If these statistical measures were not available then the methods described in section 16.1.3 of the Cochrane Handbook (version 5.1.0, updated March 2011) were applied. 4.3.3.1.1 Generic inverse variance If a study reported only the summary statistic and 95% CI the generic-inverse variance method was used to enter data into RevMan5.283 If the control event rate was reported this was used to generate the absolute risk difference in GRADEpro.138 If multivariate analysis was used to derive the summary statistic but no adjusted control event rate was reported no absolute risk difference was calculated. Statistical heterogeneity was assessed for each meta-analysis estimate by considering the chi- squared test for significance at p<0.1 or an I-squared (I2 ) inconsistency statistic (with an I-squared value of more than 50% indicating significant heterogeneity) as well as the distribution of effects. Where significant heterogeneity was present, predefined subgrouping of studies was carried out as specified a priori in the review protocols (appendix A). If the subgroup analysis resolved heterogeneity within all of the derived subgroups, then each of the derived subgroups were adopted as separate outcomes (providing at least 1 study remained in each subgroup. Assessments of potential differences in effect between subgroups were based on the chi- squared tests for heterogeneity statistics between subgroups. Any subgroup differences were interpreted with caution as separating the groups breaks the study randomisation and as such is subject to uncontrolled confounding. For some questions additional subgrouping was applied, and this is documented in the individual review question protocols (see appendix A). These additional subgrouping strategies were applied independently, so subunits of subgroups were not created, unlike the situation with strata. Other subgrouping strategies were only used if the age category subgroup was unable to explain heterogeneity, then these further subgrouping strategies were applied in order of priority. 