidences of injection site and systemic clinical adverse experiences after single MMRV dose compared with MMR+V or MMR vaccination in healthy children aged 9-24 months
Symptoms
MMRV vs. MMR+V MMRV vs. MMR
MMRV group MMR+V group
Pooled RR (95%CI)
I2 (%)
No. of studies
MMRV group MMR group
Pooled RR (95%CI)
I2 (%)
No. of studies
Local solicited symptoms(days 0-3)
Pain Any 9.36%(443/4731) 8.67%(163/1879) 1.06(0.89-1.26) 0 8 11.81%(398/3371) 9.54%(226/2369) 1.12(0.95-1.32) 0 6
Grade 3 0.08%(4/4731) 0.05%(1/1879) 0.95(0.14-6.20) 0 8 0.12%(4/3371) 0.13%(3/2369) 0.94(0.21-4.13) 0 6
Redness Any 21.58%(1021/4731) 19.16%(360/1879) 1.06(0.95-1.18) 23 8 18.45%(622/3371) 16.21%(384/2369) 1.08(0.96-1.22) 24 6
Grade 3 0.27%(13/4731) 0.27%(5/1879) 1.04(0.43-2.55) 0 8 0.44%(15/3371) 0.34%(8/2369) 1.18(0.50-2.79) 0 6
Swelling Any 7.21%(341/4731) 6.23%(117/1879) 1.12(0.91-1.38) 0 8 5.87%(198/3371) 4.60%(109/2369) 1.22(0.96-1.55) 0 6
Grade 3 0.19%(9/4731) 0.21%(4/1879) 0.73(0.27-2.00) 0 8 0.12%(4/3371) 0%(0/2369) 5.89(0.72-48.16) 0 6
Solicited general symptoms(days 0-42)
Fever (days 0-14) ≥38.0℃(rectal) 59.81%(1878/3140) 42.65%(633/1484) 1.37(1.21-1.54) 59 6 58.63%(1876/3200) 43.44%(917/2111) 1.33(1.26-1.41) 0 5
>39.5℃(rectal) 10.45%(328/3140) 7.01%(104/1484) 1.44(1.16-1.78) 0 6 11.34%(363/3200) 7.15%(151/2111) 1.60(1.33-1.92) 19 5 Related 30.04%(313/1042) 25.19%(100/397) 1.07(0.89-1.29) 0 2 40.23%(461/1146) 27.99%(346/1236) 1.46(1.30-1.64) 0 2
Fever (days 0-42) ≥38.0℃(rectal) 66.49%(3145/4730) 52.90%(994/1879) 1.25(1.19-1.31) 38 8 65.44%(1971/3012) 52.91%(1154/2181) 1.19(1.13-1.25) 0 5
>39.5℃(rectal) 15.31%(724/4730) 11.50%(216/1879) 1.32(1.14-1.52) 23 8 15.01%(452/3012) 10.64%(232/2181) 1.38(1.19-1.61) 42 5 Related 36.32%(958/2638) 24.83%(182/733) 1.34(0.99-1.81) 74 4 40.19%(385/958) 29.48%(385/1306) 1.36(1.21-1.52) 0 2
Fever (days 0-42)
>38.9℃ oral equivalent or warm to touch
36.51%(1691/4632) 31.58%(570/1805) 1.12(1.04-1.21) 25 5 ND ND NE 0
Rash Any 19.33%(312/1614) 19.60%(88/449) 1.00(0.81-1.25) 0 3 19.27%(292/1515) 10.77%(156/1449) 1.10(0.89-1.35) 24 4
Any Grade 3 1.95%(30/1535) 1.61%(6/372) 0.87(0.37-2.06) NA 2 0%(0/174) 0%(0/255) NE NA 1
Any Related 6.94%(112/1614) 7.35%(33/449) 0.92(0.62-1.37) 0 3 4.74%(12/253) 1.51%(5/332) 2.31(0.89-6.02) 0 2
Local 0.49%(10/2021) 0.59%(6/1010) 0.90(0.32-2.50) 23 3 1.12%(31/2762) 1.24%(23/1851) 1.14(0.63-2.05) 0 3
Local Grade 3 0.21%(4/1870) 0%(0/866) 4.46(0.24-82.80) NA 2 0.27%(4/1499) 0%(0/735) 4.42(0.24-81.91) NA 1
Generalized 19.90%(620/3116) 16.85%(241/1430) 1.23(1.07-1.40) 0 5 15.91%(363/2281) 10.88%(194/1783) 1.20(0.83-1.74) 76 2
Generalized G3 1.27%(14/1103) 0.55%(2/361) 1.90(0.50-7.23) 0 2 ND ND NE 0
Generalized Related 4.44%(49/1103) 2.77%(10/361) 1.96(0.43-8.94) 56 2 3.44%(27/784) 4.28%(45/1051) 0.80(0.50-1.28) NA 1 Measles/Rubella like 3.82%(305/7988) 2.77%(93/3358) 1.44(1.15-1.81) 4 10 5.33%(147/2759) 3.30%(61/1849) 1.45(1.06-1.98) 0 3 Varicella like 2.32%(189/8137) 2.08%(73/3505) 1.22(0.93-1.60) 0 13 2.82%(58/2054) 1.37%(12/875) 1.95(1.04-3.66) 0 3 Parotid/Salivary
gland swelling
Any 0.11%(5/4651) 0.22%(4/1802) 0.50(0.15-1.63) 0 7 0.38%(11/2933) 0.29% (6/2104) 1.13(0.39-3.29) 0 4
Grade 3 0%(0/4651) 0.06%(1/1802) 0.17(0.01-4.07) NA 7 0%(0/2149) 0%(0/1053) NE 3
Related 0.04%(1/2638) 0.14%(1/733) 0.33(0.05-2.34) 0 4 0%(0/174) 0%(0/255) NE 1
Meningism Any 0.19%(9/4730) 0.05%(1/1879) 1.29(0.39-4.20) 0 8 0.09%(2/2228) 0.09%(1/1130) 0.98(0.09-10.77) NA 4
Grade 3 0.06%(3/4651) 0%(0/1802) 0.82(0.13-5.13) 0 7 0%(0/2149) 0%(0/1053) NE 3
Related 0.08%(2/2638) 0%(0/733) 0.99(0.10-9.48) 0 4 0%(0/174) 0%(0/255) NE 1
Unsolicited adverse events(days 0-42)
Any adverse events 51.40%(2128/4140) 47.93%(740/1544) 1.11(1.04-1.18) 0 5 53.67%(1596/2974) 41.26%(888/2152) 1.06(0.99-1.12) 0 4 Upper respiratory infection 16.39%(1448/8836) 16.04%(513/3198) 1.05(0.96-1.15) 11 9 12.21%(363/2974) 7.34%(158/2152) 1.01(0.84-1.22) 0 4
Irritability 10.31%(572/5550) 8.54%(149/1744) 1.29(1.09-1.54) 0 4 ND ND NE 0
Otitis media 8.17%(692/8465) 7.15%(220/3075) 1.13(0.98-1.31) 32 8 7.00%(139/1987) 5.61%(45/802) 0.99(0.71-1.37) 0 2 Diarrhoea 7.60%(564/7420) 7.59%(203/2676) 1.04(0.89-1.22) 0 6 7.03%(209/2974) 5.07%(109/2152) 0.97(0.77-1.22) 0 4
Rhinorrhea 6.91%(299/4325) 7.12% (109/1531) 0.96(0.78-1.19) 0 3 ND ND NE 0
Cough 5.96%(486/8152) 6.49%(189/2914) 0.97(0.83-1.14) 0 7 8.88%(264/2974) 5.53%(119/2152) 1.05(0.83-1.32) 51 4 Vomiting 5.52%(322/5830) 5.96%(136/2281) 0.93(0.76-1.13) 0 4 6.51%(141/2167) 4.66%(50/1072) 1.11(0.80-1.55) 11 3 Rhinitis 4.84%(256/5290) 4.48%(86/1920) 1.08(0.85-1.38) 13 6 11.60%(345/2974) 6.22%(134/2152) 1.09(0.87-1.38) 13 4 Pharyngitis 4.33%(335/7731) 4.27%(121/2836) 1.16(0.95-1.42) 22 7 8.41%(235/2794) 5.21%(98/1882） 1.37(1.09-1.72) 31 3 Viral infection 3.72%(244/6560) 3.93%(99/2518) 0.96(0.76-1.21) 16 5 3.77%(75/1987) 4.74%(38/802) 0.80(0.55-1.18) 40 2
Bronchitis 3.24%(56/1731) 2.71%(20/737) 1.20(0.73-1.97) 18 4 2.60%(21/807) 3.70%(40/1080) 0.70(0.42-1.18) NA 1
Gastroenteritis 2.53%(145/5733) 2.46%(52/2111) 1.10(0.81-1.51) 0 6 2.78%(5/180) 1.48%(4/270) 1.88(0.51-6.89) NA 1
Conjuntivitis 2.47%(125/5055) 2.21%(39/1768) 1.10(0.77-1.57) 0 4 ND ND NE 0
Anorexia 2.20%(103/4688) 1.58%(27/1712) 1.38(0.92-2.08) 47 4 ND ND NE 0
Bronchiolitis 1.27%(55/4315) 1.24%(19/1535) 1.20(0.71-2.01) 0 3 ND ND NE 0
Unsolicited SAEs (days 0-42)
Any 1.13%(74/6544) 1.10%(29/2644) 1.10(0.73-1.67) 0 6 1.04%(21/2024) 0.60%(5/829) 1.52(0.59-3.95) 0 2
Any related 0.12%(6/5081) 0.09%(2/2107) 0.95(0.24-3.79) 0 4 0.10%(2/2024) 0%(0/829) 0.69(0.03-14.17) NA 2
Related febrile seizures 0.81%(7/8644) 0.03%(1/3361) 1.34(0.33-5.47) 0 10 0.06%(3/5055) 0.02%(1/4598) 1.00(0.10-9.57) NA 5 Note: ND, no reported data; NE, no estimated RR; NS, no reported study; RR, relative risk; SAEs, serious adverse events;
Any: any symptom irrespective of intensity grade or relationship to vaccination;
Grade 3: solicited symptoms were defined as grade 3 as follows: (1) pain: cries when limb was moved or spontaneously painful except defined as prevents normal everyday activities and necessitated medical advice in Study Nolan 2002; (2) redness and swelling: injection site surface diameter >20mm; (3) fever: rectal temperature >39.5℃ or axillary temperature >39.0℃; (4) rash: more than 150 lesions; (5) parotid/salivary gland swelling: with accompanying general symptoms; (6) meningism: prevented normal everyday activities;
Related: symptoms considered by the investigator to have a causal relationship to investigational vaccine;
I2: a Mantel-Haenszel fixed-effects model was used to calculate when the test for heterogeneity was not statistically significant (P>0.10), otherwise the DerSimonian-Laird random-effects model was employed; NA: Only one study was included in the meta-analysis in case of that, other studies with the numbers of events in both groups were zero were excluded automatically by the software.
Otitis media: in this part, included Study Cha 2014 reported the incidence of acute otitis media.