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Systematic review: early feeding practices and the risk of coeliac disease. A 2022 update and revision.
Szajewska, H, Shamir, R, Stróżyk, A, Chmielewska, A, Zalewski, BM, Auricchio, R, Koletzko, S, Korponay-Szabo, IR, Mearin, ML, Meijer, C, et al
Alimentary pharmacology & therapeutics. 2023;(1):8-22
Abstract
BACKGROUND The effects of early feeding practices on the risk of coeliac disease (CD) remain debated. AIMS To update evidence on these practices on the risk of CD and/or CD-related autoimmunity (CDA), defined as anti-transglutaminase or anti-endomysial antibody positivity METHODS We searched MEDLINE, EMBASE and the Cochrane Library to May 2022 for randomised controlled trials (RCTs) and observational studies. RESULTS We included 36 publications (30 studies). In the population at genetic risk of developing CD (HLA DQ2/DQ8-positive), exclusive or any breastfeeding and longer breastfeeding duration did not reduce the risk of developing CD/CDA during childhood. While a meta-analysis of four case-control studies showed a decreased risk for CD when gluten was introduced during breastfeeding, this was not shown in RCTs and cohort studies. Age at gluten introduction was not associated with cumulative CD/CDA risk, although two RCTs suggested that earlier gluten introduction was associated with earlier CDA appearance. Evidence from six observational studies suggests that consumption of a higher amount of gluten at weaning and/or thereafter may increase CD risk. There is insufficient evidence to determine the amount of gluten associated with an increased CD/CDA risk. Regarding whether infant feeding practices modulate the risk conferred by different HLA genotypes results were inconsistent. CONCLUSIONS For the population at genetic risk of CD, breastfeeding and age at gluten introduction have no effect on its cumulative incidence during childhood. There is some evidence for an effect of the amount of gluten consumed at weaning and/or thereafter on CD/CDA risk.
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Circulating miRNAs as Potential Biomarkers for Celiac Disease Development.
Tan, IL, Coutinho de Almeida, R, Modderman, R, Stachurska, A, Dekens, J, Barisani, D, Meijer, CR, Roca, M, Martinez-Ojinaga, E, Shamir, R, et al
Frontiers in immunology. 2021;:734763
Abstract
BACKGROUND & AIMS Celiac disease (CeD), an immune-mediated disease with enteropathy triggered by gluten, affects ~1% of the general European population. Currently, there are no biomarkers to predict CeD development. MicroRNAs (miRNAs) are short RNAs involved in post-transcriptional gene regulation, and certain disease- and stage-specific miRNA profiles have been found previously. We aimed to investigate whether circulating miRNAs can predict the development of CeD. METHODS Using next-generation miRNA-sequencing, we determined miRNAs in >200 serum samples from 53 participants of the PreventCD study, of whom 33 developed CeD during follow-up. Following study inclusion at 3 months of age, samples were drawn at predefined ages, diagnosis (first anti-transglutaminase antibody (TGA) positivity or diagnostic biopsy) and after the start of a gluten-free diet (GFD). This allowed identification of circulating miRNAs that are deregulated before TGA positivity. For validation of the biomarkers for CeD and GFD response, two additional cohorts were included in subsequent meta-analyses. Additionally, miRNAs were measured in duodenal biopsies in a case-control cohort. RESULTS 53 circulating miRNAs were increased (27) or decreased (26) in CeD versus controls. We assessed specific trends in these individual miRNAs in the PreventCD cohort by grouping the pre-diagnostic samples of the CeD patients (all had negative TGA) by how close to seroconversion (first sample positive TGA) the samples were taken. 8/53 miRNAs differed significantly between controls and samples taken <1 year before TGA positivity: miR-21-3p, miR-374a-5p, 144-3p, miR-500a-3p, miR-486-3p let-7d-3p, let-7e-5p and miR-3605-3p. 6/26 downregulated miRNAs reconstituted upon GFD, including miR-150-5p/-3p, whereas no upregulated miRNAs were downregulated upon GFD. 15/53 biomarker candidates also differed between CeD biopsies and controls, with a concordant direction, indicating that these circulating miRNAs might originate from the intestine. CONCLUSIONS We identified 53 circulating miRNAs that are potential early biomarkers for CeD, of which several can be detected more than a year before TGA positivity and some start to normalize upon GFD.
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Systematic Review with Meta-Analysis: Lactobacillus reuteri DSM 17938 for Treating Acute Gastroenteritis in Children. An Update.
Patro-Gołąb, B, Szajewska, H
Nutrients. 2019;11(11)
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Acute gastroenteritis (AGE) is a common health problem in children and, globally, diarrhoea is one of the leading causes of death in children younger than the age of 5 years. Probiotics have been extensively studied as a supportive treatment regimen in children with AGE and shown to be effective in reducing both diarrhoea duration and severity, and potentially reducing the duration of hospitalization. The aim of this systematic review and meta-analysis of four randomised controlled trials including 347 children was to provide an update on the research into a particular strain of Lactobacillus reuteri for the treatment of AGE. The meta-analysis showed a significantly reduced duration of illness and hospitalisation, as well as increased cure rate on day 1 and 2, but not 3, 4 or 5. Based on two of the four trials there was no difference in number of watery stools on day 1, 2, 3 or 4. The authors note that the clinical relevance of the findings was limited due to the small effect size and methodological limitations of the included studies.
Abstract
The effectiveness of Lactobacillus reuteri DSM 17938 (L. reuteri) for the management of acute gastroenteritis (AGE) has been recently questioned. We performed a systematic review to update evidence on L. reuteri for treating AGE in children. We searched MEDLINE, EMBASE, the Cochrane Library databases, and additional data sources from January 2016 (end of search for our 2016 systematic review) to August 2019. The primary outcomes were stool volume and duration of diarrhea. Four RCTs were included. None of them evaluated stool volume. Compared with placebo or no treatment, L. reuteri reduced diarrhea duration (four RCTs, n = 347, mean difference, MD -0.87 days, 95% CI [-1.43, -0.31]). L. reuteri use was also associated with a reduced duration of hospitalization (three RCTs, n = 284, MD -0.54 days, 95% CI [-1.09, 0.0]). The small effect sizes of limited clinical relevance and methodological limitations of the included trials should be noted when interpreting these findings.
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Probiotics for Preterm Infants: A Strain-Specific Systematic Review and Network Meta-analysis.
van den Akker, CHP, van Goudoever, JB, Szajewska, H, Embleton, ND, Hojsak, I, Reid, D, Shamir, R, ,
Journal of pediatric gastroenterology and nutrition. 2018;(1):103-122
Abstract
OBJECTIVES Several randomized controlled trials (RCTs) on the use of probiotics to reduce morbidity and mortality in preterm infants have provided inconsistent results. Although meta-analyses that group all of the used strains together are suggesting efficacy, it is not possible to determine the most effective strain that is more relevant to the clinician. We therefore used a network meta-analysis (NMA) approach to identify strains with greatest efficacy. METHODS A PubMed search identified placebo-controlled or head-to-head RCTs investigating probiotics in preterm infants. From trials that recorded mortality, necrotizing enterocolitis, late-onset sepsis, or time until full enteral feeding as outcomes, data were extracted and Bayesian hierarchical random-effects models were run to construct a NMA. RESULTS Fifty-one RCTs involving 11,231 preterm infants were included. Most strains or combinations of strains were only studied in one or a few RCTs. Only 3 of 25 studied probiotic treatment combinations showed significant reduction in mortality rates. Seven treatments reduced necrotizing enterocolitis incidence, 2 reduced late-onset sepsis, and 3 reduced time until full enteral feeding. There was no clear overlap of strains, which were effective on multiple outcome domains. CONCLUSIONS This NMA showed efficacy in reducing mortality and morbidity only in a minority of the studied strains or combinations. This may be due to an inadequate number, or size, of RCTs, or due to a true lack of effect for certain species. Further large and adequately powered RCTs using strains with the greatest apparent efficacy will be needed to more precisely define optimal treatment strategies.
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Lactobacillus rhamnosus GG in the Primary Prevention of Eczema in Children: A Systematic Review and Meta-Analysis.
Szajewska, H, Horvath, A
Nutrients. 2018;(9)
Abstract
Current guidelines recommend the use of probiotics to reduce the risk of eczema. It remains unclear which strain(s) to use. We systematically evaluated data on the efficacy of Lactobacillus rhamnosus GG (LGG) supplementation prenatally and/or postnatally for the primary prevention of eczema. The Cochrane Library, MEDLINE, and EMBASE databases were searched up to August 2018, with no language restrictions, for systematic reviews of randomized controlled trials (RCTs) and RCTs published afterwards. The primary outcome was eczema. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). A random-effects model was used to pool data. Heterogeneity was explored using the I² statistics. The GRADE criteria were used to assess the overall quality of evidence supporting the primary outcome. Seven publications reporting 5 RCTs (889 participants) were included. High to moderate certainty in the body of evidence suggests that LGG supplementation (regardless of the timing of administration) did not reduce the risk of eczema. There was also no consistent effect on other allergic outcomes. This meta-analysis shows that LGG was ineffective in reducing eczema. It does not support the general recommendation to use probiotics for preventing eczema, unless specific strains would be indicated.
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Systematic review with meta-analysis: early infant feeding and coeliac disease--update 2015.
Szajewska, H, Shamir, R, Chmielewska, A, Pieścik-Lech, M, Auricchio, R, Ivarsson, A, Kolacek, S, Koletzko, S, Korponay-Szabo, I, Mearin, ML, et al
Alimentary pharmacology & therapeutics. 2015;(11):1038-54
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Abstract
BACKGROUND New evidence emerged on early feeding practices and the risk of coeliac disease. AIM: To systematically update evidence on these practices to find out whether there is a need to revise current recommendations. METHODS MEDLINE, EMBASE and the Cochrane Library were searched from July 2012 (end of last search) to February 2015 for studies of any design that assessed the effect of gluten consumption and breastfeeding on the development of coeliac disease and/or coeliac disease-related autoimmunity. RESULTS We identified 21 publications, including two, new, large, randomised controlled trials performed in high-risk infants. Exclusive or any breastfeeding, as well as breastfeeding at the time of gluten introduction, did not reduce the risk of developing coeliac disease during childhood. For infants at high risk of developing coeliac disease, gluten introduction at 4 months of age in very small amounts, or at 6 or 12 months of age, resulted in similar rates of coeliac disease diagnosis in early childhood. Later gluten introduction was associated with later development of coeliac specific autoimmunity and coeliac disease during childhood, but not total risk reduction. Observational studies indicate that consumption of a higher amount of gluten at weaning may increase the risk for coeliac disease development. CONCLUSIONS Infant feeding practices (breastfeeding, time of gluten introduction) have no effect on the risk of developing coeliac disease during childhood (at least at specific timeframes evaluated in the included studies), necessitating an update of current European recommendations.
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Yogurt for treating acute gastroenteritis in children: Systematic review and meta-analysis.
Patro-Gołąb, B, Shamir, R, Szajewska, H
Clinical nutrition (Edinburgh, Scotland). 2015;(5):818-24
Abstract
BACKGROUND In May 2014, the updated guidelines for the management of acute gastroenteritis (AGE) were published. The use of yogurt in the nutritional management of AGE was not addressed, although it is frequently used in many countries for this purpose. We aimed to systematically evaluate the efficacy of yogurt consumption for the management of AGE in children. DESIGN In this systematic review, a number of databases, including MEDLINE, EMBASE, and the Cochrane Library, with no language restrictions, were searched up to July 2014 for randomized controlled trials (RCTs) evaluating the effect of yogurt consumption in children with AGE. The risk of bias was assessed using the Cochrane risk of bias tool. RESULTS Four RCTs (n = 448) that were generally low in methodological quality, all performed in hospital setting, were included. Compared with placebo/no intervention, yogurt consumption had no significant effect on stool volume. The data on the effect of yogurt consumption on the duration of diarrhea and stool frequency were not consistent. The chance of treatment success (or failure) was similar in both groups. Compared with placebo, the duration of hospitalization was shorter in children who received yogurt, but the difference was of a borderline significance. Total weight gain increased for those treated with yogurt. CONCLUSIONS The consumption of yogurt had a positive effect on weight gain, but no consistent effect on AGE outcomes in hospitalized children. Given the limited data and the methodological limitations of the included trials, the evidence should be viewed with caution. The effect of yogurt consumption in the ambulatory setting is unknown.
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Meta-analysis shows limited evidence for using Lactobacillus acidophilus LB to treat acute gastroenteritis in children.
Szajewska, H, Ruszczyński, M, Kolaček, S
Acta paediatrica (Oslo, Norway : 1992). 2014;(3):249-55
Abstract
UNLABELLED A meta-analysis of four randomised controlled trials of varying methodological quality, involving 304 children aged 1-48 months, showed that Lactobacillus acidophilus LB (LB) reduced the duration of diarrhoea in hospitalised, but not outpatient, children compared with a placebo. The chance of a cure on day three was similar in both groups, but LB increased the chance of cure on day four. CONCLUSION There is limited evidence to recommend LB for treating paediatric diarrhoea.
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Lactobacillus reuteri DSM 17938 for managing infant colic: protocol for an individual participant data meta-analysis.
Sung, V, Cabana, MD, D'Amico, F, Deshpande, G, Dupont, C, Indrio, F, Mentula, S, Partty, A, Savino, F, Szajewska, H, et al
BMJ open. 2014;(12):e006475
Abstract
INTRODUCTION Infant colic, or excessive crying of unknown cause in infants less than 3 months old, is common and burdensome. Its aetiology is undetermined, and consensus on its management is still lacking. Recent studies suggest a possible link between infant colic and gut microbiota, indicating probiotics to be a promising treatment. However, only a few strains have been tested, and results from randomised controlled trials are conflicting. It is important to clarify whether probiotics are effective for treating infant colic in general, and to identify whether certain subgroups of infants with colic would benefit from particular strains of probiotics. METHODS AND ANALYSIS Through an individual participant data meta-analysis (IPDMA), we aim to identify whether the probiotic Lactobacillus reuteri DSM 17938 is effective in the management of infant colic, and to clarify whether its effects differ according to feeding method (breast vs formula vs combined), proton pump inhibitor exposure, and antibiotic exposure. The primary outcomes are infant crying duration and treatment success (at least 50% reduction in crying time from baseline) at 21 days postintervention. Individual participant data from all studies will be modelled simultaneously in multilevel generalised linear mixed-effects regression models to account for the nesting of participants within studies. Subgroup analyses of participant-level and intervention-level characteristics will be undertaken on the primary outcomes to assess if the intervention effect differs between certain groups of infants. ETHICS AND DISSEMINATION Approved by the Royal Children's Hospital Human Research Ethics Committee (HREC 34081). Results will be reported in a peer-reviewed journal in 2015. TRIAL REGISTRATION NUMBER PROSPERO CRD42014013210.
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Meta-analysis: Lactobacillus reuteri strain DSM 17938 (and the original strain ATCC 55730) for treating acute gastroenteritis in children.
Szajewska, H, Urbańska, M, Chmielewska, A, Weizman, Z, Shamir, R
Beneficial microbes. 2014;(3):285-93
Abstract
Lactobacillus reuteri ATCC 55730 has been shown to provide a moderate clinical effect in the treatment of acute gastroenteritis (AGE) in children. However, as the L. reuteri ATCC 55730 strain was found to carry potentially transferable resistance traits for tetracycline and lincomycin, it was replaced by a new strain, L. reuteri DSM 17938, without unwanted plasmid-borne antibiotic resistance. Bioequivalence of the two strains has been suggested. We aimed to systematically evaluate data on the effectiveness of L. reuteri DSM 17938 and the original strain, L. reuteri ATCC 55730, in the treatment of AGE in children. The Cochrane Library, MEDLINE, and EMBASE databases, reference lists, and abstract books of major scientific meetings were searched in August 2013, with no language restrictions, for relevant randomised controlled trials (RCTs). Two RCTs (n=196) that evaluated L. reuteri DSM 17938 and three RCTs (n=156) that evaluated L. reuteri ATCC 55730, which involved hospitalised children aged 3 to 60 months, met the inclusion criteria. Compared with placebo or no treatment, DSM 17938 significantly reduced the duration of diarrhoea (mean difference -32 h, 95% confidence interval (CI): -41 to -24) and increased the chance of cure on day 3 (relative risk: 3.5, 95% CI: 1.2 to 10.8, random effects model). Similar results were obtained with the original strain, L. reuteri ATCC 55730. In conclusion, in hospitalised children, use of both strains of L. reuteri reduced the duration of diarrhoea, and more children were cured within 3 days. Data from outpatients and countryspecific cost-effectiveness analyses are needed. Given the limited data and the methodological limitations of the included trials, the evidence should be viewed with caution.