Zinc supplementation improved length growth only in anemic infants in a multi-country trial of iron and zinc supplementation in South-East Asia.

Data from 4 randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam, the South-East Asian Multicountry Trial on Iron and Zinc supplementation in Infants (SEAMTIZI), were pooled to investigate the effects of iron and zinc supplementation infant growth. Infants (n = 2451) aged 4-6 mo old were supplemented with iron (10 mg/d) and/or zinc (10 mg/d) for 6 mo. Overall, neither iron nor zinc supplementation prevented the progressive growth faltering during infancy, which is common in many developing countries. However, infants who received zinc were less likely to be stunted at the end of the supplementation period (odds ratio 0.80; 95% CI 0.64-1.0). Boys had a 30% higher risk of being stunted at the end of the study than girls (P < 0.01). Baseline factors modified the effect of supplementation, with infants anemic at baseline (hemoglobin < 105 g/L) benefiting from zinc supplementation, with an estimated increase in height-for-age Z-score (HAZ) score of 0.17 (P < 0.01), but with no effect of zinc supplementation on growth in infants not anemic at baseline. Iron supplementation negatively affected linear growth in infants with a birth weight of >3500 g (estimated effect size, -0. 14 HAZ score; P < 0.01), but with no significant effect in infants with a lower birth weight. This study shows that blanket supplementation of infants with iron or zinc will not be beneficial to all recipients and may have adverse effects in some. Hence, interventions such as iron and zinc supplementation for infants should be restricted to subgroups in which there is a clear benefit and baseline factors should be considered and characterized before implementing new policies.

Sex differences in prevalence of anaemia and iron deficiency in infancy in a large multi-country trial in South-East Asia.

To evaluate effects of Fe supplementation and sex on the prevalence of anaemia and Fe status in infants in South-East Asia, biochemical data from four parallel, randomized, double-blind trials with Fe and/or Zn supplementation in infants (n 2452) in Indonesia, Thailand and Vietnam was pooled. At recruitment (5 months of age), Hb concentrations were slightly but significantly lower in boy infants compared with girl infants (108.7 g/l v. 111.4 g/l, P = 0.04). At 11 months of age, boy infants not receiving Fe had significantly lower Hb (106.2 g/l v. 111.0 g/l, P < 0.001) and lower serum ferritin concentrations (14.3 microg/l v. 21.1 g/l, P < 0.001) than girl infants not receiving Fe. Consequently, boy infants had a relative risk of 1.6 (95% CI 1.3, 2.1) to be anaemic, and of 3.3 (95% CI 2.1, 5.0) for having Fe deficiency anaemia compared with girl infants. Fe supplementation significantly increased Hb concentrations in both boys and girls. There was no sex difference in Fe status in infants receiving Fe for 6 months. This study shows that the markedly higher risk for anaemia and Fe deficiency indicates higher Fe requirements in boy than in girl infants. In South-East Asia, standard infant feeding practices do not provide sufficient Fe to meet requirements of infants, especially boys. Current daily recommended intake for Fe in infancy is the same for boy and girl infants however. Our findings suggest that in especially the second half of infancy, Fe requirements for boy infants are approximately 0.9 mg/d higher than for girl infants.

Combined iron and zinc supplementation in infants improved iron and zinc status, but interactions reduced efficacy in a multicountry trial in southeast Asia.

Deficiencies of iron and zinc are prevalent worldwide. Interactions between these micronutrients therefore have important consequences, also for supplementation. To investigate effects on hemoglobin and zinc concentrations and interactions of iron and zinc supplementation in infants, data from 4 parallel, randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam were pooled. Infants (n=2468), aged 4-6 mo, were supplemented daily with iron (10 mg) and/or zinc (10 mg) for 6 mo. At 3 sites, infants were given vitamin A capsules (VAC) at recruitment. Combined supplementation reduced prevalences of anemia by 21% (P<0.01) and zinc deficiency by 10% (P<0.05) but was less effective (P<0.05) than supplementation with either iron (28% reduction in anemia) or zinc alone (18% reduction in zinc deficiency). Iron reduced the effect of zinc supplementation (interaction P<0.01), but had no separate effect on zinc status, whereas zinc supplementation had a negative effect on hemoglobin concentrations (-2.5 g/L, P<0.001), independent of iron supplementation (Pinteraction=0.25). The effect of iron supplementation on hemoglobin concentrations was almost twice as large in boys than in girls (effect size 12.0 vs. 6.8 g/L, respectively). In infants not receiving iron, VAC administration tended to be associated with lower (3.2%, P=0.07) hemoglobin concentrations. Combined supplementation of iron and zinc was safe and effective in reducing the high prevalences of anemia and iron and zinc deficiencies. Zinc supplementation may negatively affect iron status but iron supplementation does not seem to affect zinc status. Furthermore, VAC administration in the absence of iron supplementation may increase the incidence of anemia.