Iron deficiency anemia (IDA) is a major public health problem in sub-Saharan Africa. The efficacy of
iron fortification against IDA is uncertain in
malaria-endemic settings. The objective of this study was to evaluate the efficacy of a complementary food (CF) fortified with
sodium iron EDTA (
NaFeEDTA) plus either
ferrous fumarate (FeFum) or
ferric pyrophosphate (FePP) to combat IDA in preschool-age children in a highly
malaria endemic region. This is a secondary analysis of a nine-month cluster-randomized controlled trial conducted in south-central Côte d'Ivoire. 378 children aged 12-36 months were randomly assigned to no food intervention (n = 125; control group), CF fortified with 2 mg
NaFeEDTA plus 3.8 mg FeFum for six days/week (n = 126; FeFum group), and CF fortified with 2 mg
NaFeEDTA and 3.8 mg FePP for six days/week (n = 127; FePP group). The outcome measures were
hemoglobin (Hb), plasma
ferritin (PF),
iron deficiency (PF < 30 μg/L), and
anemia (Hb < 11.0 g/dL). Data were analyzed with random-effect models and PF was adjusted for
inflammation. The prevalence of Plasmodium falciparum
infection and
inflammation during the study were 44-66%, and 57-76%, respectively. There was a significant time by treatment interaction on IDA (p = 0.028) and a borderline significant time by treatment interaction on
iron deficiency with or without
anemia (p = 0.068). IDA prevalence sharply decreased in the FeFum (32.8% to 1.2%, p < 0.001) and FePP group (23.6% to 3.4%, p < 0.001). However, there was no significant time by treatment interaction on Hb or total
anemia. These data indicate that, despite the high endemicity of
malaria and elevated
inflammation biomarkers (C-reactive protein or α-1-acid-glycoprotein), IDA was markedly reduced by provision of
iron fortified CF to preschool-age children for 9 months, with no significant differences between a combination of
NaFeEDTA with FeFum or
NaFeEDTA with FePP. However, there was no overall effect on
anemia, suggesting most of the
anemia in this setting is not due to ID. This trial is registered at clinicaltrials.gov (NCT01634945).