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• Lactobacillus GG for preterm infants
  Michael P Meyer
  Published on: 22 March 2016

• Published on: 22 March 2016

  Lactobacillus GG for preterm infants

  • Michael P Meyer, Neonatal consultant
  • Other Contributors:
    • Paolo Manzoni Neonatology

  The recent review by Millar et al [1] discusses routine introduction of probiotics to preterm infants to prevent necrotizing enterocolitis (NEC). Although a recent Cochrane meta analysis [2] provides compelling evidence for the effectiveness of probiotics, the authors (and others) argue that pooling data from studies where different probiotic strains were used, is inappropriate. In addition, Millar et al regard lactobac...

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  The recent review by Millar et al [1] discusses routine introduction of probiotics to preterm infants to prevent necrotizing enterocolitis (NEC). Although a recent Cochrane meta analysis [2] provides compelling evidence for the effectiveness of probiotics, the authors (and others) argue that pooling data from studies where different probiotic strains were used, is inappropriate. In addition, Millar et al regard lactobacillus GG (LGG) as a less suitable probiotic for preterm infants. They point to a (non significant) increase in sepsis in 2 studies using LGG but have not included data from another 3 published studies (see reference 2 for two further studies by Manzoni et al, and reference 3). They cite a Finnish centre where LGG has been used for NEC prophylaxis for 12 years; although the incidence of NEC was not significantly reduced after LGG introduction, the intervention was regarded as safe [4].Safety of LGG routine administration over a 6 year period has also been recently reported for VLBW neonates at two large Italian NICUs [5]. In addition, normal 12-month neurological follow-up compared to placebo has been reported [3]

  Millar et al also point to reports of bacteremia with LGG, particularly with short gut syndrome. This risk is very small, is present with other probiotics, but is probably better recognized with LGG because it has been most extensively studied [6]. Looking at the current randomized controlled trials on LGG, there is now combined experience in over 600 preterm infants [2, 3, plus an extension of the Manzoni et al 2009 study, 7]. The odds ratio of NEC (8 of 772 in the pooled treatment arm compared to 36 of 807 receiving placebo) is 0.22 (95%CI 0.1-0.5); that of sepsis (57/623 compared to 85/641) is 0.66 (95% CI 0.46-0.95) and mortality 0.66 (95% CI 0.37-1.2). In this pooled analysis, some infants receiving LGG also got lactoferrin (LF). Omitting studies where LF was also used reduces numbers significantly and widens confidence intervals, but overall trends are in the same direction (NEC 0.58 CI 0.2-1.6, sepsis 0.88 CI 0.58-1.35, mortality 0.58 CI 0.2-1.6).

  The editorial also raises the issue of the potential development of antibiotic resistance and colonisation with pathogens following probiotic use. No plasmids containing transferable or antibiotic resistance are present in LGG [6]. Furthermore, colonization with Candida species is reduced [3]. It therefore appears that LGG is eminently suitable for preterm infants and the pooled results for LGG are similar to the overall probiotic meta analysis [2]. Therefore, informed consent for placebo controlled trials will need to be consistent with current evidence of the effectiveness of LGG and other probiotics. We believe the time is for head to head probiotic comparative and follow up studies, rather than further placebo controlled trials. Although cross contamination is a potential confounding factor, the same weakness applies to the non treatment arm in placebo controlled studies and could be clarified by microbiological surveillance.

  M P Meyer Neonatal consultant, Middlemore Hospital and University of Auckland, New Zealand

  P Manzoni Neonatology and NICU, AO OIRM-Ospedale S.Anna. Torino, Italy

  References

  1 Millar M, Wilks M, Fleming P, Costeloe K. Should the use of probiotics in the preterm be routine? Arch Dis Child Fetal Neonatal Ed 2012;97:F70-F74

  2. AlFaleh K, Anabrees J, Bassler D, Al-Kharfi T. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database of Systematic Reviews 2011, Issue 3. Art. No.: CD005496. DOI: 10.1002/14651858.CD005496.pub3.

  3. Romeo M, Romeo D, Trovato L, et al. Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome. J Perinatol 2011;31:63-69

  4. Luoto R, Isolauri E, Lehtonen L Safety of Lactobacillus GG probiotic in infants with Very Low Birth Weight: twelve years of experience. Clin Infect Dis 2010;50(9):1327-1328

  5. Manzoni P, Lista G, Gallo E, et al. Routine Lactobacillus rhamnosus GG administration in VLBW infants: A retrospective, 6-year cohort study. Early Hum Dev 87S (2011) S35-S38

  6. Snydman D. The safety of probiotics. Clin Infect Dis 2008; 46:S104 -111

  7. Manzoni P, Rinaldi M, Meyer M, et al Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in preterm very low birth weight neonates: a randomized trial. E-PAS 2011 3535.7

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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