title: Neonatal erythropoiesis and subsequent anemia in HIV-positive and HIV-negative Zimbabwean babies during the first year of life: a longitudinal study.
abstract: BACKGROUND
  Anemia is common in HIV infection and independently associated with disease progression and mortality. The pathophysiology of HIV-related anemia is not well understood especially in infancy.
  
  
  METHODS
  We conducted a longitudinal cohort study nested within the Zimbabwe Vitamin A for Mothers and Babies Project. We measured hemoglobin, erythropoietin (EPO), serum transferrin receptor (TfR) and serum ferritin at 6 weeks, 3 and 6 months of age and hemoglobin at 9 and 12 months in 3 groups of randomly selected infants: 136 born to HIV-negative mothers, and 99 born to HIV-positive mothers and who were infected themselves by 6 weeks of age, and 324 born to HIV-positive mothers but who did not become infected in the 6 months following birth.
  
  
  RESULTS
  At one year of age, HIV-positive infants were 5.26 (adjusted odds ratio, P < 0.001) times more likely to be anemic compared to HIV-negative infants. Among, HIV-negative infants, EPO was or tended to be inversely associated with hemoglobin and was significantly positively associated with TfR throughout the first 6 months of life; TfR was significantly inversely associated with ferritin at 6 months; and EPO explained more of the variability in TfR than did ferritin. Among infected infants, the inverse association of EPO to hemoglobin was attenuated during early infancy, but significant at 6 months. Similar to HIV-negative infants, EPO was significantly positively associated with TfR throughout the first 6 months of life. However, the inverse association between TfR and ferritin observed among HIV-negative infants at 6 months was not observed among infected infants. Between birth and 6 months, mean serum ferritin concentration declined sharply (by approximately 90%) in all three groups of babies, but was significantly higher among HIV-positive compared to HIV-negative babies at all time points.
  
  
  CONCLUSIONS
  HIV strongly increases anemia risk and confounds interpretation of hematologic indicators in infants. Among HIV-infected infants, the EPO response to anemia is attenuated near the time of infection in the first weeks of life, but normalizes by 6 months.
authors.affiliation: Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA. millermeli@mail.nih.gov
authors.forename: Melissa F
authors.initials: MF
authors.lastname: Miller
authors.forename: Jean H
authors.initials: JH
authors.lastname: Humphrey
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Iliff
authors.forename: Lucie C
authors.initials: LC
authors.lastname: Malaba
authors.forename: Nkosinathi V
authors.initials: NV
authors.lastname: Mbuya
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Stoltzfus
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000209:etiology* / Q000503:physiopathology*; D015331:Cohort Studies; D004920:Erythropoiesis / Q000502:physiology*; D004921:Erythropoietin / Q000097:blood; D005260:Female; D005293:Ferritins / Q000097:blood; D018023:HIV Seronegativity / Q000502:physiology*; D006679:HIV Seropositivity / Q000150:complications* / Q000503:physiopathology*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D016017:Odds Ratio; D011990:Receptors, Transferrin / Q000097:blood; D012307:Risk Factors; D015030:Zimbabwe
chemical_list: D006454:Hemoglobins; D011990:Receptors, Transferrin; D004921:Erythropoietin; D005293:Ferritins