Table 2 Characteristics of the included studies

Wysoski et al. 2017

[24]

Poland, 2017, RCT, non blinded

908

PCV13 (Prevenar™, Pfizer) DTaP/HBV/IPVHIb (Infarix Hexa™, GSK)

2, 3, 4 m/12 m

Paracetamol Syr (15 mg/kg/dose) Ibuprofen Syr (10 mg/kg/dose) 2 or 3doses/6–8 h for 24 h.

t:0 h or t: 6-8 h

ΙgG GMCs 1 m post-primary and booster dose (sp cut off: GMCs ≥0.35 μg/ml-non-22F ELISA) OPA GMTs in study subset

Post Primary: GMCs for all serotypes in PARA lower vs NPARA

(Serotypes 3, 4, 5, 6B, 23 in IPARA, p < 0.0125).

OPA GMTs detected no differences.

Post booster: No effect

Falup et al. 2017

[23]

Romania, 2016, RCT, Open label, unblinded

850

PCV10 (Synflorix™, GSK) DTPa-HBV-IPV/Hib (Infanrix Hexa™, GSK)

3, 4, 5 m/12–15 m

Paracetamol Syr (15 mg/kg/dose) Ibuprofen Syr (10 mg/kg/dose) 3 doses/ 6–8 h for 24 h.

t:0 h or t: 4-6 h

ΙgG GMCs 1 m post-primary and booster dose (sp cut off: GMCs ≥0,2 μg/ml-22F-inhibition ELISA)

Post primary: % GMCs ≥0.2 μg/mL lower in IPARA and DPARA vs NPARA (highest difference for 6B serotype)

GMCS for serotypes 1, 4, 5, 9 V, 14, 18C in IPARA and 1,6B in DPARA lower vs NPARA.

Post booster: GMCs in IPARA-ΝPARA and the majority of participants in DPARA-IPARA lower vs NPARA-NPARA

Prymula et al. 2014

[22]

Czech Republic, 2014, RCT, Open label, unblinded

558

PCV7 (Prevenar™, Pfizer)

4CMenB (Bexsero™, Novartis) DTaP-HBV-IPV/Hib (Infanrix Hexa GSK)

2, 3, 4 m/12 m

Paracetamol Syr (10-15 mg/kg) 3 doses/ 4–6 h for 24 h.

t:0 h

ΙgG GMCs 1 m post-primary and booster dose (sp cut-off: GMCs ≥0.35 μg/ml non-22F ELISA)

GMCs for all serotypes in PARA lower vs NPARA (no statistical significance)

Prymula et al. 2013

[17]

Czech Republic, 2012, RCT, unblinded (Follow up of Prymula et al. 2009)

443

PCV10 (Synflorix GSK)

31–44 m (2nd booster dose)

Paracetamol only at primary and 1st booster dose

ΙgG GMCs before and 7–10 days after 2nd booster dose (sp cut-off: GMCs ≥0,2 μg/ml-22F-inhibition ELISA)

OPA GMTs

Before the 2nd booster: GMCs for serotypes 1, 4, 5 in PARA lower vs NPARA (borderline statistical significance). Higher OPA GMTs for serotypes 4, 5, 19F in NPARA.

Post 2nd booster: GMCs with serotypes 1, 4, 9 V, 7B lower in PARA. Immunological memory robust increase in GMCs and OPA GMTs- irrespective of paracetamol use. No effect on nasopharyngeal carriage.

Prymula et al. 2009

[21]

Czech Republic, 2009, RCT, unblinded

459

PCV10 (Synflorix GSK) DTaP/HBV/IPV/HIb (Infarix Hexa GSK) HRV (Rotarix GSK)

3, 4, 5 m./12–15 m

Paracetamol Supp (80-125 mg/dose) 3 doses/ 6–8 h for 1 24 h)

t:0 h

ΙgG GMCs 1 m post-primary and booster dose (sp cut-off: GMCs ≥0,2 μg/ml-22F-inhibition ELISA)

OPA GMTs

Post primary: GMCs for all serotypes, % GMCs ≥0·20 μg/mL for 6B serotype and OPA GMTs for serotypes 1, 5, 6B lower in IPARA (p < 0,05) vs NPARA Post toddler dose: GMCs persisted lower in IPARA for all serotypes, apart from 19F (p < 0,05). OPA GMTs for 1, 4, 5, 6B, 19F serotypes in IPARA lower vs NPARA (p < 0,05). Similar booster response.