“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,” they wrote in the journal The Lancet.
The findings of the randomised controlled phase three study went against that of a 2014 Chochrane review, which “strongly supported” the use of lactobacillus alone or in combination with bifidobacterium in clinical practice for the prevention of severe NEC and all-cause mortality in preterm infants.
In this highly-awaited latest study, 650 infants between 23 and 30 weeks' gestational age within 48 hours of birth were given probiotic-fortified formula enterally and 660 infant formula alone.
The probiotic dose given to the infants from 24 hospitals in England was between 8.2 to 9.2 log10 CFU (colony forming units).
The researchers tracked the probiotic’s impact on NEC, blood culture positive sepsis more than 72 hours after birth and death before discharge from hospital.
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. The UK’s National Health Service (NHS) says NEC is the most common surgical emergency in newborn babies.
However the results showed little difference across groups.
In the probiotic group, 61 infants (9%) had necrotising enterocolitis compared with 66 (10%) in the placebo group.
In the probiotics group 73 (11%) of infants had sepsis compared with 77 (12%) in the placebo group.
Sadly 54 (8%) deaths occurred before home discharge in the probiotic group compared with 56 (9%) in the placebo group.
No probiotic-associated adverse events were reported.
Questioning sturdy science?
Online consumer advice from the NHS, which essentially equates to a systematic critique of evidence for probiotic use for things like colic, bacterial vaginosis, eczema and inflammatory bowel disease, was by contrast reasonably complimentary of the potential to help protect premature babies.
“There's some evidence that probiotics can reduce the likelihood of premature babies contracting NEC,” the service wrote on its website.
Professor Kate Costeloe, a consultant neonatologist at the Homerton University Hospital NHS Foundation Trust and one of the authors behind the paper, told us “the advice has always been unreliable and this study strengthens that view”.
Costeloe said what needed to be added to the NHS advice was that “some probiotics may help some babies”.
“One of the main problems with advice that has been given out by probiotic enthusiasts is that probiotics help and that it doesn't much matter what you use. I would suggest that we don't yet know which probiotics and which babies. Our trial, which is the largest and probably the best designed to date, showed no benefit whatsoever for the probiotic we gave in the population we studied.”
In an accompanying comment for the paper, Dr Thomas Abrahamsso of Linköping University in Sweden echoed this: “These findings stress the fact that only probiotic strains that have been proven effective in clinical trials should be used in clinical practice.
“Also, they emphasise the general recommendation that treatment should always be preceded by randomised controlled trials with a high level of quality. Meta-analyses with substantial heterogeneity of the included trials are not sufficient.”
He added the researchers had been disappointed by the negative results.
Industry response: Well-designed and large-scale
Carine Lambert, executive director of the International Probiotics Association (IPA) Europe, praised the study for being well-designed, large and conducted according to GCP (Good Clinical Practice) standards.
“Importantly, the probiotic was shown to be safe in this vulnerable group of preterm babies.”
Yet she added: “The authors comment that a major limitation of the trial, however, was the high rate of probiotic colonisation observed in the placebo group, which may have masked any probiotic benefit.
“This, and other observations, may help in the design of future studies into how probiotics may help prevent NEC.”
The study was funded by the UK National Institute for Health Research Health Technology Assessment programme.
Source: The Lancet
Published online ahead of print, DOI: http://dx.doi.org/10.1016/S0140-6736(15)01027-2
“Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial”
Authors: K. Costeloe, P. Hardy, E. Juszczak, M. Wilks and M. R. Millar