Delaying Iron Therapy until 28 Days after Antimalarial Treatment Is Associated with Greater Iron Incorporation and Equivalent Hematologic Recovery after 56 Days in Children: A Randomized Controlled Trial.
Study Goal
The researchers aimed to determine whether delaying iron supplementation after antimalarial treatment improves iron absorption and hematologic recovery in children with malaria and anemia.
Results Summary
Delaying iron supplementation improved iron incorporation compared to immediate supplementation, but both groups showed equivalent hematologic recovery by day 56. Immediate iron supplementation led to better iron status markers at day 28, but no long-term differences were observed.
Population
Children aged 6-59 months with malaria and hemoglobin concentrations of 50.0-99.9 g/L in Uganda.
Effective Dosage
Not specified in the abstract.
Duration
56 days (with iron supplementation starting either immediately or 28 days later).
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
delayed iron supplementation | increase | percentage of iron incorporation | children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L | 16.5% ± 1.7% compared with 7.9% ± 0.5% | was greater | #1 |
immediate iron supplementation | neutral | percentage of iron incorporation | children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L | 7.9% ± 0.5% | was | #2 |
delayed iron supplementation | no change | concentrations of hemoglobin | children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L | - | did not differ | #3 |
delayed iron supplementation | no change | concentrations of ZPP | children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L | - | did not differ | #4 |
delayed iron supplementation | no change | plasma ferritin | children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L | - | did not differ | #5 |
delayed iron supplementation | no change | soluble transferrin receptor (sTfR) | children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L | - | did not differ | #6 |
delayed iron supplementation | no change | hepcidin | children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L | - | did not differ | #7 |
delayed iron supplementation | no change | C-reactive protein | children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L | - | did not differ | #8 |
delayed iron supplementation | decrease | hemoglobin | children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L | 105 ± 15.9 g/L compared with 112 ± 12.4 g/L | reflected poorer iron status | #9 |
delayed iron supplementation | decrease | ferritin | children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L | 39.3 μg/L; 23.5, 65.7 μg/L compared with 79.9 μg/L; 58.3, 110 μg/L | reflected poorer iron status | #10 |
delayed iron supplementation | increase | sTfR | children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L | 8.9 mg/L; 7.4, 10.7 mg/L compared with 6.7 mg/L; 6.1, 7.5 mg/L | reflected poorer iron status | #11 |
delayed iron supplementation | decrease | hepcidin | children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L | 13.3 ng/mL; 8.3, 21.2 ng/mL compared with 38.8 ng/mL; 28.3, 53.3 ng/mL | reflected poorer iron status | #12 |
delayed iron supplementation | increase | iron incorporation | Ugandan children with malaria and anemia | - | improves incorporation | #13 |
delayed iron supplementation | no change | hematologic recovery | Ugandan children with malaria and anemia | - | leads to equivalent hematologic recovery | #14 |
BACKGROUND: Iron therapy begun concurrently with antimalarial treatment may not be well absorbed because of malaria-induced inflammation. Delaying the start of iron therapy may permit better iron absorption and distribution. OBJECTIVE: We compared erythrocyte iron incorporation in children who started iron supplementation concurrently with antimalarial treatment or 28 d later. We hypothesized that delayed iron supplementation would be associated with greater incorporation and better hematologic recovery. METHODS: We enrolled 100 children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L who presented to Mulago Hospital, Kampala, into a randomized trial of iron therapy. All children were administered antimalarial treatment. Children with zinc protoporphyrin (ZPP) ≥80 μmol/mol heme were randomly assigned to start iron supplementation concurrently with the antimalarial treatment [immediate iron (I) group] or 28 d later [delayed iron (D) group]. All children were administered iron-stable isotope (57)Fe on day 0 and (58)Fe on day 28. We compared the percentage of iron incorporation at the start of supplementation (I group at day 0 compared with D group at day 28, aim 1) and hematologic recovery at day 56 (aim 2). RESULTS: The percentage of iron incorporation (mean ± SE) was greater at day 28 in the D group (16.5% ± 1.7%) than at day 0 in the I group (7.9% ± 0.5%; P < 0.001). On day 56, concentrations of hemoglobin and ZPP and plasma ferritin, soluble transferrin receptor (sTfR), hepcidin, and C-reactive protein did not differ between the groups. On day 28, the hemoglobin (mean ± SD) and plasma iron markers (geometric mean; 95% CI) reflected poorer iron status in the D group than in the I group at this intervening time as follows: hemoglobin (105 ± 15.9 compared with 112 ± 12.4 g/L; P = 0.04), ferritin (39.3 μg/L; 23.5, 65.7 μg/L compared with 79.9 μg/L; 58.3, 110 μg/L; P = 0.02), sTfR (8.9 mg/L; 7.4, 10.7 mg/L compared with 6.7 mg/L; 6.1, 7.5 mg/L; P = 0.01), and hepcidin (13.3 ng/mL; 8.3, 21.2 ng/mL compared with 38.8 ng/mL; 28.3, 53.3 ng/mL; P < 0.001). CONCLUSIONS: Delaying the start of iron improves incorporation but leads to equivalent hematologic recovery at day 56 in Ugandan children with malaria and anemia. These results do not demonstrate a clear, short-term benefit of delaying iron. This trial was registered at clinicaltrials.gov as NCT01754701.