Copyright restrictions may apply JAMA Pediatrics Journal Club Slides: Probiotic in Colic, Regurgitation, & Constipation Indrio F, Di Mauro A, Riezzo G, et al. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial. JAMA Pediatr. Published online January 13, doi: /jamapediatrics

Copyright restrictions may apply Background Infantile colic, gastroesophageal reflux (GER), and constipation are common gastrointestinal disorders that lead to referral to a pediatrician during the first 6 months of life. These conditions are often responsible for hospitalization, feeding changes, use of drugs, parental anxiety, and loss of parental working days with relevant health and social consequences. Study Objective To investigate whether oral supplementation with Lactobacillus reuteri DSM during the first 3 months of life can reduce the following: –Onset of colic, GER, and constipation in term newborns. –Socioeconomic impact of these conditions. Introduction

Copyright restrictions may apply Study Design Multicenter, double-blind, randomized clinical trial in 589 term newborns (age <1 week) born at 9 different neonatal units in Italy between September 1, 2010, and October 30, Setting In a structured diary, parents recorded the number of episodes per day of: –Regurgitation. –Inconsolable crying episodes (minutes per day as already described in the literature). –Evacuations per day. Parents also recorded number of office visits, diet changes, hospitalizations, loss of working days, and use of medications. Patients 589 Infants were randomly allocated to receive L reuteri DSM or placebo daily for 90 days. Methods

Copyright restrictions may apply Methods Outcomes Reduction of incidence of colic, GER, and constipation during the first 3 months of life. Cost-benefit analysis of probiotic supplementation. Limitations Loss to follow-up of 16.8% of children enrolled in the trial. An unselected population was recruited, with possible risk of overtreating healthy neonates.

Copyright restrictions may apply Results Primary Outcome at 1 Month of Life

Copyright restrictions may apply Results Primary Outcome at 3 Months of Life

Copyright restrictions may apply Secondary Outcome at 3 Months of Life Results

Copyright restrictions may apply Comment Daily administration of L reuteri DSM early in life decreased the reported incidence of inconsolable crying, regurgitation, and functional constipation in the first 3 months of life. Supplementation was estimated to generate savings for families and society (from lower utilization of health care services). To our knowledge, this is the first clinical trial to address the use of a probiotic to prevent gastrointestinal disorders in neonates.

Copyright restrictions may apply Comment Early life events could increase visceral sensitivity and mucosal permeability, alter the balance of the enteric microflora, and increase mucosal and neurogenic low-grade inflammation, altering the signal of the gut-brain-microbiota axis. Driving a change of colonization during the first weeks of life through giving lactobacilli may promote an improvement in intestinal permeability, visceral sensitivity, and mast cell density. Probiotic administration may represent a viable strategy for preventing gastrointestinal conditions in infants.

Copyright restrictions may apply If you have questions, please contact the corresponding author: –Flavia Indrio, MD, Department of Pediatrics, Aldo Moro University of Bari, Policlinico, Piazza G Cesare 11, Bari, Italy Funding/Support This study was supported by BioGaia AB, Sweden, which provided active study product and placebo. Conflict of Interest Disclosures None reported. Contact Information