Probiotics and Time to Achieve Full Enteral Feeding in Human Milk-Fed and Formula-Fed Preterm Infants: Systematic Review and Meta-Analysis

Abstract

Probiotics have been linked to a reduction in the incidence of necrotizing enterocolitis and late-onset sepsis in preterm infants. Recently, probiotics have also proved to reduce time to achieve full enteral feeding (FEF). However, the relationship between FEF achievement and type of feeding in infants treated with probiotics has not been explored yet. The aim of this systematic review and meta-analysis was to evaluate the effect of probiotics in reducing time to achieve FEF in preterm infants, according to type of feeding (exclusive human milk (HM) vs. formula). Randomized-controlled trials involving preterm infants receiving probiotics, and reporting on time to reach FEF were included in the systematic review. Trials reporting on outcome according to type of feeding (exclusive HM vs. formula) were included in the meta-analysis. Fixed-effect or random-effects models were used as appropriate. Results were expressed as mean difference (MD) with 95% confidence interval (CI). Twenty-five studies were included in the systematic review. In the five studies recruiting exclusively HM-fed preterm infants, those treated with probiotics reached FEF approximately 3 days before controls (MD −3.15 days (95% CI −5.25/−1.05), p = 0.003). None of the two studies reporting on exclusively formula-fed infants showed any difference between infants receiving probiotics and controls in terms of FEF achievement. The limited number of included studies did not allow testing for other subgroup differences between HM and formula-fed infants. However, if confirmed in further studies, the 3-days reduction in time to achieve FEF in exclusively HM-fed preterm infants might have significant implications for their clinical management.

Lactobacillus Acidophilus/Bifidobacterium Infantis Probiotics Are Beneficial to Extremely Low Gestational Age Infants Fed Human Milk

“…In the current cohort study, we noted a promoting effect of probiotics on weight gain and growth velocities in HM-fed infants. Previous studies revealed inconsistent results that were not necessarily adjusted for the type of feeding [27][28][29][30]. A meta-analysis of 15 studies including 3751 infants <32 weeks and <1500 g birth weight demonstrated no significant effects of probiotics on weight gain [31].…”

Probiotics and Prebiotics in Infant Formulae

“…In a review on the effects of a variety of immunonutrients in the prevention of necrotizing enterocolitis [35], the authors gathered sufficient data supporting supplementation of infant formulae with probiotics. Several meta-analyses combined these randomized controlled trials and observational studies demonstrated that the use of probiotics was beneficial for the prevention of severe necrotizing enterocolitis, late-onset sepsis, and all-cause mortality in very-low-birth-weight infants, as well as the time to achieve full enteral feeding in preterm infants [36][37][38]. By contrast, no differences were observed in a multicenter study involving 1315 preterm newborns fed with a hydrolyzed formula supplemented and nonsupplemented with the probiotic Bifidobacterium breve BBG-001 [39]; the results of this trial provide no evidence of benefit of this probiotic intervention in reducing late-onset sepsis and necrotizing enterocolitis or death.…”

Inherited nongenetic influences on the gut microbiome and immune system

“…Preterm infants fed donor milk had gut microbiomes that more closely resembled infants fed their mother's own milk compared with formula fed infants (Parra‐Llorca et al, ). In addition, some groups have tested the viability of “spiking” donor milk with infants' own mothers milk to inoculate the infants with a personalized microbiome (Cacho et al, ), a concept similar to a recent push to include probiotics in infant formula (Aceti et al, ; Cavallaro, Villamor‐Martínez, Filippi, Mosca, & Villamor, ; Mugambi, Musekiwa, Lombard, Young, & Blaauw, ; Rautava et al, ; Villamor‐Martínez et al, ). These interventions showcase the importance of breastfeeding, or in lieu of breastfeeding, a diet reflecting the myriad of components maternally transferred that support the development of the offspring's immune system and shape gut homeostasis during early life.…”