Randomised trial to assess benefits and safety of vitamin A supplementation linked to immunisation in early infancy

J. Martines, P. Arthur, R. Bahl, M. K. Bhan, B. R. Kirkwood, Lawrence Hale Moulton, M. E. Panny, Malathi Ram, B. Underwood

Research output: Contribution to journalArticle

Abstract

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 200,000 IU vitamin A, and their infants were given 25,000 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 25,000 IU and those in the control group received 100,000 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 ≤ 0 70 μmol/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.

Original languageEnglish (US)
Pages (from-to)1257-1263
Number of pages7
JournalThe Lancet
Volume352
Issue number9136
DOIs
StatePublished - Oct 17 1998
Externally publishedYes

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Vitamin A
Immunization
Safety
Mothers
Diphtheria
Whooping Cough
Tetanus
Measles
Poliomyelitis
Morbidity
Placebos
Vitamin A Deficiency
Control Groups
Ghana
Peru
Intention to Treat Analysis
Poisons
Postpartum Period
India
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Medicine(all)

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Randomised trial to assess benefits and safety of vitamin A supplementation linked to immunisation in early infancy. / Martines, J.; Arthur, P.; Bahl, R.; Bhan, M. K.; Kirkwood, B. R.; Moulton, Lawrence Hale; Panny, M. E.; Ram, Malathi; Underwood, B.

In: The Lancet, Vol. 352, No. 9136, 17.10.1998, p. 1257-1263.

Research output: Contribution to journalArticle

Martines, J, Arthur, P, Bahl, R, Bhan, MK, Kirkwood, BR, Moulton, LH, Panny, ME, Ram, M & Underwood, B 1998, 'Randomised trial to assess benefits and safety of vitamin A supplementation linked to immunisation in early infancy', The Lancet, vol. 352, no. 9136, pp. 1257-1263. https://doi.org/10.1016/S0140-6736(98)02487-8
Martines, J. ; Arthur, P. ; Bahl, R. ; Bhan, M. K. ; Kirkwood, B. R. ; Moulton, Lawrence Hale ; Panny, M. E. ; Ram, Malathi ; Underwood, B. / Randomised trial to assess benefits and safety of vitamin A supplementation linked to immunisation in early infancy. In: The Lancet. 1998 ; Vol. 352, No. 9136. pp. 1257-1263.
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AU - Bahl, R.

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AU - Kirkwood, B. R.

AU - Moulton, Lawrence Hale

AU - Panny, M. E.

AU - Ram, Malathi

AU - Underwood, B.

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N2 - 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 200,000 IU vitamin A, and their infants were given 25,000 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 25,000 IU and those in the control group received 100,000 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 ≤ 0 70 μmol/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.

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