Probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum) prevent NEC in VLBW infants fed breast milk but not formula

Abstract

Background: Specific probiotics prevent necrotizing enterocolitis (NEC). A mixture of lactobacilli and bifidobacteria (Infloran) was highly effective in Asian very-low-birth-weight (VLBW) infants. We analyzed the effect of Infloran on NEC, NEC severity, and the influence of enteral feedings (breast milk vs. formula) on NEC prevention in a cohort of European VLBW infants. Methods: Infloran was implemented for routine use at our department. VLBW infants receiving probiotics were prospectively followed (2010)(2011)(2012) and compared with historic controls (2008)(2009). Data on NEC, neonatal morbidity, feeding tolerance, and descriptive parameters on NEC cases were analyzed. results: Infloran had no statistically significant impact on NEC (controls: 24/233 (10.3%); probiotics: 16/230 (7%); P = 0.2). However, NEC was significantly reduced in infants of the probiotics group who were fed any breast milk (20/179 (11.2%) vs. 10/183 (5.5%); P = 0.027), whereas it was ineffective in infants exclusively fed formula (4/54 (7.4%) vs. 6/44 (13.6%); P = 0.345). Occurrence of severe NEC (IIIb), time until full feeds, and gastric residuals were similar. conclusion: Infloran was of lower efficacy in a European VLBW cohort and showed a reduction of NEC only in infants fed breast milk. Future studies should investigate the influence of feeding formula or breast milk on the effect of probiotics.n ecrotizing enterocolitis (NEC) is an important cause of mortality and morbidity in premature infants (1). Although its pathogenesis is incompletely understood, a relation to an immature intestinal barrier, aberrant bacterial colonization, and enteral feedings is well established (2). Due to the seriousness of the disease, preventive strategies like the use of human milk and standardized feeding protocols (3-5) are of highest interest.Probiotics are microorganisms that confer a health benefit after ingestion (6). They are generally regarded as safe, and only single cases of sepsis were described in patients with major comorbidities (7). In preterm infants, probiotics may act beneficially by improving the intestinal barrier (8) and promoting a healthy gut microflora (9). Furthermore, they exert antiinflammatory effects on the gut epithelium (10) and improve local and systemic immune responses (11) that may strengthen a preterm infant's still immature immune defense. In the recent past, a preventive effect against NEC was assumed (12), and a variety of probiotic preparations were studied in randomized trials. Meta-analyses of these trials reported on a reduction of NEC in very-low-birth-weight (VLBW) infants by 65% (13,14), and the use of probiotics in clinical routine was recommended. Based on these suggestions, we decided to introduce probiotics for NEC prophylaxis as standard of care at our department. The probiotic preparation Infloran (Laboratorio Farmaceutico, Mede, Italia) consists of a mixture of Lactobacillus acidophilus and Bifidobacterium infantis and was chosen as its use was suggested by European experts (14) and it was available ...

The “Golden Age” of Probiotics: A Systematic Review and Meta-Analysis of Randomized and Observational Studies in Preterm Infants

“…Eight studies [48,51,52,53,54,58,59,60] reported on late-onset sepsis. The administration of probiotics reduced the incidence of sepsis in VLBW infants by 19% (RR 0.81, 95% CI 0.69-0.96, p = 0.01; Fig.…”

“…Using the probiotic preparation Infloran (a mixture of L. acidophilus and B. infantis ), 1 RCT trial demonstrated a reduction of NEC and mortality by approximately 80% [32]. Pooled analyses of 4 observational studies [50,51,53,59] showed a statistically significant 51% reduction of NEC and 46% reduction of mortality. Recently, a large observational multicentre study conducted by Denkel et al [71] demonstrated that the routine use of dual-strain probiotics (Infloran) in German neonatal wards significantly reduced the risk of NEC, overall mortality, and late-onset sepsis.…”

Prophylactic Probiotics for Preterm Infants: A Systematic Review and Meta-Analysis of Observational Studies

“…Two studies [13,14] had insufficient data presentation (only on preterm neonates) and were therefore not included in the meta-analysis calculation. Hence, 12 studies were pooled in the meta-analysis, including a total of 10,800 neonates [15,16,17,18,19,20,21,22,23,24,25,26]. Details of the selection process are shown in figure 1.…”

“…The included studies covered a large geographical area. All included studies were longitudinal cohort studies, either retrospective [15,16,19,22,23], prospective [17,18,20,21,24,26] or with a historical control group [25]. Ten of the included studies were single-center studies and 2 were multicenter [17,23].…”

Probiotics for preterm infants — The story searching for an end

“…), the difficulty in accessing safe and clinical proven probiotic products, and the risk of probiotic sepsis. Almost all other issues, including 'We don't know how probiotics work', 'Probiotics are not needed if the infant is fed breastmilk -the nature's synbiotic, or when the baseline incidence of NEC is low', 'The PIPs trial showed that not all probiotic strains are effective, and challenged the previous meta-analyses', 'There is not enough data on extremely low birth weight (ELBW) infants, and probiotics may not have significant benefits in this population', have been addressed over the last few years [3][4][5][6][7]. Probiotic sepsis is easy to treat compared to sepsis by other potentially disastrous (e.g.…”