Association between Age, Weight, and Dose and Clinical Response to Probiotics in Children with Acute Gastroenteritis

David Schnadower; Robert E Sapien; T Charles Casper; Cheryl Vance; Phillip I Tarr; Karen J O'Connell; Adam C Levine; Cindy G Roskind; Alexander J Rogers; Seema R Bhatt; Prashant Mahajan; Elizabeth C Powell; Cody S Olsen; Marc H Gorelick; J Michael Dean; Stephen B Freedman; Pediatric Emergency Care Applied Research Network (PECARN) Probiotics Study

doi:10.1093/jn/nxaa313

Association between Age, Weight, and Dose and Clinical Response to Probiotics in Children with Acute Gastroenteritis

J Nutr. 2021 Jan 4;151(1):65-72. doi: 10.1093/jn/nxaa313.

Authors

David Schnadower¹, Robert E Sapien², T Charles Casper³, Cheryl Vance⁴, Phillip I Tarr⁵, Karen J O'Connell⁶, Adam C Levine⁷, Cindy G Roskind⁸, Alexander J Rogers⁹, Seema R Bhatt¹, Prashant Mahajan⁹, Elizabeth C Powell¹⁰, Cody S Olsen³, Marc H Gorelick¹¹, J Michael Dean³, Stephen B Freedman¹²; Pediatric Emergency Care Applied Research Network (PECARN) Probiotics Study

Affiliations

¹ Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
² Department of Emergency Medicine, University of New Mexico, Albuquerque, NM, USA.
³ Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
⁴ Departments of Emergency Medicine and Pediatrics, University of California, Davis, School of Medicine, Sacramento, CA, USA.
⁵ Division of Gastroenterology, Hepatology, & Nutrition, Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
⁶ Division of Emergency Medicine, Children's National Health System, Department of Pediatrics and Emergency Medicine, The George Washington School of Medicine and Health Sciences, Washington, DC, USA.
⁷ Department of Emergency Medicine, Rhode Island Hospital/Hasbro Children's Hospital and Brown University, Providence, RI, USA.
⁸ Division of Emergency Medicine, Department of Pediatrics, Columbia University College of Physicians & Surgeons, New York, NY, USA.
⁹ Departments of Emergency Medicine and Pediatrics, University of Michigan, Ann Arbor, MI, USA.
¹⁰ Division of Emergency Medicine, Department of Pediatrics, Ann & Robert H Lurie Children's Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹¹ Central Administration, Children's Minnesota, Minneapolis, MN, USA.
¹² Sections of Pediatric Emergency Medicine and Gastroenterology, Department of Pediatrics, Alberta Children's Hospital, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Abstract

Background: Gastroenteritis is a common and impactful disease in childhood. Probiotics are often used to treat acute gastroenteritis (AGE); however, in a large multicenter randomized controlled trial (RCT) in 971 children, Lactobacillus rhamnosus GG (LGG) was no better than placebo in improving patient outcomes.

Objectives: We sought to determine whether the effect of LGG is associated with age, weight z score and weight percentile adjusted for age and sex, or dose per kilogram administered.

Methods: This was a preplanned secondary analysis of a multicenter double-blind RCT of LGG 1 × 1010 CFU twice daily for 5 d or placebo in children 3-48 mo of age with AGE. Our primary outcome was moderate to severe gastroenteritis. Secondary outcomes included diarrhea and vomiting frequency and duration, chronic diarrhea, and side effects. We used multivariable linear and nonlinear models testing for interaction effects to assess outcomes by age, weight z score and weight percentile adjusted for age and sex, and dose per kilogram of LGG received.

Results: A total of 813 children (84%) were included in the analysis; 413 received placebo and 400 LGG. Baseline characteristics were similar between treatment groups. There were no differential interaction effects across ranges of age (P-interaction = 0.32), adjusted weight z score (P-interaction = 0.43), adjusted weight percentile (P-interaction = 0.45), or dose per kilogram of LGG received (P-interaction = 0.28) for the primary outcome. Whereas we found a statistical association favoring placebo at the extremes of adjusted weight z scores for the number of vomiting episodes (P-interaction = 0.02) and vomiting duration (P-interaction = 0.0475), there were no statistically significant differences in other secondary outcome measures (all P-interactions > 0.05).

Conclusions: LGG does not improve outcomes in children with AGE regardless of the age, adjusted weight z score, and adjusted weight percentile of participants, or the probiotic dose per kilogram received. These results further strengthen the conclusions of low risk of bias clinical trials which demonstrate that LGG provides no clinical benefit in children with AGE.This trial was registered at clinicaltrials.gov as NCT01773967.

Keywords: emergency medicine; gastroenteritis; pediatric; probiotic; randomized controlled trial; secondary analysis.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Body Weight*
Child, Preschool
Double-Blind Method
Gastroenteritis / drug therapy*
Humans
Infant
Probiotics / administration & dosage
Probiotics / therapeutic use*

Associated data

ClinicalTrials.gov/NCT01773967

Abstract

Publication types

MeSH terms

Associated data

Grants and funding