The N3RO trial: a randomised controlled trial of docosahexaenoic acid to reduce bronchopulmonary dysplasia in preterm infants < 29 weeks' gestation

Carmel T Collins; Robert A Gibson; Maria Makrides; Andrew J McPhee; Thomas R Sullivan; Peter G Davis; Marta Thio; Karen Simmer; Victor S Rajadurai; N3RO Investigative Team

doi:10.1186/s12887-016-0611-0

The N3RO trial: a randomised controlled trial of docosahexaenoic acid to reduce bronchopulmonary dysplasia in preterm infants < 29 weeks' gestation

BMC Pediatr. 2016 Jun 1:16:72. doi: 10.1186/s12887-016-0611-0.

Authors

Carmel T Collins^{1

2

3}, Robert A Gibson^{4

5}, Maria Makrides^{6

4

7}, Andrew J McPhee^{4

8}, Thomas R Sullivan⁹, Peter G Davis^{10

11

12}, Marta Thio^{10

11

12

13}, Karen Simmer^{14

15}, Victor S Rajadurai^{16

17}; N3RO Investigative Team

Collaborators

N3RO Investigative Team:
Philip Ryan, Scott Morris, Michael Stark, Javeed Travadi, Ian Wright, Kenneth Tan, James Holberton, Gillian Opie, Ian Callander, Jacqueline Stack, Doron Shein, Sarah Bellhouse, Srinivas Bolisetty, Kei Lui, Helen Liley, Mary Berry, Deborah Harris, MeiChien Chua, Pooja Agarwal

Affiliations

¹ Women's and Children's Health Research Institute, North Adelaide, South Australia, Australia. carmel.collins@sa.gov.au.
² Healthy Mother's, Babies and Children, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia. carmel.collins@sa.gov.au.
³ Discipline of Paediatrics, School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia. carmel.collins@sa.gov.au.
⁴ Healthy Mother's, Babies and Children, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
⁵ School of Agriculture, Food and Wine, The University of Adelaide, Adelaide, South Australia, Australia.
⁶ Women's and Children's Health Research Institute, North Adelaide, South Australia, Australia.
⁷ Discipline of Paediatrics, School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.
⁸ Neonatal Services, Women's and Children's Health Network, Adelaide, South Australia, Australia.
⁹ School of Public Health, The University of Adelaide, Adelaide, South Australia, Australia.
¹⁰ Newborn Research Centre, The Royal Women's Hospital, Melbourne, VIC, Australia.
¹¹ Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, Australia.
¹² Clinical Sciences, The Murdoch Children's Research Institute, Parkville, VIC, Australia.
¹³ PIPER-Neonatal Retrieval Service, The Royal Children's Hospital, Melbourne, VIC, Australia.
¹⁴ Centre of Neonatal Research and Education, The University of Western Australia, Perth, WA, Australia.
¹⁵ King Edward Memorial Hospital and Princess Margaret Hospital for Children, Subiaco, WA, Australia.
¹⁶ Department Neonatology, KK Women's and Children's Hospital, Singapore, Singapore.
¹⁷ Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Abstract

Background: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and long-term respiratory and neurological morbidity in very preterm infants. While survival rates of very preterm infants have increased over the past two decades there has been no decrease in the rate of BPD in surviving infants. Evidence from animal and human studies has suggested potential benefits of docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid, in the prevention of chronic lung disease. This randomised controlled trial aims to determine the effectiveness of supplementary DHA in reducing the rate of BPD in infants less than 29 weeks' gestation.

Methods/design: This is a multicentre, parallel group, randomised, blinded and controlled trial. Infants born less than 29 weeks' gestation, within 3 days of first enteral feed and with parent informed consent are eligible to participate. Infants will be randomised to receive an enteral emulsion containing DHA or a control emulsion without DHA. The DHA emulsion will provide 60 mg/kg/day of DHA. The study emulsions will continue to 36 weeks' postmenstrual age (PMA). The primary outcome is BPD as assessed by the requirement for supplemental oxygen and/or assisted ventilation at 36 weeks' PMA. Secondary outcomes include the composite of death or BPD; duration of respiratory support and hospitalisation, major neonatal morbidities. The target sample size is 1244 infants (622 per group), which will provide 90 % power to detect a clinically meaningful absolute reduction of 10 % in the incidence of BPD between the DHA and control emulsion (two tailed α =0.05).

Discussion: DHA supplementation has the potential to reduce respiratory morbidity in very preterm infants. This multicentre trial will provide evidence on whether an enteral DHA supplement reduces BPD in very preterm infants.

Trial registration: Australia and New Zealand Clinical Trial Registry: ACTRN12612000503820 . Registered 09 May 2012.

Keywords: Bronchopulmonary dysplasia; Docosahexaenoic acid; Infant; Preterm; n-3 long chain polyunsaturated fatty acids.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Bronchopulmonary Dysplasia / prevention & control*
Clinical Protocols
Dietary Supplements*
Docosahexaenoic Acids / therapeutic use*
Double-Blind Method
Emulsions
Enteral Nutrition
Female
Follow-Up Studies
Humans
Infant, Newborn
Infant, Premature
Male
Treatment Outcome

Substances

Emulsions
Docosahexaenoic Acids

Associated data

ANZCTR/ACTRN12612000503820