Randomised controlled trial of perinatal vitamin D supplementation to prevent early-onset acute respiratory infections among Australian First Nations children: the 'D-Kids' study protocol

Michael J Binks; Amy S Bleakley; Susan J Pizzutto; Michelle Lamberth; Verity Powell; Jane Nelson; Adrienne Kirby; Peter S Morris; David Simon; E Kim Mulholland; Geetha Rathnayake; Amanda J Leach; Heather D'Antoine; Paul V Licciardi; Tom Snelling; Anne B Chang

doi:10.1136/bmjresp-2023-001646

Randomised controlled trial of perinatal vitamin D supplementation to prevent early-onset acute respiratory infections among Australian First Nations children: the 'D-Kids' study protocol

BMJ Open Respir Res. 2023 Aug;10(1):e001646. doi: 10.1136/bmjresp-2023-001646.

Authors

Michael J Binks¹, Amy S Bleakley², Susan J Pizzutto², Michelle Lamberth^{2

3}, Verity Powell^{2

3}, Jane Nelson², Adrienne Kirby⁴, Peter S Morris^{2

5}, David Simon³, E Kim Mulholland^{6

7}, Geetha Rathnayake⁸, Amanda J Leach², Heather D'Antoine², Paul V Licciardi^{6

9}, Tom Snelling^{10

11}, Anne B Chang^{2

12}

Affiliations

¹ Child Health Division, Menzies School of Health Research, Charles Darwin University, Casuarina, Northern Territory, Australia Michael.Binks@menzies.edu.au.
² Child Health Division, Menzies School of Health Research, Charles Darwin University, Casuarina, Northern Territory, Australia.
³ Department of Obstetrics and Gynaecology, Royal Darwin Hospital, Tiwi, Northern Territory, Australia.
⁴ National Health and Medical Research Council Clinical Trials Centre, University of Sydney CAR, Glebe, New South Wales, Australia.
⁵ Department of Paediatrics, Royal Darwin Hospital, Tiwi, Northern Territory, Australia.
⁶ New Vaccines Research Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
⁷ Epidemiology and Public Health, London School of Hygiene & Tropical Medicine, London, UK.
⁸ Virtus Diagnostics, Sydney, New South Wales, Australia.
⁹ Department of Paediatrics, University of Melbourne VCCC, Parkville, Victoria, Australia.
¹⁰ School of Public Health, The University of Sydney, Sydney, New South Wales, Australia.
¹¹ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia, Australia.
¹² Centre for Children's Health Research, Queensland University of Technology, Brisbane, Queensland, Australia.

Abstract

Introduction: Globally, acute respiratory infections (ARIs) are a leading cause of childhood morbidity and mortality. While ARI-related mortality is low in Australia, First Nations infants are hospitalised with ARIs up to nine times more often than their non-First Nations counterparts. The gap is widest in the Northern Territory (NT) where rates of both acute and chronic respiratory infection are among the highest reported in the world. Vitamin D deficiency is common among NT First Nations neonates and associated with an increased risk of ARI hospitalisation. We hypothesise that perinatal vitamin D supplementation will reduce the risk of ARI in the first year of life.

Methods and analysis: 'D-Kids' is a parallel (1:1), double-blind (allocation concealed), randomised placebo-controlled trial conducted among NT First Nations mother-infant pairs. Pregnant women and their babies (n=314) receive either vitamin D or placebo. Women receive 14 000 IU/week or placebo from 28 to 34 weeks gestation until birth and babies receive 4200 IU/week or placebo from birth until age 4 months. The primary outcome is the incidence of ARI episodes receiving medical attention in the first year of life. Secondary outcomes include circulating vitamin D level and nasal pathogen prevalence. Tertiary outcomes include infant immune cell phenotypes and challenge responses. Blood, nasal swabs, breast milk and saliva are collected longitudinally across four study visits: enrolment, birth, infant age 4 and 12 months. The sample size provides 90% power to detect a 27.5% relative reduction in new ARI episodes between groups.

Ethics and dissemination: This trial is approved by the NT Human Research Ethics Committee (2018-3160). Study outcomes will be disseminated to participant families, communities, local policy-makers, the broader research and clinical community via written and oral reports, education workshops, peer-reviewed journals, national and international conferences.

Trial registration number: ACTRN12618001174279.

Keywords: Bacterial Infection; Infection Control; Innate Immunity; Pneumonia; Respiratory Infection; Viral infection.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Australia / epidemiology
Child
Dietary Supplements
Double-Blind Method
Female
Hospitalization
Humans
Infant
Infant, Newborn
Pregnancy
Randomized Controlled Trials as Topic
Vitamin D Deficiency* / drug therapy
Vitamin D Deficiency* / epidemiology
Vitamin D Deficiency* / prevention & control
Vitamin D*

Substances

Vitamin D