A double blind randomized controlled trial in neonates to determine the effect of vitamin A supplementation on immune responses: The Gambia protocol

BMC Pediatrics

Andrew M Prentice²  Katie L Flanagan³  Lindsay Kendall¹  Anthony JC Fulford²  Mathilde Savy²  Suzanna LR McDonald² 

[1] Statistics, MRC Gambia Unit, PO Box 273, Banjul, The Gambia;Medical Research Council (MRC) International Nutrition Group (ING), London School of Hygiene & Tropical Medicine (LSHTM), Keppel Street, WC1E 7HT, United Kingdom & MRC Keneba, London, The Gambia;Department of Immunology, Monash University, Melborne VIC 3181, Australia

关键词: Double blind randomised control trial;    Africa;    Immune responses;    Vitamin A supplementation;    Neonatal;   

Others  :  1138922
DOI  :  10.1186/1471-2431-14-92

 received in 2014-02-25, accepted in 2014-03-27,  发布年份 2014

【 摘 要 】

Background

Vitamin A supplementation significantly reduces all-cause mortality when given between 6–59 months of age, but has a null or detrimental effect when given between 1–5 months. Studies of neonatal vitamin A supplementation conducted across Africa and South Asia have produced conflicting findings. These age-pattern variations might result from immunological interactions between vitamin A supplementation and vaccines. Knowledge on the potential immunological sequelae of human neonatal vitamin A supplementation is so scarce that the foremost aim of this study is to seek indicative data on aspects of immunity likely to be affected by neonatal vitamin A supplementation. The objective of this trial is to test whether human neonatal vitamin A supplementation modulates immune function including improved thymic maturation in infancy and improved systemic immune responses to routine immunization.

Methods/design

In an area of moderate vitamin A deficiency in a peri-urban area of The Gambia, 200 mother–infant pairs were enrolled in a double-blind randomised controlled trial. Within 48 hours of birth, neonates were randomised with stratification by birth weight and sex to receive either an oral dose of 50,000 IU vitamin A or placebo. Expanded Programme of Immunisation birth vaccinations were administered after supplementation, with subsequent vaccinations administered at 8, 12 and 16 weeks of age. A range of immunological outcomes were examined up to 17 weeks of age, with additional morbidity and anthropometry follow-up carried out throughout the first year of life. The primary endpoint of this trial is the frequency of circulating T regulatory (T_reg) cells expressing gut homing receptors in infants at 17 week post-supplementation, with secondary outcomes including thymus maturation and B cell immune responses.

Discussion

Indicative immunological data from this trial (and its Bangladeshi counterpart), will complement the larger randomised controlled trials (conducted in India, Tanzania and Ghana), on the effectiveness and safety of neonatal vitamin A supplementation in improving infant survival. Combined these trials, in addition to the existing trials, will inform policy.

Trial registration

clinicaltrials.gov NCT01476358

【 授权许可】

   
2014 McDonald et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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