Dietary interventions for recurrent abdominal pain in childhood

Abstract

Background: This is an update of the original Cochrane review, last published in 2009 (Huertas-Ceballos 2009). Recurrent abdominal pain (RAP), including children with irritable bowel syndrome, is a common problem affecting between 4% and 25% of school-aged children. For the majority of such children, no organic cause for their pain can be found on physical examination or investigation. Many dietary inventions have been suggested to improve the symptoms of RAP. These may involve either excluding ingredients from the diet or adding supplements such as fibre or probiotics.

Objectives: To examine the effectiveness of dietary interventions in improving pain in children of school age with RAP.

Search methods: We searched CENTRAL, Ovid MEDLINE, Embase, eight other databases, and two trials registers, together with reference checking, citation searching and contact with study authors, in June 2016.

Selection criteria: Randomised controlled trials (RCTs) comparing dietary interventions with placebo or no treatment in children aged five to 18 years with RAP or an abdominal pain-related, functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006).

Data collection and analysis: We used standard methodological procedures expected by Cochrane. We grouped dietary interventions together by category for analysis. We contacted study authors to ask for missing information and clarification, when needed. We assessed the quality of the evidence for each outcome using the GRADE approach.

Main results: We included 19 RCTs, reported in 27 papers with a total of 1453 participants. Fifteen of these studies were not included in the previous review. All 19 RCTs had follow-up ranging from one to five months. Participants were aged between four and 18 years from eight different countries and were recruited largely from paediatric gastroenterology clinics. The mean age at recruitment ranged from 6.3 years to 13.1 years. Girls outnumbered boys in most trials. Fourteen trials recruited children with a diagnosis under the broad umbrella of RAP or functional gastrointestinal disorders; five trials specifically recruited only children with irritable bowel syndrome. The studies fell into four categories: trials of probiotic-based interventions (13 studies), trials of fibre-based interventions (four studies), trials of low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diets (one study), and trials of fructose-restricted diets (one study).We found that children treated with probiotics reported a greater reduction in pain frequency at zero to three months postintervention than those given placebo (standardised mean difference (SMD) -0.55, 95% confidence interval (CI) -0.98 to -0.12; 6 trials; 523 children). There was also a decrease in pain intensity in the intervention group at the same time point (SMD -0.50, 95% CI -0.85 to -0.15; 7 studies; 575 children). However, we judged the evidence for these outcomes to be of low quality using GRADE due to an unclear risk of bias from incomplete outcome data and significant heterogeneity.We found that children treated with probiotics were more likely to experience improvement in pain at zero to three months postintervention than those given placebo (odds ratio (OR) 1.63, 95% CI 1.07 to 2.47; 7 studies; 722 children). The estimated number needed to treat for an additional beneficial outcome (NNTB) was eight, meaning that eight children would need to receive probiotics for one to experience improvement in pain in this timescale. We judged the evidence for this outcome to be of moderate quality due to significant heterogeneity.Children with a symptom profile defined as irritable bowel syndrome treated with probiotics were more likely to experience improvement in pain at zero to three months postintervention than those given placebo (OR 3.01, 95% CI 1.77 to 5.13; 4 studies; 344 children). Children treated with probiotics were more likely to experience improvement in pain at three to six months postintervention compared to those receiving placebo (OR 1.94, 95% CI 1.10 to 3.43; 2 studies; 224 children). We judged the evidence for these two outcomes to be of moderate quality due to small numbers of participants included in the studies.We found that children treated with fibre-based interventions were not more likely to experience an improvement in pain at zero to three months postintervention than children given placebo (OR 1.83, 95% CI 0.92 to 3.65; 2 studies; 136 children). There was also no reduction in pain intensity compared to placebo at the same time point (SMD -1.24, 95% CI -3.41 to 0.94; 2 studies; 135 children). We judged the evidence for these outcomes to be of low quality due to an unclear risk of bias, imprecision, and significant heterogeneity.We found only one study of low FODMAP diets and only one trial of fructose-restricted diets, meaning no pooled analyses were possible.We were unable to perform any meta-analyses for the secondary outcomes of school performance, social or psychological functioning, or quality of daily life, as not enough studies included these outcomes or used comparable measures to assess them.With the exception of one study, all studies reported monitoring children for adverse events; no major adverse events were reported.

Authors' conclusions: Overall, we found moderate- to low-quality evidence suggesting that probiotics may be effective in improving pain in children with RAP. Clinicians may therefore consider probiotic interventions as part of a holistic management strategy. However, further trials are needed to examine longer-term outcomes and to improve confidence in estimating the size of the effect, as well as to determine the optimal strain and dosage. Future research should also explore the effectiveness of probiotics in children with different symptom profiles, such as those with irritable bowel syndrome.We found only a small number of trials of fibre-based interventions, with overall low-quality evidence for the outcomes. There was therefore no convincing evidence that fibre-based interventions improve pain in children with RAP. Further high-quality RCTs of fibre supplements involving larger numbers of participants are required. Future trials of low FODMAP diets and other dietary interventions are also required to facilitate evidence-based recommendations.

Conflict of interest statement

The work of the evidence synthesis team is funded by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care South West Peninsula (PenCLAHRC). However, the Funder had no role in the review itself.

Tamsin V Newlove‐Delgado: none known. Alice E Martin: none known. Rebecca A Abbott: none known. Alison Bethel: none known. Joanna Thompson‐Coon: none known. Rebecca Whear: none known Stuart Logan: none known.

The authors who practice clinical paediatrics are Alice E Martin and Stuart Logan. Alice is a Paediatric Trainee and works under the guidance of various Consultant Paediatricians. Stuart is a Consultant Paediatrician and treats children according to current best evidence, in light of their preference. There are therefore no conflicts of interest with this review.

Figures

1

PRISMA study flow diagram

2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

4

Forest plot of comparison: 1 Probiotics versus placebo, outcome: Improvement in pain 0 to 3 months' postintervention.

5

Forest plot of comparison: 2 Fibre versus placebo, outcome: Improvement in pain 0 to 3 months' postintervention.

1.1. Analysis

Comparison 1 Probiotics versus placebo, Outcome 1 Change in pain frequency: 0 to 3 months' postintervention.

1.2. Analysis

Comparison 1 Probiotics versus placebo, Outcome 2 Change in pain frequency: 0 to 3 months' postintervention. Sensitivity analysis.

1.3. Analysis

Comparison 1 Probiotics versus placebo, Outcome 3 Change in pain intensity: 0 to 3 months' postintervention.

1.4. Analysis

Comparison 1 Probiotics versus placebo, Outcome 4 Change in pain intensity: 0 to 3 months' postintervention. Sensitivity analysis.

1.5. Analysis

Comparison 1 Probiotics versus placebo, Outcome 5 Improvement in pain: 0 to 3 months' postintervention.

1.6. Analysis

Comparison 1 Probiotics versus placebo, Outcome 6 Improvement in pain: 0 to 3 months' postintervention. Sensitivity analysis.

1.7. Analysis

Comparison 1 Probiotics versus placebo, Outcome 7 Improvement in pain: 0 to 3 months' postintervention. Subgroup analysis (irritable bowel syndrome).

1.8. Analysis

Comparison 1 Probiotics versus placebo, Outcome 8 Improvement in pain: 3 to 6 months' postintervention.

2.1. Analysis

Comparison 2 Fibre versus placebo, Outcome 1 Change in pain intensity: 0 to 3 months' postintervention.

2.2. Analysis

Comparison 2 Fibre versus placebo, Outcome 2 Improvement in pain: 0 to 3 months' postintervention.

References

References to studies included in this review Asgarshirazi 2015 {published data only}

Bausserman 2005 {published data only} Chumpitazi 2015 {published data only} Eftekhari 2015 {published data only} Feldman 1985 {published data only} Francavilla 2010 {published data only} Gawronska 2007 {published data only} Giannetti 2017 {published data only (unpublished sought but not used)} Guandalini 2010 {published data only} Horvath 2013 {published data only} Kianifar 2015 {published data only} Romano 2010 {published and unpublished data} Romano 2013 {published data only} Sabbi 2011 {published data only} Saneian 2015 {published data only} Shulman 2016 {published and unpublished data} Weizman 2016 {published data only} Wirth 2014 {published data only} Young 1997 {published data only} References to studies excluded from this review Agah 2015 {published data only} Christensen 1982 {published data only} Chumpitazi 2014 {published data only} Dearlove 1983 {published data only} Edwards 1991 {published data only} Lebenthal 1981 {published data only} References to studies awaiting assessment Jarocka‐Cyrta 2002 {published data only} Additional references Abbott 2017 Abu‐Arafeh 1995 Apley 1958 Asgarshirazi 2016 [pers comm] Bain 1974 Balshem 2011 Bayless 1971 Bieri 1990 Claar 2006 Deeks 2011 Devanarayana 2011 Drossman 1995 Drossman 2016 Eccleston 2014 Farquar 1956 GRADEpro GDT 2015 [Computer program] Guy 1976 Harvey 1973 Hicks 2001 Higgins 2003 Higgins 2011a Higgins 2011b Higgins 2011c Hockaday 1992 Horst 2014 Horvath 2011 Horvath 2012 Huertas‐Ceballos 2008a Huertas‐Ceballos 2008b Hyams 1995 Konijnenberg 2005 Korterink 2015 Lewis 1997 Martin 2014a McGrath 1996 Moher 2009 Muller‐Lissner 2003 Nanayakkara 2016 Painter 1964 Paul 2013 Peltonen 1970 Quigley 2008 Rao 2015 Rasquin 2006 Review Manager 2014 [Computer program] Roalfe 2008 Romano 2014 [pers comm] Rubin 1967 Rutten 2015 Sandberg 1973 Scharff 1997 Schünemann 2011a Schünemann 2011b Shelby 2013 Speer 1954 Stickler 1979 Stone 1970 Stowens 1970 Størdal 2005 Sutton 2000 Svedlund 1988 Symon 1986 The Grade Working Group 2013 Thompson 2000 Varni 2015 von Baeyer 2009 Walker 1998 Walker 2006 Wilhelm 2008 Williams 1996 Wong 1988 Youssef 2006 Youssef 2008 References to other published versions of this review Huertas‐Ceballos 2009 Martin 2014b