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Necrotizing enterocolitis (NEC) is a disease mainly of preterm infants with a 30–50% mortality rate and long-term morbidities for survivors. Treatment strategies are limited and have not improved in decades, prompting research into prevention strategies, particularly with probiotics. Recent work with the probiotic B. infantis EVC001 suggests that this organism may generate a more appropriate microbiome for preterm infants who generally have inappropriate gut colonization and inflammation, both risk factors for NEC. Experimental NEC involving Paneth cell disruption in combination with bacterial dysbiosis or formula feeding was induced in P14-16 C57Bl/6 mice with or without gavaged B. infantis. Following completion of the model, serum, small intestinal tissue, the cecum, and colon were harvested to examine inflammatory cytokines, injury, and the microbiome, respectively. EVC001 treatment significantly decreased NEC in a bacterial dysbiosis dependent model, but this decrease was model-dependent. In the NEC model dependent on formula feeding, no difference in injury was observed, but trending to significant differences was observed in serum cytokines. EVC001 also improved wound closure at six and twelve hours compared to the sham control in intestinal epithelial monolayers. These findings suggest that B. infantis EVC001 can prevent experimental NEC through anti-inflammatory and epithelial barrier restoration properties.

Background: Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity in preterm infants, and prevention and treatment strategies have remained largely unchanged over the past several decades. As understanding of the microbiome has increased, probiotics have been hypothesized as a possible strategy for decreasing rates of NEC, and several studies have noted significant decreases in rates of NEC after initiation of probiotics in preterm infants. However, a recent AAP report cited caution on the use of probiotic use in part because studies of probiotic use in ELBW infants are lacking. As our unit began routine use of probiotics for all infants <33 weeks in 2015 and we are a leading institution for intact survival of ELBW infants, we attempted to answer if probiotic use can impact the rate of NEC in VLBW and ELBW infants.Methods: We conducted a single-center retrospective chart review of infants with modified Bell's stage ≥2a NEC for the 4 years prior to and 5 years after initiation of a protocol involving routine supplementation of a multispecies probiotic to premature infants at the University of Iowa, Stead Family Children's Hospital. The primary outcome measures were rates of modified Bell's stage ≥2a NEC and all-cause pre-discharge mortality at our institution before and after initiation of routine probiotic supplementation in 2015.Results: In our institution, neither the rates of modified Bell's stage ≥2a NEC, nor the rates of all-cause mortality were significantly altered in very low birth weight (VLBW) infants by the initiation of routine probiotic use (NEC rates pre-probiotic 2.1% vs. post-probiotic 1.5%; all-cause mortality rates pre-probiotic 8.4% vs. post-probiotic 7.4%). Characteristics of our two cohorts were overall similar except for a significantly lower 5-minute APGAR score in infants in the post-probiotic epoch (pre-probiotic 8 vs. post-probiotic 6 p = 0.0316), and significantly more infants in the post-probiotic epoch received probiotics (pre-probiotics 0% vs. post-probiotics 65%; p < 0.0001). Similarly, probiotic use had no impact on the incidence of NEC when we restricted our data to only extremely low birth weight (ELBW) infants (pre-probiotics 1.6% vs post-probiotics 4.1%). When we restricted our analysis to only inborn infants, probiotics still had no impact on NEC rates in VLBW infants (1.5% pre- and 1.1% post-probiotic, p = 0.61) or ELBW infants (2% pre- and 2.1% post-probiotic, p = 0.99)Conclusions: Contrary to other studies, we found no significant difference in rates of modified Bell's stage ≥2a NEC or all-cause pre-discharge mortality in VLBW infants following routine administration of a multispecies probiotic supplement.

Objective: To evaluate the outcomes of extremely premature infants who received inhaled nitric oxide (iNO) for hypoxic respiratory failure (HRF).Study Design: Retrospective analysis of 107 infants born 22-26 weeks gestation who received iNO for HRF at a single institution. Infants were categorized as positive, negative, or no responders based on change in FiO 2 or OI. Underlying physiology of HRF was determined.Results: 63% of infants had a positive response; they received iNO earlier and were more likely to have acute pulmonary hypertension. Positive response correlated with decreased incidence of death or grade 3 BPD at 36 weeks postmenstrual age, as compared to a negative response.Conclusions: Extremely premature infants have a positive response rate to iNO comparable to term infants when used for acute pulmonary hypertension in the transitional period. Infants with a negative response to iNO had worse outcomes, necessitating the determination of the underlying physiology of HRF prior to iNO initiation.

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