Probiotics for Prevention of Severe Necrotizing Enterocolitis: Experience of New Zealand Neonatal Intensive Care Units

Abstract

Introduction: Necrotizing enterocolitis (NEC) affects mainly preterm infants, has a multifactorial etiology and is associated with intestinal dysbiosis and disordered immunity. Use of probiotics for prophylaxis is beneficial with studies indicating reduction in NEC ≥ stage 2, late onset sepsis (LOS) and mortality. However, not all studies have shown a reduction, there are questions regarding which probiotic to use, whether infants <1,000 g benefit and the risk of probiotic sepsis. All neonatal intensive care units in New Zealand (NZ) use probiotics and contribute to an international database (Australian and New Zealand Neonatal Network or ANZNN). Objective: To use ANZNN data to investigate the experience of NZ neonatal units with probiotics for NEC prevention in a setting where the baseline incidence of severe NEC was low, to compare results of 2 commonly used probiotic regimes and report on the extremely low birth weight subgroup. Method: Outcomes before (Pre group 2007-2010) and after (Probiotic group 2013-2015) starting routine probiotics for preterm infants <1,500 g or <32 weeks were compared. Clinicians reviewed cases to ensure they met database criteria. Five units used Infloran (Bifidobacterium bifidum and Lactobacillus acidophilus) and 1 unit used Lactobacillus GG (LGG) and bovine lactoferrin (bLF). Results: Four thousand five hundred and twenty nine infants were included and Pre and Probiotic groups were well-balanced with regard to gestation, birth weight and gender. The incidence of NEC in the Probiotic group was 1.6 and 2.7% in the pre group (corrected OR 0.62 CI 0.41-0.94). There was one case of probiotic sepsis. There was no significant difference between the Infloran and LGG/bLF combinations in regard to observed NEC rates. Late onset sepsis rates were significantly lower in the Probiotic group (p < 0.01). Conclusions: Introduction of probiotics for preterm infants in NZ has been associated with significant reductions in NEC and late onset sepsis.

The effect of daily probiotics on the incidence and severity of necrotizing enterocolitis in infants with very low birth weight

“…32 A recent large ret rospective study of neonatal units in New Zealand also found a significant decrease in lateonset sepsis and necro tizing enterocolitis from 2.6% to 1.8% (OR 0.62, 95% CI 0.41-0.94) despite a low baseline incidence of necrotizing enterocolitis. 33 Although breast milk was used more at onset of feeding in their probiotic group, multivariate logistic regression showed minimal effect by confounders. At the BCWH NICU, the use of maternal and donor breast milk did not change significantly before and after probiotic introduction (88% v. 92%, p = 0.16).…”

Therapeutic applications and biological activities of bacterial bioactive extracts

“…Necrotizing enterocolitis (NEC) is an inflammatory disease that affects premature infants and is characterized by necrosis of the distal small intestine and colon (Meyer et al 2020 ). Short-chain fatty acids produced by Bifidobacterium infantis demonstrated anti-inflammatory activities in mature enterocytes and immunocytes (Zheng et al 2020 ) which suggests the symbiotic action of breast milk and probiotics in preventing necrotizing enterocolitis (Repa et al 2015 ).…”

Microbiota Signals during the Neonatal Period Forge Life-Long Immune Responses

“…Both approaches seem to restore the microbiome, it has a similar composition to that of naturally delivered newborns [ 253 , 254 , 255 ]. Finally, using probiotics in the neonatal period apparently diminishes the incidence of NEC [ 256 , 257 ]; however, studies with long-term follow-up and a significant number of participants are needed.…”