Date	Event	Description
29 March 2019	New citation required and conclusions have changed	With this 2019 update, further information on the effect of PHiD‐CV10/11 for the prevention of acute otitis media (AOM) has become available. Administration of the licenced CRM197‐PCV7 and PHiD‐CV10 during early infancy is associated with large relative risk reductions in pneumococcal AOM. However, the effects of these vaccines on all‐cause AOM is far more uncertain. We found no evidence of a beneficial effect on all‐cause AOM of administering pneumococcal conjugate vaccines (PCVs) in high‐risk infants, after early infancy (i.e. in children aged one year and above) and in older children with a history of respiratory illness. Compared to control vaccines, PCVs were associated with an increase in mild local reactions (redness, swelling), fever, and pain/tenderness, but we found no evidence of a difference in more severe local reactions, fever, or serious adverse events judged to be causally related to vaccination.
29 March 2019	New search has been performed	We updated the searches and included three new publications: two new randomised controlled trials (RCTs) (Tregnaghi 2014; Vesikari 2016), and one new trial publication (Sáez‐Llorens 2017), which reported outcome data relevant for this review as part of a secondary analysis of Tregnaghi 2014. We excluded five new trial publications (secondary analyses of previously included RCTs) (Palmu 2014; Palmu 2015a; Palmu 2015b; Palmu 2018; Sarasoja 2013), since they did not report outcome data relevant to this review. We did not identify any ongoing studies. The 14 included publications in this review originate from 11 RCTs (60,733 children) in total: Black 2000/Fireman 2003; Dagan 2001; Eskola 2001/Palmu 2009; Jansen 2008; Kilpi 2003; O'Brien 2008; Prymula 2006; Tregnaghi 2014/Sáez‐Llorens 2017; van Kempen 2006; Veenhoven 2003; Vesikari 2016. Seven trials (59,415 children), Black 2000/Fireman 2003; Eskola 2001/Palmu 2009; Kilpi 2003; O'Brien 2008; Prymula 2006; Tregnaghi 2014/Sáez‐Llorens 2017; Vesikari 2016, included infants who predominantly received primary vaccinations before six months of age (Black 2000/Fireman 2003; Eskola 2001/Palmu 2009; Kilpi 2003; O'Brien 2008; Prymula 2006; Tregnaghi 2014/Sáez‐Llorens 2017; Vesikari 2016), while the other four trials (1318 children), Dagan 2001; Jansen 2008; van Kempen 2006; Veenhoven 2003, assessed the effects of PCVs administered at a later age on AOM in either healthy infants, Dagan 2001, or in children with a history of respiratory illness or frequent AOM (Jansen 2008; van Kempen 2006; Veenhoven 2003). We added 'adverse effects' as co‐primary outcome.
21 February 2014	New search has been performed	With this update, more precise information on the effect of PCV7 for the prevention of otitis media has become available. We judged the quality of the evidence for PCV7 in both early infancy and older children to be high, with further research very unlikely to change our confidence in the estimate of effect. Based on current evidence of the effects of pneumococcal conjugate vaccines (PCVs) for preventing acute otitis media (AOM), the licenced 7‐valent PCV has modest beneficial effects in healthy infants with a low baseline risk of AOM. Administering PCV7 in high‐risk infants, after early infancy, and in older children with a history of AOM appears to have no benefit in preventing further episodes. Several randomised controlled trials (RCTs) with different (newly licensed, multivalent) PCVs administered during early infancy to establish their effects on AOM are currently ongoing. The results of these studies may provide a better understanding of the role of the newly licenced, multivalent PCVs in preventing AOM. Also, the impact of the carrier protein D, as used in certain pneumococcal vaccines for AOM, needs to be further established.
3 December 2013	New search has been performed	Three new review authors joined the team to update this review. The updated search (November 2007 to December 2013) retrieved 171 records. After removal of duplicates 165 records remained. After full‐text review, three new publications (Palmu 2009; Prymula 2006; van Kempen 2006) remained for inclusion. One study was an additional analysis of the previous included Eskola 2001 study. We identified five ongoing RCTs (NCT00466947; NCT00861380; NCT01545375; NCT01735084; NCT01174849). The 11 included studies in this review concerned a total of nine RCTs: (1) Black 2000/Fireman 2003; (2) Dagan 2001; (3) Eskola 2001/Palmu 2009; (4) Kilpi 2003; (5) Prymula 2006; (6) van Kempen 2006; (7) Veenhoven 2003; (8) Jansen 2008; and (9) O'Brien 2008. Five trials (Black 2000/Fireman 2003; Eskola 2001/Palmu 2009; Kilpi 2003; O'Brien 2008; Prymula 2006) (n = 47,108) included healthy infants and studied the effect of PCV administered in early infancy on otitis media (OM), while the other four trials (n = 1318), Dagan 2001; Jansen 2008; van Kempen 2006; Veenhoven 2003, assessed the effects of PCV administered at a later age on OM in either healthy infants, Dagan 2001, or in children with a known history of respiratory disease including OM (Jansen 2008; van Kempen 2006; Veenhoven 2003).
29 April 2008	New citation required but conclusions have not changed	New review authors
28 April 2008	Amended	Converted to new review format
15 November 2007	New search has been performed	Searches conducted
26 November 2003	New citation required and conclusions have changed	Substantive amendment
29 June 2003	New search has been performed	Searches conducted
19 August 2000	New search has been performed	Searches conducted