Probiotics-Prime Time For Routine Use!

http://www.jpeds.com/article/S0022-3476(13)01596-5/fulltext
ProPrems trial is very compelling as 95% of the study participants received breast milk!


Probiotic supplementation in preterm infants is perhaps the best studied yet least used therapy in neonatal medicine.¹, ² All recently published meta-analyses have reported significant impacts on important clinical outcomes.³, ⁴, ⁵ In the updated Cochrane meta-analysis,³ which includes 24 trials, there is a significant decrease in necrotizing enterocolitis (NEC) (relative risk [RR] 0.43, 95% CI 0.33-0.56; risk difference [RD] −0.03, 95% CI −0.04 to −0.02; P < .00001) and all-cause mortality (RR 0.65, 95% CI 0.52-0.81; RD −0.01, 95% CI −0.02 to −0.00, P = .01). Length of stay was 3-4 days shorter. There was no probiotic-related sepsis, although this is rarely reported outside trials.⁶

Probiotics are still infrequently used in North America. In 2012, only 8%-9% of very low birth weight (VLBW) infants in the Vermont Oxford Network received probiotics.⁷ It is time to consider changing guidance and practice.⁸ The authors of this editorial have differed on whether we have sufficient evidence to introduce prophylactic treatment. Tarnow-Mordi et al argued in 2010 that “the evidence that probiotics reduce mortality rates is as conclusive as that for surfactant for respiratory distress syndrome, cooling for hypoxic ischemic encephalopathy, or antenatal corticosteroids for threatened preterm labor.”⁹ In a companion commentary, Soll argued that the decision was far less clear.¹⁰ Trials had used multiple agents and doses. Few had studied extremely low birth weight infants, and few infants had received breast milk.
Many of these arguments have now been addressed. Wang reports subgroups of trials using Bifidobacteria alone, Lactobacilli alone, or the 2 combined.⁵ In all 3 subgroups, there were significant reductions, by about two-thirds, in the RR of NEC. The recently updated Cochrane Review includes 17 trials of >4900 VLBW infants.³ The RR risk of severe NEC for probiotics versus control was 0.41 (95% CI 0.31-0.56; RD −0.03, 95% CI −0.05 to −0.02; P < .00001). The treatment of 33 VLBW infants would prevent 1 case of severe NEC. The ProPrems study in 1099 very preterm infants in Australia and New Zealand is the largest ever randomized trial of probiotics.¹¹ Although there was no decrease in sepsis or the control mortality rate of 5.1%, the rate of NEC was halved (4.4% vs 2.2%; RR 0.46, 95% CI 0.23-0.93; P = .03), even though >95% of infants received breast milk.