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Open Access Highly Accessed Study protocol

The ProPrems trial: investigating the effects of probiotics on late onset sepsis in very preterm infants

Suzanne M Garland123*, Jacinta M Tobin4, Marie Pirotta5, Sepehr N Tabrizi123, Gillian Opie6, Susan Donath7, Mimi LK Tang38, Colin J Morley9, Leah Hickey19, Linh Ung19, Susan E Jacobs9 and the ProPrems Study Group

Author Affiliations

1 Women's Centre for Infectious Diseases, Bio 21 Institute, 30 Flemington Road, Parkville, Victoria 3052, Australia

2 University of Melbourne Department of Obstetrics and Gynaecology, The Royal Women's Hospital, 20 Flemington Road, Parkville, Victoria 3052, Australia

3 Murdoch Children's Research Institute, Royal Children's Hospital, 50 Flemington Road, Parkville, Victoria 3052, Australia

4 Department of Medical Education, University of Melbourne, Grattan Street, Carlton, Victoria 3053, Australia

5 Department of General Practice, University of Melbourne, 200 Berkeley Street, Carlton, Victoria 3053, Australia

6 Neonatal Services, Mercy Hospital for Women, 163 Studley Road, Heidelberg, Victoria 3084, Australia

7 Clinical Epidemiological and Biostatistics Unit, Royal Children's Hospital, 50 Flemington Road, Parkville, Victoria 3052, Australia

8 Department of Paediatrics, University of Melbourne, Parkville, Victoria 3052, Australia

9 Neonatal Services, The Royal Women's Hospital, 20 Flemington Road, Parkville, Victoria 3052, Australia

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BMC Infectious Diseases 2011, 11:210  doi:10.1186/1471-2334-11-210

Published: 4 August 2011

Abstract

Background

Late onset sepsis is a frequent complication of prematurity associated with increased mortality and morbidity. The commensal bacteria of the gastrointestinal tract play a key role in the development of healthy immune responses. Healthy term infants acquire these commensal organisms rapidly after birth. However, colonisation in preterm infants is adversely affected by delivery mode, antibiotic treatment and the intensive care environment. Altered microbiota composition may lead to increased colonisation with pathogenic bacteria, poor immune development and susceptibility to sepsis in the preterm infant.

Probiotics are live microorganisms, which when administered in adequate amounts confer health benefits on the host. Amongst numerous bacteriocidal and nutritional roles, they may also favourably modulate host immune responses in local and remote tissues. Meta-analyses of probiotic supplementation in preterm infants report a reduction in mortality and necrotising enterocolitis. Studies with sepsis as an outcome have reported mixed results to date.

Allergic diseases are increasing in incidence in "westernised" countries. There is evidence that probiotics may reduce the incidence of these diseases by altering the intestinal microbiota to influence immune function.

Methods/Design

This is a multi-centre, randomised, double blinded, placebo controlled trial investigating supplementing preterm infants born at < 32 weeks' gestation weighing < 1500 g, with a probiotic combination (Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis). A total of 1,100 subjects are being recruited in Australia and New Zealand. Infants commence the allocated intervention from soon after the start of feeds until discharge home or term corrected age. The primary outcome is the incidence of at least one episode of definite (blood culture positive) late onset sepsis before 40 weeks corrected age or discharge home. Secondary outcomes include: Necrotising enterocolitis, mortality, antibiotic usage, time to establish full enteral feeds, duration of hospital stay, growth measurements at 6 and 12 months' corrected age and evidence of atopic conditions at 12 months' corrected age.

Discussion

Results from previous studies on the use of probiotics to prevent diseases in preterm infants are promising. However, a large clinical trial is required to address outstanding issues regarding safety and efficacy in this vulnerable population. This study will address these important issues.

Trial registration

Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN012607000144415

The product "ABC Dophilus Probiotic Powder for Infants®", Solgar, USA has its 3 probiotics strains registered with the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ - German Collection of Microorganisms and Cell Cultures) as BB-12 15954, B-02 96579, Th-4 15957.