Study | Country | Age at recruitment, yr | Baseline anemia, iron deficiency status | Intervention | Control | No. randomized | Duration | Outcomes |
---|---|---|---|---|---|---|---|---|
Ayoya et al.17,18 | Mali | 7–12 | Anemic, iron status unknown | Ferrous sulfate 100 mg + anthelmintic therapy | Anthelmintic therapy | Total: 202; iron: 105; placebo: 97 | 12 wk | Anemia, hemoglobin, malaria, ferritin, soluble transferrin receptor, cognitive score |
Berger et al.19 | Bolivia | 3.3–8.3 | Anemic, iron status unknown | Ferrous sulfate calculated to 3–4 mg/kg/d as closest amount to 20 mg or 36 mg/d | Placebo (once per wk) | Total: 115; iron: 58; placebo: 57 | 16 wk (4 mo) | Anemia, hemoglobin, zinc protoporphyrin |
Boivin et al.20 | Zaire | Mean age 7.7 | Anemia, iron status unknown | 20 mL of iron supplementation (formulation not stated) ± levamisole | No intervention ± levamisole | Total: 47; iron: 7; placebo: 15; iron + anthelmintic: 17; placebo + levamisole: 8 | 4 wk, 30 d | Data not extractable (all data presented as levamisole v. no levamisole) (not included in analysis) |
Bradfield et al.21 | Peru | 7–13 | Anemia and iron status unknown | Ferrous sulfate 5 mg ± anthelmintic therapy | Placebo ± anthelmintic therapy | Total: 87; iron: 51; placebo: 10; iron + anthelmintic: 16; placebo + anthelmintic: 10 | 10 wk | Hemoglobin, hematocrit, no. with helminth infection |
Charoenlarp22 | Thailand | 5–14 | Anemia and iron status unknown | Ferrous gluconate (300 mg) ± folate | Placebo ± folate | Total: 437; iron: 214; placebo: 223 | 3 mo | Hematocrit |
Charoenlarp et al.23 | Thailand | 6–12 | Anemia and iron status unknown | Ferrous sulfate (200 mg) ± mebendazole (if hookworms present) | Placebo ± mebendazole (if hookworms present) | Total: 72; iron: 33; placebo: 39 | 5 mo | Hemoglobin, hematocrit |
Chwang et al.24 | Indonesia | 8.2–13.5 | Subgroups: anemic, not anemic, iron deficient, not iron deficient, iron deficiency anemia, nonanemic noniron deficient | Ferrous sulfate (10 mg) | Placebo | Total: 139; iron: 59; placebo: 60 | 12 wk | Hemoglobin, serum iron, transferrin saturation, total iron binding capacity, height, weight, arm circumference, morbidity score; z scores for height, weight, arm circumference |
de Silva et al.25 | Sri Lanka | 5–10 | Anemia and iron status unknown | Ferrous sulfate (60 mg elemental iron) | Placebo | Total: 363; iron: 261; placebo: 102 | 8 wk | Anemia, iron deficiency, hemoglobin, ferritin, no. of URTI episodes, URTI episodes with fever, total no. of days sick with URTI, constipation, vomiting, GI upset |
Fallahi et al.26 | Iran | Grade 5 (about age 11 yr) | Anemia and iron status unknown | Ferrous sulfate (20 mg) + zinc | Zinc | Total: 54; iron: 26; placebo: 28 | 4 mo | Hemoglobin, ferritin, zinc, retinol |
Gebreselassie27 | Ethiopia | 5–14 | Anemic and iron deficient | Ferrous sulfate (300 mg) | Placebo | Total: 480; iron: 239; placebo: 241 | 3 mo | Anemia, iron deficiency, hemoglobin, ferritin, malaria, splenomegaly |
Gopaldas et al.28–31 | India | 8–15 | Iron status unknown. Subgroups: anemic, nonanemic | Ferrous sulfate (30 mg or 40 mg) | Placebo | Total: 210; iron: 140; placebo: 70 | 60 d | Hemoglobin, cognitive scores, exercise tests |
Greisen32 | Zambia | 5–15 | Anemic, iron status unknown | Ferrous fumarate (300 mg) ± folate | Placebo ± folate | Total: 430; iron: 218; placebo: 212 | 7 wk | Hemoglobin |
Harvey et al.33 | Papua New Guinea | 8–12 | Anemic, iron status unknown | Ferrous sulfate (200 mg) | Placebo | Total: 300; iron: 156; placebo: 144 | 16 wk | Hemoglobin, gastrointestinal upset, malaria |
Kashyap et al.34 | India | 8–15 | Anemia and iron status unknown | Ferrous sulfate (200 mg) | Placebo | Total: 130; iron: 65; placebo: 65 | 8 mo | Hemoglobin, cognitive scores |
Konofal et al.35 | France | 5–8 | Anemia status unknown, iron deficient | Ferrous sulfate (300 mg) | Placebo | Total: 23; iron: 18; placebo: 5 | 3 mo | Hemoglobin, ferritin, serum iron, transferrin saturation, constipation and abdominal pain |
Latham et al.36 | Kenya | Mean age control: 8.1; iron: 7.9 | Anemia and iron status unknown | Ferrous sulfate (400 mg) + albendazole | Placebo + albendazole | Total: 55; iron: 29; placebo: 26 | 15 wk | Hemoglobin, height, weight, arm circumference, malaria, Ascaris infection |
Lawless et al.37 | Kenya | 6–11 | Anemia and iron status unknown | Ferrous sulfate (150 mg) | Placebo | Total: 86; iron: 42; placebo: 44 | 14 wk | Hemoglobin, ferritin, height, weight, z scores for height and weight |
Nchito et al.38–40 | Zambia | 7–15 (mean 10.2) | Anemia and iron status unknown | Ferrous dextran (60 mg elemental iron) ± multivitamin | Placebo ± multivitamin | Total: 215; iron: 61; placebo: 50; Iron + multivitamin: 57; placebo + multivitamin: 47 | 10 mo | Ascaris infection |
Paracha et al.41 | Pakistan | 11 | Subgroups: anemic, not anemic, iron deficient, not iron deficient, iron deficient anemia, nonanemic noniron deficient | Ferrous gluconate (76 mg elemental iron) + multivitamin | Placebo + multivitamin | Total: 119; iron: 61; placebo: 58 | 11 wk | Hemoglobin, hematocrit, MCV, MCH, MCHC, ferritin, transferrin saturation |
Perrone et al.42 | Italy | 4–11 | Not anemic, iron status unknown | Iron polymaltose (12.5 mg elemental iron) | Placebo | Total: 16; iron: 8; placebo: 8 | 1 yr | Ferritin, zinc, serum copper, z scores for weight and height |
Pollitt et al.43,44 | Thailand | 9–11 | Subgroups: anemic, not anemic, iron deficient, not iron deficient, iron deficient anemia, iron deficient not anemic, nonanemic noniron deficient | Ferrous sulfate (50 mg/100 mg) + albendazole | Placebo + albendazole | Total: 1358; iron: 679; placebo: 679 | 16 wk | Hemoglobin, ferritin, transferrin saturation, cognitive scores |
Powers et al.45 | Gambia | 4–12 | Anemia and iron status unknown | Ferrous sulfate (200 mg) | Placebo | Total: 50; iron: 25; placebo: 25 | 6 wk | Hemoglobin, hematocrit, MCV, MCH, serum iron |
Richard et al.46 | Peru | 0.5–15 | Anemia and iron status unknown | Ferrous sulfate (15 mg elemental iron) ± zinc | Placebo ± zinc | Total: 836; iron: 208; placebo: 209; iron + zinc: 210; placebo + zinc: 209 | 7 mo | Hemoglobin, zinc, malaria, lower respiratory tract infection, diarrhea |
Rico et al.47–50 | Mexico | 6–8 | Anemia and iron status unknown | Ferrous fumarate (10 mg elemental iron) ± zinc | Placebo or zinc | Total: 590; iron: 141; placebo: 151; iron + zinc: 152; placebo + zinc: 146 | 6 mo | Hemoglobin, ferritin, zinc, lead, height, weight, cognitive scores |
Rosales et al.51 | Guatemala | 8–11 | Anemia and iron status unknown | Iron citrate (20 mg elemental iron) ± zinc | Placebo ± zinc | Total: 64; iron: 15; placebo: 15; iron + zinc: 19; placebo + zinc: 15 | 8 wk | Iron deficiency, zinc deficiency, hemoglobin, ferritin, zinc, CRP |
Sen et al.52,53 | India | 9–13 | Anemia and iron status unknown | Unknown (100 mg elemental iron) + folic acid | Control | Total: 110; iron: 59; placebo: 41 | 1 yr | Hemoglobin, cognitive scores, maximum steps climbed, recovery time |
Sen et al.54 | India | 9–13 | Iron status unknown. Subgroups: anemic, not anemic | Unknown (elemental iron 100 mg) | Control | Total: 100; iron: 59; placebo: 41 | 1 yr | Hemoglobin |
Seshadri et al. (study 1) 28,55 | India | 5–8 | Anemia and iron status unknown | Unknown (20 mg elemental iron) + folic acid | Control | Total: 97; iron: 63; placebo: 34 | 60 d | Hemoglobin, IQ (performance, verbal total) |
Seshadri et al. (study 2)28,55 | India | 5–6 | Anemic, iron status unknown | Unknown (40 mg elemental iron) + folic acid | Placebo | Total: 28; iron: 14; placebo: 14 | 60 d | Hemoglobin, IQ (performance, verbal, total) |
Seshadri et al. (study 4)28 | India | 8–15 | Iron status unknown. Subgroups: anemic, nonanemic | Unknown (60 mg elemental iron) | Placebo | Total: 130; iron: 65; placebo: 65 | 12 mo | Anemia, iron deficiency, hemoglobin, IQ (performance, verbal, total) |
Soemantri et al.56 | Indonesia | 8.1–11.6 | Subgroups: anemic, not anemic, iron deficient, not iron deficient, iron deficient anemia, iron deficient not anemic, nonanemic noniron deficient | Ferrous sulfate (10 mg/kg/d) | Placebo | Total: 130; iron: 71; placebo: 59 | 3 mo | Hemoglobin, transferrin saturation, cognitive scores |
Sungthong et al.57,58 | Thailand | 6–13 | Anemia and iron status unknown | Ferrous sulfate (300 mg) + albendazole | Placebo + albendazole | Total: 263; iron: 140; placebo: 123 | 16 wk | Hemoglobin, ferritin, height, weight, z scores for height and weight, cognitive scores |
Note: CRP = C-reactive protein, GI = gastrointestinal IQ = intelligence quotient, MCH = mean cell hemoglobin, MCHC = mean cell hemoglobin concentration, MCV = mean cell volume, URTI = upper respiratory tract infection.
↵* Two included studies52,53,54 used clustered randomization at the school level but the reported data were not clearly adjusted for clustering. We imputed the design effect for hemoglobin from a recent Cochrane review,8 and the intra-cluster correlation coefficient for physical activity and cognitive assessment from other cluster RCTs reporting these outcomes;59,60 sample size was then adjusted by dividing by the design effect.