Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants

Abstract

Lin H, Su B, Chen A, Lin TW, Tsai C, Yeh T, et al. Pediatrics 2005;115:1-4.Context Necrotizing enterocolitis (NEC) is a worldwide problem in very low birth weight (VLBW) infants, with highly variable incidence affecting 2.6% to 28% of these infants.Objectives To evaluate the efficacy of probiotics in reducing the incidence and severity of NEC in VLBW infants.Design Prospective, masked, randomized control trial.Setting A level III neonatal center in the central part of Taiwan.Participants 367 VLBW (<1500 g) infants who started to feed enterally and survived beyond the 7th day after birth.Interventions Infants in the study group were fed with Infloran (Lactobacillus acidophilus and Bifidobacterium infantis) 125 mg/kg with breast milk twice daily until discharge. Infants in the control group were fed with breast milk alone.Main outcome measures Death or NEC (≥ stage 2).Results The incidence of death or NEC (≥ stage 2) was significantly lower in the study group (5% vs 12.8%, P = .009, number needed to treat [NNT] = 13). The incidence of NEC (≥ stage 2) also was significantly lower in the study when compared with the control group (1.1% vs 5.3%, P = .04, NNT = 24). There were six cases of severe NEC (Bell stage 3) in the control group and none in the study group. None of the positive blood cultures grew Lactobacillus or Bifidobacterium species.Conclusions Infloran as probiotics fed enterally with breast milk reduces the incidence and severity of NEC in VLBW infants.Comment There is a strong rationale to prevent NEC with probiotic agents. Premature infants may be colonized with pathogenic bacteria and develop an aberrant fecal flora that contributes to the pathogenesis of NEC.1Kliegman R.M. Willoughby R.E. Prevention of necrotizing enterocolitis with probiotics.Pediatrics. 2005; 115: 171-172PubMed Google Scholar Probiotics may improve intestinal immune regulation, enhance mucin production, produce antibacterial agents, stimulate IgA production, block mucosal binding, reduce mucosal permeability, and produce anti-inflammatory cytokines.The well-designed study by Lin and co-workers demonstrates the efficacy of probiotics in preventing NEC. Unfortunately, the study did not have the power to define the risk of serious infections from probiotic bacteria. Although most probably rare, sepsis, meningitis, endocarditis, pneumonia, and abscesses have been reported in immunocompetent and immunocompromised adults and children treated with probiotics.Further studies in premature infants should confirm efficacy but must address safety. Based on the literature, it would be wise to avoid prophylactic use of probiotics in premature infants with congenital or acquired immunodeficiencies, congenital heart disease, or gastrointestinal compromise (ileus, mucositis, diarrhea, suspected or documented NEC). The probiotic organism should be the least virulent and have a favorable antibiotic susceptibility profile (this needs to be rechecked during hospitalization because resistance may develop). In the meantime, premature infants should be fed human milk because it encourages the growth of endogenous probiotic organisms. Lin H, Su B, Chen A, Lin TW, Tsai C, Yeh T, et al. Pediatrics 2005;115:1-4. Context Necrotizing enterocolitis (NEC) is a worldwide problem in very low birth weight (VLBW) infants, with highly variable incidence affecting 2.6% to 28% of these infants. Objectives To evaluate the efficacy of probiotics in reducing the incidence and severity of NEC in VLBW infants. Design Prospective, masked, randomized control trial. Setting A level III neonatal center in the central part of Taiwan. Participants 367 VLBW (<1500 g) infants who started to feed enterally and survived beyond the 7th day after birth. Interventions Infants in the study group were fed with Infloran (Lactobacillus acidophilus and Bifidobacterium infantis) 125 mg/kg with breast milk twice daily until discharge. Infants in the control group were fed with breast milk alone. Main outcome measures Death or NEC (≥ stage 2). Results The incidence of death or NEC (≥ stage 2) was significantly lower in the study group (5% vs 12.8%, P = .009, number needed to treat [NNT] = 13). The incidence of NEC (≥ stage 2) also was significantly lower in the study when compared with the control group (1.1% vs 5.3%, P = .04, NNT = 24). There were six cases of severe NEC (Bell stage 3) in the control group and none in the study group. None of the positive blood cultures grew Lactobacillus or Bifidobacterium species. Conclusions Infloran as probiotics fed enterally with breast milk reduces the incidence and severity of NEC in VLBW infants. Comment There is a strong rationale to prevent NEC with probiotic agents. Premature infants may be colonized with pathogenic bacteria and develop an aberrant fecal flora that contributes to the pathogenesis of NEC.1Kliegman R.M. Willoughby R.E. Prevention of necrotizing enterocolitis with probiotics.Pediatrics. 2005; 115: 171-172PubMed Google Scholar Probiotics may improve intestinal immune regulation, enhance mucin production, produce antibacterial agents, stimulate IgA production, block mucosal binding, reduce mucosal permeability, and produce anti-inflammatory cytokines. The well-designed study by Lin and co-workers demonstrates the efficacy of probiotics in preventing NEC. Unfortunately, the study did not have the power to define the risk of serious infections from probiotic bacteria. Although most probably rare, sepsis, meningitis, endocarditis, pneumonia, and abscesses have been reported in immunocompetent and immunocompromised adults and children treated with probiotics. Further studies in premature infants should confirm efficacy but must address safety. Based on the literature, it would be wise to avoid prophylactic use of probiotics in premature infants with congenital or acquired immunodeficiencies, congenital heart disease, or gastrointestinal compromise (ileus, mucositis, diarrhea, suspected or documented NEC). The probiotic organism should be the least virulent and have a favorable antibiotic susceptibility profile (this needs to be rechecked during hospitalization because resistance may develop). In the meantime, premature infants should be fed human milk because it encourages the growth of endogenous probiotic organisms.