Table 1.
Summary of clinical studies on iron deficiency, iron supplementation, and malaria.
| References | Study design | Population | Country, malaria info | Results |
|---|---|---|---|---|
| CHILDREN—INTERVENTIONAL STUDIES | ||||
| Sazawal et al., 2006 | Randomized placebo controlled | 7950 children given iron and folic acid | Zanzibar, intense malaria transmission | Trial stopped early because of safety concerns. 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 hospital treatment for an adverse event and 11% (95% CI 1–23, p = 0.03) more likely to be admitted to hospital; there were also 15% (95% CI 7–41, p = 0.19) more deaths in these groups |
| 8120 children given iron, folic acid and zinc | ||||
| 8006 control children | ||||
| Ages 1–35 months | ||||
| Tielsch et al., 2006 | Randomized placebo controlled | 8337 children given iron and folic acid | Nepal, no malaria | Daily supplementation of young children in southern Nepal with iron and folic acid with or without zinc had no effect on their risk of death, but might protect against diarrhea, dysentery, and acute respiratory illness |
| 9230 children given iron, folic acid and zinc | ||||
| 8683 control children | ||||
| Ages 1–36 months | ||||
| Veenemans et al., 2011 | 2 × 2 Factorial trial | 145 children given zinc only | Tanzania, intense malaria transmission | When data was analyzed by iron status at baseline, multi-nutrient supplementation increased the overall number of malaria episodes in children with iron deficiency by 41%, whereas multi-nutrient supplementation had no effect on the number of malaria episodes among children who were iron-replete at baseline |
| 148 children given both zinc and multi-nutrients (including iron) | ||||
| 146 children given multi-nutrients (including iron) without zinc | ||||
| 148 children given placebo | ||||
| Ages 6–60 months | ||||
| Zlotkin et al., 2013 | Cluster randomized, double blind | 967 children given micronutrient powder with iron | Ghana, intense malaria transmission | Malaria incidence was significantly lower in the iron group compared with the no iron group during the intervention period (risk ratio [RR], 0.87; 95% CI, 0.78–0.96). In secondary analyses, these differences were no longer statistically significant after adjusting for baseline iron deficiency and anemia status overall (RR, 0.87; 95% CI, 0.75–1.01) |
| 991 children given micronutrient powder without iron | Insecticide treated bednets provided at enrollment | |||
| Ages 6–35 months | ||||
| Subgroup analysis of 704 children who had anemia at baseline and for whom additional blood samples were obtained at the end of the intervention period found only a small mean increase in hemoglobin in the iron group (mean change of 0.08 g/dL measured), indicating that the micronutrient powder had limited efficacy in this trial | ||||
| Esan et al., 2013 | 2-arm, double-blind, randomized | 100 children received multivitamins plus iron | Malawi, intense malaria transmission | Children who received iron had a better CD4 percentage response at 3 months, but an increased incidence of malaria at 6 months (incidence rate, 120.2 vs. 71.7; adjusted incidence rate ratio [aIRR], 1.81 [95% CI, 1.04–3.16]; p = 0.04), especially during the first 3 months (incidence rate, 78.1 vs. 36.0; aIRR, 2.68 [95% CI, 1.08–6.63]; p = 0.03) |
| 96 children received multivitamins alone | ||||
| HIV infected children aged 6–59 months with moderate anemia (Hgb = 7.0–9.9 g/dL); 3 months of treatment, 6 months follow up | ||||
| CHILDREN—OBSERVATIONAL STUDIES | ||||
| Nyakeriga et al., 2004 | 2 Cross sectional studies | Study 1: | Kenya, intense malaria transmission | Incidence of clinical malaria was significantly lower among children with iron deficiency anemia (incidence-rate ratio [IRR], 0.70; 95% confidence interval [CI], 0.51–0.99; P < 0.05) |
| Iron replete (n = 95) | ||||
| Iron deficient (n = 78) | ||||
| Study 2: | ||||
| Iron replete (n = 104) | ||||
| Iron deficient (n = 91) | ||||
| Ages 8 months-8 years | ||||
| Gwamaka et al., 2012 | Longitudinal | 785 children monitored for 3 years | Tanzania, intense malaria transmission | Iron deficiency anemia at routine, well-child visits significantly decreased the odds of subsequent parasitemia (23% decrease, p < 0.001) and subsequent severe malaria (38% decrease, p = 0.04). Iron deficiency anemia was also associated with 60% lower all-cause mortality (p = 0.04) and 66% lower malaria-associated mortality (p = 0.11) |
| Jonker et al., 2012 | Longitudinal | 727 children monitored for 1 year | Malawi, intense malaria transmission | Children with iron deficiency anemia at baseline had a lower incidence of malaria parasitemia and clinical malaria during a year of follow-up; adjusted hazard ratios 0.55 (95% CI:0.41–0.74) and 0.49 (95% CI:0.33–0.73), respectively |
| PREGNANT WOMEN—OBSERVATIONAL | ||||
| Kabyemela et al., 2008 | Cross sectional | 445 pregnant women (120 primigravidae, 112 secundigravidae, and 213 multigravidae) | Tanzania, intense malaria transmission | Iron deficiency decreased the risk of placental malaria |
| Senga et al., 2011 | Case-Control | Pregnant women (112 cases with placental malaria, 110 controls with no evidence of placental infection) | Malawi, intense malaria transmission | Iron deficiency decreased risk of acute, chronic and past placental malaria. The association was greater in the multigravidae group |