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1.
Evaluating the impact of lactase supplementation on infant colic: Study protocol for a systematic review of randomized controlled trials.
Kozłowska-Jalowska, A, Stróżyk, A, Horvath, A, Szajewska, H
JPGN reports. 2024;(1):5-9
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Abstract
Infant colic is a common functional gastrointestinal disorder that affects infants during their first months of life. The etiology of this condition remains unclear. However, some studies suggest lactase deficiency may be a contributing factor. Currently, the evidence on dietary treatment and lactase supplementation for management of infant colic is limited. We aim to systematically review evidence on the efficacy and safety of using a lactase supplementation for managing infant colic. The Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), MEDLINE, and EMBASE will be searched to identify randomized controlled trials comparing oral lactase supplementation with placebo or no intervention in infants aged less than 6-month-old with infant colic using any recognized definition. The risk of bias will be assessed using the second version of the Cochrane Collaboration's risk-of-bias tool. The main outcome will be the number of responders in each group after treatment, defined as infants who experienced a decrease in daily crying as reported by the study authors. Additional outcomes will include the duration and frequency of crying episodes, infant sleep duration, parental satisfaction, discomfort of infants, number of hospital admissions, family quality of life, and adverse events during the intervention. The study findings will be published in a peer-reviewed journal and will be submitted to relevant conferences.
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Reevaluating the FDA's warning against the use of probiotics in preterm neonates: A societal statement by ESPGHAN and EFCNI.
van den Akker, CHP, Embleton, ND, Lapillonne, A, Mihatsch, WA, Salvatore, S, Canani, RB, Dinleyici, EC, Domellöf, M, Guarino, A, Gutiérrez-Castrellón, P, et al
Journal of pediatric gastroenterology and nutrition. 2024
Abstract
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.
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Synbiotics in the Management of Pediatric Gastrointestinal Disorders: Position Paper of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications.
Hojsak, I, Kolaček, S, Mihatsch, W, Mosca, A, Shamir, R, Szajewska, H, Vandenplas, Y, ,
Journal of pediatric gastroenterology and nutrition. 2023;(1):102-108
Abstract
BACKGROUND Synbiotics are a mixture comprising of live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host. There is an increasing number of studies investigating their role in different diseases and disorders. AIM: The purpose of this article is to provide recommendations for the use of synbiotics in the management of pediatric gastrointestinal disorders. The recommendations are developed by the ESPGHAN Special Interest Group on Gut Microbiota and Modifications. METHODS From existing literature databases, we searched and appraised all systematic reviews and/or meta-analyses, and subsequently published randomized controlled trials (RCTs) that compared the use of synbiotics, in all delivery vehicles and formulations, at any dose, compared to no synbiotics. Synbiotics which are part of infant formula were not assessed. The recommendations were formulated only if at least 2 RCTs that used a well-defined synbiotic were available. RESULTS Based on the currently available evidence, no recommendation can be formulated in favor or against the use of evaluated synbiotic combination in the treatment of acute gastroenteritis, prevention of necrotizing enterocolitis, Helicobacter pylori infection, inflammatory bowel disease, functional gastrointestinal disorders, and allergy in infants and children. CONCLUSIONS There is a need for more, well-designed RCTs on the role of synbiotics in gastrointestinal disorders with the same outcome measures to enable the inter-studies comparisons.
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Infantile Colic and Long-Term Outcomes in Childhood: A Narrative Synthesis of the Evidence.
Indrio, F, Dargenio, VN, Francavilla, R, Szajewska, H, Vandenplas, Y
Nutrients. 2023;(3)
Abstract
About 1 in 4 infants comes forward with prolonged crying, agitation, or infant colic (IC) during the first three months of life and is referred for medical evaluation. The pathogenesis remains poorly understood, as do its implications for future health. The aim of this narrative review was to critically examine and discuss the available literature on long-term consequences of excessive crying and/or colic. Most studies display an association between IC and the onset of functional gastrointestinal disorders (FGIDs) years later, probably related to the presence of common etiopathogenetic factors (environmental, dietary, intestinal dysmotility, visceral hypersensitivity). Although allergic disease in first-degree relatives may be a risk factor for IC, the latter does not appear to be a risk factor for subsequent atopic disease in the individual. Overall, there seems to be a relationship between IC and subsequent headaches, of the migraine type. Similarly, behavioral problems in children with a history of IC appear to be associated with higher parental stress scores. However, the current evidence is based on associations, and currently, a causal relationship between excessive crying and IC and long-term consequences remains not documented.
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Probiotics for the Management of Pediatric Gastrointestinal Disorders: Position Paper of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications.
Szajewska, H, Berni Canani, R, Domellöf, M, Guarino, A, Hojsak, I, Indrio, F, Lo Vecchio, A, Mihatsch, WA, Mosca, A, Orel, R, et al
Journal of pediatric gastroenterology and nutrition. 2023;(2):232-247
Abstract
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.
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Recommendations to Improve Quality of Probiotic Systematic Reviews With Meta-Analyses.
McFarland, LV, Hecht, G, Sanders, ME, Goff, DA, Goldstein, EJC, Hill, C, Johnson, S, Kashi, MR, Kullar, R, Marco, ML, et al
JAMA network open. 2023;(12):e2346872
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Abstract
IMPORTANCE Systematic reviews and meta-analyses often report conflicting results when assessing evidence for probiotic efficacy, partially because of the lack of understanding of the unique features of probiotic trials. As a consequence, clinical decisions on the use of probiotics have been confusing. OBJECTIVE To provide recommendations to improve the quality and consistency of systematic reviews with meta-analyses on probiotics, so evidence-based clinical decisions can be made with more clarity. EVIDENCE REVIEW For this consensus statement, an updated literature review was conducted (January 1, 2020, to June 30, 2022) to supplement a previously published 2018 literature search to identify areas where probiotic systematic reviews with meta-analyses might be improved. An expert panel of 21 scientists and physicians with experience on writing and reviewing probiotic reviews and meta-analyses was convened and used a modified Delphi method to develop recommendations for future probiotic reviews. FINDINGS A total of 206 systematic reviews with meta-analysis components on probiotics were screened and representative examples discussed to determine areas for improvement. The expert panel initially identified 36 items that were inconsistently reported or were considered important to consider in probiotic meta-analyses. Of these, a consensus was reached for 9 recommendations to improve the quality of future probiotic meta-analyses. CONCLUSIONS AND RELEVANCE In this study, the expert panel reached a consensus on 9 recommendations that should promote improved reporting of probiotic systematic reviews with meta-analyses and, thereby, assist in clinical decisions regarding the use of probiotics.
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Strain-Specificity of Probiotics in Pediatrics: A Rapid Review of the Clinical Evidence.
Jankiewicz, M, Łukasik, J, Kotowska, M, Kołodziej, M, Szajewska, H
Journal of pediatric gastroenterology and nutrition. 2023;(2):227-231
Abstract
OBJECTIVE The dogma of probiotic strain-specificity is widely accepted. However, only the genus- and species-specific effects of probiotics are supported by evidence from clinical trials. The aim of this rapid review was to assess clinical evidence supporting the claim that the efficacy of probiotics in the pediatric population is strain-specific. METHODS The Cochrane Library, MEDLINE, and EMBASE databases were searched (up to August 2022) for randomized controlled trials (RCTs) conducted in children aged 0-18 years evaluating the effects of prophylactic or therapeutic administration of probiotics (well-characterized at the strain level) for conditions such as antibiotic-associated diarrhea, acute diarrhea, necrotizing enterocolitis, respiratory tract infections, Helicobacter pylori infection, and atopic dermatitis. To allow evaluation of strain-specificity, a trial could only be included in the review if at least one additional RCT assessed the effect of a different strain of the same species against the same comparator. RCTs without proper strain-level data were excluded. In the absence of identifying head-to-head strain versus strain RCTs, indirect comparisons were made between interventions. RESULTS Twenty-three RCTs were eligible for inclusion. Out of the 11 performed comparisons, with 1 exception (two Lacticaseibacillus paracasei strains in reducing atopic dermatitis symptoms), no significant differences between the clinical effects of different strains of the same probiotic species were found. CONCLUSIONS Head-to-head comparison is an optimal study design to compare probiotic strains, but such comparisons are lacking. Based on indirect comparisons, this rapid review demonstrates insufficient clinical evidence to support or refute the claim that probiotic effects in children are strain-specific.
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Targeting the gut-lung axis by synbiotic feeding to infants in a randomized controlled trial.
Sjödin, KS, Sjödin, A, Ruszczyński, M, Kristensen, MB, Hernell, O, Szajewska, H, West, CE
BMC biology. 2023;21(1):38
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Plain language summary
Infants are at increased risk of infections, and respiratory tract infections are a leading cause of morbidity and mortality globally. Although the respiratory and gastrointestinal tracts are separate, they share a mucosal immune system called the “gut-lung axis.” The aim of this study was to compare the impacts of feeding prebiotic infant formula with the same prebiotic infant formula supplemented with probiotic Lactobacillus F19 (synbiotics) until 6 months of age on infant gut microbiota development in the first year of life. This study was a multicentre, double-blind randomised controlled study. Infants were randomised to control group - prebiotic formula or experimental group - synbiotic formula. Results showed additional benefit of feeding specific synbiotics to formula-fed infants over prebiotics only. In fact, synbiotic feeding led to the underrepresentation of Klebsiella [bacteria], enrichment of bifidobacteria, and slight increases in microbial degradation metabolites. Authors concluded that their findings support future clinical evaluation of synbiotic formula in the prevention of infections and associated antibiotic treatment as a primary outcome when breastfeeding is not feasible.
Abstract
BACKGROUND Formula-fed infants are at increased risk of infections. Due to the cross-talk between the mucosal systems of the gastrointestinal and respiratory tracts, adding synbiotics (prebiotics and probiotics) to infant formula may prevent infections even at distant sites. Infants that were born full term and weaned from breast milk were randomized to prebiotic formula (fructo- and galactooligosaccharides) or the same prebiotic formula with Lactobacillus paracasei ssp. paracasei F19 (synbiotics) from 1 to 6 months of age. The objective was to examine the synbiotic effects on gut microbiota development. RESULTS Fecal samples collected at ages 1, 4, 6, and 12 months were analyzed using 16S rRNA gene sequencing and a combination of untargeted gas chromatography-mass spectrometry/liquid chromatography-mass spectrometry. These analyses revealed that the synbiotic group had a lower abundance of Klebsiella, a higher abundance of Bifidobacterium breve compared to the prebiotic group, and increases in the anti-microbial metabolite d-3-phenyllactic acid. We also analyzed the fecal metagenome and antibiotic resistome in the 11 infants that had been diagnosed with lower respiratory tract infection (cases) and 11 matched controls using deep metagenomic sequencing. Cases with lower respiratory tract infection had a higher abundance of Klebsiella species and antimicrobial resistance genes related to Klebsiella pneumoniae, compared to controls. The results obtained using 16S rRNA gene amplicon and metagenomic sequencing were confirmed in silico by successful recovery of the metagenome-assembled genomes of the bacteria of interest. CONCLUSIONS This study demonstrates the additional benefit of feeding specific synbiotics to formula-fed infants over prebiotics only. Synbiotic feeding led to the underrepresentation of Klebsiella, enrichment of bifidobacteria, and increases in microbial degradation metabolites implicated in immune signaling and in the gut-lung and gut-skin axes. Our findings support future clinical evaluation of synbiotic formula in the prevention of infections and associated antibiotic treatment as a primary outcome when breastfeeding is not feasible. TRIAL REGISTRATION ClinicalTrials.gov NCT01625273 . Retrospectively registered on 21 June 2012.
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Managing food allergy: GA2LEN guideline 2022.
Muraro, A, de Silva, D, Halken, S, Worm, M, Khaleva, E, Arasi, S, Dunn-Galvin, A, Nwaru, BI, De Jong, NW, Rodríguez Del Río, P, et al
The World Allergy Organization journal. 2022;(9):100687
Abstract
Food allergy affects approximately 2-4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy.
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Early Feeding Practices and Celiac Disease Prevention: Protocol for an Updated and Revised Systematic Review and Meta-Analysis.
Szajewska, H, Shamir, R, Chmielewska, A, Stróżyk, A, Zalewski, BM, Auricchio, R, Koletzko, S, Korponay-Szabo, IR, Mearin, L, Meijer, C, et al
Nutrients. 2022;(5)
Abstract
Uncertainty remains in regard to when, how, and in what form gluten should be introduced into the diet, particularly of infants genetically predisposed to developing celiac disease (CD). MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials databases will be searched from inception. Randomized controlled trials (RCTs) and observational studies (cohort, case-control, or cross-sectional studies) investigating the association between early feeding practices and the risk of CD and/or CD autoimmunity will be included. In prospective studies, participants will be infants regardless of the risk of developing CD. For retrospective studies, participants will be children or adults with CD or presenting with positive serology indicative of CD. Interventions will be gluten-containing products of any type. Exposures will be breastfeeding and/or the introduction of gluten-containing products of any type. In control groups, there will be no exposure, different degrees of exposure (partial vs. exclusive breastfeeding, different amounts of gluten, etc.), or a placebo. The primary outcome measure will be CD or CD autoimmunity (i.e., anti-transglutaminase or anti-endomysial antibodies). At least two reviewers will independently assess the risk of bias using a validated risk assessment tool depending on study design. Disagreements will be resolved by discussion to achieve a consensus with the involvement of one or more additional reviewers if required. If appropriate, data will be pooled. If not, a narrative synthesis will be performed. The findings will be submitted to a peer-reviewed journal.