Objective: To investigate whether monthly administration of vitamin A at routine immunisation produces any side-effects, and to examine the effect of this supplementation on the vitamin A nutrition status of infants.
Design: A double-blind randomised placebo-controlled clinical trial.
Setting: Immunisation clinic of a large diarrhoea treatment centre.
Subjects: Infants aged 6-17 weeks who will receive their first diphtheria-pertussis-tetanus/oral polio vaccine (DPT/OPV) dose.
Methods: Infants were randomly assigned to receive either 25,000 IU vitamin A or placebo. Three such doses were given with each immunisation dose at monthly intervals. Infants were examined by a physician before and during 24 h after the doses and any signs of toxicity were recorded. Venous blood was drawn at entry and 1 month after the 3rd dose for retinol assay.
Results: One hundred and one infants received vitamin A and 98 received placebo. Decreased feeding, irritability, diarrhoea, and vomiting were comparable between the two groups. In the vitamin A group five infants developed bulging fontanelle; three of them developed it once (after 1st, 2nd and 3rd dose respectively), one developed it twice (after both the 2nd and 3rd dose), and the other infant after all three doses. In the placebo group a single child developed bulging fontanelle after the 3rd dose. In all the cases the bulging disappeared within 48 h of onset except in one infant, in whom it subsided at 60 h. The total bulging episodes in the vitamin A and placebo groups were 8 and 1 respectively (RR = 7.7; P < 0.04). However, none of these infants had irritability. At entry fasting retinol level was < 10 micrograms/dl in 35% infants and in 87% infants it was < 20 micrograms/dl. After the third dose fasting retinol level was marginally better in the vitamin A group (mean +/- s.d.: 21.9 +/- 8.2 vs 19.2 +/- 7.8; P = 0.05). However, 47% infants receiving supplementation still had serum retinol level <20 micrograms/dl.
Conclusion: The results suggest that administration of 25,000 IU of vitamin A in young infants along with routine immunisations, though associated with increased incidence of transient bulging fontanelle without any associated adverse signs or symptoms, may still be inadequate to prevent deficiency in this population.
Sponsorship: This study was funded by the United States Agency for International Development (USAID) under grant no. DPE-5986-A-1009-00 with the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B). The ICDDR,B is supported by countries and agencies which share its concern for the health problems of developing countries.