A randomized clinical trial was conducted to examine the effect of antenatal vitamin A supplementation on vertical transmission of HIV, birth weight, and other health outcomes in Malawi. Preliminary analysis shows that cumulative vertical transmission rates were 27.3 percent in the vitamin A and 32.0 percent in the placebo group (p=0.25) by 12 months of age. At this time, greater than 99 percent of women were still breastfeeding their infants. The incidence of low birth weight (less that 2500 gms) was 14.0 percent and 21.1 percent in the vitamin A and placebo groups, respectively (p less than 0.03). Vitamin A significantly reduced low birth weight in a multivariate analysis controlling for maternal age, body mass index, and CD4+ count. During this study, preliminary studies were conducted to examine the relationship between mastitis, breastmilk HIV load, and vertical transmission. Mastitis is an inflammatory condition in the breast characterized by an opening of paracellular pathways in milk secretory glands. Serum-derived components such as sodium and inflammatory cells such as lymphocytes (presumably including HIV-infected lymphocytes and infectious virions) enter the breast milk. Breastmilk sodium levels are a sensitive indicator of mastitis. At 6 weeks post-delivery, 16.4 percent of women had an elevated breastmilk sodium level consistent with mastitis. Vertical transmission to 6 weeks of age was 45.4 percent among women with elevated breastmilk sodium versus 23.6 percent among women with normal breastmilk sodium (p less than 0.001). Elevated breastmilk sodium was associated with higher vertical transmission (O.R. 2.38, 95 percent C.I. 1.29-4.39, p less than 0.005), adjusting for maternal plasma HIV load. In a nested substudy, women with (cases) and without (control) elevated breastmilk sodium were matched by plasma HIV load and CD4+ lymphocyte count. Cases has a median breastmilk HIV load of 1765 copies/mL compared with undetectable load in controls (p less than 0.0001). Higher breastmilk HIV load was associated with higher vertical transmission (p less than 0.007). Mastitis appears to be an important risk factor for vertical transmission of HIV in breastfeeding populations. In the competing continuation, follow-up of mothers and infants in the clinical trial will be completed until the end of breastfeeding. The relationship between mastitis and breastmilk HIV load and the epidemiology and microbiology of mastitis will be examined in a new cohort of HIV-infected lactating women.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD032247-06
Application #
6387658
Study Section
Special Emphasis Panel (ZRG1-AARR-6 (01))
Program Officer
Nugent, Robert
Project Start
1995-07-01
Project End
2003-07-31
Budget Start
2001-08-01
Budget End
2003-07-31
Support Year
6
Fiscal Year
2001
Total Cost
$503,697
Indirect Cost
Name
Johns Hopkins University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Semba, Richard D; Ndugwa, Christopher; Perry, Robert T et al. (2005) Effect of periodic vitamin A supplementation on mortality and morbidity of human immunodeficiency virus-infected children in Uganda: A controlled clinical trial. Nutrition 21:25-31
Dancheck, Barbara; Nussenblatt, Veronique; Ricks, Michelle O et al. (2005) Breast milk retinol concentrations are not associated with systemic inflammation among breast-feeding women in Malawi. J Nutr 135:223-6
Semba, Richard D; Bloem, Martin W (2004) Measles blindness. Surv Ophthalmol 49:243-55
Semba, Richard D; de Pee, Saskia; Panagides, Dora et al. (2004) Risk factors for xerophthalmia among mothers and their children and for mother-child pairs with xerophthalmia in Cambodia. Arch Ophthalmol 122:517-23
van Lettow, Monique; Fawzi, Wafaie W; Semba, Richard D (2003) Triple trouble: the role of malnutrition in tuberculosis and human immunodeficiency virus co-infection. Nutr Rev 61:81-90
Semba, R D; de Pee, S; Panagides, D et al. (2003) Risk factors for nightblindness among women of childbearing age in Cambodia. Eur J Clin Nutr 57:1627-32
Semba, R D; Bloem, M W (2002) The anemia of vitamin A deficiency: epidemiology and pathogenesis. Eur J Clin Nutr 56:271-81
Clark, T D; Mmiro, F; Ndugwa, C et al. (2002) Risk factors and cumulative incidence of anaemia among human immunodeficiency virus-infected children in Uganda. Ann Trop Paediatr 22:11-7
Semba, R D; Yuniar, Y; Gamble, M V et al. (2002) Assessment of vitamin A status of preschool children in Indonesia using plasma retinol-binding protein. J Trop Pediatr 48:84-7
Kumwenda, Newton; Miotti, Paolo G; Taha, Taha E et al. (2002) Antenatal vitamin A supplementation increases birth weight and decreases anemia among infants born to human immunodeficiency virus-infected women in Malawi. Clin Infect Dis 35:618-24

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