Randomized placebo-controlled clinical trial of the effect of a single high dose or daily low doses of vitamin A on the morbidity of hospitalized, malnourished children.

The effect of high-dose vitamin A supplementation on recovery from morbidity and on recovery from nosocomial morbidity of hospitalized children has been poorly studied and results are conflicting. The effect of daily, low doses has never been assessed. We investigated the effect of a single high dose and daily, low doses of vitamin A on diarrhea, acute lower respiratory tract infections (ALRIs), and all-cause fevers in 900 hospitalized preschool-age children in the Democratic Republic of Congo in a randomized, double-blind, placebo-controlled clinical trial. The high-dose treatment group received 200,000 IU vitamin A (100,000 IU if aged <12 mo) orally on the day of admission, the low-dose treatment group received 5000 IU vitamin A/d until discharge. Data on all-cause morbidity were collected daily. Mortality rates were not significantly different among the 3 groups. High-dose vitamin A supplementation had no significant effect on the duration of moderate or severe diarrhea nor on the duration and incidence of ALRIs and all-cause fevers. Children in the high-dose group with no edema had an increased risk of severe nosocomial diarrhea (relative risk: 2.42; 95% CI: 1.15, 5.11). Low-dose vitamin A supplementation significantly reduced the incidence of severe diarrhea in severely malnourished children (relative risk: 0.21; 95% CI: 0.07, 0.62) but showed no significant effect on the duration of moderate or severe diarrhea or on the duration and incidence of ALRIs and all-cause fevers. Supplementation with high doses of vitamin A did not reduce morbidity in this population of malnourished and subclinically vitamin A-deficient children; daily, low doses appeared more beneficial for severely malnourished children.