Effect of routine probiotic, Lactobacillus reuteri DSM 17938, use on rates of necrotizing enterocolitis in neonates with birthweight &lt; 1000 grams: a sequential analysis

Hunter, Chelsea E.; Dimaguila, Mary Ann V.T.; Gál, Péter; Wimmer, John; Ransom, J. Laurence; Carlos, Rita Q.; Smith, McCrae; Davanzo, Christie C

doi:10.1186/1471-2431-12-142

Cited by 81 publications

(97 citation statements)

References 21 publications

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“…[46][47][48] A report from a single site in the USA 46 compared the incidence of NEC in 79 babies (of birthweight ≤ 1000 g) born between 2009 and 2011 in whom L. reuteri was routinely administered and babies born in the previous 5 years; detailed feeding data were not reported and infants who died in the first week were excluded. A reduction in NEC Bell stage ≥ 2 from 15.1% to 2.5% was reported (p = 0.0475); there were baseline differences in the characteristics of the babies and between-year variation in NEC incidence.…”

Section: Observational Studies/historic Comparisonsmentioning

confidence: 99%

A randomised controlled trial of the probiotic Bifidobacterium breve BBG-001 in preterm babies to prevent sepsis, necrotising enterocolitis and death: the Probiotics in Preterm infantS (PiPS) trial

Costeloe

Bowler

Brocklehurst

et al. 2016

Health Technol Assess

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BackgroundNecrotising enterocolitis (NEC) and late-onset sepsis remain important causes of death and morbidity in preterm babies. Probiotic administration might strengthen intestinal barrier function and provide protection; this is supported by published meta-analyses, but there is a lack of large well-designed trials.ObjectiveTo test the use of the probioticBifidobacterium brevestrain BBG-001 to prevent NEC, late-onset sepsis and death in preterm babies while monitoring probiotic colonisation of participants.DesignDouble-blind, randomised, placebo-controlled trial.SettingRecruitment was carried out in 24 hospitals, and the randomisation programme used a minimisation algorithm. Parents, clinicians and outcome assessors were blinded to the allocation.ParticipantsBabies born between 23 and 30 weeks’ gestation and randomised within 48 hours of birth. Exclusions included life-threatening or any gastrointestinal malformation detected within 48 hours of birth and no realistic chance of survival.InterventionsActive intervention: 1 ml ofB. breveBBG-001 in one-eighth-strength infant formula Neocate®(Nutricia Ltd, Trowbridge, UK), (6.7 × 107to 6.7 × 109colony-forming units) per dose administered enterally. Placebo: 1 ml of one-eighth-strength infant formula Neocate. Started as soon as practicable and continued daily until 36 weeks’ postmenstrual age.Main outcome measuresPrimary outcomes were an episode of bloodstream infection, with any organism other than a skin commensal, in any baby between 72 hours and 46 weeks’ postmenstrual age; an episode of NEC Bell stage ≥ 2 in any baby; and death before discharge from hospital. Secondary outcomes included stool colonisation withB. breve.ResultsIn total, 654 babies were allocated to receive probiotic and 661 to receive placebo over 37 months from July 2010. Five babies were withdrawn; 650 babies from the probiotic group and 660 from the placebo group were included in the primary analysis. Baseline characteristics were well balanced. There was no evidence of benefit for the primary outcomes {sepsis: 11.2% vs. 11.7% [adjusted relative risk (RR) 0.97, 95% confidence interval (CI) 0.73 to 1.29]; NEC Bell stage ≥ 2: 9.4% vs. 10.0% [adjusted RR 0.93, 95% CI 0.68 to 1.27]; and death: 8.3% vs. 8.5% [adjusted RR 0.93, 95% CI 0.67 to 1.30]}.B. brevecolonisation status was available for 1186 (94%) survivors at 2 weeks’ postnatal age, of whom 724 (61%) were positive: 85% of the probiotic group and 37% of the placebo group. There were no differences for subgroup analyses by minimisation criteria and by stool colonisation withB. breveat 2 weeks. No harms associated with the interventions were reported.LimitationsCross-colonisation of the placebo arm could have reduced statistical power and confounded results; analyses suggest that this did not happen.ConclusionsThis is the largest trial to date of a probiotic intervention. It shows no evidence of benefit and does not support routine use of probiotics for preterm infants.Future work recommendationsThe increasing understanding of the pathogenesis of NEC and sepsis will inform the choice of probiotics for testing and better define the target population. Future Phase III trials should incorporate monitoring of the quality and viability of the intervention and colonisation rates of participants; cluster design should be considered.Trial registrationCurrent Controlled Trials ISRCTN05511098 and EudraCT 2006-003445-17.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 66. See the NIHR Journals Library website for further project information.

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Section: Observational Studies/historic Comparisonsmentioning

confidence: 99%

A randomised controlled trial of the probiotic Bifidobacterium breve BBG-001 in preterm babies to prevent sepsis, necrotising enterocolitis and death: the Probiotics in Preterm infantS (PiPS) trial

Costeloe

Bowler

Brocklehurst

et al. 2016

Health Technol Assess

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“…6,7 Our recently published retrospective case series in neonates with birth weights of #1000 g documented an even larger reduction in NEC rates in this high-risk population. 8 NEC rates were reduced from 15.1% before routine Lactobacillus reuteri prophylaxis to 2.5% after routine prophylaxis with L. reuteri. Some authors caution against routine use of probiotics, citing concerns with product quality, confusion over the best strains of probiotic to select, and possible adverse effects.…”

Section: Introductionmentioning

confidence: 99%

“…Data for this analysis include neonates administered L. reuteri DSM 17938 at a dose of 0.1 mL (approximately 550 million colony-forming units) daily, as in our original publication, 8 and an additional 43 neonates administered a dose of 0.2 mL daily (110 million colony-forming units). This was a retrospective chart review of 354 consecutive patients comparing the rates of NEC in neonates with birth weight # 1000 g, before introduction of L. reuteri (January 2004-June 2009), with routine use of L. reuteri in neonates # 1000 g birth weight (July 2009-June 2012), and was approved by the institutional review board and exempted from needing informed consent.…”

Section: Data Collectionmentioning

confidence: 99%

“…9,10 However, given the positive weight of evidence, it may be time to consider selected probiotic products for routine use in neonatal intensive care units (NICUs). To expand the debated issues further, we have performed a pharmacoeconomic analysis of our L. reuteri prophylaxis strategy utilizing the data from our recently published paper, 8 and our additional experience with a higher-dose strategy.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacoeconomic impact of use of the probiotic Lactobacillus reuteri DSM 17938 for prevention of necrotizing enterocolitis in extremely low-birth-weight infants

Dimaguila¹,

Gál²,

Wilson³

et al. 2013

RRN

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Background:A recent study showed that use of Lactobacillus reuteri as probiotic prophylaxis decreased the necrotizing enterocolitis (NEC) rate from 15.1% to 2.5% in neonates with birth weight below 1000 g. Given the controversies surrounding use of probiotics in neonatal intensive care units, we address one additional aspect of routine implementation of probiotics for NEC prophylaxis -the pharmacoeconomic impact. Methods: Using data from our initial published experience, and continuing data collection after instituting a higher dose of L. reuteri, we measured the reduction in NEC in neonates with birth weight below 1000 g. Cost savings from prior studies examining the cost and outcomes of medical and surgical NEC were used to calculate the financial impact of routine L. reuteri DSM 17938 prophylaxis. Results: Medical records for 354 neonates were reviewed, 232 in the years before introduction of L. reuteri prophylaxis and 79 who received L. reuteri prophylaxis dosed at 0.1 mL daily and 43 neonates given a total daily dose of 0.2 mL as one or two doses. The incidence of NEC was significantly lower in the neonates who received L. reuteri (two of 122 neonates [1.6%] versus 35 of 232 neonates [15.1%]). The expected benefits for our neonatal intensive care unit per 100 extremely low-birth-weight neonates treated were four fewer deaths, five fewer cases of medical NEC, eight fewer cases of surgical NEC, one less patient with short-bowel syndrome, and a cost saving of approximately $2.2 million. Conclusion: Prophylactic initiation of L. reuteri as a probiotic for prevention of NEC in neonates with birth weight # 1000 g is a cost-effective strategy during their stay in neonatal intensive care.

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“…A retrospective study that looked at a cohort of VLBW neonates with NEC (#1000 g) showed that infants administered Lactobacillus reuteri DSM 17938 had a lower incidence of NEC (64). In addition, multiple meta-analyses of prospective, randomized, placebo-controlled trials analyzed the impact of probiotics on reducing the prevalence of NEC in premature infants (65)(66)(67).…”

Section: Management Strategiesmentioning

confidence: 99%

Probiotics, Prebiotics, and Synbiotics for the Prevention of Necrotizing Enterocolitis

Johnson‐Henry

Abrahamsson

et al. 2016

Advances in Nutrition

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Necrotizing enterocolitis (NEC) is a devastating intestinal disease in preterm infants characterized by barrier disruption, intestinal microbial dysbiosis, and persistent inflammation of the colon, which results in high mortality rates. Current strategies used to manage this disease are not sufficient, although the use of human breast milk reduces the risk of NEC. Mother's milk is regarded as a fundamental nutritional source for neonates, but pasteurization of donor breast milk affects the composition of bioactive compounds. Current research is evaluating the benefits and potential pitfalls of adding probiotics and prebiotics to pasteurized milk so as to improve the functionality of the milk and thereby reduce the burden of illness caused by NEC. Probiotics (live micro-organisms that confer health to the host) and prebiotics (nondigestible oligosaccharides that stimulate the growth of healthy bacteria) are functional foods known to mediate immune responses and modulate microbial populations in the gut. Clinical research shows strain-and compoundspecific responses when probiotics or prebiotics are administered in conjunction with donor breast milk for the prevention of NEC. Despite ongoing controversy surrounding optimal treatment strategies, randomized controlled studies are now investigating the use of synbiotics to reduce the incidence and severity of NEC. Synbiotics, a combination of probiotics and prebiotics, have been proposed to enhance beneficial health effects in the intestinal tract more than either agent administered alone. This review considers the implications of using probiotic-, prebiotic-, and synbioticsupplemented breast milk as a strategy to prevent NEC and issues that could be encountered with the preparations. Adv Nutr 2016;7:928-37.

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Effect of routine probiotic, Lactobacillus reuteri DSM 17938, use on rates of necrotizing enterocolitis in neonates with birthweight < 1000 grams: a sequential analysis

Cited by 81 publications

References 21 publications

A randomised controlled trial of the probiotic Bifidobacterium breve BBG-001 in preterm babies to prevent sepsis, necrotising enterocolitis and death: the Probiotics in Preterm infantS (PiPS) trial

A randomised controlled trial of the probiotic Bifidobacterium breve BBG-001 in preterm babies to prevent sepsis, necrotising enterocolitis and death: the Probiotics in Preterm infantS (PiPS) trial

Pharmacoeconomic impact of use of the probiotic Lactobacillus reuteri DSM 17938 for prevention of necrotizing enterocolitis in extremely low-birth-weight infants

Probiotics, Prebiotics, and Synbiotics for the Prevention of Necrotizing Enterocolitis

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