Effect of zinc supplementation on mortality in children aged 1-48 months: a community-based randomised placebo-controlled trial.

BACKGROUND: Studies from Asia have suggested that zinc supplementation can reduce morbidity and mortality in children, but evidence from malarious populations in Africa has been inconsistent. Our aim was to assess the effects of zinc supplementation on overall mortality in children in Pemba, Zanzibar. METHODS: We enrolled 42,546 children aged 1-36 months, contributing a total of 56,507 child-years in a randomised, double-blind, placebo-controlled trial in Pemba, Zanzibar. Randomisation was by household. 21 274 children received daily supplementation with zinc 10 mg (5 mg in children younger than 12 months) for mean 484.7 days (SD 306.6). 21,272 received placebo. The primary endpoint was overall mortality, and analysis was by intention to treat. This study is registered as an International Standard Randomised Clinical Trial, number ISRCTN59549825. FINDINGS: Overall, there was a non-significant 7% (95% CI -6% to 19%; p=0.29) reduction in the relative risk of all-cause mortality associated with zinc supplementation. INTERPRETATION: We believe that a meta-analysis of all studies of mortality and morbidity, will help to make evidence-based recommendations for the role of zinc supplementation in public health policy to improve mortality, morbidity, growth, and development in young children.

Maternal reports of sleep in 6-18 month-old infants from Nepal and Zanzibar: association with iron deficiency anemia and stunting.

BACKGROUND: Infants with iron deficiency anemia (IDA) and stunting explore and interact less with their environment. They may also be fatigued more often, suggesting their sleep may be affected. It is unclear whether fatigue in these infants is due to poor nighttime sleep or if it is compensated for with frequent naps or longer sleep. AIMS: In 2 studies from Pemba Island, Zanzibar and 1 from Nepal we investigated the relationship between IDA, stunting, and maternal reports of sleep in 6-18 mo old infants. METHODS: Parents reported on the number and duration of naps, hours of nighttime sleep, and frequency of night waking. Anemia was defined as Hb<10 g/dL, iron deficiency as zinc protoporphyrin (ZPP > or = 90 micromol/mol heme), stunting as HAZ<-2 SD, and IDA as Hb<10 g/dL and ZPP > or = 90 micromol/mol heme. RESULTS: The prevalence of IDA and stunting was 34-84% and 22-37%, respectively. Most infants napped during the day and took approximately 1.5 naps (mean nap duration 1.4-1.7 h). Mean nighttime sleep duration was 8.3-9.7 h and infants awoke 2.1-2.5 times per night. Both IDA and stunting were associated with differences in reported sleep characterized by shorter night sleep duration and higher frequency of night waking; stunting was also related to shorter nap duration. CONCLUSIONS: We found reduced sleep duration and increased night waking among infants with IDA and stunting. Because sleep plays an essential role in infant development, our findings indicate a clear need for further research into these relationships.

Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial.

BACKGROUND: Anaemia caused by iron deficiency is common in children younger than age 5 years in eastern Africa. However, there is concern that universal supplementation of children with iron and folic acid in areas of high malaria transmission might be harmful. METHODS: We did a randomised, placebo-controlled trial, of children aged 1-35 months and living in Pemba, Zanzibar. We assigned children to daily oral supplementation with: iron (12.5 mg) and folic acid (50 mug; n=7950), iron, folic acid, and zinc (n=8120), or placebo (n=8006); children aged 1-11 months received half the dose. Our primary endpoints were all-cause mortality and admission to hospital. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59549825. FINDINGS: The iron and folic acid-containing groups of the trial were stopped early on Aug 19, 2003, on the recommendation of the data and safety monitoring board. To this date, 24 076 children contributed a follow-up of 25,524 child-years. Those who received iron and folic acid with or without zinc were 12% (95% CI 2-23, p=0.02) more likely to die or need treatment in hospital for an adverse event and 11% (1-23%, p=0.03) more likely to be admitted to hospital; there were also 15% (-7 to 41, p=0.19) more deaths in these groups. INTERPRETATION: Routine supplementation with iron and folic acid in preschool children in a population with high rates of malaria can result in an increased risk of severe illness and death. In the presence of an active programme to detect and treat malaria and other infections, iron-deficient and anaemic children can benefit from supplementation. However, supplementation of those who are not iron deficient might be harmful. As such, current guidelines for universal supplementation with iron and folic acid should be revised.

Is the exclusion of children under 24 months from anthelmintic treatment justifiable?

There are no reports documenting toxicity or adverse effects after treatment of children aged < 24 months with benzimidazole derivatives and there is an urgent need to clarify this point in light of the potential detrimental effect that soil-transmitted helminthiasis has on this age-group. A total of 653 treatments (317 mebendazole 500 mg; 336 placebo) were administered in 1996/97 to 212 children aged < 24 months as part of a 1-year anthelmintic drug study conducted among preschool-age children in Tanzania. Data on fever, cough, diarrhoea, dysentery and acute respiratory illness were collected 1 week following the treatment. No differences between the occurrence of adverse effects in the 2 groups were observed. In light of the potential nutritional benefit achieved by regular deworming in this young age-group, the policy that excludes children aged < 24 months from treatment should be re-considered.

Low-dose daily iron supplementation for 12 months does not increase the prevalence of malarial infection or density of parasites in young Zanzibari children.

Conflicting evidence exists on the possible role of iron supplementation in the predisposition to malaria infection or the enhancement of its clinical severity. Where anemia prevalence is >40%, current guidelines are to provide low-dose daily iron to young children for up to 18 mo. Earlier studies used doses higher than the current guidelines, intermittent doses, or have supplemented for durations < or = 4 mo. We aimed to assess the effect of low-dose, long-term iron supplementation on malaria infection using a double-blind, placebo-controlled, randomized design, and to examine possible subgroup effects by season and child age. The study was conducted in Pemba Island, Zanzibar, where Plasmodium falciparum malaria has year-round high transmission. A community-based sample of 614 children 4-71 mo old was randomly allocated to 10 mg/d iron or placebo for 12 mo. Outcome measures were the prevalence and density of malaria infection, which was assessed by blood films at monthly intervals. At baseline, 94.4% were anemic (hemoglobin < 110 g/L), 48.1% were stunted (height-for-age Z-score less than -2) and >80% had malaria-positive blood films. No significant differences in malariometric indices were observed between children in the iron-supplemented and placebo groups. Parasite density was higher in certain months and in younger children, but iron supplementation was not associated with any malarial infection outcome in any season or age subgroup. We conclude that in this environment of high malaria transmission, daily oral low-dose supplementation of iron for 12 mo did not affect the prevalence of malaria infection or parasite density.