Randomised trial to assess benefits and safety of vitamin A supplementation linked to immunisation in early infancy. WHO/CHD Immunisation-Linked Vitamin A Supplementation Study Group.

BACKGROUND

The benefits and safety of vitamin A supplementation linked to immunisation in infancy need to be assessed before it can be widely recommended. We assessed the safety and benefits of maternal postpartum and infant vitamin A supplementation administered with each of the three diphtheria-tetanus-pertussis (DPT) and poliomyelitis immunisations and with a fourth dose with measles immunisation.

METHODS

From January, 1995, we enrolled 9424 mother-infant pairs from Ghana, India, and Peru in this randomised, double-blind, placebo-controlled trial. 4716 mothers of infants in the vitamin A group received 200000 IU vitamin A, and their infants were given 25000 IU vitamin A with each of the first three doses of DPT/poliomyelitis immunisation at 6, 10, and 14 weeks. In the control group, 4708 mothers and their infants received placebo at the same times. At 9 months, with measles immunisation, infants in the vitamin A group were given a further dose of 25000 IU and those in the control group received 100000 IU vitamin A. Infants were followed up to age 12 months. The primary outcome measures were vitamin A status, signs of acute toxic effects, anthropometric indicators, and severe morbidity. Analysis was by intention to treat.

FINDINGS

3933 (93%) of the eligible 4212 infants on vitamin A and 3938 (93%) of the eligible 4227 controls received all four study doses. At the 6-month follow-up, there was a small decrease in vitamin A deficiency in the vitamin A group compared with controls (serum retinol < or =0.70 micromol/L 101 [29.9%] vs 122 [37.1%; 95% CI of the difference -14.3% to -0.2%]). This effect was no longer apparent at 9 and 12 months. There were no significant between-group differences in mortality throughout the study. The rate ratio to compare all deaths up to age 9 months in the two groups was 0.96 (95% CI 0.73 to 1.27). Fewer than 1% of the infants had bulging fontanelle. The intervention had no effect on anthropometric status, or on overall or severe morbidity.

INTERPRETATION

The trial confirmed the safety of the intervention, but shows no sustained benefits in terms of vitamin A status beyond age 6 months or infant morbidity.