Filteau S, Baisley K, Chisenga M, Kasonka L, Gibson RS; CIGNIS Study Team. Provision of micronutrient-fortified food from 6 months of age does not permit HIV-exposed uninfected Zambian children to catch up in growth to HIV-unexposed children: a randomized controlled trial. J Acquir Immune Defic Syndr. 2011 56(2):166-75.
In HIV-exposed but uninfected (HIV-EU) children, growth is poorer and mortality is higher than that of HIV-unexposed children.(1) The reasons for this are not clear but may be due to lower birth weight,(2) varied breastfeeding practices, dietary factors, exposure to antiretrovirals during breastfeeding or during prevention of mother-to-child transmission (PMTCT) efforts, or to an increased number of infections. Some studies have shown that these children catch up in growth, while others do not. (2, 3) Primary results from the Chilenje Infant Growth, Nutrition and Infection Study (CIGNIS) have been reported(4) and showed that the fortified diet improved hemoglobin and iron status of all children and reduced stunting at 18 months among non-breastfed children of HIV-infected mothers. Although this study focused on children who were HIV-exposed, many other studies outside the HIV literature have indicated that micronutrients alone may not be sufficient for growth improvement in children with significant early growth impairment, particularly stunting, and in cases in which the general food supply is inadequate. A comprehensive review of multiple interventions for undernourished and malnourished children indicated that the following showed the most benefit: food supplementation (protein and calories) for populations with inadequate food supply; consistent breastfeeding; and iron and zinc supplementation to pregnant mothers to reduce low birth weight infants.(5) If food supply is adequate, the micronutrients including iron, zinc, Vitamin A and iodized salt have been shown to improve growth among infants. A recently updated Cochrane review evaluated whether micronutrient supplements are effective in reducing mortality and morbidity among HIV infected children and adults. Of 30 trials reviewed, only one showed improved early child growth in African children provided with multiple micronutrient supplements.(6)
To determine whether providing HIV-EU infants with a diet supplemented with micronutrients, compared to a diet with similar calories but with fewer micronutrients, can improve growth measures to the same extent as in HIV-unexposed infants.
Chilenje, Lusaka, Zambia. Infants who were six months old, in generally good health and whose mother's HIV status were known.
This trial was part of CIGNIS, with detailed methods and results on the prevalence of stunting at 18 months already published.(4) Enrolled children were randomized to two flours based on maize beans, bambara nuts and groundnuts; both flours contained recommended macronutrient content; the fortified flour contained micronutrients recommended by the WHO for infants 9-11 months old with low breastmilk intake.(7) Porridge and breastmilk consumption was measured every month, along with anthropometric measurements every three months up to 18 months (12 months of follow-up). Analysis was restricted to children who completed 18 months of follow-up and who remained HIV negative. Random effects regression was used to account for repeated measures over time.
A total of 743 infants were recruited and randomized, with analysis among 507 who remained HIV uninfected and with known HIV status of mother (12 died, 155 withdrew from the study, 13 became HIV infected). Among those receiving the basal porridge (n=256), 190 were HIV-unexposed, and 66 were HIV-exposed; among those receiving the fortified porridge (n=251), 192 were HIV-unexposed, and 59 were HIV-exposed. At baseline, all anthropometric measures were significantly lower among HIV-EU children; almost all HIV uninfected mothers were still breastfeeding (97%), but a large proportion of HIV infected women either had never breastfed (25%) or had stopped before six months (34%). During the study, consumption of the porridge was higher among children whose mothers were HIV-infected and/or were not breastfeeding. During follow-up, there were decreases in length, weight, head and MUAC Z-scores, and increases in skinfold Z-scores in both HIV-EU and HIV unexposed children. In adjusted analysis, there was a slight increase in mean head circumference and weight-for-age Z-scores in the fortified arm but only in children who were HIV unexposed. Adjusting for treatment arm, socio-economic status (SES), breastfeeding, and gender, the mean head and MUAC Z-scores were significantly lower in HIV-EU compared with HIV unexposed children. At six and 12 months, sub-scapular skin-fold Z-scores were lower among HIV-EU children, but at 18 months there was no significant different between children in different maternal HIV groups. Among both HIV-EU and HIV-unexposed children, the children who were still breastfeeding at later visits had lower measures of length and weight than those who were no longer breastfeeding.
The richly fortified diet which provided additional micronutrients improved the weight and head circumference of the HIV-unexposed children but did not benefit growth measures among the HIV-EU children. The authors indicate that the overall stunting rate at 18 months was 20%, which was less than the prevalence of stunting of 36% among Chilenje clinic children who were not part of the CIGNIS study.
This was a high quality RCT; however, the authors used sequential allocation to arms rather than actual randomization. It was not stated whether the study involved blinding or whether intention-to-treat analysis was employed.
The main implications for this study are that there are multiple factors which contribute to reduced growth, particularly in settings in which all children are below international standards by six months. Supplemental feeding with fortified cereals and micronutrients is not sufficient, when started at this age. Whether children were HIV-exposed or unexposed, or received the basal or the richly fortified diet, all had some reduction in all growth measurements over time, although these reductions were lowest for those who had the rich diet and whose mothers were not HIV-infected. However, the consumption of porridge by infants was lower than the estimated consumption used as the basis for the micronutrient concentrations in the fortified diet, and so supplementary feeding might not have been adequate. Data from this study suggest that more prolonged breastfeeding (to 18 months) if not supplemented appropriately, may also result in some growth impairment. Probably the best interventions to improve growth and reduce stunting involve better health and nutrition of the mother to reduce low birth weight, encouraging early breastfeeding, and overcoming impoverished conditions in the community that primarily affect women.
- Bailey RC, Kamenga MC, Nsuami MJ, et al. Growth of children according to maternal and child HIV, immunological and disease characteristics: a prospective cohort study in Kinshasa, Democratic Republic of Congo. Int J Epidemiol. 1999;28:532-540.
- Lepage P, Msellati P, Hitimana DG, et al. Growth of human immunodeficiency type 1-infected and uninfected children: a prospective cohort study in Kigali, Rwanda, 1988 to 1993. Pediatr Infect Dis J. 1996;15:479-485.
- Makasa M, Kasonka L, Chisenga M, et al. Early growth of infants of HIV-infected and uninfected Zambian women. Trop Med Int Health. 2007;12:594-602.
- Chilenje Infant Growth, Nutrition and Infection (CIGNIS) Study Team. Micronutrient fortification to improve growth and health of maternally HIV-unexposed and exposed Zambian infants: a randomised controlled trial. PLoS One. 2010 Jun 17;5(6):e11165. PubMed PMID: 20567511;
- Bhutaa, Z et al. Maternal and Child Undernutrition 3; What works? Interventions for maternal and child undernutrition and survival. Lancet 2008; 371: 417-40.
- Irlam JH, Visser MM, Rollins NN, Siegfried N. Micronutrient supplementation in children and adults with HIV infection. Cochrane Database Syst Rev. 2010 8;12.
- World Health Organization. The WHO Child Growth Standards.
- Dewey K, Brown K. Update on technical issues concerning complementary feeding of young children in developing countries and implications for intervention programs. Special issue based on a World Health Organization expert consultation on complementary feeding. Food Nutr Bull. 2003;24:5-28.