Evidence-Based Research in Pediatric Nutrition

H. Szajewska, R. Shamir

• Publisher: S. Karger
• Year: 2013
• ISBN:
  9783318024579
• Topic: Médecine
• Subtopic: Périnatalogie et néonatologie

Recognition of evidence-based medicine is not only increasing rapidly, but it has become essential to pediatric nutrition. Starting with some methodological issues - discussing systemic reviews, meta-analyses and clinical trials - this publication then concisely summarizes current knowledge as well as ignorance and uncertainty regarding selected aspects of childhood nutrition. These aspects include functional gastrointestinal disorders, issues concerning various kinds of milk, complementary foods, enteral nutrition, celiac disease or obesity. Contents are based on evidence and summarize current guidelines; moreover, when there is no clear evidence, they provide some food for thought.

Issues in Infant Feeding

Szajewska H, Shamir R (eds): Evidence-Based Research in Pediatric Nutrition.
World Rev Nutr Diet. Basel, Karger, 2013, vol 108, pp 40-48 (DOI: 10.1159/000351483)

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Probiotics, Prebiotics, and Dietary Fiber in the Management of Functional Gastrointestinal Disorders

Andrea Horvath · Hania Szajewska

Department of Paediatrics, The Medical University of Warsaw, Warsaw, Poland

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Abstract

At best, currently available therapies provide symptomatic relief from functional gastrointestinal disorders (FGD). No existing therapy, however, can influence the natural course of any of these disorders, prompting interest in new and safe treatment options. This paper summarizes the clinical evidence from randomized controlled trials (RCTs) and their meta-analyses of the effectiveness of probiotics, prebiotics, and dietary fiber in the treatment of FGD in the pediatric population. While it is too soon to recommend the routine use of any probiotics for treating FGD, some of these therapeutic options can provide a health benefit to patients, and therefore can be discussed with patients and/or caregivers. Lactobacillus reuteri DSM 17938 has consistently improved symptoms of infantile colic. The use of Lactobacillus GG moderately increased treatment success in children with abdominal pain-related FGD, particularly among children with irritable bowel syndrome. Also, data from one trial suggest that VSL#3 seems to be effective in ameliorating symptoms and improving the quality of life of children affected by irritable bowel syndrome. L. reuteri DSM 17938 may help infants with constipation. Limited evidence suggests that administration of a fiber supplement is more effective than placebo for the treatment of childhood constipation.

Copyright © 2013 S. Karger AG, Basel

Functional gastrointestinal disorders (FGD), now diagnosed according to the Rome III criteria, are defined as a variable combination of chronic or recurrent gastrointestinal symptoms not explained by structural or biochemical abnormalities [1, 2]. At best, currently known therapies provide symptomatic relief. No available therapy, however, can influence the natural course of any of these disorders. Recently, probiotics, prebiotics, and dietary fiber have been proposed as a treatment for FGD. The exact mechanism by which probiotics may exert their action in patients with FGD remains unknown. Moreover, the probiotics' activity depends on the strain selection and, possibly, the dose. Nevertheless, several plausible mechanisms have been proposed based on results of in vitro and animal studies, some of which may provide evidence attesting to the benefit of the use of probiotics in patients with FGD. The mechanisms of highest importance are the enhancement of colonization resistance and inhibitory effects against pathogens. These include activation of direct inhibitors called bacteriocins, reduction of luminal pH through short-chain fatty acid production (which also inhibits some pathogens), competition for nutrients and adhesion to the gut wall, immunomodulatory activity, and the effect on colonocyte gene expression (e.g. expression of mucin genes) [3]. For prebiotics, the plausible mechanisms by which they may exert their actions in patients with FGD include changes in the intestinal microbiota by selective stimulation of the growth of potentially protective bacteria (bifidobacteria and, in part, also lactobacilli) along with simultaneous inhibition of potentially pathogenic microorganisms, changes in the composition of stool and gas, stabilization of the intestinal environment by a reduction in the pH and release of short-chain organic acids such as butyrate, downregulation of the local proinflammatory response, and control of intestinal motor functions [3]. In the case of dietary fiber, the considered mechanisms include increased stool bulk, reduced transit time, and bacterial fermentation of fiber to short-chain fatty acids.

This paper briefly summarizes the clinical evidence from randomized controlled trials (RCTs) and their meta-analyses of the effectiveness of probiotics, prebiotics, and dietary fiber in the treatment of FGD in the pediatric population. Studies were identified by searches of Medline and the Cochrane Library as well as through evaluation of the existing reviews and references from relevant articles.

Infantile Colic

According to the Rome III criteria, the diagnostic criteria for infantile colic must include all of the following in infants from birth to 4 months of age: paroxysms of irritability, fussing, or crying that start and stop without obvious cause, episodes lasting 3 h or more per day and occurring at least 3 days per week for at least 1 week, and no failure to thrive [1].

Probiotics

It was documented in an open RCT that administration of Lactobacillus reuteri ATCC 55730 compared with simethicone improved colicky symptoms in breast-fed infants within 1 week of treatment [4]. As this strain was found to carry potentially transferable resistance traits for tetracycline and lincomycin, it has been replaced by L. reuteri DSM 17938 with no unwanted plasmid-borne resistances. Two RCTs have examined the effects of using L. reuteri DSM 17938 for the management of infantile colic. In the first double-blind RCT, it was shown that compared with placebo, L. reuteri DSM 17938 administered at a dose of 108 colony-forming units per day to 46 breast-fed infants improved symptoms of infantile colic [5]. A more recent double-blind RCT also found that the administration of L. reuteri DSM 17938 at a dose 108 colony-forming units for 21 days to exclusively or predominantly breast-fed infants was associated with treatment success at 1, 2, 3, and 4 weeks after randomization. In addition, throughout the study period, the median crying time was significantly reduced in the probiotic group compared with the control group [6]. It has been proposed that the beneficial result is due to the effect of L. reuteri on gut motility and function, colonic sensory nerves, colon contractile activity, and pain perception [7-9], although these kinds of mechanisms have been documented only in preterm infants [10]. Additional mechanisms include anti-inflammatory effects documented both in vitro and in vivo or interactions with altered gut microbiota [11, 12].

In summary, given the lack of effective therapy for infantile colic and the generally good safety profile of probiotics used in otherwise healthy populations, the use of L. reuteri DSM 17938 could be discussed with caregivers. Studies of the effects of probiotics in formula-fed infants would be helpful to provide a more detailed and precise recommendation.

Abdominal Pain-Related Functional Gastrointestinal Disorders

According to the Rome III criteria, abdominal pain-related FGD in children may be categorized as functional dyspepsia, irritable bowel syndrome (IBS), abdominal migraine, and functional abdominal pain [2].

Probiotics

A Cochrane systematic review (search date: December 2006) concluded that there is no evidence that Lactobacillus supplementation is effective in the management of children with recurrent abdominal pain [13]. A more recent meta-analysis (search date: December 2010) evaluated the efficacy of using a single probiotic microorganism, e.g. Lactobacillus rhamnosus GG (LGG), for the treatment of abdominal painrelated FGD in children [14]. Compared with placebo, LGG supplementation was associated with a significantly higher rate of treatment responders (defined as no pain or a decrease in pain intensity) in the overall population with abdominal pain-related FGD (3 RCTs, n = 290; relative risk (RR) 1.31, 95% CI 1.08-1.59, number needed to treat (NNT) 7, 95% CI 4-22) and in the IBS subgroup (3 RCTs, n = 167; RR 1.70, 95% CI 1.27-2.27, NNT 4, 95% CI 3-8). However, no difference was found in the rate of treatment responders between children with functional abdominal pain or functional dyspepsia who received placebo or LGG. The intensity of pain was significantly reduced in the overall study population and in the IBS subgroup. The frequency of pain was significantly reduced in the IBS subgroup only.

One multicenter, cross-over RCT involving 59 children aged 4-18 years with IBS defined according to the Rome II criteria studied a combination of probiotic strains containing B. breve, B. longum, B. infantis, L. acidophilus, L. plantarum, L. casei, L. bulgaricus, and S. thermophilus (known as VSL#3). Compared to placebo, administration of VSL#3 resulted in a significant improvement in the subjective assessment of relief of symptoms (the primary outcome) (p < 0.05). Additionally, there was an improvement in 3 of 4 secondary endpoints, including abdominal pain/discomfort (p < 0.05), abdominal bloating/gassiness (p < 0.05), and family assessment of life disruption (p < 0.01). No significant difference was found between groups (p = 0.06) in the stool pattern [15]. These findings are in line with the evidence obtained in adults.

In summary, evidence of the effectiveness of probiotics for the treatment of abdominal pain-related FGD in the pediatric population is scant. The use of LGG moderately increases treatment success in children with abdominal pain-related FGD, particularly among children with IBS. Similarly, VSL#3 seems to be effective in ameliorating symptoms and improving the quality of life of children affected by IBS.

Fibers

For the pediatric population, one systematic review (search date: December 2011) evaluated the effect of dietary fibers for treating abdominal pain-related FGD [16]. Only 3 RCTs were identified, which enrolled a total of 167 children and adolescents (5-17 years) with recurrent abdominal pain. Only 1 study used the Rome III criteria. Patients were supplemented with different dietary fiber types (e.g. crushed crispbread, cookies, or glucomannan (GNN), a soluble fiber of the Japanese konjac plant) for 4-6 weeks. The use of dietary fibers did not influence the proportion of responders to treatment, and improvement did not occur in reported clinically relevant outcomes, such as no pain or a significant decrease in pain intensity. The conclusions are in line with the findings of a previously published Cochrane Review [13].

In summary, currently available evidence does not suggest that supplementation with fiber as a dietary manipulation may be useful for treating children with abdominal pain-related FGD.

Functional Constipation

According to the Rome III criteria, constipatio...