Effects of iron supplements and perinatal factors on fetal hemoglobin disappearance in LBW infants

Pediatr Res. 2014 Nov;76(5):477-82. doi: 10.1038/pr.2014.116. Epub 2014 Aug 13.

Abstract

Background: The homeostatic mechanisms of iron metabolism and erythropoiesis in infants are unclear. Infants synthesize both fetal hemoglobin (HbF) and adult hemoglobin (HbA), and it is not known how the hemoglobin switch is regulated. We hypothesized that iron supplements to infants affect the disappearance of HbF.

Methods: We randomized 285 low-birth-weight infants (2,000-2,500 g) into three intervention groups receiving 0, 1, or 2 mg/kg/d of iron supplements from 6 wk to 6 mo of age. In the present secondary analysis, we analyzed iron status, total hemoglobin (Hb), and HbF fraction at 6 wk, 12 wk, and at 6 mo and calculated absolute levels of HbF.

Results: We observed dose-dependent increased levels of Hb in iron-supplemented groups at 6 mo of age. However, for absolute HbF concentration, there was no similar effect of intervention. Mean (SD) HbF was 81.2 (16.8), 37.0 (13.8), and 8.1 (5.6) g/l at 6 wk, 12 wk, and 6 mo, respectively, similar in all groups. In linear regression analyses, postconceptional age turned out as the major predictor of HbF, independent of gestational age at birth.

Conclusion: Our hypothesis was rejected. Instead, we confirmed a close correlation to postconceptional age, supporting a genetically programmed switch, insensitive to most environmental factors including birth.

Trial registration: ClinicalTrials.gov NCT00558454.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Biomarkers / blood
  • Chi-Square Distribution
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Ferrous Compounds / administration & dosage*
  • Fetal Hemoglobin / metabolism*
  • Hematinics / administration & dosage*
  • Hemoglobin A / metabolism*
  • Humans
  • Infant, Low Birth Weight / blood*
  • Infant, Newborn
  • Iron / blood*
  • Linear Models
  • Male
  • Multivariate Analysis
  • Sweden
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Ferrous Compounds
  • Hematinics
  • ferrous succinate
  • Hemoglobin A
  • Fetal Hemoglobin
  • Iron

Associated data

  • ClinicalTrials.gov/NCT00558454