The effect of iron-fortified complementary food and intermittent preventive treatment of malaria on anaemia in 12- to 36-month-old children: a cluster-randomised controlled trial.

BACKGROUND: Iron deficiency (ID) and malaria co-exist in tropical regions and both contribute to high rates of anaemia in young children. It is unclear whether iron fortification combined with intermittent preventive treatment (IPT) of malaria would be an efficacious strategy for reducing anaemia in young children. METHODS: A 9-month cluster-randomised, single-blinded, placebo-controlled intervention trial was carried out in children aged 12-36 months in south-central Côte d'Ivoire, an area of intense and perennial malaria transmission. The study groups were: group 1: normal diet and IPT-placebo (n = 125); group 2: consumption of porridge, an iron-fortified complementary food (CF) with optimised composition providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferrous fumarate 6 days per week (CF-FeFum) and IPT-placebo (n = 126); group 3: IPT of malaria at 3-month intervals, using sulfadoxine-pyrimethamine and amodiaquine and no dietary intervention (n = 127); group 4: both CF-FeFum and IPT (n = 124); and group 5: consumption of porridge, an iron-fortified CF with the composition currently on the Ivorian market providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferric pyrophosphate 6 days per week (CF-FePP) and IPT-placebo (n = 127). The primary outcome was haemoglobin (Hb) concentration. Linear and logistic regression mixed-effect models were used for the comparison of the five study groups, and a 2 × 2 factorial analysis was used to assess treatment interactions of CF-FeFum and IPT (study groups 1-4). RESULTS: After 9 months, the Hb concentration increased in all groups to a similar extent with no statistically significant difference between groups. In the 2 × 2 factorial analysis after 9 months, no treatment interaction was found on Hb (P = 0.89). The adjusted differences in Hb were 0.24 g/dl (95 % CI -0.10 to 0.59; P = 0.16) in children receiving IPT and -0.08 g/dl (95 % CI -0.42 to 0.26; P = 0.65) in children receiving CF-FeFum. At baseline, anaemia (Hb <11.0 g/dl) was 82.1 %. After 9 months, IPT decreased the odds of anaemia (odds ratio [OR], 0.46 [95 % CI 0.23-0.91]; P = 0.023), whereas iron-fortified CF did not (OR, 0.85 [95 % CI 0.43-1.68]; P = 0.68), although ID (plasma ferritin <30 µg/l) was decreased markedly in children receiving iron fortified CF (OR, 0.19 [95 % CI 0.09-0.40]; P < 0.001). CONCLUSIONS: IPT alone only modestly decreased anaemia, but neither IPT nor iron fortified CF significantly improved Hb concentration after 9 months. Additionally, IPT did not augment the effect of the iron fortified CF. CF fortified with highly bioavailable iron improved iron status but not Hb concentration, despite three-monthly IPT of malaria. Thus, further research is necessary to develop effective combination strategies to prevent and treat anaemia in malaria endemic regions. TRIAL REGISTRATION: http://www.clinicaltrials.gov ; identifier NCT01634945; registered on July 3, 2012.

Iron Fortified Complementary Foods Containing a Mixture of Sodium Iron EDTA with Either Ferrous Fumarate or Ferric Pyrophosphate Reduce Iron Deficiency Anemia in 12- to 36-Month-Old Children in a Malaria Endemic Setting: A Secondary Analysis of a Cluster-Randomized Controlled Trial.

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).