Feeding Activated Bifidobacterium Infantis EVC001 to Very Low Birth Weight Infants Is Associated with Significant Reduction in Rates of Necrotizing Enterocolitis

Background:

Background: Necrotizing enterocolitis (NEC) is a neonatal inflammatory intestinal disease that disproportionately affects preterm, very low birth weight (VLBW) infants, carrying an overall mortality of 23.5%, and up to 50% for surgical NEC. NEC has been strongly linked to preterm gut dysbiosis; thus, changing the intestinal microbiota through enteral probiotic supplementation may attenuate dysbiotic NEC. Bifidobacterium longum infantis (B. infantis) is a mutualist colonizer of the human milk-fed infant gut, and B infantis EVC001 (EVC001) is safe, colonizes the neonatal intestine, lowers NEC-associated bacterial load, and decreases enteric inflammation. EVC001 as a single-strain probiotic has yet to be associated with a reduction in NEC in preterm infants; this study investigated the effects of enteral EVC001 on NEC rates in VLBW infants in a single Level IV NICU.

Methods:

Methods: This was a retrospective observational analysis of 2 cohorts of VLBW infants (+/-B. infantis EVC001) at OHSU from 2014 to 2020. Outcomes included NEC rates and NEC-associated mortality, including subgroup analysis of ELBW infants. Fisher’s exact test and log binomial models were used to determine differences between cohorts and risk reduction of NEC. Adjusted number needed to treat was calculated from the cohort coefficient of the model.

Results:

Results: 483 infants met inclusion criteria, consisting of 301 infants not exposed to B. infantis EVC001 (No EVC001) and 182 infants exposed to EVC001 (EVC001-fed). There were no significant differences in measured covariates between the two cohorts with the exception of sex and antenatal steroid administration (Table). The mean gestational age (GA) at birth for both cohorts was 28 weeks, and mean birth weight was 1045 grams for the No EVC001 and 1048 grams for the EVC001-fed cohorts. There were no significant differences between cohorts for covariates in the subgroup analysis of ELBW infants. The difference in rates of NEC between VLBW cohorts was significant (No EVC001 11.0% vs. EVC001-fed 2.7%, P = 0.0008). The EVC001-fed cohort had a 73% risk reduction of NEC versus the No EVC001 cohort (aRR 0.270, 95% CI 0.094, 0.614, P = 0.0054) with an adjusted number needed to treat (aNNT) of 12.4 (95% CI 10.0, 23.5). There was no NEC-related mortality in the EVC001-fed cohort, a significant difference from the No EVC001 cohort (0% vs. 2.7%, P = 0.0274). There was a similar reduction in NEC rates for ELBWs (19.2% versus 5.3%, P = 0.0059), aRR (0.283; 95% CI 0.085, 0.698, P = 0.0167) and mortality (5.6% vs. 0%, P = 0.0468) (Figure). There were no EVC001-related complications.

Conclusion:

Conclusion: B. infantis EVC001 feeding was associated with a significant reduction in NEC rates and NEC-related mortality in an observational study of 483 VLBW infants. B. infantis EVC001 supplementation may be considered safe and effective for reducing NEC morbidity and mortality.