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Cited by 208Probiotics and Fermented FoodsViral gastroenteritis research and epidemiologyInfant Nutrition and Health

Lactobacillus rhamnosus GG versus Placebo for Acute Gastroenteritis in Children

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Schnadower, David, Tarr, Phillip I., Casper, T. Charles, Gorelick, Marc H., Dean, J. Michael, O’Connell, Karen J., Mahajan, Prashant, Levine, Adam C. +11 more·2018·New England Journal of Medicine
DOI 10.1056/nejmoa1802598PMC PMC6358014
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Abstract

BACKGROUND: Acute gastroenteritis develops in millions of children in the United States every year, and treatment with probiotics is common. However, data to support the use of probiotics in this population are limited. METHODS: colony-forming units twice daily or matching placebo. Follow-up surveys were conducted daily for 5 days and again 14 days after enrollment and 1 month after enrollment. The primary outcome was moderate-to-severe gastroenteritis, which was defined as an illness episode with a total score on the modified Vesikari scale of 9 or higher (scores range from 0 to 20, with higher scores indicating more severe disease), within 14 days after enrollment. Secondary outcomes included the duration and frequency of diarrhea and vomiting, the duration of day-care absenteeism, and the rate of household transmission (defined as the development of symptoms of gastroenteritis in previously asymptomatic household contacts). RESULTS: Among the 971 participants, 943 (97.1%) completed the trial. The median age was 1.4 years (interquartile range, 0.9 to 2.3), and 513 participants (52.9%) were male. The modified Vesikari scale score for the 14-day period after enrollment was 9 or higher in 55 of 468 participants (11.8%) in the L. rhamnosus GG group and in 60 of 475 participants (12.6%) in the placebo group (relative risk, 0.96; 95% confidence interval, 0.68 to 1.35; P=0.83). There were no significant differences between the L. rhamnosus GG group and the placebo group in the duration of diarrhea (median, 49.7 hours in the L. rhamnosus GG group and 50.9 hours in the placebo group; P=0.26), duration of vomiting (median, 0 hours in both groups; P=0.17), or day-care absenteeism (median, 2 days in both groups; P=0.67) or in the rate of household transmission (10.6% and 14.1% in the two groups, respectively; P=0.16). CONCLUSIONS: Among preschool children with acute gastroenteritis, those who received a 5-day course of L. rhamnosus GG did not have better outcomes than those who received placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01773967 .).

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  • The identity and viability of probiotic organisms were evaluated by bacteriology and molecular methods in seven studies, and independently of the study team in two of these.

    “The identity and viability of probiotic organisms were evaluated by bacteriology and molecular methods in seven studies (Freedman 2015; Freedman 2018a; Hong Chau 2018; Mao 2008; Rosenfeldt 2002a; Rosenfeldt 2002b; Schnadower 2018), and were evaluated independently of the study team in two of these studies (Freedman 2015; Schnadower 2018).”

    From Probiotics for treating acute infectious diarrhoea (2020) · cites this paper as Schnadower 2018

    The Methods section (“Testing of Stool Samples and L. rhamnosus GG Testing”; page not provided) says the trial’s probiotic capsules were independently tested for contaminants and viability. The Results section reports colony-forming-unit measurements. Our copy does not say that molecular methods were used to verify the probiotic’s identity; its PCR testing concerned stool pathogens. This paper also does not establish the citing sentence’s totals of seven studies and two independently evaluated studies. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Schnadower 2018 reported similar rates of adverse events in the two groups, except wheezing was more common in children receiving L rhamnosus GG than controls (5/472 versus 0/479; P = 0.03), and serious adverse events occurred in a similar number in each group.

    “Schnadower 2018 reported similar rates of adverse events in the two groups, except that wheezing was more common in children receiving L rhamnosus GG than in controls (5/472 versus 0/479 children; P = 0.03; borderline statistical significance in view of multiple comparisons); SAEs occurred in a similar number of children in each group.”

    From Probiotics for treating acute infectious diarrhoea (2020) · cites this paper as Schnadower 2018

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    Experimental — accuracy not yet measured

  • Two recently conducted large trials in children did not show a probiotic effect for the number of children with diarrhoea lasting ≥ 48 hours or for mean duration of diarrhoea.

    “A notable finding was that two recently conducted large trials undertaken in children did not show a probiotic effect for the number of children with diarrhoea lasting ≥ 48 hours (Analysis 1.1) or for mean duration of diarrhoea (Analysis 1.2; Freedman 2018a; Schnadower 2018).”

    From Probiotics for treating acute infectious diarrhoea (2020) · cites this paper as Schnadower 2018

    The Results > Secondary Outcomes section reports no significant difference in diarrhea duration between the probiotic and placebo groups. The Abstract > Results gives median durations, not mean durations. Our copy does not report a comparison of the number of children whose diarrhea lasted at least 48 hours; its 48-hour subgroup concerns symptoms before treatment. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Two recent studies each recruited a large number of participants, potentially making a significant contribution to the evidence base.

    “Finally, two recent studies each recruited a large number of participants, potentially making a significant contribution to the evidence base (Freedman 2018a; Schnadower 2018).”

    From Probiotics for treating acute infectious diarrhoea (2020) · cites this paper as Schnadower 2018

  • A recent large, well-conducted trial of L rhamnosus GG in children in the USA did not observe a probiotic effect.

    “Of note, a recent large, well‐conducted trial of L rhamnosus GG in children in the USA did not observe a probiotic effect (Schnadower 2018).”

    From Probiotics for treating acute infectious diarrhoea (2020) · cites this paper as Schnadower 2018

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References 42 · Cited by 208

Research works printed but not linked: 38

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Authors
Schnadower, D., Tarr, P. I., Casper, T. C., Gorelick, M. H., Dean, J. M., O’Connell, K. J., Mahajan, P., Levine, A. C., Bhatt, S. R., Roskind, C. G., Powell, E. C., Rogers, A. J., Vance, C., Sapien, R. E., Olsen, C. S., Metheney, M., Dickey, V. P., Hall-Moore, C., & Freedman, S. B.
Affiliations
  • Cincinnati Children's Hospital Medical Center (US)
  • University of Minnesota (US)
  • Northwestern University (US)
  • From the Divisions of Pediatric Emergency Medicine (D.S., V.P.D.) and Gastroenterology, Hepatology, and Nutrition (P.I.T., C.H.-M.), Department of Pediatrics, Washington University School of Medicine, St. Louis; the Department of Pediatrics, University of Utah, Salt Lake City (T.C.C., J.M.D., C.S.O., M.M.); Central Administration, Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis (M.H.G.); the Division of Emergency Medicine, Children’s National Health System,...
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2018-11-22
Volume
379
Issue
21
Pages
2002-2014
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa1802598
PMC
PMC6358014
OpenAlex
W2901355211
Cited by
208
References
42
Citations by year
2026: 10 · 2025: 16 · 2024: 15 · 2023: 13 · 2022: 28 · 2021: 36 · 2020: 44 · 2019: 41 · 2018: 5
FWCI
29.57
Type
journal article
Language
en
Open access
Licence
www.nejmgroup.org/legal/terms-of-use.htm (vor)
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Maternal and Child Health Bureau (U03MC00001, U03MC00003, U03MC00006, U03MC00007, U03MC00008, U03MC22684, U03MC22685)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD071915)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
  • Health Sciences › Medicine › Infectious Diseases › Viral gastroenteritis research and epidemiology
  • Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
Keywords
acute gastroenteritis, probiotics, children, diarrhea, vomiting, household transmission, preschool children, disease duration, household contacts, rotavirus, norovirus, enteric pathogens
MeSH terms
Acute Disease, Child, Preschool, Diarrhea, Double-Blind Method, Female, Gastroenteritis, Humans, Infant, Male, Prospective Studies, Vomiting, Treatment Failure, Probiotics, Lacticaseibacillus rhamnosus

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