Micronutrient fortification to improve growth and health of maternally HIV-unexposed and exposed Zambian infants: a randomised controlled trial

Abstract

Background: The period of complementary feeding, starting around 6 months of age, is a time of high risk for growth faltering and morbidity. Low micronutrient density of locally available foods is a common problem in low income countries. Children of HIV-infected women are especially vulnerable. Although antiretroviral prophylaxis can reduce breast milk HIV transmission in early infancy, there are no clear feeding guidelines for after 6 months. There is a need for acceptable, feasible, affordable, sustainable and safe (AFASS by WHO terminology) foods for both HIV-exposed and unexposed children after 6 months of age.

Methods and findings: We conducted in Lusaka, Zambia, a randomised double-blind trial of two locally made infant foods: porridges made of flour composed of maize, beans, bambaranuts and groundnuts. One flour contained a basal and the other a rich level of micronutrient fortification. Infants (n = 743) aged 6 months were randomised to receive either regime for 12 months. The primary outcome was stunting (length-for-age Z<-2) at age 18 months. No significant differences were seen between trial arms overall in proportion stunted at 18 months (adjusted odds ratio 0.87; 95% CI 0.50, 1.53; P = 0.63), mean length-for-age Z score, or rate of hospital referral or death. Among children of HIV-infected mothers who breastfed <6 months (53% of HIV-infected mothers), the richly-fortified porridge increased length-for-age and reduced stunting (adjusted odds ratio 0.17; 95% CI 0.04, 0.84; P = 0.03). Rich fortification improved iron status at 18 months as measured by hemoglobin, ferritin and serum transferrin receptors.

Conclusions: In the whole study population, the rich micronutrient fortification did not reduce stunting or hospital referral but did improve iron status and reduce anemia. Importantly, in the infants of HIV-infected mothers who stopped breastfeeding before 6 months, the rich fortification improved linear growth. Provision of such fortified foods may benefit health of these high risk infants.

Trial registration: Controlled-Trials.com ISRCTN37460449.

Figure 1. Flow diagram of participants through the study.

All recruited children were included in the analysis of hospital referral and death. Two children in the richly fortified group who were seen at 18 months had missing length data at that visit and are not included in the analysis of stunting. ¹Reasons for withdrawal up to 12m: basal porridge (N = 46): moved away (15), family against (10), problems with porridge (2), would not say/other (19); richly fortified porridge (N = 52): moved away (18), family against (10), would not say/other (24). ²Reasons for withdrawal from 12–18m: basal porridge (N = 30): moved away (13), family against (1), problems with porridge (2), would not say/other (14); richly fortified porridge (N = 27): moved away (8), family against (1), problems with porridge (1), would not say/other (17).

Figure 2. Kaplan-Meier estimates of survivor function for hospital referral or death.

All 12 deaths occurred in hospital. Dropouts were censored at the date of last project visit. Admitted children became at risk again on discharge from hospital. In Figure 2b. ‘neg’ = HIV-uninfected mother; ‘pos’ = HIV-infected mother; HIV-unknown women are not included. There were no significant differences by treatment either overall (P = 0.31) or within maternal HIV status groups (P = 0.98 for children of HIV-negative mothers and P = 0.07 for children of HIV-positive mothers).