Reducing Lead Burden and Improving Iron Status with Iron Fortification Using NaFeEDTA: A Double-Blind, Randomized, Placebo- Controlled Intervention Trial (RCT) in Lead-exposed Moroccan Children

Abstract

Objectives: Lead absorption from oral exposures may be increased in children with iron deficiency anemia (IDA). Therefore, iron fortification could be an effective adjunctive strategy to reduce lead burden in many urban areas in low-income and rapidly-developing countries. We investigated the effect of iron fortification with and without NaEDTA (a lead chelator) in Moroccan children; primary outcomes were serum ferritin and blood lead levels (BLL). Methods: Using a 2-by-2 factorial design, an RCT was done in children (n=453) receiving wheat-based biscuits containing either 1) 10 mg of FeSO4, 2) 10 mg of Fe as NaFe(III)EDTA, 3) NaEDTA alone or 4) control for 28 weeks. Biomarkers of iron status and lead burdenwere assessed by using a sparse serial sampling design. Cognition was assessed using the Kaufman Assessment Battery. Results: Iron status improved significantly in both iron groups: mean serum ferritin increased by 15.3 µg/L, 14.9µg/L and 4 µg/L in the FeSO4, NaFe(III)EDTA and EDTA groups respectively, compared to control (p<0.0001). IDA was significantly reduced in both iron groups (p<0.001). Mean BLL were reduced by 4.2 ng/g and 8.1 ng/g in the FeSO4 and NaFe(III)EDTA, compared to the control group. Conclusions: Both fortificants improved iron status similarly, and both reduced blood lead levels compared to control, but the reduction in BLL was two-fold greater with NaFe(III)EDTA. This is the first RCT to clearly demonstrate a reduction of BLL after iron fortification, and suggests additional benefit from supplying the iron as NaFe(III)EDTA. Analysis of the sparse serial sampling data will provide the kinetics of this effect.