Background Recent systematic reviews and meta-analyses on the efficacy of probiotics in the treatment of functional constipation in children have yielded conflicting results. Objectives The aim of this study was to critically review and update the evidence in this field by mapping all the steps involved against those reported in previous reviews, in an attempt to understand the nature of their conflicting results. Methods Four literature databases, trial registries, and citations were searched through December 1, 2018. We included randomized controlled trials (RCTs) that assessed the effects of probiotics compared with placebo or treatment as usual on defecation frequency [bowel movements (BMs)/wk] or treatment success rates in children with functional constipation. Independent reviewers extracted the data and assessed risk of bias in each RCT. Data were pooled with (inverse variance) random-effects models. Results We identified 17 RCTs, of which 14 and 11 provided sufficient data to enable meta-analysis of the effects of probiotics compared with control on defecation frequency (n = 965) or treatment success (n = 835), respectively. When compared to (any) control intervention, probiotics did not significantly increase defecation frequency [weighted mean difference (WMD): 0.28 BMs/wk; 95% CI: −0.12, 0.69; P = 0.165] but were more efficacious in achieving treatment success (RR: 1.24; 95% CI: 1.03, 1.50; P = 0.024). These effects did not differ by type of control (i.e., active or inactive) intervention. However, in analyses confined to the RCTs that were free of high risk of bias (only 5), probiotics did not confer any beneficial effects on defecation frequency (WMD: −0.55 BMs/wk; 95% CI: −1.37, 0.26; P = 0.185) and achievement of treatment success (RR: 1.01; 95% CI: 0.90, 1.13; P = 0.873), compared with control interventions. Conclusions The current evidence thus does not support the use of probiotics as a single or coadjuvant therapy for treatment of functional constipation in children and refutes recently published reviews reporting favorable effects of probiotics. Conflicting findings of previous reviews resulted from methodologic errors, highlighting the susceptibility of evidence synthesis to oversights in study selection, quality assessments, and data extraction and collation. This review was registered at PROSPERO as CRD42019119109.

High risk of bias associated with missing outcome data (MOD) in meta-analyses (MAs) of the effects of lifestyle interventions during pregnancy on postpartum weight retention (PPWR) casts doubt on whether such interventions can be relied upon as truly effective. This systematic overview of three MAs (19 RCTs), each with high MOD rates in the subset of RCTs included, examined how MOD were addressed in the estimation of summary intervention effects. All MAs reported beneficial and statistically significant intervention effects estimated based on complete case analyses, deemed valid if MOD was missing at random (MAR). Therefore, we conducted sensitivity analyses using pattern mixture models and informative missingness parameters (describing how the outcome in the missing participants may be related to the outcome in the completers), to ascertain the robustness of the estimates to reasonable deviations from the MAR assumption. In plausible scenarios where the response in intervention group participants with versus without MOD was worse (by just 0.5 kg), effect estimates were attenuated in all MAs and no longer statistically significant in two MAs. Statistical significance was retained when all 19 RCTs identified across MAs were examined together in a broader meta-analysis: À0.63 kg (95%CI À0.17, À0.08), but the clinical relevancy of effects of this magnitude remains unclear.

Background High risk of bias associated with missing outcome data (MOD) in meta-analyses (MAs) of the effects of lifestyle interventions during pregnancy on postpartum weight retention (PPWR), casts doubt on whether such interventions can be relied upon as truly effective, since estimates are deemed valid only if MOD was missing at random (MAR). Methods We conducted a systematic overview of MAs to examine the impact of MOD on the estimation of meta-analytic summary intervention effects and conducted sensitivity analyses using pattern mixture models and informative missingness parameters (describing how the outcome in the missing participants may be related to the outcome in the completers), to ascertain the robustness of the estimates to reasonable deviations from the MAR assumption. Results Three relevant MAs were identified, all with high MOD rates in the RCTs included (median>30%), and all reporting beneficial intervention effects on PPWR (in kg) estimated based on complete case analyses: [-0.78 (95%CI: -1.39,-0.16), -0.81 (-1.57,-0.06), and -0.94 (-1.52,-0.37)] in MAs of any lifestyle, exercise, or diet + exercise interventions, respectively. In plausible scenarios where the outcome for the intervention group in participants with vs without MOD was worse (by 0.5kg), effect estimates were attenuated in all and no longer significant in 2 of the MAs [-0.58 (-1.29,0.13), -0.70 (-1.50,0.10) and -0.88 (-1.73,-0.02)]. Conclusions Statistical significance was retained when all 19 RCTs identified across MAs were meta-analysed: -0.63 (-0.17,-0.08). Key messages The clinical relevancy of effects of this magnitude remains unclear.

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