BEVERLY HILLS, CALIF. — Two meta-analyses have concluded that probiotics are effective in preventing necrotizing enterocolitis in premature infants, but there is no agreement on which probiotic preparations are best.
With an overall mortality of 15%–50%—approaching 100% in stage III disease—necrotizing enterocolitis (NEC) is one of the most worrisome consequences of prematurity. Even infants who survive the disorder face several adverse outcomes including short bowel syndrome, bowel strictures, liver failure, and possibly neurocognitive deficits, Dr. Maria Oliva-Hemker said at the International Probiotics Association World Congress.
According to a meta-analysis incorporating seven randomized controlled trials and 1,393 infants, probiotics were associated with a 64% decrease in the risk of developing stage II NEC (Lancet 2007;369: 1614–20). Another meta-analysis incorporating five randomized controlled trials and 1,207 infants concluded that probiotics were associated with a 57% decrease in the risk of developing stage II or stage III NEC (Cochrane Database Syst. Rev. 2008;23:CD005496). Both results were statistically significant.
The Lancet meta-analysis further concluded that probiotics were associated with a statistically significant 53% reduction in all-cause neonatal mortality as well as a significant decrease in the time needed to reach full feeds.
The Cochrane meta-analysis found no statistically significant effect of probiotics on the number of days the infants received total parenteral nutrition, on the hospital length of stay, or on weight gain.
Although the meta-analyses support the use of probiotics, they provide little guidance on which probiotic preparations to use. No two of the seven studies in the Lancet meta-analysis used the same probiotic preparation. The organisms were Bifidobacterium breve; B. lactis; Lactobacillus GG; L. casei; Saccharomyces boulardii; a combination of L. acidophilus and B. infantis; and a combination of B. infantis, S. thermophilus, and B. bifidus. The preparations were generally given in a dose of 109 colony-forming units once or twice a day.
When the pathophysiology of NEC is considered, it makes sense probiotics might have an effect on the disorder, said Dr. Oliva-Hemker of the department of pediatrics, Johns Hopkins University, Baltimore.
“The majority of [premature] children are born by C-section. They have less chance of being breast-fed. They are exposed not to their mothers' flora in the vagina or the breast but [potential infection] in the NICU. And they are more often than not exposed to multiple antibiotics,” she said. “This leads to a delayed establishment [and aberrant composition] of the microbiota. All this, together with inadequate development of the immune system, a bad barrier, and inadequate humoral and cell-mediated immune responses, [show] how everything can come together in a perfect storm, developing NEC in a particular infant.”
It's not known what probiotics do to counter this process. They may modulate early bacterial colonization, enhance intestinal barrier function, inhibit adherence and colonization of pathogens, or they may modulate inflammatory pathways.
Dr. Oliva-Hemker said 25 infants need to be treated with probiotics to prevent one case of NEC. This may seem a large number, but given the consequences of NEC, it may be possible to justify the cost-benefit ratio. But “even though we might have a short-term benefit of preventing NEC, we don't know what the long-term consequences to those children will be.”
Dr. Oliva-Hemker disclosed that she receives grant support from and serves on the speakers bureau of Nestlé Nutrition, conducts research for Centocor Inc., and serves as a consultant for Abbott Immunology.