Relation between the response to iron supplementation and sickle cell hemoglobin phenotype in preschool children in western Kenya.
BACKGROUND
Iron supplementation has been associated with greater susceptibility to malaria and lower hematologic responses in pregnant Gambian women with sickle cell trait (HbAS) than in similar women with the normal (HbAA) phenotype. It is not known whether a similar interaction exists in children.


OBJECTIVE
Our aim was to determine the influence of the HbAS phenotype on hematologic responses and malaria after iron supplementation in anemic (hemoglobin: 70-109 g/L) children aged 2-35 mo.


METHODS
We conducted a double-blind, randomized, placebo-controlled trial (HbAS, n = 115; HbAA, n = 408) of intermittent preventive treatment with sulfadoxine pyrimethamine (IPT-SP) at 4 and 8 wk and daily supervised iron for 12 wk.


RESULTS
The mean difference in hemoglobin concentrations at 12 wk between children assigned iron and placebo iron, after adjustment for the effect of IPT-SP, was 9.1 g/L (95% CI: 6.4, 11.8) and 8.2 g/L (4.0, 12.4) in HbAA and HbAS children, respectively (P for interaction = 0.68). Although malaria parasitemia and clinical malaria occurred more often in HbAS children in the iron group than in those in the placebo iron group, this difference was not significant; incidence rate ratios were 1.23 (95% CI: 0.64, 2.34) and 1.41 (0.39, 5.00), respectively. The corresponding incidence rate ratios in HbAA children in the same groups were 1.07 (95% CI: 0.77, 1.48) and 0.59 (0.35, 1.01), respectively. The corresponding interactions between the effects of iron and hemoglobin phenotype were not significant.


CONCLUSIONS
There was no evidence for a clinically relevant modification by the hemoglobin S phenotype of the effects of iron supplementation in the treatment of mild anemia. The benefits of iron supplementation are likely to outweigh possible risks associated with malaria in children with the HbAA or HbAS phenotype.
Division of Parasitic Diseases, National Center for Infectious Diseases, Atlanta, GA, USA.
Dianne J
DJ
Terlouw
Meghna R
MR
Desai
Kathleen A
KA
Wannemuehler
Simon K
SK
Kariuki
Christine M
CM
Pfeiffer
Piet A
PA
Kager
Ya Ping
YP
Shi
Feiko O
FO
Ter Kuile
D000740:Anemia / Q000150:complications* / Q000188:drug therapy; D000962:Antimalarials / Q000627:therapeutic use; D002675:Child, Preschool; D019587:Dietary Supplements; D004198:Disease Susceptibility; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D007223:Infant; D007501:Iron / Q000008:administration & dosage / Q000009:adverse effects*; D007630:Kenya; D008288:Malaria / Q000453:epidemiology* / Q000517:prevention & control; D008297:Male; D010641:Phenotype; D011739:Pyrimethamine / Q000627:therapeutic use; D012805:Sickle Cell Trait; D013413:Sulfadoxine / Q000627:therapeutic use
D000962:Antimalarials; D004338:Drug Combinations; D006454:Hemoglobins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D007501:Iron; D011739:Pyrimethamine