The probiotic Bifidobacterium breve does not help prevent late-onset sepsis or necrotizing enterocolitis, suggests research published in The Lancet.
The results of a new phase 3 randomized controlled trial contradict previous work showing potential benefits of Bifidobacterium breve (BBG-001).
Previous studies into probiotics for treating very preterm infants have been carried out, but the rigor and generalizability of some of the trials have been questioned, and researchers disagree on whether they should be used routinely.
The new study was carried out by Prof. Kate Costeloe – from Barts and the London School of Medicine and Dentistry, Queen Mary University of London in the UK – and colleagues.
The authors set out to test the effectiveness of the probiotic B. breve in reducing necrotizing enterocolitis, late-onset sepsis and death in preterm infants.
Necrotizing enterocolitis is the most serious gastrointestinal disease in preterm infants. Together with sepsis, it is a growing cause of mortality now that more preterm infants survive the first week of life. Both conditions tend to progress rapidly, and they involve multiple organ systems and an intense inflammatory response.
Treatment is not usually completely successful, and survivors can experience poor growth and developmental delay. Preventive treatments are therefore urgently needed.
B. breve was chosen as the intervention because, when the trial was designed in 2005, it was the only probiotic reported to show any benefit, although that was only nutritional. In addition, it had been routinely used for several years in Japan.
From 2010-13, 1,315 infants were studied, 654 of whom were given probiotic and 661 placebo.
Rates of the primary outcomes did not differ significantly between the probiotic and placebo groups.
The effect of B. breve on each condition was as follows:
- Necrotizing enterocolitis occurred in 61 infants or 9% of the probiotic group, compared with 66 infants or 10% of the placebo group
- Sepsis developed in 73 infants or 11% of the probiotics group, compared with 77 infants or 12% of the placebo group
- Death before discharge occurred in 54 infants or 8% of the probiotic group, compared with 56 infants or 9% of the placebo group.
No probiotic-associated adverse events were reported.
The authors stress that while there were no safety issues with the probiotic preparation used in this study, contamination of products is possible.
In 2014, a health alert was issued following a case in the US of fatal fungal infection in a preterm infant due to contamination of a product used in two published trials.
The researchers warn that most probiotic products are not produced to pharmaceutical standards, and that unregulated use outside a trial protocol could be risky.
They point out that the current results contrast with those of a previous major study, a meta-analysis in the Cochrane Review, which suggested a significant reduction in necrotizing enterocolitis and mortality as a result of probiotic administration.
The present results confirm findings by the ProPrems study, that B, breve has no benefit in preventing sepsis or death. ProPrems researchers observed reduced necrotizing enterocolitis, but in a setting where the likelihood of this complication was already limited.
The authors say:
“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.”
In a linked comment, Dr. Thomas Abrahamsson, from the Division of Pediatrics at Linköping University in Sweden, urges clinical practitioners only to use probiotic strains that have been proven effective in clinical trials, and he emphasizes the need for all treatment to be preceded by high-quality randomized controlled trials.
The authors conclude that the role of gut microbes in the pathogenesis of necrotizing enterocolitis is widely accepted and that, ultimately, probiotics may prove an effective therapy, but research does not yet support routine administration of probiotics to preterm infants.
Medical News Today reported recently that a probiotic formula could help prevent cow’s milk allergy.