Probiotika zur Behandlung von funktionellen Bauchschmerzen bei Kindern
Información
- DOI:
- https://doi.org/10.1002/14651858.CD012849.pub2Copiar DOI
- Base de datos:
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- Cochrane Database of Systematic Reviews
- Versión publicada:
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- 17 febrero 2023see what's new
- Tipo:
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- Intervention
- Etapa:
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- Review
- Grupo Editorial Cochrane:
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Grupo Cochrane de Salud digestiva
- Copyright:
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- Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Autores
Contributions of authors
Chris Wallace took the lead in writing the review; performed screening of titles and abstracts, and full‐text articles; extracted data and contacted authors; checked the quality of data extraction; analysed and interpreted data; undertook and checked risk of bias assessment; performed statistical analysis; checked the quality of the statistical analysis; produced the first draft of the review; contributed to writing and editing the review; made an intellectual contribution to the review; approved the final review prior to submission.
Morris Gordon performed screening of titles and abstracts, and full‐text articles; extracted data and contacted authors; analysed and interpreted data; checked risk of bias assessment; checked the quality of statistical analysis; contributed to writing and editing the review; made an intellectual contribution to the review; approved the final review prior to submission.
Vassiliki Sinopoulou performed screening of titles and abstracts, and full‐text articles; extracted data and contacted authors; checked the quality of data extraction; analysed and interpreted data; undertook and checked risk of bias assessment; performed statistical analysis; checked the quality of the statistical analysis; contributed to writing and editing the review; made an intellectual contribution to the review; approved the final review prior to submission.
Anthony Akobeng initiated and conceptualised the review; supported the analysis; approved the final review prior to submission.
Sources of support
Internal sources
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None, UK
There was no internal funding for this review, however three of the authors (CW, MG and VS) are employed by the University of Central Lancashire and part of their post is to carry out Cochrane systematic reviews.
External sources
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None, Other
None
Declarations of interest
Chris Wallace: none known.
Morris Gordon: no relevant interests; Co‐ordinating Editor, Cochrane Gut.
Vassiliki Sinopoulou: none known.
Anthony K Akobeng: no relevant interests; Physician, Sidra Medicine; Co‐ordinating Editor, Cochrane Gut.
Acknowledgements
Partial funding for the Cochrane Inflammatory Bowel Disease Group (1 April 2016 to 31 March 2018) has been provided by Crohn's and Colitis Canada (CCC). The search strategies were designed and run by Yuhong Yuan (Information Specialist at Cochrane Gut).
Cochrane Gut supported the authors in the development of this review and co‐ordinated the initial peer review process involving: Miranda van Tilburg, Marshall University (clinical/content); Yvan Vandenplas, Vrije Universiteit Brussel, UZ Brussel, KidZ Health Castle (clinical/content); Mahdi Sepidarkish, Babol University of Medical Sciences (statistics). Morris Gordon and Anthony Akobeng are members of Cochrane Gut but were not involved in the editorial process or decision‐making for this review.
The following people conducted the editorial process for this review:
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Sign‐off Editor (final editorial decision): Robert Boyle, Imperial College London, UK; Co‐ordinating Editor of Cochrane Skin.
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Managing Editor (selected peer reviewers, collated peer reviewer comments, provided editorial guidance to authors, edited the article): Joey Kwong, Cochrane Central Editorial Service.
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Editorial Assistant (conducted editorial policy checks and supported editorial team): Leticia Rodrigues, Cochrane Central Editorial Service.
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Copy Editor (copy‐editing and production): Jenny Bellorini, c/o Cochrane Central Production Service.
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Peer reviewers (provided comments and recommended an editorial decision): Nuala Livingstone, Cochrane Evidence Production and Methods Directorate (methods review); Robin Featherstone, Cochrane Central Editorial Service (search review).
Version history
| Published | Title | Stage | Authors | Version |
| 2023 Feb 17 | Probiotics for management of functional abdominal pain disorders in children | Review | Morris Gordon, Chris Wallace, Vassiliki Sinopoulou, Anthony K Akobeng | |
| 2017 Nov 01 | Probiotics for management of functional abdominal pain disorders in children | Protocol | Morris Gordon, Michael Farrell, Adrian G Thomas, Anthony K Akobeng, Chris Wallace | |
Differences between protocol and review
In the original protocol, we had not specified how we would analyse our data in case of high statistical heterogeneity. We have now clarified that data were not pooled for meta‐analysis if a high degree of statistical heterogeneity was detected (I2 > 75%). In case of a high degree of statistical heterogeneity, we investigated whether this could be explained based on clinical grounds or risk of bias, in which case we planned sensitivity analyses. If we could not find any such reasons for the high statistical heterogeneity we planned to present the results narratively, in detail.
The protocol was written seven years ago, meaning that many parts of it were outdated when work started on this review. Therefore, several updates to the protocol were made a priori, and in accordance with current Cochrane standards. The changes include updating the methodology sections to meet modern Cochrane standards, amending texts for clarity and comprehensiveness, and an updated search strategy.
Another difference is the addition of complete resolution of pain as a primary outcome. Originally, we had considered this would be presented under the outcome global improvement/treatment success, however as it is a clinically relevant outcome with huge importance for patients and their families, we decided to add it as a separate outcome when we found out a number of studies were reporting it as such.
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
Medical Subject Headings Check Words
Adolescent; Child; Child, Preschool; Humans;
PICO
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1: Probiotic versus placebo, Outcome 1: Treatment success
Comparison 1: Probiotic versus placebo, Outcome 2: Treatment success (sensitivity analysis: fixed‐effect model)
Comparison 1: Probiotic versus placebo, Outcome 3: Complete resolution of pain
Comparison 1: Probiotic versus placebo, Outcome 4: Complete resolution of pain (sensitivity analysis: risk of bias)
Comparison 1: Probiotic versus placebo, Outcome 5: Severity of pain
Comparison 1: Probiotic versus placebo, Outcome 6: Frequency of pain (episodes per week)
Comparison 1: Probiotic versus placebo, Outcome 7: Frequency of pain (episodes per week) (sensitivity analysis: risk of bias)
Comparison 1: Probiotic versus placebo, Outcome 8: Withdrawals due to adverse events
Comparison 1: Probiotic versus placebo, Outcome 9: Adverse events
Comparison 2: Synbiotics versus placebo, Outcome 1: Treatment success
Comparison 2: Synbiotics versus placebo, Outcome 2: Treatment success (sensitivity analysis: fixed‐effect model)
Comparison 2: Synbiotics versus placebo, Outcome 3: Treatment success (sensitivity analysis: risk of bias)
Comparison 2: Synbiotics versus placebo, Outcome 4: Complete resolution of pain
Comparison 2: Synbiotics versus placebo, Outcome 5: Complete resolution of pain (sensitivity analysis: risk of bias)
Comparison 2: Synbiotics versus placebo, Outcome 6: Severity of pain
Comparison 2: Synbiotics versus placebo, Outcome 7: Frequency of pain (episodes per week)
Comparison 2: Synbiotics versus placebo, Outcome 8: Withdrawals due to adverse events
Comparison 2: Synbiotics versus placebo, Outcome 9: Adverse events
| Probiotic compared to placebo for management of functional abdominal pain disorders in children | ||||||
| Patient or population: children (4 to 18 years) with functional abdominal pain disorders | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with placebo | Risk with probiotics | |||||
| Treatment success (at study end, as reported by study authors) | Study population | RR 1.57 (1.05 to 2.36) | 554 (6 studies) | ⊕⊕⊝⊝ | — | |
| 339 per 1000 | 532 per 1000 | |||||
| Complete resolution of pain (at study end, as reported by study authors) | Study population | RR 1.55 (0.94 to 2.56) | 460 (6 studies) | ⊕⊝⊝⊝ Very low b | — | |
| 272 per 1000 | 422 per 1000 (256 to 696) | |||||
| Severity of pain (at study end, using the Faces Pain Scale) | Severity of pain using the Faces Pain Scale when comparing probiotics versus placebo: SMD ‐0.28 (95% CI ‐0.67 to 0.12) | 665 participants | ⊕⊝⊝⊝ | — | ||
| Frequency of pain (at study end, episodes per week) | Frequency of pain episodes (per week) when comparing probiotics versus placebo: MD ‐0.43 (95% CI ‐0.92 to 0.07) | 605 participants | ⊕⊝⊝⊝ | — | ||
| Withdrawals due to adverse events | Study population | RR 1.00 (0.07 to 15.12) | 544 | ⊕⊝⊝⊝ Very low e | — | |
| 4 per 1000 | 4 per 1000 | |||||
| Serious adverse events | There were no SAEs reported within these studies in either group. | 685 | ⊕⊝⊝⊝ Very low e | — | ||
| Adverse events (any) | Study population | RR 1.00 (0.07 to 15.12) | 489 | ⊕⊝⊝⊝ Very low e | — | |
| 4 per 1000 | 4 per 1000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded one level due to inconsistency (I² = 59% for both outcomes) and one level for risk of bias. bDowngraded three levels due to very high inconsistency (I² = 70%) and risk of bias (allocation concealment, attrition and reporting bias). cDowngraded three levels due to very high inconsistency (I² = 70%) and risk of bias (reporting bias). dDowngraded one level due to risk of bias. eDowngraded two levels due to imprecision because of very low numbers of adverse event cases and one level due to risk of bias. | ||||||
| Synbiotic compared to placebo for management of functional abdominal pain disorders in children | ||||||
| Patient or population: children (4 to 18 years) with functional abdominal pain disorders | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with placebo | Risk with synbiotic | |||||
| Treatment success (at study end, as reported by study authors) | Study population | RR 1.34 (1.03 to 1.74) | 310 | ⊕⊕⊝⊝ | — | |
| 350 per 1000 | 469 per 1000 | |||||
| Complete resolution of pain (at study end, as reported by study authors) | Study population | RR 1.65 (0.97 to 2.81) | 131 (2 studies) | ⊕⊕⊝⊝ | — | |
| 319 per 1000 | 405 per 1000 | |||||
| Severity of pain (at study end, using the Faces Pain Scale) | Severity of pain measured using the Faces Pain Scale for synbiotics versus placebo: MD ‐0.21 (95% CI ‐0.78 to 0.37) | 319 (4 studies) | ⊕⊝⊝⊝ | — | ||
| Frequency of pain (at study end, episodes per week) | The mean in the placebo group was 3.4 | MD 1.26 lower | — | 80 (1 study) | ⊕⊝⊝⊝ | — |
| Withdrawals due to adverse events | Study population | RR 4.58 | 302 | ⊕⊝⊝⊝ | — | |
| 7 per 1000 | 31 per 1000 | |||||
| Serious adverse events | There were no SAEs reported within these studies in either group | 302 | ⊕⊝⊝⊝ | — | ||
| Adverse events (any) | Study population | RR 2.88 | 189 | ⊕⊝⊝⊝ | — | |
| 11 per 1000 | 30 per 1000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded one level for imprecision due to low participant numbers. bDowngraded one level due to risk of bias. cDowngraded two levels due to very serious unexplained heterogeneity, and one level due to risk of bias. dDowngraded two levels for severe risk of bias, due to unclear/high risk of bias for the single study that provided data for this outcome. eDowngraded two levels due to very serious imprecision from very low event numbers, and one level due to risk of bias. | ||||||
| Study ID | Interventional agent | Dosage (amount and frequency) | Control | Dosage (amount and frequency) | Trial registered(prospective/retrospective/none) | Trial registry outcomes published? | Conflicts of interest |
|---|---|---|---|---|---|---|---|
| Synbiotic group: Bifidobacterium coagulans + fructo‐oligosaccharide | 150 million spores of Bifidobacterium coagulans + fructo‐oligosaccharide twice daily | Peppermint group: peppermint oil (Colpermin)
Placebo group: folic acid | Peppermint group: 187 mg 3 times daily
Placebo group: 1 mg once daily | Prospective | Yes | None declared | |
| Synbiotic group: Bifidobacterium lactis B94 + inulin | 5 × 109 CFU Bifidobacterium lactis 900 mg inulin twice daily | Probiotic group: Bifidobacterium lactis
Prebiotic group: inulin
| Probiotic group: 5 × 109 CFU twice daily
Prebiotic group: 900 mg twice daily
| None | NA | None declared, no financial support received | |
| Synbiotic group: Lactobacillus GG + inulin | 1 x 1010 bacteria/capsule twice daily | Prebiotic group: inulin | Dose unstated (1 capsule twice daily) | None | NA | None declared | |
| Probiotic group: Lactobacillus reuteri | 1 x 108 CFU (5 drops per day) | Placebo group: unidentified placebo | Unstated | Retrospective | Yes | None declared, financial support from Zanjan University of Medical Sciences | |
| Probiotic group: Lactobacillus rhamnosus GG | 3 x 109 CFU twice daily | Placebo group: inert powder | Unstated dose twice daily | Retrospective | Yes | None declared, no financial support received | |
| Probiotic group: Lactobacillus rhamnosus GG | 3 x 109 CFU twice daily | Placebo group: powder | Unstated dose twice daily | None | NA | None declared, financial support from the Medical University of Warsaw | |
| Giannetti 2017 (cross‐over) | Probiotic group: Bifidobacterium longum BB536/ Bifidobacterium infantis M‐63/Bifidobacterium breve M‐16V | 1 sachet daily (3 billion/1 billion/1 billion per bacterium) | Placebo group: unidentified placebo | Unstated (1 sachet daily) | Retrospective | Yes | None declared |
| Guandalini 2010 (cross‐over) | Probiotic group: a patented probiotic preparation, which contains live, freeze‐dried lactic acid bacteria, at a total concentration of 450 billion lactic acid bacteria per sachet, comprising 8 different strains: Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus casei, Lactobacillus bulgaris and Streptococcus thermophilus | 1 sachet once daily if 4 to 11 years old or twice daily if 12 to 18 years old | Placebo group: unidentified placebo | 1 sachet once daily if 4 to 11 years old or twice daily if 12 to 18 years old) | None | NA | None declared, funding from locally available grants; no industry support other than providing probiotic and placebo products |
| Probiotic group: Lactobacillus reuteri DSM 17938 (tablet also containing isomalt, xylitol, sucrose distearate, hydrogenated palm oil, lemon‐lime flavouring and citric acid) | 1 x 108 CFU once daily (1 x 450 mg chewable tablet) | Placebo group: tablet containing isomalt, xylitol, sucrose distearate, hydrogenated palm oil, lemon‐lime flavouring and citric acid | Once daily (1 x 450 mg chewable tablet) | Prospective | Yes | None declared, no industry support other than providing probiotic and placebo products | |
| Probiotic group: Lactobacillus reuteri DSM 17938 (tablet also containing isomalt, xylitol, sucrose distearate, hydrogenated palm oil, lemon‐lime flavouring and citric acid) | 1 x 108 CFU once daily (1 x 450 mg chewable tablet) | Placebo group: tablet containing isomalt, xylitol, sucrose distearate, hydrogenated palm oil, lemon‐lime flavouring and citric acid | Once daily (one x 450 mg chewable tablet) | Prospective | Yes | Three contributing authors (Iva Hojsak, Sanja Kolacek, Zrinjka Misak) received either payment/honoraria for lectures or consultation, travel grants or lecture fees from several industry sources. All other authors declare no conflict of interest. | |
| Synbiotic group: Lactobacillus GG + inulin | 1 x 1010 CFU capsule twice daily | Prebiotic group: inulin | Unstated dose (1 capsule twice daily) | Prospective | Yes | None declared, funding received from Mashhad University of Medical Sciences, Iran | |
| Probiotic group: Lactobacillus reuteri DSM 17938 | 2 x 108 CFU (in the form of 2 chewable tablets once daily) | Placebo group: unidentified placebo | Unstated (2 chewable tablets once daily) | Prospective | Yes | Three contributing authors received research grants from BioGaia, 2 authors have been speakers for Biogaia and the remaining author had no conflicts to declare | |
| Synbiotic group | Not stated | Placebo group: unidentified | Not stated | None | NA | Abstract only, none declared | |
| Probiotic group: Lactobacillus reuteri | 1 x 108 CFU twice daily in the form of chewable tables | Placebo group: unidentified | Unstated dose (twice daily in the form of chewable tablets) | None | NA | None declared, funding from research centre | |
| Probiotic group: Lactobacillus reuteri DSM 17938 (product also containing sunflower oil, medium‐chain triglyceride oil from coconut oil) | 1 x 108 CFU twice daily in the form of a 10 mL bottle | Placebo group: product containing sunflower oil, medium‐chain triglyceride oil from coconut oil | 10 mL bottle twice daily | None | NA | None declared | |
| Probiotics group: Lactobacillus GG | Unstated dose | Placebo group: unidentified placebo | Unstated dose | None | NA | Abstract only, none declared | |
| Synbiotic group: Bacillus coagulans + fructo‐oligosaccharide | 150 million spores + fructo‐oligosaccharides 100 mg twice daily in the form of tablets | Placebo group: unidentified placebo | 1 tablet twice daily | Prospective | Yes | None declared, funding from Isfahan University of Medical Sciences | |
| Probiotic group: Lactobacillus reuteri DSM 17938 | 1 x 108 CFU once daily in the form of chewable tablet | Placebo group: unidentified placebo | Once daily in the form of chewable tablet | Prospective | Yes | One author (Zvi Weizman) has been a speaker for Biogaia AB which supplied the probiotic. No other conflicts of interest declared, and statement that Biogaia had no role in 'conception, design, and conduct of the study'. | |
| CFU: colony‐forming unit | |||||||
| Study ID | Methods of diagnosis | FAPD diagnosis | Separate data per sub‐diagnosis reported (yes/no) | Age range | Number of participants | Length of intervention | Time points of outcome measurements |
|---|---|---|---|---|---|---|---|
| Rome III | FAP/IBS/FD | No | 4 to 13 | 54 | 1 month | End of intervention | |
| Rome III | IBS | Not relevant as they only included one | 4 to 16 | 76 | 4 weeks | End of intervention | |
| Rome II | IBS | Not relevant as they only included one | 5 to 17 | 50 | 6 weeks | End of intervention | |
| Rome III | FAP | Not relevant as they only included one | 4 to 16 | 80 | 4 weeks | End of intervention; 4 weeks after end of intervention | |
| Rome II | FAP/IBS | Yes | 5 to 14 | 136 | 8 weeks | End of intervention; 8 weeks after end of intervention | |
| Rome II | FAP/IBS/FD | Yes | 6 to 16 | 104 | 4 weeks | End of intervention | |
| Giannetti 2017 (cross‐over) | Rome III | IBS/FD | Yes | 8 to 17 | 48 | 2 week run‐in period 6 weeks pre‐cross‐over phase 2 weeks washout 6 weeks post‐cross‐over phase | At the end of each period/phase and data combined at the end per intervention |
| Guandalini 2010 (cross‐over) | Rome II | IBS | Not relevant as they only included one | 4 to 18 | 59 | 2 week run‐in period 6 weeks pre‐cross‐over phase 2 weeks washout 6 weeks post‐cross‐over phase | Every 2 weeks and data combined at the end per intervention |
| Rome III | FAP/IBS | No | 4 to 18 | 55 | 12 weeks | 1 month into intervention; end of intervention; 1 month after end of intervention | |
| Rome III | FAP/IBS | No | 4 to 18 | 46 | 12 weeks | 1 month into intervention; end of intervention; 1 month after end of intervention | |
| Rome III | IBS | Not relevant as they only included one | 4 to 18 | 52 | 1 month | Weekly until end of intervention | |
| Rome III | FAP | Not relevant as they only included one | 5 to 16 | 48 | 4 weeks | At 2 weeks and end of intervention | |
| Rome III | FAP/FD | No | Not stated | 80 | 8 weeks | End of intervention | |
| Rome III | FAP/IBS/FD/abdominal migraine | Yes | 6 to 16 | 125 | 4 weeks | At 2 weeks and end of intervention | |
| Rome III | FAP | Not relevant as they only included one | 6 to 16 | 60 | 4 weeks | End of intervention; 4 weeks after end of intervention | |
| Unstated | FAP | Not relevant as they only included one | Unstated | 61 | 6 weeks | End of intervention; 4 weeks after end of intervention | |
| Rome III | FAP | Not relevant as they only included one | 6 to 18 | 115 | 4 weeks | End of intervention; 8 weeks after end of intervention | |
| Rome III | FAP | Not relevant as they only included one | 6 to 15 | 101 | 4 weeks | End of intervention; 4 weeks after end of intervention | |
| FAP: functional abdominal pain | |||||||
| Study ID | 1a. Global improvement or treatment success | 1b. Complete resolution of pain | 1c. Severity of pain | 1d. Frequency of pain |
|---|---|---|---|---|
| NR | NR | Intervention group: 3.93 ± 1.06 Control group: 4.24 ± 1.33 | Intervention group: 2.14 ± 0.87 Control group: 3.40 ± 1.41 | |
| NR | Intervention group 1: 9/26 Intervention group 2: 7/25 Control group: 3/25 | NR | NR | |
| Intervention group: 11/32 Control group: 10/32 | NR | Change in pain intervention group: ‐1.3 (± 0.3) Change in pain control group: ‐1.7 (± 0.6) | NR | |
| No pain episodes per week, end of first month Intervention group: 20; control group: 26
No pain episodes per week, end of second month Intervention group: 19; control group: 21 | NR | End of first month intervention group: mean (SD) 2.50 (1.45); control group: mean (SD) 2.08 (1.56)
End of second month intervention group: mean (SD) 2.53 (1.43); control group: mean (SD) 2.25 (1.46) | At first month intervention group: mean (SD) 0.68 (0.76); control group: mean (SD) 0.40 (0.59)
At second month intervention group: mean (SD) 0.70 (0.75); control group: mean (SD) 0.53 (0.59) | |
| Decrease of at least 50% in the number of episodes and intensity of pain at 12 weeks Intervention group: 48/69; control group: 37/67
Decrease of at least 50% in the number of episodes and intensity of pain at end of follow‐up Intervention group: 53/69; control group: 43/67 | NR | At 12 weeks intervention group: mean (SD) 2.3 (1.3); control group: 3.4 (2.1)
At end of follow‐up intervention group: mean (SD) 0.9 (0.5); control group: 1.5 (1.0) | Number of episodes per week at 12 weeks intervention group: 1.1 (0.8); control group: 2.2 (1.2)
At end of follow‐up intervention group: 0.9 (0.5); control group: 1.5 (1.0) | |
| NR | Intervention group: 13/52 (FD 1/10, IBS 6/18, FAP 6/24)
Control group: 5/52 (FD 2/10, IBS 6/18, FAP 2/23) | At 4 weeks Intervention group: mean 2.5 (SD ± 1.9) (FD 2.9 ± 1.5, IBS 2.2 ± 2.1, FAP 2.6 ± 2.0) Control group: mean 2.9 (SD ± 1.5) (FD 1.9 ± 1.3, IBS 3.2 ± 1.5, FAP 3.0± 1.5) | At 4 weeks Intervention group: mean 2.2 (SD ± 1.7) (FD 2.7 ± 1.3, IBS 1.8 ± 1.7, FAP 2.3 ± 1.8) Control group: mean 2.6 (SD ± 1.4) (FD 2.0 ± 1.6, IBS 3.1 ± 1.1, FAP 2.4 ± 1.4) | |
| Giannetti 2017 (cross‐over) | NR | Not clear as the authors have combined pre‐ and post‐ cross‐over data | Not clear as the authors have combined pre‐ and post‐ cross‐over data | Not clear as the authors have combined pre‐ and post‐ cross‐over data |
| Guandalini 2010 (cross‐over) | NR | NR | Not clear as the authors have combined pre‐ and post‐ cross‐over data | Not clear as the authors have combined pre‐ and post‐ cross‐over data |
| NR | Intervention group: 16/26 Control group: 16/29 | End of first month intervention group/control group: 0.75/0.96 End of second month intervention group/control group: 0.17/0.64 End of third month intervention group/control group: 0.32/0.71 End of fourth month intervention group/control group: 0.21/0.6
Difference in the severity of pain between first and fourth month, Wong‐Baker FACES/day intervention group: median 0.42 (range 0.31 to 2.9); control group: median 0.23 (range 1.2 to 2.2) | Number of days without pain intervention group at 4 months: 89.5 (range 5 to 108); control group at 4 months: 51 (range 0 to 107) | |
| NR | Intervention group: 10/24 Control group: 9/22 | End of first month intervention group/control group: 1.35 (IQR 0.64 to 1.98)/1.1 (IQR 0.76 to 2.04) End of second month intervention group/control group: 1.0 (IQR 0.09 to 2.12)/0.8 (IQR 0.37 to 1.68) End of third month intervention group/control group: 0.83 (IQR 0.025 to 2.26)/0.78 (IQR 0.43 to 2.0) End of fourth month intervention group/control group: 0.035 (IQR 0 to 1.0)/0.81 (IQR 0.2 to 1.48)
Change in severity of pain from 1st to 4th month intervention group: 0.55 (IQR 0.28 to 0.55); control group: median 0.36 (IQR ‐0.14 to 0.36) | Number of days without pain intervention group at 4 months: 90 (IQR 54 to 99); control group at 4 months: 59.5 (IQR 21.5 to 89.25) | |
| NR | NR | 1 week: intervention group/control group 1.5 (1.0)/1.8 (0.6) 2 weeks: intervention group/control group 1.2 (1.1)/1.9 (0.8) 3 weeks: intervention group/control group 1.0 (0.9)/1.8 (0.6) 4 weeks: intervention group/control group 0.8 (0.9)/1.5 (0.8) | NR | |
| Reduction in pain score of greater than 50% at 4 weeks intervention group: 19/27 (70.4%); control group: 16/27 (58.3%)
Reduction in pain score of greater than 50% at 8 weeks intervention group: 17/25 (65.4%); control group: 13/23 (56.5%) | NR | Intervention group/control group: mean (SD) 2 weeks: 10.4 (18.8)/12.2 (17.3) 4 weeks: 4.3 (8.5)/4.0 (5.6) 8 weeks: 7.2 (17.7)/2.5 (3.4) | Intervention group/control group: mean (SD) 2 weeks: 5.6 (8.1)/8.2 (10.7) 4 weeks: 2.9 (4.5)/3.1 (4.1) 8 weeks: 4.8 (9.9)/2.8 (3.3) | |
| NR | Intervention group: 25/39 Control group: 18/41 | NR | NR | |
| Intervention group = 32/65 (FAP 13/28, FD 11/16, IBS 6/15, AM 2/6)
Control group = 8/60 (FAP 8/29, FD 0/13, IBS 0/6, AM, 0/3)
| NR (in Rahmani 2020, treatment success was defined as pain intensity = 0) | Text: severity at 4 weeks in intervention group = 1.3 ± 1.1 (Table 1 reports: 1.1 ± 1.3)
Text: severity at 4 weeks in control group = 1 ± 2 (Table 1 reports: 2 ± 1)
FAP (intervention group/control group): 1.2 ± 1.3; 2 ± 1 FD (intervention group/control group): 0.8 ± 1.5; 2.0 ± 6 IBS (intervention group/control group): 1.4 ± 1.4; 2.8 ± 0.8 AM (intervention group/control group): 1.3 ± 1.5; 2.3 ± 0.5 | Text: frequency of repetitive pain at 4 weeks intervention group 3.6 ± 2.2 (Table 1 reports: intervention group 2.2 ± 3.6)
Text: frequency of repetitive pain at 4 weeks control group 4.6 ± 4.9 (Table 1 reports: control group 4.9 ± 4.6)
FAP (intervention group/control group): 2.1 ± 2.7; 4.1 ± 4.4 FD (intervention group/control group): 1.6 ± 3.0; 6.0 ± 5.0 IBS (intervention group/control group): 3.7 ± 5.5; 6.3 ± 0.8 AM (intervention group/control group): 1.1 ± 0.9; 1.3 ± 0.5 | |
| NR | NR | Mean (SD) as we interpreted it from the figures: Week 4 intervention group/control group: 1.25 (0.9)/2 (0.8) Week 8 intervention group/control group: 1 (0.7)/2 (0.8) | Mean (SD) as we interpreted it from the figures: Week 4 intervention group/control group: 1.4 (1.1)/2.2 (0.5) per day Week 8 intervention group/control group: 2.1 (0.6)/2 (0.5) per day | |
| NR | NR | NR | NR | |
| Response at week 4 intervention group: 27/45; control group: 17/43
Response at week 12 intervention group: 29/45; control group: 23/43 | NR | Change in pain scale from start of intervention to week 4 intervention group: mean ‐1.7 (SD ± 1.5); control group: mean ‐1.6 (SD ± 1.5)
Change in pain scale from start of intervention to week 12 intervention group: mean ‐2.1 (SD ± 1.4); control group: mean ‐1.8 (SD ± 1.4) | NR | |
| NR | NR | Improvement in intensity of abdominal pain at 4 weeks intervention group: mean 4.3 (SD ± 2.7); control group: mean 7.2 (SD ± 3.1)
Improvement in intensity of abdominal pain at end 8 weeks intervention group: mean 4.8 (SD ± 3.3); control group: mean 6.4 (SD ± 4.1) | Number of episodes of pain per week at 4 weeks intervention group: mean 1.9 (SD ± 0.8); control group: mean 3.6 (SD ± 1.7)
Number of episodes of pain per week at 8 weeks intervention group: mean 3.4 (SD ± 2.6); control group: mean 4.4 (SD ± 2.9)
| |
| Numbers presented as per the original study reports. AM: abdominal migraine | ||||
| Study ID | 2a. Serious adverse events | 2b. Withdrawal due to adverse events | 2c. Adverse events | 2d. School performance | 2e. Social and psychological functioning | 2f. Quality of life |
|---|---|---|---|---|---|---|
| 0 | 0 | 0 | NR | NR | NR | |
| NR | Intervention group 1: 3 | Intervention group 1: 3 | NR | NR | NR | |
| 0 | 0 | 0 | NR | NR | NR | |
| 0 | 0 | 0 | NR | NR | NR | |
| NR | NR | NR | NR | NR | NR | |
| 0 | 0 | 0 | School absenteeism at end of intervention | NR | NR | |
| Giannetti 2017 (cross‐over) | 0 | 0 | 0 | NR | NR | NR |
| Guandalini 2010 (cross‐over) | 0 | 0 | 0 | NR | NR | Questionnaire of disruption to family life (change in score) Intervention group: mean ‐0.9 (SD ± 0.2); control group: mean ‐0.51 (SD ± 0.3) |
| NR | 0 | NR | NR | NR | NR | |
| 0 | 0 | 0 | NR | NR | NR | |
| 0 | 0 | 0 | NR | Functional changes on a 3 point Likert scale at end of intervention Intervention group: mean 2.4 (SD ± 0.5); control group: mean 1.9 (SD ± 0.4) | NR | |
| 0 | 0 | 0 | Average number of school absences per week at end of follow‐up Intervention group: mean 0.0 (SD ± 0.0); control group: mean 0.11 (SD ± 0.52) | NR | NR | |
| NR | NR | NR | NR | NR | NR | |
| NR | NR | NR | NR | NR | NR | |
| 0 | 0 | 0 | NR | NR | NR | |
| NR | NR | NR | NR | NR | NR | |
| 0 | Intervention group: 5; control group:0 | NR as numbers of people with adverse events
Total number of adverse events intervention group: 45; control group: 43 | NR | NR | NR | |
| 0 | 0 | 0 | Days of school absenteeism over 4 weeks Intervention group: mean 2.7 (SD ± 0.9); control group: mean 1.9 (SD ± 1.1) | NR | NR | |
| Numbers presented as per the original study reports. NR: not reported | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Treatment success Show forest plot | 6 | 554 | Risk Ratio (M‐H, Random, 95% CI) | 1.57 [1.05, 2.36] |
| 1.1.1 Lactobacillus reuteri | 3 | 259 | Risk Ratio (M‐H, Random, 95% CI) | 1.57 [0.73, 3.37] |
| 1.1.2 Lactobacillus rhamnosus GG | 2 | 245 | Risk Ratio (M‐H, Random, 95% CI) | 1.57 [0.73, 3.34] |
| 1.1.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 2.33 [0.68, 8.01] |
| 1.2 Treatment success (sensitivity analysis: fixed‐effect model) Show forest plot | 6 | 554 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.49 [1.23, 1.80] |
| 1.2.1 Lactobacillus reuteri | 3 | 259 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.58 [1.17, 2.12] |
| 1.2.2 Lactobacillus rhamnosus GG | 2 | 245 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.36 [1.07, 1.72] |
| 1.2.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.33 [0.68, 8.01] |
| 1.3 Complete resolution of pain Show forest plot | 6 | 460 | Risk Ratio (M‐H, Random, 95% CI) | 1.55 [0.94, 2.56] |
| 1.3.1 Lactobacillus reuteri | 4 | 306 | Risk Ratio (M‐H, Random, 95% CI) | 1.35 [0.76, 2.41] |
| 1.3.2 Lactobacillus rhamnosus GG | 1 | 104 | Risk Ratio (M‐H, Random, 95% CI) | 2.60 [1.00, 6.77] |
| 1.3.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 2.33 [0.68, 8.01] |
| 1.4 Complete resolution of pain (sensitivity analysis: risk of bias) Show forest plot | 5 | 335 | Risk Ratio (M‐H, Random, 95% CI) | 1.18 [0.84, 1.67] |
| 1.4.1 Lactobacillus reuteri | 3 | 181 | Risk Ratio (M‐H, Random, 95% CI) | 1.01 [0.76, 1.34] |
| 1.4.2 Lactobacillus rhamnosus GG | 1 | 104 | Risk Ratio (M‐H, Random, 95% CI) | 2.60 [1.00, 6.77] |
| 1.4.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 2.33 [0.68, 8.01] |
| 1.5 Severity of pain Show forest plot | 7 | 665 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.28 [‐0.67, 0.12] |
| 1.5.1 Faces scales | 6 | 524 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.19 [‐0.61, 0.23] |
| 1.5.2 Combination VAS‐Faces scale | 1 | 141 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.76 [‐1.10, ‐0.41] |
| 1.6 Frequency of pain (episodes per week) Show forest plot | 6 | 605 | Mean Difference (IV, Random, 95% CI) | ‐0.43 [‐0.92, 0.07] |
| 1.6.1 Lactobacillus reuteri | 4 | 360 | Mean Difference (IV, Random, 95% CI) | ‐0.43 [‐1.42, 0.56] |
| 1.6.2 Lactobacillus rhamnosus GG | 2 | 245 | Mean Difference (IV, Random, 95% CI) | ‐0.57 [‐0.81, ‐0.33] |
| 1.7 Frequency of pain (episodes per week) (sensitivity analysis: risk of bias) Show forest plot | 4 | 400 | Mean Difference (IV, Random, 95% CI) | ‐0.58 [‐0.81, ‐0.35] |
| 1.7.1 Lactobacillus reuteri | 2 | 155 | Mean Difference (IV, Random, 95% CI) | ‐0.12 [‐2.80, 2.55] |
| 1.7.2 Lactobacillus rhamnosus GG | 2 | 245 | Mean Difference (IV, Random, 95% CI) | ‐0.57 [‐0.81, ‐0.33] |
| 1.8 Withdrawals due to adverse events Show forest plot | 8 | 544 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.07, 15.12] |
| 1.8.1 Lactobacillus reuteri | 6 | 390 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.8.2 Lactobacillus rhamnosus GG | 1 | 104 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.8.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.07, 15.12] |
| 1.9 Adverse events Show forest plot | 7 | 489 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.07, 15.12] |
| 1.9.1 Lactobacillus reuteri | 5 | 335 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.9.2 Lactobacillus rhamnosus GG | 1 | 104 | Risk Ratio (M‐H, Random, 95% CI) | Not estimable |
| 1.9.3 Bifidobacterium lactis | 1 | 50 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.07, 15.12] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Treatment success Show forest plot | 4 | 310 | Risk Ratio (M‐H, Random, 95% CI) | 1.34 [1.03, 1.74] |
| 2.2 Treatment success (sensitivity analysis: fixed‐effect model) Show forest plot | 4 | 310 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.36 [1.04, 1.77] |
| 2.3 Treatment success (sensitivity analysis: risk of bias) Show forest plot | 3 | 230 | Risk Ratio (M‐H, Random, 95% CI) | 1.27 [0.88, 1.82] |
| 2.4 Complete resolution of pain Show forest plot | 2 | 131 | Risk Ratio (M‐H, Random, 95% CI) | 1.65 [0.97, 2.81] |
| 2.5 Complete resolution of pain (sensitivity analysis: risk of bias) Show forest plot | 1 | 51 | Risk Ratio (M‐H, Random, 95% CI) | 2.88 [0.88, 9.44] |
| 2.6 Severity of pain Show forest plot | 4 | 319 | Mean Difference (IV, Random, 95% CI) | ‐0.21 [‐0.78, 0.37] |
| 2.6.1 Likert scales | 2 | 124 | Mean Difference (IV, Random, 95% CI) | ‐0.13 [‐1.21, 0.94] |
| 2.6.2 Faces scales | 1 | 115 | Mean Difference (IV, Random, 95% CI) | ‐0.30 [‐0.81, 0.21] |
| 2.6.3 Visual analogue scales | 1 | 80 | Mean Difference (IV, Random, 95% CI) | ‐0.31 [‐0.84, 0.22] |
| 2.7 Frequency of pain (episodes per week) Show forest plot | 1 | 80 | Mean Difference (IV, Random, 95% CI) | ‐1.26 [‐1.77, ‐0.75] |
| 2.8 Withdrawals due to adverse events Show forest plot | 4 | 302 | Risk Ratio (M‐H, Random, 95% CI) | 4.58 [0.80, 26.19] |
| 2.9 Adverse events Show forest plot | 3 | 189 | Risk Ratio (M‐H, Random, 95% CI) | 2.88 [0.32, 25.92] |
