When poorly conducted systematic reviews and meta-analyses can mislead: a critical appraisal and update of systematic reviews and meta-analyses examining the effects of probiotics in the treatment of functional constipation in children

Abstract

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.

Exploring perceptions, barriers and use of systematic reviews amongst nutrition professionals and nutrition students

“…This aligns with previous results, with this term ranking second as a term misunderstood by dietitians in a similar study . This pattern of results are of interest given the rapid increase in the publication of both SRs and meta‐analyses, as well as continuing concern regarding the quality of many of these analyses . These results highlight the need for opportunities for training and mentoring for those conducting SRs, including a specific focus on meta‐analyses, to improve confidence in interpreting results, and ensure SRs produced in the field of nutrition are of high methodological quality.…”

Functional Constipation and the Gut Microbiome in Children: Preclinical and Clinical Evidence

“…Only one RCT showed significant improvement in stool frequency and consistency, and reduction in abdominal pain using Lactobacillus casei rhamnosus Lcr35 (64), however, these findings were contradicted by a later trial (65), and the pooled results of the two RCTs showed no statistical significance for treatment success (66). Previous systematic reviews (66)(67)(68)(69) have also demonstrated insufficient evidence to recommend the use of prebiotics, probiotics, or synbiotics in the treatment of childhood FC, and highlighted important inconsistencies and methodologic errors in prior systematic reviews (70). Table 2 depicts the characteristics of studies assessing the effects of probiotics on children with constipation.…”

Paediatric constipation for general paediatricians: Review using a case‐based and evidence‐based approach

“…33 A combined high dose of PEG with sodium picosulphate shortens the time needed 34 ( 38 Targeting treatments for the dysbiosis of constipation by probiotics, prebiotics, antibiotics have been popular and have been evaluated in a number of trials. However, the current evidence does not support the use of probiotics as a single or coadjuvant therapy in the treatment of constipation [39][40][41] Recently 'faecal microbiota transplant' has been introduced in adults as a new and promising therapeutic option.42 However, there is no data in children and it is not recommended at present. • Prucalopride a highly specific 5-HT4 receptor agonist with enterokinetic properties and has been found to safe to use in children with FC.…”

“…Probiotics have no significant effect on treatment success rate compared with placebo. Probiotic supplementation might result in reduced frequency of glycerin enema use and abdominal pain Harris et al 41 17 RCTs n = 965…”