Prophylactic Probiotics for Prevention of Necrotizing Enterocolitis in Very Low Birth Weight Newborns

Samanta, Moumita; Sarkar, Mihir; Ghosh, Pramit; Ghosh, Jayanta; Sinha, Malay K; Chatterjee, Sukanta

doi:10.1093/tropej/fmn091

Cited by 188 publications

(153 citation statements)

References 14 publications

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“…When recruitment to the PiPS trial began in 2010, four [20][21][22][23] further trials with clinical primary outcomes had been published.…”

Section: Randomised Controlled Trialsmentioning

confidence: 99%

“…The third and fourth RCTs with clinical primary outcomes were published in 2008 and 2009, a single-site trial from a hospital in India 22 and a multicentre trial from Taiwan. 23 In the trial from India, a combination of B. infantis, B. bifidum, B. longum and L. acidophilus given with breast milk twice daily to 186 babies of < 32 weeks' gestation and birthweight < 1500 g was compared with breast milk alone.…”

Section: Randomised Controlled Trialsmentioning

confidence: 99%

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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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“…When recruitment to the PiPS trial began in 2010, four [20][21][22][23] further trials with clinical primary outcomes had been published.…”

Section: Randomised Controlled Trialsmentioning

confidence: 99%

Section: Randomised Controlled Trialsmentioning

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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“…Only one trial reported significantly lower risk for sepsis in the probiotic group 45 , and another reported higher risk for sepsis in the probiotic group, which was not significant after adjustment for gestation and birth weight 46 . Statistically significant difference in incidence of blood culture positive sepsis has been demonstrated in some other studies 47,22 . There are two ongoing large trials (PIPS and Propem) evaluating effects of probiotics on sepsis.…”

Section: Studies On Use Of Probiotics In Preterm Infantsmentioning

confidence: 56%

“…Evidence indicates that to be functional, probiotics have to be viable and in sufficient dosage levels, typically 10 6 to 10 7 colony-forming units (CFU)/g of product 19,20 . Based on the median dose used in the randomized controlled trial (RCTs) in preterm neonates , a daily dose of 3 × 10 9 cfu/day may be appropriate for neonates of less than 32 weeks gestation 21,22 .…”

Section: Monostrain or Multistrain Probioticsmentioning

confidence: 99%

Probiotics in Neonatal Infection :A Review

Moni

Shamsuzzaman

Shahidullah

2017

Bangladesh J Med Microbiol

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“…Historical data suggests that by and large probiotics can be safely employed for use in newborns and infants for various indications [7][8][9][10][11][12][13][14][15][16][17][18][19] and these organisms are considered as GRAS (Generally Regarded as Safe).…”

Section: Introductionmentioning

confidence: 99%

Role of Synbiotics in Improvement of Feed Tolerance and Weight Gain in the Newborns

Sonawane¹,

Patil²,

Godbole³

et al. 2014

mvpjms

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Objective: To study the effect of Synbiotics on weight gain and feed tolerance of newborns. Methods: This prospective interventional trial included 50 newborns treated with a dietary supplement containing Synbiotics in addition to the routine treatment and 48 newborns served as control without Synbiotics supplement. The primary outcome was weight gain and feed tolerance. Results: Newborns in the Synbiotics group reached the full feeds earlier as compared to those in Control group (7.5 ± 4.26 days Vs 14.02 ± 7.88 days p=0.532) along with better weight gain(14.61 ± 9.6 grams per day Vs 2.97 ± 3.81 grams per day p=0.0000001). Conclusions: Newborns receiving Synbiotics are more likely to reach full feeds earlier and show better weight gain.

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Prophylactic Probiotics for Prevention of Necrotizing Enterocolitis in Very Low Birth Weight Newborns

Cited by 188 publications

References 14 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

Probiotics in Neonatal Infection :A Review

Role of Synbiotics in Improvement of Feed Tolerance and Weight Gain in the Newborns

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