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Probiotic does not prevent GI complications, death in preterm infants
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A phase 3 randomized controlled trial showed no benefit of the probiotic Bifidobacterium breve BBG-001 for preventing necrotizing enterocolitis, late-onset sepsis and mortality in very preterm infants.
“The results of this trial contrast with the conclusions of the meta-analysis in the Cochrane review that report significant reductions in necrotizing enterocolitis and mortality associated with probiotic administration,” the researchers wrote. Furthermore, a previous trial included in the Cochrane review (the ProPrems study) showed similar results, but used a different probiotic. “These two large trials suggest that, while probiotics are generally safe in the short term, they are not universally effective, and that different strains and combinations should be investigated separately.”
From July 2010 through July 2013, the researchers recruited 1,315 infants born between 23 and 30 weeks of gestation at 24 hospitals in Southeast England, and randomly assigned them to receive daily B. breve BBG-001 given enterally in an elemental formula (n = 654) or placebo (n = 661). Clinicians and families were masked to randomization, and necrotizing enterocolitis, sepsis more than 72 hours after birth and death before hospital discharge served as primary outcomes.
Intention-to-treat analysis showed no significant differences in outcomes between groups. Necrotizing enterocolitis occurred in 9% of the treatment group compared with 10% of the placebo group (adjusted RR = 0.93; 95% CI, 0.68-1.27). Sepsis occurred in 11% of the treatment group compared with 12% of the placebo group (aRR = 0.97; 95% CI, 0.73-1.29). Mortality before discharge occurred in 8% of the treatment group compared with 9% of the placebo group (aRR = 0.93; 95% CI, 0.67-1.3).
No adverse events related to the probiotic intervention occurred, though “possibly more worrying is the possibility of contamination of products, highlighted by a health alert issued in 2014 following the reporting of a case in the U.S. of fatal fungal infection in a preterm infant attributed to contamination of the product used in two published trials,” the researchers wrote. “This serves as a reminder that most probiotic products are not produced to pharmaceutical standards and that their unregulated use outside a trial protocol might not be risk free.”
The researchers concluded that the importance of the role of the microbiome in necrotizing enterocolitis is well established, and that the understanding of therapeutic applications of probiotics in this patient population is advancing. “In the meantime, the evidence from this trial does not support the routine administration of probiotics to the preterm infant and the validity of combining trials of different probiotics to perform meta-analyses must be questioned,” they wrote.
“These findings stress the fact that only probiotic strains that have been proven effective in clinical trials should be used in clinical practice,” Thomas Abrahamsson, MD, from the division of pediatrics at Linköping University in Sweden, said in a related commentary. “Also, they emphasize the general recommendation that treatment should always should be preceded by randomized controlled trials with a high level of quality. Meta-analyses with substantial heterogeneity of the included trials are not sufficient.” – by Adam Leitenberger
Disclosures: Costeloe reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures. Abrahamsson reports he has received funding for a clinical trial from Biogaia AB, Sweden, unrelated to his commentary.
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