Podcast: Probiotics for prevention of necrotising enterocolitis in very preterm or very low birthweight infants

The Cochrane Neonatal Group has produced more than 400 reviews in the last 25 years and strives to keep these up to date as new research becomes available. In October 2020, they produced the third update of the review of probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. We asked lead author, William McGuire from the University of York in the United Kingdom, to tell us about the latest evidence.

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Monaz: Hello, I'm Monaz Mehta, editor in the Cochrane Editorial and Methods department. The Cochrane Neonatal Group has produced more than 400 reviews in the last 25 years and strives to keep these up to date as new research becomes available. In October 2020, they produced the third update of the review of probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. We asked lead author, William McGuire from the University of York in the United Kingdom, to tell us about the latest evidence.

Bill: Thanks Monaz. About one in twenty babies who are born very preterm, which is before 32 weeks gestation, or weigh less than 1.5 kg, develop a severe bowel disorder called necrotising enterocolitis. This condition, which is called "NEC" for short, causes part of the bowel to become inflamed, infected and die. The babies usually need a long period of intensive care and sometimes bowel surgery, with approximately 20% dying. And, if they survive, infants who develop NEC, especially if it's associated with bloodstream infections, have an increased risk of neurodevelopmental problems and disability.
We're not sure what causes NEC but feeding with human milk rather than cow's milk formula has been shown to reduce the risk in very preterm infants. This suggests that human, but not formula, milk contains substances that promote the growth of probiotic micro-organisms ("good" bacteria and yeast) in the infant's bowel, at the expense of pathogenic micro-organisms that can cause bloodstream infection. 
This has encouraged research into whether giving very preterm infants probiotic supplements in their milk might help prevent NEC, infection, and death and disability. Our review looks at this research and we have brought together 56 randomised trials, with, in total, more than 10,000 infant participants. The trials were mostly small (fewer than 200 participants), and about half had design flaws that might bias their findings. 
Our combined analyses show that giving probiotics to very preterm and very low birth weight infants may reduce the risk of NEC, and probably reduces the risk of death and serious infection, but there is no evidence on disability or developmental outcomes. 
However, despite these trial data, we still need to be cautious. Firstly, the certainty of the evidence for the effect on NEC is low because many of the trials were subject to biases that could exaggerate any benefits, and secondly, the findings are likely to have been distorted by selective publication of small trials that showed large effects. Similarly, the effect on mortality is not certain and when we limited the meta-analysis to trials at low risk of bias, this no longer showed that probiotics reduce the risk of death. A third limitation to applying the review findings in practice is that few trials provided data for infants at highest risk of NEC, which include the extremely preterm who are born before 28 weeks and the extremely low birth weight who weigh less than 1 kg at birth. Finally, another major challenge in applying the review's findings is that the probiotic preparations tested varied greatly between trials. We noted 27 different categories of probiotic species or combination, and these varied further depending on the strain used.
In conclusion, given the low to moderate level of certainty about the effects of probiotic supplements on the risk of NEC and associated morbidity and mortality for very preterm or very low birth weight infants, it's appropriate for investigators to determine whether families and clinicians would support further, large, high-quality trials to provide evidence of sufficient quality and applicability to inform policy and practice.

Monaz: If you'd like to read more about the variety of research in this latest update, and watch for further updates if more studies become available, it's available online. If you go to Cochrane Library dot com and search 'probiotics for NEC' you'll see the link.

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