Vitamin supplementation for prevention of mother-to-child transmission of HIV and pre-term delivery: a systematic review of randomized trial including more than 2800 women

AIDS Research and Therapy

Edward J Mills²  Ping Wu¹  Dugald Seely³  Gordon H Guyatt² 

[1] Division of Clinical Epidemiology, Canadian College Of Naturopathic Medicine, Toronto, Canada

[2] Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada

[3] Hospital for Sick Children, University of Toronto, Toronto, Canada

关键词: Preterm delivery;    Mother-to-child transmission;    Vitamin A;    Vitamins;    HIV;   

Others  :  790105
DOI  :  10.1186/1742-6405-2-4

 received in 2005-01-20, accepted in 2005-05-06,  发布年份 2005

【 摘 要 】

Background

Observational studies have suggested that low serum vitamin levels are associated with increased mother-to-child transmission (MTCT) of HIV and increased preterm delivery. We aimed to determine the efficacy of vitamins on the prevention of MTCT and preterm delivery by systematically reviewing the available randomized controlled trials [RCTs]. We conducted systematic searches of 7 electronic databases. We extracted data from the RCTs independently, in duplicate.

Results

We included 4 trials in our review. Of the three trials on Vitamin A, two suggested no difference in MTCT, while the third and largest trial (n = 1078) suggested an increased risk of MTCT (Relative Risk 1.35, 95% Confidence Interval [CI], 1.11–1.66, P = 0.009). Two of the vitamin A trials addressed the impact of supplementation on pre-term delivery; one suggested a benefit (RR 0.65, 95% CI, 0.44–0.94) and the other no difference. All three vitamin A trials found no significant effect on infant mortality at 1 year. Of the two trials that looked at multivitamin use, only one addressed the prevention of MTCT, and found a non-significant RR of 1.04 (95% CI, 0.82–1.32). Two of the multivitamin trials found no significant effects on pre-term delivery. The single multivitamin trial examining children's mortality at 1 year yielded a non-significant RR of 0.91 (95% CI, 0.17–1.17).

Conclusion

Randomized trials of vitamins to prevent MTCT have yielded conflicting results without strong evidence of benefit and have failed to exclude the possibility of harm.

【 授权许可】

   
2005 Mills et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]UNAIDS: Report on the global AIDS epidemic. 2004.
• [2]Brocklehurst P: Interventions for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database Syst Rev 2002, CD000102.
• [3]Brocklehurst P, Volmink J: Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database Syst Rev 2002, CD003510.
• [4]Sherr L: Preventing HIV transmission during pregnancy and delivery: a review. AIDS STD Health Promot Exch 1997, 4-6.
• [5]Semba RD, Miotti PG, Chiphangwi JD, Dallabetta G, Yang LP, Saah A, Hoover D: Maternal vitamin A deficiency and infant mortality in Malawi. J Trop Pediatr 1998, 44(4):232-234.
• [6]Semba RD, Miotti PG, Chiphangwi JD, Liomba G, Yang LP, Saah AJ, Dallabetta GA, Hoover DR: Infant mortality and maternal vitamin A deficiency during human immunodeficiency virus infection. Clin Infect Dis 1995, 21(4):966-972.
• [7]Semba RD, Miotti PG, Chiphangwi JD, Saah AJ, Canner JK, Dallabetta GA, Hoover DR: Maternal vitamin A deficiency and mother-to-child transmission of HIV-1. Lancet 1994, 343(8913):1593-1597.
• [8]Greenberg BL, Semba RD, Vink PE, Farley JJ, Sivapalasingam M, Steketee RW, Thea DM, Schoenbaum EE: Vitamin A deficiency and maternal-infant transmissions of HIV in two metropolitan areas in the United States. Aids 1997, 11(3):325-332.
• [9]Dreyfuss ML, Fawzi WW: Micronutrients and vertical transmission of HIV-1. Am J Clin Nutr 2002, 75(6):959-970.
• [10]Fawzi WW, Hunter DJ: Vitamins in HIV disease progression and vertical transmission. Epidemiology 1998, 9(4):457-466.
• [11]John GC, Nduati RW, Mbori-Ngacha D, Overbaugh J, Welch M, Richardson BA, Ndinya-Achola J, Bwayo J, Krieger J, Onyango F, Kreiss JK: Genital shedding of human immunodeficiency virus type 1 DNA during pregnancy: association with immunosuppression, abnormal cervical or vaginal discharge, and severe vitamin A deficiency. J Infect Dis 1997, 175(1):57-62.
• [12]Filteau SM, Rollins NC, Coutsoudis A, Sullivan KR, Willumsen JF, Tomkins AM: The effect of antenatal vitamin A and beta-carotene supplementation on gut integrity of infants of HIV-infected South African women. J Pediatr Gastroenterol Nutr 2001, 32(4):464-470.
• [13]Fawzi WW, Msamanga GI, Spiegelman D, Urassa EJ, McGrath N, Mwakagile D, Antelman G, Mbise R, Herrera G, Kapiga S, Willett W, Hunter DJ: Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania. Lancet 1998, 351(9114):1477-1482.
• [14]Meade MO, Richardson WS: Selecting and appraising studies for a systematic review. Ann Intern Med 1997, 127(7):531-537.
• [15]Altman DG: Systematic reviews of evaluations of prognostic variables. In: Systematic reviews in Healthcare, Meta-analysis in context 2001, BMJ:London.
• [16]Higgins JP, Thompson SG: Quantifying heterogeneity in a meta-analysis. Stat Med 2002, 21(11):1539-1558.
• [17]Coutsoudis A, Pillay K, Spooner E, Kuhn L, Coovadia HM: Randomized trial testing the effect of vitamin A supplementation on pregnancy outcomes and early mother-to-child HIV-1 transmission in Durban, South Africa. South African Vitamin A Study Group. Aids 1999, 13(12):1517-1524.
• [18]Kumwenda N, Miotti PG, Taha TE, Broadhead R, Biggar RJ, Jackson JB, Melikian G, Semba RD: Antenatal vitamin A supplementation increases birth weight and decreases anemia among infants born to human immunodeficiency virus-infected women in Malawi. Clin Infect Dis 2002, 35(5):618-624.
• [19]Fawzi WW, Msamanga GI, Hunter D, Renjifo B, Antelman G, Bang H, Manji K, Kapiga S, Mwakagile D, Essex M, Spiegelman D: Randomized trial of vitamin supplements in relation to transmission of HIV-1 through breastfeeding and early child mortality. Aids 2002, 16(14):1935-1944.
• [20]Friis H, Gomo E, Nyazema N, Ndhlovu P, Krarup H, Kaestel P, Michaelsen KF: Effect of multimicronutrient supplementation on gestational length and birth size: a randomized, placebo-controlled, double-blind effectiveness trial in Zimbabwe. Am J Clin Nutr 2004, 80(1):178-184.
• [21]Joubert G, Steinberg H, van der Ryst E, Chikobvu P: Consent for participation in the Bloemfontein vitamin A trial: how informed and voluntary? Am J Public Health 2003, 93(4):582-584.
• [22]Fawzi WW, Msamanga G, Hunter D, Urassa E, Renjifo B, Mwakagile D, Hertzmark E, Coley J, Garland M, Kapiga S, Antelman G, Essex M, Spiegelman D: Randomized trial of vitamin supplements in relation to vertical transmission of HIV-1 in Tanzania. J Acquir Immune Defic Syndr 2000, 23(3):246-254.
• [23]Gates S, Brocklehurst P: How should randomised trials including multiple pregnancies be analysed? Bjog 2004, 111(3):213-219.
• [24]Fawzi W, Msamanga G, Antelman G, Xu C, Hertzmark E, Spiegelman D, Hunter D, Anderson D: Effect of prenatal vitamin supplementation on lower-genital levels of HIV type 1 and interleukin type 1 beta at 36 weeks of gestation. Clin Infect Dis 2004, 38(5):716-722.
• [25]Fawzi WW, Msamanga GI, Spiegelman D, Wei R, Kapiga S, Villamor E, Mwakagile D, Mugusi F, Hertzmark E, Essex M, Hunter DJ: A randomized trial of multivitamin supplements and HIV disease progression and mortality. N Engl J Med 2004, 351(1):23-32.
• [26]Fawzi W: Micronutrients and human immunodeficiency virus type 1 disease progression among adults and children. Clin Infect Dis 2003, 37 Suppl 2:S112-6.
• [27]McClelland RS, Baeten JM, Overbaugh J, Richardson BA, Mandaliya K, Emery S, Lavreys L, Ndinya-Achola JO, Bankson DD, Bwayo JJ, Kreiss JK: Micronutrient Supplementation Increases Genital Tract Shedding of HIV-1 in Women: Results of a Randomized Trial. J Acquir Immune Defic Syndr 2004, 37(5):1657-1663.
• [28]van Lettow M, Harries AD, Kumwenda JJ, Zijlstra EE, Clark TD, Taha TE, Semba RD: Micronutrient malnutrition and wasting in adults with pulmonary tuberculosis with and without HIV co-infection in Malawi. BMC Infect Dis 2004, 4(1):61. BioMed Central Full Text
• [29]Kupka R, Msamanga GI, Spiegelman D, Morris S, Mugusi F, Hunter DJ, Fawzi WW: Selenium status is associated with accelerated HIV disease progression among HIV-1-infected pregnant women in Tanzania. J Nutr 2004, 134(10):2556-2560.
• [30]WMA: Ethical Principles for Medical Research Involving Human Subjects. WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI 2004, http://www.wma.net/e/policy/b3.htm:(Accessed March 25, 2005).
• [31]Brocklehurst P, French R: The association between maternal HIV infection and perinatal outcome: a systematic review of the literature and meta-analysis. Br J Obstet Gynaecol 1998, 105(8):836-848.
• [32]Nations U: Universal Declaration of Human Rights. United Nations 1998., Article 25