ArticlesEffectiveness of an early supplementation scheme of high-dose vitamin A versus standard WHO protocol in Gambian mothers and infants: a randomised controlled trial
Introduction
Meta-analyses show that vitamin A supplementation of preschool children in vitamin A deficient populations reduces all-cause mortality by 30%.1, 2 Supplementation with a standard WHO protocol (200 000 IU to mothers early postpartum, 100 000 IU to infants at 9 months, and 200 000 IU at 4–6 month intervals thereafter) has been adopted as national policy in most developing countries.3, 4
Initially, supplements were not given to young infants because of concerns about possible toxicity.5 However, WHO sponsored a multi-centre trial of 200 000 IU of vitamin A to mothers early postpartum, and 25 000 IU to infants at their three initial expanded programme on immunisation (EPI) visits at 6, 10, and 14 weeks.6 The trial did not detect toxicity and did not show any increase in plasma vitamin A, growth, or morbidity. This disappointing result prompted the International Vitamin A Consultative Group (IVACG) to recommend a higher dosing schedule of two 200 000 IU doses to mothers early postpartum, and 50 000 IU to infants at their EPI visits.7 Doses were calculated to build up body stores in babies who were born to vitamin A deficient mothers.8 The proposed high-dose regimen has not been tested formally, and a recent trial has suggested that lower doses than WHO standard regimen might preferentially reduce mortality in older children (6 months to 5 years).9 This result highlights the need to understand better the mechanisms by which vitamin A exerts its effect on mortality.
We used a randomised double-blind controlled trial to compare the efficacy of the IVACG early high-dose protocol with that of the WHO protocol by the assessment of adverse events at dosing, maternal and infant vitamin A concentrations, mucosal integrity, growth and morbidity patterns, and measurements of infant immunity.
Section snippets
Study design
The study was done in Keneba and five surrounding villages in the West Kiang District of The Gambia. Descriptions of this area, with special reference to vitamin A status, have been published elsewhere.10, 11 All pregnant mothers were identified by the local mobile midwifery team and provisionally enrolled at 30 weeks' gestation. Recruitment of patients was completed at delivery after appropriate consent procedures, if a cord blood sample was successfully obtained and in the absence of these
Results
Of the 220 mother–infant pairs originally recruited, 197 completed the full protocol. The distribution and reasons for dropouts are shown in figure 1. Table 3 shows baseline characteristics of the infants. Inspection of adverse events yielded no episodes that indicated adverse reactions to vitamin A. There were two neonatal deaths in each group, two infant deaths in the high-dose group, and none in the WHO-dose group, but this difference was not significant. Figure 2 illustrates the growth of
Discussion
The trial was powered to test for differential effect on a number of health-related outcomes, including growth, morbidity, acute-phase markers of subclinical infections, haematological and immune outcomes (haemoglobin and lymphocyte subpopulations), susceptibility of respiratory mucosa to colonisation and of gastric mucosa to infection, and the integrity of maternal mammary and infant gut epithelia. Overall, however, none of these outcomes had any additional benefit for the proposed high-dose
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