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

Lancet. 1998 Oct 17;352(9136):1257-63.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage
  • Double-Blind Method
  • Female
  • Ghana
  • Humans
  • Immunization*
  • India
  • Infant
  • Infant, Newborn
  • Male
  • Measles Vaccine / administration & dosage
  • Milk, Human / metabolism
  • Peru
  • Poliovirus Vaccine, Inactivated / administration & dosage
  • Postpartum Period
  • Treatment Outcome
  • Vitamin A / administration & dosage*
  • Vitamin A / adverse effects
  • Vitamin A / blood
  • Vitamin A Deficiency / prevention & control*


  • Diphtheria-Tetanus-Pertussis Vaccine
  • Measles Vaccine
  • Poliovirus Vaccine, Inactivated
  • Vitamin A