Effect on longitudinal growth and anemia of zinc or multiple micronutrients added to vitamin A: a randomized controlled trial in children aged 6-24 months

Abstract

Background: The benefits of zinc or multiple micronutrient supplementations in African children are uncertain. African children may differ from other populations of children in developing countries because of differences in the prevalence of zinc deficiency, low birth weight and preterm delivery, recurrent or chronic infections such as HIV, or the quality of complementary diets and genetic polymorphisms affecting iron metabolism.The aim of this study was to ascertain whether adding zinc or multiple micronutrients to vitamin A supplementation improves longitudinal growth or reduces prevalence of anemia in children aged 6-24 months.

Methods: Randomized, controlled double-blinded trial of prophylactic micronutrient supplementation to children aged 6-24 months. Children in three cohorts - 32 HIV-infected children, 154 HIV-uninfected children born to HIV-infected mothers, and 187 uninfected children born to HIV-uninfected mothers - were separately randomly assigned to receive daily vitamin A (VA) [n = 124], vitamin A plus zinc (VAZ) [n = 123], or multiple micronutrients that included vitamin A and zinc (MM) [n = 126].

Results: Among all children there were no significant differences between intervention arms in length-for-age Z scores (LAZ) changes over 18 months. Among stunted children (LAZ below -2) [n = 62], those receiving MM had a 0.7 Z-score improvement in LAZ versus declines of 0.3 in VAZ and 0.2 in VA (P = 0.029 when comparing effects of treatment over time). In the 154 HIV-uninfected children, MM ameliorated the effect of repeated diarrhea on growth. Among those experiencing more than six episodes, those receiving MM had no decline in LAZ compared to 0.5 and 0.6 Z-score declines in children receiving VAZ and VA respectively (P = 0.06 for treatment by time interaction). After 12 months, there was 24% reduction in proportion of children with anemia (hemoglobin below 11 g/dL) in MM arm (P = 0.001), 11% in VAZ (P = 0.131) and 18% in VA (P = 0.019). Although the within arm changes were significant; the between-group differences were not significant.

Conclusions: Daily multiple micronutrient supplementation combined with vitamin A was beneficial in improving growth among children with stunting, compared to vitamin A alone or to vitamin A plus zinc. Effects on anemia require further study.

Trial registration: This study is registered with ClinicalTrials.gov, number. NCT00156832.

Figure 1

Participant flowchart.

Figure 2

Longitudinal changes in length-for-age Z score by HIV cohort (n = 317). (P = 0.001 for cohort by time interaction).

Figure 3

Longitudinal changes in length-for-age Z score in children who were stunted at baseline, all cohorts combined (n = 62). (P = 0.029 for treatment by time interaction).

Figure 4

Longitudinal changes in length-for-age Z score in HIV-infected children (n = 25). (P = 0.042 for treatment by time interaction).

Figure 5

Longitudinal changes in length-for-age Z score among HIV-uninfected children experiencing. a) > 4 episodes of diarrhea peryear (n = 74). (P = 0.007 for treatment by time interaction). b) > 6 episodes of diarrhea per year (n = 34). (P = 0.067 for treatment by time interaction).