BMJ 1999;318:570-575 ( 27 February )

General Practice

Double blind, cluster randomised trial of low dose supplementation with vitamin A or beta  carotene on mortality related to pregnancy in Nepal

Editorial by Olsen

Keith P West Jr, professor, a Joanne Katz, professor, a Subarna K Khatry, project director, b Steven C LeClerq, research associate, a Elizabeth K Pradhan, research associate, a Sharada R Shrestha, deputy project director, b Paul B Connor, data systems coordinator, a Sanu M Dali, project obstetrician- gynaecologist, b Parul Christian, assistant scientist, a Ram P Pokhrel, chairman, c Alfred Sommer, dean, a on behalf of the NNIPS-2 Study Group.

a Johns Hopkins School of Hygiene and Public Health, Division of Human Nutrition, Room 2041, 615 N Wolfe Street, Baltimore, MD 21205, USA, b Nepal Nutrition Intervention Project-Sarlahi (NNIPS), Nepal Netra Jyoti Sangh, Nepal Eye Hospital Complex, PO Box 335, Tripureswor, Kathmandu, Nepal, c Nepal Netra Jyoti Sangh, Nepal Eye Hospital Complex, PO Box 335, Tripureswor, Kathmandu

Correspondence to: Professor West kwest{at}jhsph.edu

Objective: To assess the impact on mortality related to pregnancy of supplementing women of reproductive age each week with a recommended dietary allowance of vitamin A, either preformed or as beta  carotene.
Design: Double blind, cluster randomised, placebo controlled field trial.
Setting: Rural southeast central plains of Nepal (Sarlahi district).
Subjects: 44 646 married women, of whom 20 119 became pregnant 22 189 times.
Intervention: 270 wards randomised to 3 groups of 90 each for women to receive weekly a single oral supplement of placebo, vitamin A (7000 µg retinol equivalents) or beta  carotene (42 mg, or 7000 µg retinol equivalents) for over 31/2 years.
Main outcome measures: All cause mortality in women during pregnancy up to 12 weeks post partum (pregnancy related mortality) and mortality during pregnancy to 6 weeks postpartum, excluding deaths apparently related to injury (maternal mortality).
Results: Mortality related to pregnancy in the placebo, vitamin A, and beta  carotene groups was 704, 426, and 361 deaths per 100 000 pregnancies, yielding relative risks (95% confidence intervals) of 0.60 (0.37 to 0.97) and 0.51 (0.30 to 0.86). This represented reductions of 40% (P<0.04) and 49% (P<0.01) among those who received vitamin A and beta  carotene. Combined, vitamin A or beta  carotene lowered mortality by 44% (0.56 (0.37 to 0.84), P<0.005) and reduced the maternal mortality ratio from 645 to 385 deaths per 100 000 live births, or by 40% (P<0.02). Differences in cause of death could not be reliably distinguished between supplemented and placebo groups.
Conclusion: Supplementation of women with either vitamin A or beta  carotene at recommended dietary amounts during childbearing years can lower mortality related to pregnancy in rural, undernourished populations of south Asia.


Key messages

  • Maternal vitamin A deficiency, evident as night blindness or low serum retinol concentration during pregnancy, is widely prevalent in rural south Asia

  • In Nepal, women of reproductive age who were given 7000 µg retinol equivalents of vitamin A on a weekly basis showed a reduction in mortality related to pregnancy of 40%

  • Weekly dosing with 42 mg beta  carotene (also providing 7000 µg retinol equivalents) lowered their mortality by 49%

  • Preventing maternal vitamin A deficiency in rural South Asia can lower the risk of mortality of women during and after pregnancy




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Rapid Responses:

Read all Rapid Responses

The medical treatment of malnutrition is food
Mary Black
bmj.com, 3 Mar 1999 [Full text]
There Are No Magic Pills For Reducing Pregnancy Related Mortality
H P S Sachdev
bmj.com, 17 Mar 1999 [Full text]
Authors' response
Keith P West
bmj.com, 9 Jul 1999 [Full text]
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