A problem with studies supporting the prophylactic use of probiotics for diarrhea has been the use of different preparations. Gutierrez-Castrellon and colleagues studied Lactobacillus reuteri 17938, a preparation used in several previous studies, to improve the ability to extrapolate findings across studies.
This prospective trial was conducted from 2011 through 2012 at 4 Mexican child-care centers. Children were randomly assigned to treatment or placebo groups, and both parents and investigators were blinded to study assignment. The children were 6-36 months of age, at least 37 weeks gestational age at birth, and attended one of the 4 day care centers studied. Children with low birthweight or other chronic diseases that might alter findings were excluded.
The outcome of interest in this study was a comparison of the number of days with diarrhea. A day with diarrhea was defined as any 24-hour period during which the child had 3 or more stools that were "loose or watery." Days with both loose stools and emesis were excluded. They also evaluated secondary outcomes, including number of days with respiratory tract infection symptoms, missed time at day care owing to illness, antibiotic use, and healthcare utilization. The intervention ran for 12 weeks, and the children were followed for an additional 12 weeks thereafter.
Intervention group children received 5 drops of freeze-dried Lactobacillus suspended in oil. The placebo included only the oil preparation, but the appearance and taste of the formulations were the same. The preparation was administered by the parents at the child's first morning meal.
Outcomes were assessed by parental completion of a symptom diary. However, they were also instructed to call the investigation team when their child had diarrhea, and the investigators prescribed an oral rehydration solution as indicated when a child had a diarrheal illness. Parents also reported respiratory symptoms. The parents and children had monthly follow-up visits, at which time the diaries were reviewed and symptom recording was reinforced.
The 2 arms of the study each enrolled 168 children, and the groups were similar at the time of enrollment. For the primary outcome, the treatment group had markedly fewer days of diarrhea, with an average of 0.32 day compared with 0.96 day among the control group. The benefit appeared to extend into the follow-up period (weeks 13-24), when the children were not receiving any preparations, and children in the treatment group experienced only 0.5 day of diarrhea on average compared with a mean of 1.1 days of diarrhea among the placebo group. The average duration of diarrheal episodes was also shorter for treatment group children, at 1.4 days compared with 2.5 days among the placebo group.
Both the number of respiratory tract illnesses and mean duration of respiratory symptoms per child were lower among the treatment group. Febrile episodes were also lower among treatment group children, who had 0.4 episode of fever per child during the intervention period compared with 1.1 episodes in the placebo group. The benefit of fever reduction extended into weeks 13-24.
Most of the other secondary outcomes, including school and parental work absenteeism, medical visits, and emergency department visits, all favored the treatment group. Secondary outcomes that did not significantly differ between the 2 groups included the number of emergency department visits, average weight gain during the study period, and the frequency of stools.
The investigators concluded that among healthy children in day care centers, daily administration ofLactobacillus reduced gastrointestinal illnesses as well as respiratory illnesses.
Along with a study of Lactobacillus to prevent infantile functional gastrointestinal disorders that was published recently in JAMA Pediatrics, the findings of Gutierrez-Castrellon and colleagues are interesting, although both studies need to be replicated in other populations. However, I am struck by the very similar findings between these 2 randomized, double-blind, clinical trials. Both showed substantial reductions in healthcare utilization, in addition to reductions in their primary physiologic outcomes.
Here's hoping that there is a building consensus on which product to use, leading to clinical trials that can use the same preparation, so that providers can compare and assimilate the findings from these multiple studies into some guidance on which patients might benefit from Lactobacillus administration.