Role of Probiotics for Prevention of NEC in Preterm VLBW Infants (Probiotics)

Role of Probiotics for Prevention of Necrotizing Enterocolitis in Preterm Very Low Birth Weight Infants: A Double Blind Randomized Controlled Trial

This prospective randomized double-blind control trial is carrying out in the neonatal unit of Sylhet MAG Osmani Medical College Hospital, Sylhet between July 2012 to December 2015 with the diagnosis of preterm (<33 weeks gestation) VLBW (birth weight <1500g) and fulfilling the inclusion criteria (able to tolerate oral feed and survive beyond 48h of life) were included in this study. Babies with suspicion of clinical sepsis, presence of perinatal asphyxia, major congenital anomaly and babies who expired due to other neonatal illness were excluded. Gestation was assessed from history of last menstrual period and after birth by new Ballard scores. A study protocol was approved by the Institutional Ethics Committee of Sylhet M.A.G Osmani Medical College, Sylhet.

Study Overview

• Status: Completed
• Conditions: Necrotizing Enterocolitis
• Intervention / Treatment: Dietary supplement: Probiotics; Dietary supplement: Breast milk

Detailed Description

Background: Necrotizing enterocolitis (NEC) is the most common acquired disease of the gastrointestinal tract in preterm very low birth weight infants and associated with increased morbidity and mortality. Prophylactic enteral probiotic supplementation may play a role in reducing NEC and potentially provide benefits to preterm very low birth weight neonates. The objective was to evaluate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis (NEC) in preterm very low birth weight (VLBW) infants.

This prospective, randomized double blind controlled trial is undergoing in 102 preterm (28-33 weeks gestation) VLBW (birth weight 1000-1499g) neonates fulfilling the inclusion criteria. The study group was fed with probiotics once daily with breast milk from first feeding and the control group only breast milk without the addition of probiotics. The primary outcome was the development of NEC (stage II and III). NEC is categorized by modified Bell's classification.

Probiotic supplementation reduces the frequency of necrotising enterocolitis in preterm neonates with very low birth weight. It is also associated with faster achievement of full enteral feeding and shorter duration of hospital stay.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week to 7 months (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All newborn infant preterm (<33 weeks gestation to 28 weeks gestation) VLBW (birth weight <1500gm to 1000 gm)
• Able to tolerate oral feed
• Informed consent by the parents or guardian

Exclusion Criteria:

• Evidence or suspicion of clinical sepsis before the baby is randomised
• Presence of perinatal asphyxia
• Presence of major congenital anomali
• Death within first week of life due to other neonatal illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Standard care + Breast milk+ Probiotics; The study group will be fed with probiotics at a dose of 3x109 CFU/day. (Cap TS6 probiotic + contain Bifidobacterium spp., Lactobacillus at 6x109 CFU = 6 billion CFU) dissolved with 6 ml of milk then give 3 ml (3 billion probiotics) once daily with breast milk from first feeding.	Dietary supplement: Probiotics; probiotics at a dose of 3x109 CFU/day. (Cap TS6 probiotic + contain Bifidobacterium spp., Lactobacillus at 6x109 CFU = 6 billion CFU manufactured by TENSALL BIO-TECH CO.LTD.Taiwan, distributed by Century Health Care, Bangladesh); Other Names: TS 6 Probiotics
ACTIVE_COMPARATOR: Standard care; The control group will be given standard care without the addition of probiotics	Dietary supplement: Breast milk; Normal breast milk will be given as part of standard care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Necrotizing Enterocolitis: Occurrence of NEC (stage II and III) by Modified Bell's classification	The occurrence of NEC (stage II and III) by modified Bell's classification	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enteral feeding	days to achieve full enteral feeding	10 days
Hospital stay	maximum days of hospital stay	10 days
weight in Kg	weight in kg	10 days

Collaborators and Investigators

• Sponsor: Sylhet M.A.G.Osmani Medical College
• Investigators: Study Chair: Prof. M. Monojjir Ali, FCPS, Professor and Head, Department of Paediatrics, Sylhet M.A.G.Osmani Medical College

Publications and helpful links

General Publications

• Deshpande G, Rao S, Patole S. Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials. Lancet. 2007 May 12;369(9573):1614-20. doi: 10.1016/S0140-6736(07)60748-X.
• Sharma R, Tepas JJ 3rd, Hudak ML, Mollitt DL, Wludyka PS, Teng RJ, Premachandra BR. Neonatal gut barrier and multiple organ failure: role of endotoxin and proinflammatory cytokines in sepsis and necrotizing enterocolitis. J Pediatr Surg. 2007 Mar;42(3):454-61. doi: 10.1016/j.jpedsurg.2006.10.038.
• Forchielli ML, Walker WA. The effect of protective nutrients on mucosal defense in the immature intestine. Acta Paediatr Suppl. 2005 Oct;94(449):74-83. doi: 10.1111/j.1651-2227.2005.tb02159.x.
• Neish AS, Gewirtz AT, Zeng H, Young AN, Hobert ME, Karmali V, Rao AS, Madara JL. Prokaryotic regulation of epithelial responses by inhibition of IkappaB-alpha ubiquitination. Science. 2000 Sep 1;289(5484):1560-3. doi: 10.1126/science.289.5484.1560.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: December 31, 2015
• First Submitted That Met QC Criteria: January 7, 2016
• First Posted (ESTIMATE): January 8, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): January 8, 2016
• Last Update Submitted That Met QC Criteria: January 7, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: probiotics; Necrotizing Enterocolitis; very low birth weight
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Enterocolitis; Enterocolitis, Necrotizing
• Other Study ID Numbers: SylhetMAG