Efficacy and safety of twice-weekly administration of three RDAs of iron and folic acid with and without complement of 14 essential micronutrients at one or two RDAs: a placebo-controlled intervention trial in anemic Cambodian infants 6 to 24 months of age.

OBJECTIVE: To determine the differential efficacy and safety of twice-weekly administration of 3 RDAs of iron and folic acid, with and without a complement of 2 RDAs of 11, and 1 RDA of 3 additional essential micronutrients as compared to a placebo control (PlbCON) given as foodLETs. SUBJECTS/METHODS: A total of 250 children aged 6-24 months were enrolled after recruitment by village health workers; 19 of them dropped out during the trial. Children were assigned to one of three treatment arms and followed for 20.5 weeks; 41 supervised twice-weekly dosings of 30 mg of iron plus folic acid, either with or without accompanying micronutrients or placebo were given as foodLETs, a tool for ready-to-eat fortification in infant food. Initial and final measurements of anthropometry and blood biomarkers for hematological, iron stores and inflammatory status, as well as for abnormal hemoglobin (Hb), were obtained. Symptoms of listlessness, vomiting, watery stools and acute respiratory infections were monitored weekly. RESULTS: Iron-containing supplements increased Hb concentrations significantly (P<0.0001) and virtually eradicated any IDA, as compared to no change in hematological status in the PlbCON group (P=0.011). Iron stores, as reflected by ferritin, increased significantly with iron-containing treatments (P<0.0001). Responses were as effective in individuals with HbE as in those with exclusively HbA phenotypes. Watery stools (P=0.002) and listlessness (P=0.001) were significantly more frequent in those receiving iron and folic acid alone than in the PlbCON group. In contrast, acute respiratory infections (P=0.014) and listlessness (P=0.001) were significantly less frequent in those receiving the multiple micronutrient formulation than in the PlbCON group. CONCLUSIONS: Supplementation of micronutrients along with iron and folic acid mitigates the excess morbidity of iron-folate alone, without reducing its efficacy in correcting anemia and building iron stores. FoodLETs are a suitable vehicle to provide micronutrient supplementation to infants.