Do Probiotics Prevent Fussy Babies?

Abstract

Source: Indrio F, DiMauro A, Riezzo G, et al. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized trial. JAMA Pediatr. 2014; 168(3): 228– 233; doi: 10.1001/jamapediatrics.2013.4367Investigators from Italy aimed to determine whether early supplementation for newborns with the probiotic Lactobacillus reuteri reduces the occurrence of colic, gastroesophageal reflux, and constipation during the first 3 months of life. The investigators recruited healthy term infants <1 week old from 9 Italian pediatric centers over a period of 2 years. The infants were randomly assigned to receive drops containing L reuteri DSM 17938 or placebo for 90 days during the first 3 months of life. Both parents and investigators were blinded to the group assignments and interventions. The placebo solution was identical to the probiotic solution with the exception of live bacteria, and both were provided by BioGaia, manufacturer of L reuteri, and sponsor of the study. Parents were asked to record each day the number of episodes of regurgitation, duration of each episode of inconsolable crying, and number of bowel movements for 3 months. Data on health care utilization and parental work loss were also collected to assess the cost-effectiveness of treatment.A total of 554 newborns were enrolled in the study; data were analyzed on 238 randomized to the probiotic and 230 placebo recipients (85% of those enrolled). At the end of the trial, the mean daily duration of crying (38 vs 71 minutes; P < .01), mean number of regurgitations per day (2.9 vs 4.6; P < .01), and mean number of bowel movements per day (4.2 vs 3.6; P < .01) significantly favored the L reuteri group compared to the placebo group. The use of the study probiotic resulted in an estimated mean savings of US$118.71 per patient for the family and an additional US$140.30 for the community.The authors conclude that the prophylactic use of L reuteri in the first 3 months of life reduced the amount of inconsolable crying, regurgitation, and functional constipation in infants, and reduced costs for managing these conditions.Drs Cerezo and LeLeiko have disclosed no financial relationship relevant to this commentary. The commentary does not contain a discussion of an unapproved/investigative use of a commercial product/deviceInfant colic, regurgitation or reflux, and constipation are common and usually benign conditions. Despite their self-limiting nature, however, these conditions may lead to parental anxiety, frustration, and frequent visits to the pediatrician or emergency department. Previous studies have demonstrated that the composition of the infant intestinal microbiota, specifically the absence of lactobacilli species, is an independent risk factor for the development of colic.1 Two recent meta-analyses concluded that L reuteri may be effective prevention and treatment for infant colic in exclusively breastfed infants but that the evidence is weak for any benefit in formula-fed infants.2,3We are not, however, rushing to prescribe prophylactic L reuteri for our patients.We are skeptical about the authors’ assertion that “low-grade mucosal inflammation…” is a common finding in babies with colic, regurgitation, and constipation, or that a probiotic could offer a role in controlling this inflammation. The authors cite the loss to follow-up of 15% of the cohort as a limitation of their study and comment on the risk of overtreating normal neonates. The double-masked, placebo-controlled randomized study design did not make up for the fact that the analysis does not separate the effects of the probiotic in babies who were breastfed versus those not breastfed. Their hypothesis rests on the proposition that promoting bacterial colonization of the gut may increase intestinal health. These colonizing lactobacilli might already be present in the exclusively breastfed infants.Probiotics are undoubtedly here to stay, and will be important in managing a number of diseases, especially those with gastrointestinal symptoms. It is possible that the current findings will be replicated in a more convincing fashion. But we are not ready to endorse the use of prophylactic probiotics in otherwise healthy infants. We would want more clear evidence of efficacy and safety before considering this a reasonable addition to the neonate’s diet.There are several problems with this study. The authors excluded data on infants who received drugs such as antacids and proton-pump inhibitors; however, these are likely the infants with the most significant symptoms and excluding them may have biased the results. The adequacy of blinding wasn’t assessed, and the study was industry-sponsored. That being said, the results, particularly reduction in inconsolable crying, are compelling. Any promising treatment for infant colic is worthy of further study.