A combination of three probiotics appears to safely reduce the risk of necrotizing enterocolitis in very preterm infants, but did not reduce overall late-onset sepsis or all-cause mortality, according to a recent study.
Probiotics – potentially beneficial live microorganisms – have been previously shown to reduce necrotizing enterocolitis and all-cause mortality. They presumably contribute to a healthier gut flora because preterm infants tend to be more prone to pathogenic bacteria from the neonatal intensive care unit environment and lack the healthier flora biodiversity of term infants. Yet reductions in late-onset sepsis from probiotic administration have not been shown.
This study did find a significant reduction in late-onset sepsis only for infants born later than 28 weeks, but within too small a group (52 infants) to be reliably powered, reported Dr. Susan E. Jacobs of the Royal Women’s Hospital in Melbourne, and her colleagues (Pediatrics 2013 Nov. 18 [doi:10.1542/peds.2013-1339]).
The authors also calculated that administering probiotics to 43 very preterm infants could prevent necrotizing enterocolitis in 1 infant. Yet all-cause mortality, mortality from necrotizing enterocolitis and other secondary outcomes were not significantly different in the intervention and control groups.
The researchers randomized 1,099 very preterm infants, born before 32 complete weeks and weighing less than 1,500 g, to receive either 1.5 g daily of a probiotic combination or placebo. The probiotic powder was comprised of 1 x 109 total organisms per 1.5 g of Bifidobacterium infantis (300 x 106), Streptococcus thermophilus (350 x 106) and B. lactis (350 x 106); the placebo was maltodextrin.
The infants, born in one of eight Australian or two New Zealand hospitals during October 2007 and November 2011, were not included if they had major congenital or chromosomal abnormalities, if their mother was taking nondietary probiotic supplements, or if death within 72 hours appeared likely. At least 95% of infants in both groups received breast milk.
Among 548 infants receiving probiotics and 551 receiving placebo, 13.1% of the probiotic group and 16.2% of the control group were diagnosed with at least one episode of definite late-onset sepsis, confirmed with an isolated or cultured pathogen and occurring later than 48 hours after birth or at least 72 hours after no longer receiving antibiotics. This result revealed no significant difference between the groups (relative risk, 0.81; P = .16).
Yet among preterm infants aged at least 28 weeks, late-onset sepsis was significantly reduced in half in the probiotic subgroup. While 18 of infants (5.5%) receiving probiotics developed late-onset sepsis, 34 of the control infants (10.8%) developed it (RR, 0.51; P = .01). "These results should be interpreted cautiously, as they may be chance findings," the authors wrote.
The probiotic group, with 2% incidence, did see a small reduction in absolute risk (2.4%) of necrotizing enterocolitis of Bell stage 2 or greater, compared with the control group which had 4.4% incidence (RR, 0.46; P = .03). The number needed to treat was 43, but with a range of 23 to 333 (95% confidence interval) because of the low rates.
However, no significant difference in mortality from necrotizing enterocolitis (Bell stage 2 or more) or from all-cause mortality during the primary hospitalization or the study period was found between the two groups. The researchers also found no significant differences in a multitude of other secondary outcomes, including clinical (not definite) late-onset sepsis. The probiotics did not appear to have any adverse effects, including definite late-onset sepsis from the administered strains.
The authors emphasized caution throughout their study and the need for larger studies to detect significant clinical differences in outcomes from probiotics. "Our findings emphasize the importance of performing well-powered trials of probiotic administration in very preterm infants in different settings," they wrote.
The authors also noted that probiotics’ effectiveness for any outcome depends on dose, conditions, strains and combinations of strains. "No one has determined which is the most effective probiotic, combination of probiotics, when they should be started, what dosage should be used, or the duration of administration," the investigators said.
The study was funded by the National Health and Research Medical Council of Australia and the Royal Women’s Hospital Foundation and the Angior Family Foundation, both in Melbourne. The probiotic combination "ABC Dophilus Powder for Infants" was provided at cost by Solgar, USA, which did not provide any additional funding. The authors reported no other disclosures.