Clinical Briefs

With Comments from Russell H. Greenfield, MD, Medical Director, Carolinas Integrative Health, Carolinas HealthCare System, Charlotte, NC, Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill, NC. Dr. Greenfield is Executive Editor of Alternative Medicine Alert.

Probiotic Infant Formula and Infectious Disease Prevention

Source: Weizman Z, et al. Effect of a probiotic infant formula on infections in child care centers: Comparison of two probiotic agents. Pediatrics 2005;115:5-9.

Goal: To compare the effect of two different probiotics on preventing infections in children attending day care centers.

Design: Prospective, randomized, double-blind, placebo-controlled trial at 14 Israeli child care centers.

Subjects: Healthy infants from 4-10 months of age (n = 201).

Methods: Participants were randomized to receive standard formula (n = 60), or formula supplemented with either Bifidobacterium lactis (also called BB-12, n = 73) or Lactobacillus reuteri (n = 68) for 12 weeks. Children were evaluated at baseline, 4, 8, and 12 weeks. Parents filled out a questionnaire daily (which included questions on feeding, stools, and behavior) and were asked to report on symptoms. With onset of illness, each child was examined daily by a pediatrician. Primary outcome measures included number of days/episodes of fever, respiratory illness, or diarrhea. Secondary outcome measures focused on the need for conventional medical intervention.

Results: Those infants not receiving probiotic therapy experienced significantly more episodes of fever. The control group also had more episodes of diarrhea, which lasted longer than similar illness in the treatment groups. No difference was noted between groups with respect to incidence of respiratory tract infections. For the children who did receive probiotics, those getting L. reuteri experienced fewer days of fever, missed fewer days of child care, and had lower rates of clinic visits and antibiotic use than those in the BB-12 group.

Conclusions: Healthy infants offered formula supplemented with either BB-12 or L. reuteri experienced less febrile illness, and both fewer and shorter episodes of diarrhea, than children receiving standard formula. Effects noted were more prominent in the group receiving L. reuteri.

Study Strengths: Compared two microbes accepted as viable probiotics; amount and viability of microbes monitored every three months; degree of follow-up.

Study Weaknesses: Short duration; no fecal analysis of gut colonization.

Of Note: Infants in the study were not breastfed based on prior parental decision; information from seven children was not included in the final analysis due to non-compliance with the protocol; probiotic-supplemented infant formulas are currently available in several countries; the 21-month study period spanned two winter and two summer seasons; children with atopic disorders were not permitted to participate in the study (previous probiotic studies have suggested benefit for atopic disorders); each supplemented formula contained 1 ´ 107 colony-forming units of the specified microbe and mean daily formula intake did not differ between the groups; no adverse effects were noted; improvements with probiotic therapy in established illness were modest (e.g., differences in duration of fever and diarrhea were less than one day).

We Knew That: Probiotics may enhance host immunity beyond the gastrointestinal tract; human breast milk is a source of lactic acid bacteria for the infant gut, and breastfed infants develop a probiotic-rich intestinal milieu as compared with formula-fed infants, which may explain the lower incidence of infectious diarrhea in breastfed babies; children attending day care centers have a higher incidence of both respiratory and gastrointestinal infections; prior studies suggest that probiotic therapy may lessen the incidence of recurrent infectious disease in children attending day care centers; bifidobacteria and lactobacilli are generally regarded as safe since they are normally found in human intestines.

Clinical Import: Any means of keeping infants healthy has worldwide implications, and although some of the improvements noted in this study were modest, one need only ask any parent if one day less of their child’s illness would be deemed beneficial. The idea that taking bacteria orally could have an impact on immune system function far from the digestive tract was once incredible, but data have shown the concept to be true and research into the benefits of probiotic therapy has exploded.

This is one of the few studies pitting one microbe against another to evaluate therapeutic effectiveness. The issue is significant, as many people, patient and practitioner alike, consider probiotic therapy to be therapeutically equiva- lent across numerous microbial strains. Such a stance is incorrect. The effect of probiotic therapy is strain-specific and likely disease-specific, but with so many organisms touted as effective probiotics, it is as yet unclear which agents should be used in specific clinical situations.

This study offers a framework for comparing organisms with probiotic activity, and suggests that L. reuteri, even more than BB-12, may help keep infants healthy while attending day care. Longer trials are warranted, and data comparing L. reuteri with Lactobacillus GG (the organism currently associated with the most supportive data) in specific clinical situations would be valuable. Readers should keep in mind that probiotic therapy usually involves live organisms, which could put immunocompromised children at risk.

What to do with this article: Keep a hard copy in your file cabinet.