L.Fermentum CECT5716 and B.Breve CECT7263 on premature infants morbidities: a randomized clinical trial

Abstract

BACKGROUND: This study examined the effects of two doses of probiotics isolated from human milk on the incidences of necrotizing enterocolitis (NEC) and mortality in preterm infants. METHODS: This multicenter, randomized, double-blind study involved 583 very low birth weight preterm neonates (?32 6/7 weeks, <1500 g) who started enteral nutrition within 72 h of birth (>5 ml/kg/day) and received either a high-dose (HD, 1 × 10(9) CFU/day per strain) or a low-dose (LD, 1 × 10(6) CFU/day per strain) of Limosilactobacillus fermentum CECT5716 (LC40) and Bifidobacterium breve CECT7263 (BfM26) until 36 6/7 weeks postmenstrual age or discharge. RESULTS: The probiotic combination was well tolerated with no adverse effects. The NEC (2.5% vs. 1.3%; p = 0.156) and mortality (3.9% vs. 3.6%; p = 0.685) rates were not significantly different between the groups (HD vs. LD). These rates were lower than those reported in a co-temporal cohort in the region (SEN1500 cohort). CONCLUSION: No significant differences were found between the HD and the LD of the LC40 and BfM26 combination in the incidence of NEC and all-cause mortality. The incidence rates of death and NEC were lower in this study than in the SEN1500 cohort, suggesting that the low dose may suffice for preterm infants. This study supports the safety and tolerability of these probiotics in preterm infants. IMPACT: The study responds to scientific societies' request for more clinical trials to strengthen the currently low level of evidence on probiotics' safety and benefits for preterm infants. The study presents evidence supporting the safety and the effect of two different doses of a combination of two human milk-derived probiotic strains in preterm infants. The study indicates that a low dose of probiotics may be sufficient to achieve beneficial effects in preterm infants. These findings will inform future research on optimizing probiotic dosing in this population.