Medscape Medical News
Probiotics No Help for Colicky Infants
Lara C. Pullen, PhD
April 01, 2014
Treatment of infants with Lactobacillus reuteri DSM 17938 did not improve symptoms of colic in a recent study. These results contrast with the results of previous smaller trials and do not support a general recommendation of probiotics for the treatment of colic in infants.
Valerie Sung, MPH, from the Royal Children's Hospital, Parkville, Victoria, Australia, and colleagues published results from their double-blind, placebo-controlled, randomized trial online April 1 in BMJ. The study, with 167 infants, is the largest randomized controlled trial published to date that addresses the question of probiotics in colic.
The infants in the study were younger than 3 months and presented with symptoms that were severe enough to drive the parents to an emergency care setting. As a consequence, the investigators note, the results may not generalize to infants whose parents do not seek emergency care.
All of the infants met Wessel's criteria for crying or fussing. The researchers randomly assigned the infants to receive either probiotics (n = 85) or placebo (n = 85).
At 1 month, the infants in the probiotic group fussed or cried for 49 minutes more than those in the placebo group (95% confidence interval, 8 - 90 minutes; P = .02). The results stand in contrast with 3 other studies that investigated the same probiotic strain in infants with colic but were consistent at all measured points in this study.
The results of the current study are also consistent with the cautionary approach recommended by Elizabeth Marcus, MD, assistant professor in the Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition in Mattel Children's Hospital, University of California, Los Angeles. In a previous interview with Medscape Medical News, she noted that trial data indicating probiotics might be helpful in preventing colic should not be misinterpreted as suggesting probiotics would be useful in treating colic.
"Based on the null findings from this large, rigorous trial, and the results from the updated meta-analysis, which has potential biases, we recommend caution in formulating recommendations regarding use of L reuteri DSM 17938 for reducing crying or fussing in breastfed, and particularly in formula fed, infants with colic," the authors of the current study conclude. "Currently, there are at least five other similar randomised controlled trials taking place in different parts of the world. It will be valuable to pool data from all existing and ongoing rigorous trials into an individual patient level meta-analysis to investigate with greater certainty which subgroups of infants with colic, if any, could benefit from probiotics."
"For us to continue to perform drug intervention trials for this problem perhaps underscores our unwillingness to accept that colic is likely to represent a heterogeneous disorder with many complex inputs. As the old adage goes, 'babies cry.' Parents and their babies may be better served if we devote more resources to studying the interventions recommended long before the discovery of probiotics: reassurance, family social support, and the tincture of time," William E. Bennett, Jr, MD, from the Department of Pediatrics at Indiana University School of Medicine, writes in an accompanying editorial.
Murdoch Childrens Research Institute is supported by the Victorian government’s operational infrastructure support programme. The investigators received probiotics from Nestle Nutrition Institute and Nutricia (Danone). Sung and 3 coauthors received support from the Australian National Health and Medical Research Council for the submitted work; another coauthor is supported by a Canada research chair in community child health research and by the Child and Family Research Institute of BC Children’s Hospital; another coauthor is a member of the Nestlé Nutrition Institute Medical Advisory Board Oceania and the Nutricia Medical Advisory Board Australasia, received honorariums for speaking at symposiums sponsored by Nestlé Nutrition Institute and Nutricia (Danone), and received probiotic and placebo research products from Nestlé Research Centre Switzerland and Dicofarm Italy for studies unrelated to this trial; and another coauthor is a member of the Nestlé Nutrition Institute Medical Advisory Board Oceania and the Nutricia Medical Advisory Board Australasia and received honorariums for speaking at symposiums sponsored by Nestlé Nutrition Institute and Nutricia (Danone). Dr. Bennett and Dr. Marcus have disclosed no relevant financial relationships.
BMJ. Published online April 1, 2014.
Treating infant colic with the probiotic Lactobacillus reuteri: double blind, placebo controlled randomised trial
BMJ 2014; 348 doi: https://dx.doi.org/10.1136/bmj.g2107 (Published 1 April 2014)
Cite this as: BMJ 2014;348:g2107
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Valerie Sung, paediatrician123, Harriet Hiscock, associate professor123, Mimi L K Tang, professor123, Fiona K Mensah, statistician123, Monica L Nation, honours student23, Catherine Satzke, research fellow23, Ralf G Heine, paediatric gastroenterologist/allergist123, Amanda Stock, paediatrician1, Ronald G Barr, professor4, Melissa Wake, professor123
Author Affiliations
Correspondence to: V Sung Centre for Community Child Health, Royal Children’s Hospital, Parkville, Vic 3052, Australia valerie.sung@rch.org.au
Accepted 3 March 2014
Abstract
Objective To determine whether the probiotic Lactobacillus reuteri DSM 17938 reduces crying or fussing in a broad community based sample of breastfed infants and formula fed infants with colic aged less than 3 months.
Design Double blind, placebo controlled randomised trial.
Setting Community based sample (primary and secondary level care centres) in Melbourne, Australia.
Participants 167 breastfed infants or formula fed infants aged less than 3 months meeting Wessel’s criteria for crying or fussing: 85 were randomised to receive probiotic and 82 to receive placebo.
Interventions Oral daily L reuteri (1×108 colony forming units) versus placebo for one month.
Main outcomes measures The primary outcome was daily duration of cry or fuss at 1 month. Secondary outcomes were duration of cry or fuss; number of cry or fuss episodes; sleep duration of infant at 7, 14, and 21 days, and 1 and 6 months; maternal mental health (Edinburgh postnatal depression subscale); family functioning (paediatric quality of life inventory), parent quality adjusted life years (assessment of quality of life) at 1 and 6 months; infant functioning (paediatric quality of life inventory) at 6 months; infant faecal microbiota (microbial diversity, colonisation with Escherichia coli), and calprotectin levels at 1 month. In intention to treat analyses the two groups were compared using regression models adjusted for potential confounders.
Results Of 167 infants randomised from August 2011 to August 2012, 127 (76%) were retained to primary outcome; of these, a subset was analysed for faecal microbial diversity, E coli colonisation, and calprotectin levels. Adherence was high. Mean daily cry or fuss time fell steadily in both groups. At 1 month, the probiotic group cried or fussed 49 minutes more than the placebo group (95% confidence interval 8 to 90 minutes, P=0.02); this mainly reflected more fussing, especially for formula fed infants. The groups were similar on all secondary outcomes. No study related adverse events occurred.
ConclusionsL reuteri DSM 17938 did not benefit a community sample of breastfed infants and formula fed infants with colic. These findings differ from previous smaller trials of selected populations and do not support a general recommendation for the use of probiotics to treat colic in infants.