PiPS

Early administration to preterm infants of the probiotic bifidobacterium breve strain BBG to prevent infection and necrotising enterocolitis.

Trial started: 2010  Trial ended: 2014 

Summary

Objectives

To test the use of the probiotic Bifidobacterium breve strain BBG-001 to prevent necrotising enterocolitis (NEC), late-onset sepsis and death in preterm babies while monitoring probiotic colonisation of participants.

Methods

A double-blind, randomised, placebo-controlled trial conducted in 24 hospitals. Babies born between 23 and 30 weeks' gestation and randomised within 48 hours of birth were allocated to receive either 1 ml of B. breve BBG-001 (6.7?×?107 to 6.7?×?109 colony-forming units) or 1 ml placebo, administered enterally as soon as practicable and continued daily until 36 weeks' postmenstrual age. Parents, clinicians and outcome assessors were blinded to the allocation.

Outcome measures

Primary outcomes: An episode of bloodstream infection with any organism other than a skin commensal between 72 hours and 46 weeks' postmenstrual age; an episode of NEC (Bell stage ?2); and death before hospital discharge. Secondary outcomes: Stool colonisation with B. breve.

Results

In total, 654 babies were allocated to receive probiotic and 661 to receive placebo over 37 months from July 2010. Five babies were withdrawn; 650 babies from the probiotic group and 660 from the placebo group were included in the primary analysis. Baseline characteristics were well balanced. There was no evidence of benefit for the primary outcomes {sepsis: 11.2% vs. 11.7% [adjusted relative risk (RR) 0.97, 95% confidence interval (CI) 0.73 to 1.29]; NEC Bell stage ??2: 9.4% vs. 10.0% [adjusted RR 0.93, 95% CI 0.68 to 1.27]; and death: 8.3% vs. 8.5% [adjusted RR 0.93, 95% CI 0.67 to 1.30]}. B. breve colonisation status was available for 1186 (94%) survivors at 2 weeks’ postnatal age, of whom 724 (61%) were positive: 85% of the probiotic group and 37% of the placebo group. There were no differences for subgroup analyses by minimisation criteria and by stool colonisation with B. breve at 2 weeks. No harms associated with the interventions were reported.

Conclusions

This is the largest trial to date of a probiotic intervention in preterm infants. It showed no evidence of benefit and does not support the routine use of probiotics in this population.

Adapted from: Costeloe K, Bowler U, Brocklehurst P, et al. A randomised controlled trial of the probiotic Bifidobacterium breve BBG-001 in preterm babies to prevent sepsis, necrotising enterocolitis and death: the Probiotics in Preterm infantS (PiPS) trial. Health Technology Assessment. 2016;20(66). https://doi.org/10.3310/hta20660. © Queen's Printer and Controller of HMSO 2016. Adapted for presentation on this website.