Reevaluating the FDA's warning against the use of probiotics in preterm neonates: A societal statement by ESPGHAN and EFCNI.

The recent advisory issued by the United States Food and Drug Administration, cautioning against the routine administration of probiotics in preterm neonates, has sparked a lively debate within the scientific community. This commentary presents a perspective from members of the Special Interest Group on Gut Microbiota and Modifications within the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and other authors who contributed to the ESPGHAN position paper on probiotics for preterm infants, as well as representatives from the European Foundation for the Care of Newborn Infants. We advocate for a more nuanced and supportive approach to the use of certain probiotics in this vulnerable population, balancing the demonstrated benefits and risks.

Prebiotics in the management of pediatric gastrointestinal disorders: Position paper of the ESPGHAN special interest group on gut microbiota and modifications.

Prebiotics are substrates that are selectively utilized by host microorganisms conferring a health benefit. Compared to probiotics there are few studies with prebiotics in children. Most studies have been performed using infant formula supplemented with prebiotics, while add-on prebiotic supplementation as prevention or treatment of childhood gastrointestinal disorders has rarely been reported. The aim of this position paper was to summarize evidence and make recommendations for prebiotic supplementation in children with gastrointestinal diseases. Recommendations made are based on publications up to January 1, 2023. Within the scope of the European Society for Paediatric Gastroenterology Hepatology and Nutrition Special Interest Group on Gut Microbiota and Modifications, as in our previous biotic recommendations, at least two randomized controlled clinical trials were required for recommendation. There are some studies showing benefits of prebiotics on selected outcomes; however, we cannot give any positive recommendations for supplementing prebiotics in children with gastrointestinal disorders.

Probiotics for the Management of Pediatric Gastrointestinal Disorders: Position Paper of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications.

BACKGROUND: Probiotics, defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, are widely used despite uncertainty regarding their efficacy and discordant recommendations about their use. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Special Interest Group on Gut Microbiota and Modifications provides updated recommendations for the use of probiotics for the management of selected pediatric gastrointestinal disorders. METHODS: All systematic reviews and/or meta-analyses, as well as subsequently published randomized controlled trials (RCTs) (until December 2021), that compared the use of probiotics in all delivery vehicles and formulations, at any dose, with no probiotic (ie, placebo or no treatment), were eligible for inclusion. The recommendations were formulated only if at least 2 RCTs on a similar well-defined probiotic strain were available. The modified Delphi process was used to establish consensus on the recommendations. RESULTS: Recommendations for the use of specific probiotic strains were made for the management of acute gastroenteritis, prevention of antibiotic-associated diarrhea, nosocomial diarrhea and necrotizing enterocolitis, management of Helicobacter pylori infection, and management of functional abdominal pain disorders and infant colic. CONCLUSIONS: Despite evidence to support the use of specific probiotics in some clinical situations, further studies confirming the effect(s) and defining the type, dose, and timing of probiotics are still often required. The use of probiotics with no documented health benefits should be discouraged.

Use of Probiotics for the Management of Acute Gastroenteritis in Children: An Update.

Since the publication of the 2014 European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Working Group (WG) on Probiotics and Prebiotics guidelines for the management of acute gastroenteritis (AGE), new evidence concerning the efficacy of probiotics has become available. This document provides updated recommendations on the use of probiotics for the treatment of AGE in previously presumed healthy infants and children. A systematic literature search was performed. All pooled analyses were explicitly performed for the current report. The WG graded the recommendations and assessed the certainty of the supporting evidence using the Grading of Recommendations, Assessment Development, and Evaluations tool. The recommendations were formulated if at least 2 randomized controlled trials that used a given probiotic were available. Despite the large number of identified trials, the WG could not identify 2 randomized controlled trial of high quality for any strain that provided benefit when used for treating AGE. The WG made weak recommendations for (in descending order in terms of the number of trials evaluating any given strain): Saccharomyces boulardii (low to very low certainty of evidence); Lactobacillus rhamnosus GG (very low certainty of evidence); L reuteri DSM 17938 (low to very low certainty of evidence); and L rhamnosus 19070-2 and L reuteri DSM 12246 (very low certainty of evidence). The WG made a strong recommendation against L helveticus R0052 and L rhamnosus R0011 (moderate certainty of evidence) and a weak recommendation against Bacillus clausii strains O/C, SIN, N/R, and T (very low certainty of evidence).

Probiotics and Preterm Infants: A Position Paper by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Committee on Nutrition and the European Society for Paediatric Gastroenterology Hepatology and Nutrition Working Group for Probiotics and Prebiotics.

More than 10,000 preterm infants have participated in randomised controlled trials on probiotics worldwide, suggesting that probiotics in general could reduce rates of necrotising enterocolitis (NEC), sepsis, and mortality. Answers to relevant clinical questions as to which strain to use, at what dosage, and how long to supplement are, however, not available. On the other hand, an increasing number of commercial products containing probiotics are available from sometimes suboptimal quality. Also, a large number of units around the world are routinely offering probiotic supplementation as the standard of care despite lacking solid evidence. Our recent network meta-analysis identified probiotic strains with greatest efficacy regarding relevant clinical outcomes for preterm neonates. Efficacy in reducing mortality and morbidity was found for only a minority of the studied strains or combinations. In the present position paper, we aim to provide advice, which specific strains might potentially be used and which strains should not be used. In addition, we aim to address safety issues of probiotic supplementation to preterm infants, who have reduced immunological capacities and occasional indwelling catheters. For example, quality reassurance of the probiotic product is essential, probiotic strains should be devoid of transferable antibiotic resistance genes, and local microbiologists should be able to routinely detect probiotic sepsis. Provided all safety issues are met, there is currently a conditional recommendation (with low certainty of evidence) to provide either Lactobacillus rhamnosus GG ATCC53103 or the combination of Bifidobacterium infantis Bb-02, Bifidobacterium lactis Bb-12, and Streptococcus thermophilus TH-4 in order to reduce NEC rates.

Prophylactic use of probiotics for gastrointestinal disorders in children.

The gastrointestinal microbiome is a hot topic in clinical research. Beneficial effects of selected probiotics in the prevention of gastrointestinal disorders are mainly restricted to acute gastroenteritis, antibiotic-associated diarrhoea, infantile colic, and necrotising enterocolitis. However, no broad consensus exists to recommend the use of probiotics in the prevention of these conditions, mainly because of the different design of the studies done so far, resulting in little evidence for specific strains, dosages, and indications. More well designed studies are needed before recommendations can be proposed. At this stage, the evidence is insufficient to recommend the routine use of probiotics in infants and children for the prevention of gastrointestinal disorders.

Probiotics for the Prevention of Nosocomial Diarrhea in Children.

This document provides recommendations developed by the ESPGHAN Working Group on Probiotics and Prebiotics on the role of probiotics in the prevention of nosocomial diarrhea in children based on a systematic review of previously completed systematic reviews and of subsequently published randomized controlled trials. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation guidelines. Recommendations were given only if at least 2 randomized controlled trials examined the same probiotic strain. Based on currently available evidence the Working Group recommends using Lactobacillus rhamnosus GG if the use of probiotics for preventing nosocomial diarrhea in children is considered.

Commercial Probiotic Products: A Call for Improved Quality Control. A Position Paper by the ESPGHAN Working Group for Probiotics and Prebiotics.

Probiotics have been proposed for a number of indications ranging from the hypothetical long-term immunomodulatory effects to proven benefits in the management of different clinical conditions.An increasing number of commercial products containing probiotics are available. In those products, irrespective if it is food, food supplement, medical food, or drug, the probiotic microorganisms have to be present in a sufficient number by the end of the shelf-life, to pass through the gastrointestinal tract resisting acid and bile, to colonize the gut, and to retain functional properties required to obtain the suggested beneficial effect. Finally, it should be contamination-free.Studies organized worldwide and summarized in this article have shown that inconsistencies and deviations from the information provided on the product label are surprisingly common. Frequently strains are misidentified and misclassified, products are occasionally contaminated, sometimes with even facultative or obligatory pathogens, strains are not viable, the labeled number of colonies cannot be verified, or the functional properties are diminished to the extent that preclude the proposed health benefit. As the probiotic preparations are commonly used for a wide range of conditions, the aim of the Working Group was to summarize results of the studies looking into the quality of the probiotic products and to raise the awareness of the important issue of their quality control.Based on the results obtained, we strongly suggest a more stringent quality control process. This process should ensure that the probiotic content as mentioned on the label meets the actual content throughout the shelf life of the product, while no contamination is present.

A tool to help limit patients' sodium intake.

The average American consumes about 3400 mg/d of sodium, which is more than double the 1500 mg recommended by the American Heart Association.

Lactobacillus reuteri DSM 17938 for the Management of Functional Abdominal Pain in Childhood: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To determine whether administration of Lactobacillus reuteri DSM 17938 is beneficial in functional abdominal pain (FAP) of childhood. STUDY DESIGN: A total of 101 children, aged 6-15 years, who fulfilled the Rome III criteria for FAP were enrolled in a randomized double-blind, placebo-controlled trial, and were randomly assigned to receive either L reuteri DSM 17938 or placebo for 4 weeks, with further follow-up of additional 4 weeks. Response to therapy was based on a self-reported daily questionnaire monitoring frequency and intensity of abdominal pain, using the faces scoring system by Hicks. RESULTS: L reuteri (n = 47) was significantly superior to placebo (n = 46) in relieving frequency (1.9 ± 0.8 vs 3.6 ± 1.7 episodes/wk, P < .02) and intensity (4.3 ± 2.2 vs 7.2 ± 3.1 Hicks score/wk, P < .01) of abdominal pain following 4 weeks of supplementation. There was no difference in school absenteeism rate or other gastrointestinal symptoms, except for a lower incidence of perceived abdominal distention and bloating, favoring L reuteri. CONCLUSIONS: L reuteri DSM 17938, compared with placebo, significantly reduced the frequency and intensity of FAP in children. TRIAL REGISTRATION: ClicalTrials.gov: NCT01180556.

Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Children.

This article provides recommendations, developed by the Working Group (WG) on Probiotics of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition, for the use of probiotics for the prevention of antibiotic-associated diarrhea (AAD) in children based on a systematic review of previously completed systematic reviews and of randomized controlled trials published subsequently to these reviews. The use of probiotics for the treatment of AAD is not covered. The recommendations were formulated only if at least 2 randomized controlled trials that used a given probiotic (with strain specification) were available. The quality of evidence (QoE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation guidelines. If the use of probiotics for preventing AAD is considered because of the existence of risk factors such as class of antibiotic(s), duration of antibiotic treatment, age, need for hospitalization, comorbidities, or previous episodes of AAD diarrhea, the WG recommends using Lactobacillus rhamnosus GG (moderate QoE, strong recommendation) or Saccharomyces boulardii (moderate QoE, strong recommendation). If the use of probiotics for preventing Clostridium difficile-associated diarrhea is considered, the WG suggests using S boulardii (low QoE, conditional recommendation). Other strains or combinations of strains have been tested, but sufficient evidence is still lacking.

Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics.

The use of probiotics has been suggested in the treatment of acute gastroenteritis (AGE) in addition to early rehydration and avoidance of dietary restrictions. This document provides recommendations for the use of probiotics for the treatment of AGE in previously healthy infants and children based on a systematic review of previously completed systematic reviews and of randomized controlled trials (RCTs) published subsequently to these reviews. The recommendations were formulated only if at least 2 RCTs that used a given probiotic (with strain specification) were available. The GRADE system developed by the Grading of Recommendations, Assessment, Development, and Evaluations Working Group, was used to grade the strength of evidence and grades of recommendations used in these guidelines. It offers 4 categories of the quality of the evidence (high, moderate, low, and very low) and 2 categories of the strength of recommendation (strong or weak). The use of the following probiotics (in alphabetical order) may be considered in the management of children with AGE in addition to rehydration therapy: Lactobacillus rhamnosus GG (low quality of evidence, strong recommendation) and Saccharomyces boulardii (low quality of evidence, strong recommendation). Less compelling evidence is available for Lactobacillus reuteri DSM 17938 (very low quality of evidence, weak recommendation) and heat-inactivated Lactobacillus acidophilus LB (very low quality of evidence, weak recommendation). The latter, although traditionally discussed with other probiotics, does not fit with the definition of probiotics. Other strains or combinations of strains have been tested, but evidence of their efficacy is weak or preliminary.

Probiotics use in childhood acute diarrhea: a web-based survey.

GOALS: To evaluate practices and barriers for the use of probiotics in acute diarrhea among pediatric gastroenterologists. BACKGROUND: Probiotics have shown significant therapeutic potential in acute infectious diarrhea. However, literature data regarding practice patterns in childhood are limited. STUDY: A web-based 9-item survey among 1854 pediatric gastroenterologists worldwide. RESULTS: Only 634 (34%) responded. Forty-one were excluded owing to incomplete data. Finally 593, USA (n=407) and non-USA (n=186) participants, showed: limited use in acute diarrhea (28% and 32% prospectively), prescription of a 1 strain product only by 31% and 24%, respectively, and limited utilization in ambulatory settings (43% and 51%, respectively) and in prevention of diarrhea (2.6% and 3.4%, respectively). Most participants felt there is lack of useful clinical guidelines (91% and 84%, respectively), and found this therapy effective or very effective (54% and 62%, respectively). Dosing and duration were extremely variable, the youngest age treated ranged from 2 months to 2 years of age, and adverse effects were extremely rare. These characteristics were shared by USA and by non-USA participants, with no significant differences between groups (P>0.05). CONCLUSIONS: Many pediatric gastroenterologists worldwide do not use probiotics for acute diarrhea owing to lack of appropriate guidelines and/or poorly designed products. Therefore, worldwide health authorities should provide pharmaceutical and clinical guidelines for the appropriate use of probiotics in acute diarrhea of childhood.