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