As reported by NutraIngredients last week, a paper published in The Lancet concluded that there was no evidence that the probiotic strain Bifidobacterium breve BBG-001 can reduce the risk of necrotizing enterocolitis (NEC), late-onset sepsis and death in 1,315 preterm infants.
Sepsis is a common and potentially life-threatening condition triggered by an infection whereby the body’s immune system goes into overdrive causing widespread inflammation, swelling and blood clotting.
NEC is a serious illness in which tissues in the intestine become inflamed and start to die.
“There is no evidence of benefit for this intervention in this population; this result does not support the routine use of B. breve BBG-001 for prevention of necrotising enterocolitis and late-onset sepsis in very preterm infants,” wrote the study’s authors.
In an extensive statement sent to NutraIngredients, IPA Global and IPA Europe noted that children in the placebo group were exposed to the probiotic and this has implications for the study and its conclusions. (IPA Europe concentrates on the regulatory front in the EU but has supported the following statement because the science has global implications.)
“I feel that in this case the peer review process has missed the implications of exposure to the tested probiotic of almost half of the subjects in the placebo group. Preterm babies are a fragile population and all the care should be taken when conducting trials of this kind, but it is incorrect to make a broad conclusion that probiotics in general should not be used routinely in preterm infants as only one strain was tested in this trial,” said George Paraskevakos, IPA’s Executive Director in a statement to NutraIngredients.
“In their study, Costeloe and co-workers investigated the effect of Bifidobacterium breve BBG-001 on the risk of necrotizing enterocolitis (NEC) for preterm infants. This is one of the largest studies published on this topic to date but the authors observed no statistical difference in NEC, sepsis or death. Based on this, the authors concluded that, while the probiotic strain appeared to be safe, the results of the trial do not support the routine use of probiotics in preterm infants. However, when looking more closely at the study, there are a few interesting points that make us question these firm conclusions.
“The biggest concern is that at 36 weeks post-menstrual age, 49% of the placebo group had become colonized with the test strain and 84% of the children in the probiotic group. We suggest that these results do not allow any conclusions to be drawn. For instance, what ‘would the investigators and the journal have concluded in any similar study when half of the subjects in the placebo group had been exposed to the test product?’
“IPA recognizes the practical challenges of conducting a study like this and understands that this may reflect the real-life situation. But this is a study that aims to answer a specific question: the effect of the B. breve BBG-001 on NEC in an at-risk population. Extreme care should therefore be taken and the probiotic colonization of the placebo group suggest there were protocol violations.
“While quantitative real-time PCR was conducted with strain-specific primers, only qualitative results are presented. It would have been particularly relevant to know whether the placebo group was colonized at a lower level than the test group. This is what one might expect if there had been any accidental mix up or cross-contamination on the ward, which would have resulted in the infants being exposed to a suboptimal dose. The authors note that colonization has not been checked previously thus it is not known whether the same accidental probiotic colonization of babies in placebo groups has occurred in previous studies. Thus, an important learning from this is that colonization should always be checked in future trials.
“Fortunately, the investigators did analyze the results taking into account the probiotic colonization rates in both groups. This yielded results that were very different from the authors’ general conclusions. They showed that probiotic colonization was associated with a trend for reduced NEC (probiotic 7% vs. placebo 13%), sepsis (probiotic 9% vs. placebo 14%) and death (probiotic 3% vs. placebo 7%). It is not surprising that these are only trends, as the statistical power was insufficient for this type of sub-group analysis.
“To sum up, we do not support the conclusions of the authors, mainly due to the inappropriate conduct of the trial. Further IPA considers it incorrect to make the broad conclusion that probiotics (in general) should not be used routinely in preterm infants as only one strain was tested in this trial.
“Finally, conducting a subgroup analysis based on probiotic colonization (which, considering the high number of infants colonized in the placebo group, would seem the most appropriate analysis for this study) indicates that in fact there was a positive effect associated with the tested probiotic strain.”
To read our initial coverage on NutraIngredients.com, please click HERE.