Dietary interventions for functional abdominal pain disorders in children: a systematic review and meta-analysis

Figures & data

Table 1. Eligibility criteria

Inclusion criteria
Study was a systematic review or RCT
Study population consisted of children aged 4–18 years
Functional abdominal pain disorders (FAPDs) were diagnosed, treated, or its course followed. FAPDs included Irritable bowel syndrome (IBS); Functional dyspepsia (FD); Abdominal migraine (AM); and Functional abdominal pain – not otherwise specified (FAP-NOS).
FAPDs in alignment with Rome criteria, other international criteria, or a precise definition by the author
Dietary interventions were FODMAP diet (low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet) (Additional) fiber intake Lactulose-free diet Gluten-free diet Histamine-free diet Decrease in gas producing foods Extra fluid intake
Outcomes measures^a (assessed before and after start of dietary intervention) were Treatment success as defined by the authors (to be reported) Pain frequency or change in frequency of pain Pain intensity or change in pain intensity Withdrawal due to adverse events Quality of life or change in quality life measured using any validated defined measurement tool. Anxiety/depression using any validated defined measurement tool. Serious adverse events Adverse events Stool consistency (disease-specific (IBS-C/D)) as defined by authors (Bristol stool or similar) at study end Frequency of defecation at study end Adequate relief (as reported by patient or parent) School attendance or change in school attendance or performance
Exclusion criteria
Studies including children with Hirschsprung’s disease; Previous bowel surgery; and Complex congenital disorders.
If the range of children’s age was wider than 4–18 years, authors were requested for separate data of the children aged 4–18 years. If not available or no response the study was excluded;
Quasi randomized, none randomized, cohort, case–control, animal studies, editorial, commentary, case reports;
Abstract were considered if they met the inclusion criteria, if not enough data to judge was presented, the authors were contacted and if no response was received within 2 weeks, abstracts were excluded.
If inclusion could not be decided based on full text, authors were contacted. If no response was received within 2 weeks, the study was excluded.

^aOutcome measures were identified according to the ‘core outcome set’ for FAPDs.

Figure 1. PRISMA 2009 flow diagram.

Table 2. Study characteristics of included studies

Study	Participants	Intervention	Outcome measures and instruments
Fibers
Feldman et al. (1985); Canada	Children aged 5–15 years (N = 52) RAP (Apley Criteria)	Fiber cookie vs placebo Dosage: 5 g corn per cookie, 2 cookies a day Treatment period: 6 weeks	Treatment success Improvement: 50% decrease in frequency of attacks Instrument: Stomachache Diary (four specific times each day) Adverse effects Instrument: recorded by parents using a specially developed questionnaire, every 2 weeks
Horvath et al. (2013); Poland	Children 7–17 years (N = 89) AP-FGIDs (ROME III)	Glucomannan vs placeboDosage: 2.52 g/day, 1 sachet of 1.26 g 2 times a day Treatment period: 4 weeks	Treatment success Improvement: self-reported ‘no pain’ or a decrease of ≥ 2/6 points Instrument: FACES Pain Scale Revised Pain frequency Instrument: Self-reported on 4-point scale (pain 1–3 times per month, pain 1–2 times per week, pain >2 times per week, pain every day) Pain intensity Instrument: FACES Pain Scale Revised, 6-point Likert Scale (0 = no pain and 5 = highest pain). School attendance/performance Instrument: Self-reported absenteeism from school Adverse events reported
Romano et al. (2013); Italy	Children 8–16 years (N = 60) CAP and IBS (ROME III)	Partially Hydrolyze Guar Gum (PHGG) vs placebo Dosage: 5 g/day in 50 ml of fruit-juice, one time a day Treatment period: 4 weeks	Treatment success Improvement: reduction of the abdominal pain intensity Instrument: WBFPRS Pain frequency Instrument: Birmingham IBS symptom score, 6-point Likert scale (0 = none of the time; 5 = all of the time) Pain intensity Instrument: WBFPRS, 6-point Likert Scale (0 = no hurt; 5 = hurts worst) Defecation pattern Improvement: normalization of bowel movements (BSS 3 or 4) Instrument: BSS, 7 categories (1 = hard lump, 7 = entirely liquid) Adverse events reported
Shulman et al. (2016): United States	Children 7–18 years (N = 103) IBS (Rome II criteria)	Psyllium vs placebo Dosage: 6 g (7–11 years), 12 g (12– 18 years), single daily dose Treatment period: 6 weeks	Pain frequency Instrument: daily dairy card, number of ratings with pain ≥1 (ratings were made 3 times daily for 2 weeks) Pain intensityInstrument: daily dairy card (ratings were made 3 times daily for 2 weeks) Defecation pattern Instrument: BSS, (1–2 = constipated, 3–5 = normal, 6–7 = diarrheal) Adverse events reported
Jagadeesh et al. (2020) India	Children 4–18 years (N = 81) IBS (Rome IV criteria)	Psyllium vs placebo Dosage: daily dose not specified Treatment period: 4 weeks	Treatment success Improvement: score of <75 Instrument: IBS-SSS Pain frequencyInstrument: IBS-SSS, scored on a scale from 0 to 100. Pain intensityInstrument: IBS-SSS, scored on a scale from 0 to 100. Adverse events reported
FODMAP
Chumpitazi et al. (2015) United States	Children 7–17 years (N = 33) IBS (Rome III criteria)	Low FODMAP diet vs Typical American Childhood Diet (TACD) Dosage FODMAPs: FODMAP diet: 0,15 g/kg/day (maximum 9 g/day), TACD: 0,7 g/kg/day (maximum 50 g/day) Treatment period: 48 h Wash-out period: 5 days	Treatment success Improvement: ≥50% decrease in frequency of abdominal pain episodes Instrument: daily dairy Pain frequency Instrument: dairy, number of abdominal pain episodes (ratings were made 3 times daily for 24 h) Pain intensity Instrument: dairy, 10-point Likert scale (0 = no pain, 10 = worst pain you can imagine, ratings were made 3 times daily for 24 h) Adverse events reported
Boradyn et al. (2020) Poland	Children 5–12 years (N = 29) FAP (Rome III)/FAP – NOS (Rome IV)	Low FODMAP diet vs Diet based on the NICE guidelines Dosage in accordance with the Human Nutrition Recommendations for Polish Population for the specific age groups (4–6 , 7–9 , 10–12 years), gender, weight, and activity level. Treatment period: 4 weeks	Pain frequency Instrument: dairy, number of events Pain intensity Instrument: WBFPRS, score 0–5 Defecation pattern Instrument: BSS, (1–2 = constipated, 3–5 = normal, 6–7 = diarrheal) Adverse events reported
Fructose-restricted diet
Wirth et al. (2014); Germany	Children 3–18 years (N = 116) RAP as defined by the authors	Fructose-restricted diet vs regular diet Dosage: NA Treatment period: 2 weeks	Pain frequency Improvement: reduction in pain episodes Instrument: questionnaire, frequency of pain per week Pain intensity Instrument: questionnaire, 10-point Likert scale (0 = no pain, 10 = very strong pain)
Fructan
Chumpitazi et al. (2018); United States	Children 7–18 years (N = 31) IBS (Rome III criteria)	Fructan (Inulin-FOS*) vs placebo Dosage fructan: 0.5 g/kg/day (maximum 19 g/day) Treatment period: 72 h Wash-out period: ≥ 10 days	Pain frequency Instrument: dairy, number of abdominal pain episodes (ratings were made 3 times daily for 24 h) Pain intensity Instrument: dairy, 10-point Likert scale (0 = no pain, 10 = worst pain you can imagine, ratings were made 3 times daily for 24 h) Defecation pattern Instrument: stool diary (modified Bristol stool form) Adverse events reported
Prebiotic
Basturk et al. (2016); Turkey	Children 4–16 years (N = 76) IBS (Rome III criteria)	Synbiotic vs Probiotic vs. Prebiotic Dosage: synbiotic: 5 × 10^9 CFU B. lactis B94 and inulin 900 mg, probiotic: 5 × 10^9 CFU B. lactis, prebiotic: inulin 900 mg Treatment period: 4 weeks	Treatment success Improvement: improvement in all the presenting symptoms after 4 weeks (postprandial swelling, belching-abdominal distension, mucoid defecation, difficulty in defecation, feeling of incomplete defecation, urgent defecation) Instrument: questionnaire Defecation pattern Instrument: question “difficulty in defecation” (yes/no). Adverse events reported
Serum-derived bovine immunoglobulin
Arrouk et al. (2018); United States	Children 8–18 years (N = 15) IBS-D (Rome III criteria)	Oral serum-derived bovine immunoglobulin (SBI) vs placebo Dosage: 5 g (minimum of 50% IgG along with other serum proteins) Treatment period: 3 weeks	Pain intensity Instrument: dairy, 5-point Likert scale (0 = no pain, 4 = severe pain you) Quality of life Instrument: Peds-QoL Defecation pattern Instrument: BSS, (1–2 = constipated, 3–5 = normal, 6–7 = diarrheal) Adverse events reported
Vitamin D
El Amrousy (2018); Egypt	Children 14–18 years (N = 112) IBS (Rome III criteria) with vitamin D serum level <20 ng/ml	Oral vitamin D3 vs placebo Dosage: 1000 IU, two drops daily Treatment period: 6 months	Treatment success Improvement: A decrease of ≥50 in the total score Instrument: IBS‑SSS, total score on 5 items (severity and frequency of abdominal pain, bloating, satisfaction with bowel habits and quality of life), each item was scored on a scale from 0 to 100 Quality of life Instrument: IBS‑QoL Adverse events reported

^aInulin-FOS includes a mixture of short and long inulin-type fructans.

AP-FGIDs, abdominal pain predominant functional gastrointestinal disorders; BSS, Bristol Stool Scale; CAP, chronic abdominal pain; IBS, irritable bowel syndrome; IBS-SSS, IBS severity scoring scale; NICE, National Institute for health and Care Exellence; PedsQoL, Pediatric Quality of Life Inventory for Gastrointestinal Symptoms. RAP, recurrent abdominal pain; WBFPRS, Wong–Baker FACES Pain Rating Scale.

Table 3. Secondary outcomes

Study	Quality of life	Anxiety/depression	Adequate relief	School attendance/ performance	Defecation pattern
Fibers
Feldman; Corn	-	-	-	-	-
Horvath; Glucomannan	-	-	-	School absence: at 4 weeks 10% (Glucomannan) vs 14% (placebo) (P = .56)	-
Romano; Guar Gum	-	-	-	-	Normalization of bowel movements at 4 weeks: 40% (Guar Gum) vs 13.3% (placebo) (P = .025)
Shulman; Psyllium	-	-	-	-	Change from baseline psyllium vs placebo: lower percentage of diarrheal stools (P = .078) and higher percentage of constipated stools (P = .048)
Jagadeesh; Psyllium	-	-	-	-	-
Low-FODMAP
Chumpitazi (2015); Low FODMAP diet	-	-	-	-	-
Boradyn; Low FODMAP diet	-	-	-	-	Normalization of bowel movements at 4 weeks: 61% (FODMAP) vs 93% (placebo) (P = .106)
Fructose-restricted diet
Wirth; Fructose-restricted diet	-	-	-	-	-
Fructan
Chumpitazi (2018); Low FODMAP diet with fructan	-	-	-	-	Mean stool type did not differ between interventions^a
Prebiotic
Basturk; Inulin	-	-	-	-	Difficulty in defecation at 4 weeks in 48% probiotic vs. 22% prebiotic (P = .155)
Serum-derived bovine immunoglobulin
Arrouk; Serum-derived bovine immunoglobulin (SBI)	Significant improvement in overall PedsQOL score after treatment in SBI group (P = .01, placebo: P = .14).	-	-	-	There was no significant reduction in stool frequency per week. Improved stool form in SBI group: baseline BSS 5.3 ± 0.8^b vs. after treatment BSS 4.2 ± 1.2 (P = .05), placebo: 5.1 ± 0.6 vs. 4.2 ± 2 (P = .28).
Vitamin
El Amrousy; Vitamin D	Significant improvement in overall IBS-QOL score after treatment in Vit.D group (P < .001, placebo: P = 47).	-	-	-	-

^aNo separate results were reported for the first phase of the trial (i.e. before the cross-over occurred).

^bMean ± SD.

Figure 2. Risk of bias graph.

Figure 3. Risk of bias summary.

Figure 4. (a) and (b) Meta-analysis.

Table

AM	Abdominal migraine
CENTRAL	Cochrane Central Register of Controlled Trials
CI	Confidence intervals
COS	Core Outcome Set
FAPDs	Functional abdominal pain disorders
FAP-NOS	Functional abdominal pain – not otherwise specified
FD	Functional dyspepsia
GI	Gastrointestinal
IBS	Irritable bowel syndrome
MD	Mean differences
ORs	Odds ratios
RCTs	Randomized controlled trials
RevMan	Review Manager
RRs	Relative risks
VAS	Visual analog scale