Multiple micronutrient supplements for HIV-infected pregnant women
Biological, behavioural and contextual rationale
Supplementation with iron and folate during pregnancy has documented benefits1. There is interest in extending this supplementation to multiple micronutrients since:
- micronutrient deficiencies often co-exist
- other maternal micronutrient deficiencies may adversely affect maternal and infant health
- pregnancy is a period with fairly good access to health care so multiple micronutrients can be given and monitored easily and cheaply.
Multiple micronutrient supplementation in pregnancy for all women is being reviewed elsewhere and there is a Cochrane review2. Micronutrients have a wide range of functions. More than one micronutrient may support a single function, e.g. antioxidant defence, and a single micronutrient may act in more than one role, e.g. iron is involved in both oxygen transport and immune function. Much of the mechanistic research on single micronutrients has been conducted in animal or cell models which may not be readily applicable to the usual human situation of multiple coexisting deficiencies. On the other hand, multiple micronutrient intervention studies do not permit easy identification of the mechanism of any effects3.
This article is concerned with HIV-infected women who may require higher doses of multiple micronutrients than uninfected women. The high prevalence of HIV infection4, particularly in Africa where micronutrient deficiencies are also prevalent5, is well recognized. Micronutrient roles likely to be important for the health of HIV-infected women and their infants are immune functions, antioxidant activity, maintenance of intestinal integrity, placental functions, and promotion of growth and tissue repair.
The benefits seen in a series of studies from Tanzania using high doses (2–20 times the recommended daily allowance)6–8 and single recommended daily allowance doses 9 of vitamins B, C and E to pregnant women and the greater prevalence and severity of multiple micronutrient deficiencies in HIV-infected populations10,11, may suggest increased requirements of micronutrients for HIV-infected women. The Tanzanian trials did not include any minerals except iron; whereas the researchers argued why these were not needed in their population, it is unclear whether the supplements used in Tanzania are optimal for all populations.
There are some concerns about adverse effects of multiple micronutrient supplementation. Among non-HIV-infected Nepalese women, multiple micronutrient supplements increased birth weight but may have increased perinatal mortality12 although the increased mortality was not seen in a larger Indonesian study13. In another treatment arm of the Tanzanian trial of HIV-infected women, vitamin A was shown to increase HIV transmission through breastfeeding14. There is also a suggestion that high levels of body iron may have adverse effects in HIV infection15, similar to effects in malaria infection16. The issues of benefits and possible harms of multiple micronutrient interventions need to be investigated further in multicentre trials.
Most trials of multiple micronutrient supplements for people with HIV, including those in pregnant Tanzanian women, have been conducted before the roll out of antiretroviral therapy (ART) in Africa and Asia17, thus results regarding both efficacy and safety may not be relevant to the current context. Furthermore, recent changes in recommendations for infant feeding by HIV-infected mothers18 will also change the context by resulting in more women breastfeeding longer and more women or infants receiving ART. It is recognized that it will take time for recommendations of prolonged ART to be implemented in some areas and also that there remain areas where HIV and CD4 testing are still not possible. Where such testing is available and ART is provided, it will be simple to also provide multiple micronutrient supplements during pregnancy and breastfeeding. One issue which will need to be considered is the pill burden of HIV-infected women taking both ART and multiple micronutrients which may induce confusion or lack of compliance.
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8 Fawzi WW et al. A randomized trial of multivitamin supplements and HIV disease progression and mortality. New England Journal of Medicine, 2004, 351(1):23–32.
9 Kosuke K et al. A randomized trial to determine the optimal dosage of multivitamin supplements to reduce adverse pregnancy outcomes among HIV-infected women in Tanzania. American Journal of Clinical Nutrition, 2010, 91:391–7.
10 Papathakis PC et al. Micronutrient status during lactation in HIV-infected and HIV-uninfected South African women during the first 6 mo after delivery. American Journal of Clinical Nutrition, 2007, 85(1):182–92.
11 Tang AM et al. Micronutrients: current issues for HIV care providers. AIDS, 2005, 19(9):847–61.
12 Christian P et al. Antenatal micronutrient supplements in Nepal. The Lancet, 2005, 366(9487):711–2.
13 Shankar AH et al. Effect of maternal multiple micronutrient supplementation on fetal loss and infant death in Indonesia: a double-blind cluster-randomised trial. The Lancet, 2008, 371(9608):215–27.
14 Fawzi WW et al. Randomized trial of vitamin supplements in relation to transmission of HIV-1 through breastfeeding and early child mortality. AIDS, 2002, 16(14):1935–44.
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16 Sazawal S et al. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. The Lancet, 2006, 367(9505):133–43.
17 Drain PK et al. Micronutrients in HIV-positive persons receiving highly active antiretroviral therapy. American Journal of Clinical Nutrition, 2007, 85(2):333–45.
18 New WHO recommendations on infant feeding in the context of HIV. Geneva, World Health Organization, 2009.
The named authors alone are responsible for the views expressed in this document.
Declarations of interests
Conflict of interest statements were collected from all named authors and no conflicts were identified.