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Iron Status and Neurobehavioral Development of Premature Infants

Journal of Perinatology volume 24, pages 757–762 (2004)Cite this article

Abstract

OBJECTIVE: This study was conducted to examine the relation between iron status and neurobehavioral development in premature infants.

STUDY DESIGN: Infants born before 34 weeks postmenstrual age and who were medically stable were studied. Anemia was defined as hemoglobin ≤10 g/Dl and low iron stores as a serum ferritin concentration ≤75 μg/l. The infants were classified as anemic with low ferritin (Group 1; n=18), anemic with normal ferritin (Group 2; n=14), and nonanemic with normal ferritin (Group 3; n=21). A total of 18 reflexes were behaviorally evaluated at 37 weeks postmenstrual age and “reflex scores” were compared between the groups. Higher scores reflect a greater percentage of abnormal reflexes.

RESULTS: Infants in group 1 (anemia/low ferritin) had a significantly higher reflex score (51.45±18.32%) than infants in Group 3 (38.32±17.75%). Group 2 had an intermediate score (45.40±21.70%), but not different from the other two groups.

CONCLUSION: These data indicate that low iron status, both measured by anemia and ferritin levels, is related to poorer neurobehavioral status in premature infants.

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References

  1. Lozoff B, Brittenham GM, Viteri FE, Wolf AW, Urrutia JJ . The effects of short term oral iron therapy on developmental deficits in iron-deficiency anemic infants. J Pediatr 1982;100:351–357.

    Article  CAS  Google Scholar 

  2. Palti H, Meijer A, Adler B . Learning achievement and behavior at school of anemic and non anemic infants. Early Hum Dev 1985;10:217–223.

    Article  CAS  Google Scholar 

  3. Lozoff B, Wolf AW, Jimenez E . Iron deficiency anemia and infant development: effects of extended oral iron therapy. J Pediatr 1996;129:382–389.

    Article  CAS  Google Scholar 

  4. Hurtado EK, Claussen AH, Scott KG . Early childhood anemia and mild or moderate mental retardation. Am J Clin Nutr 1999;69:115–119.

    Article  CAS  Google Scholar 

  5. Lozoff B, Klein NK, Nelson EC, McClish DK, Manuel M, Chacon ME . Behavior of infants with iron-deficiency anemia. Child Dev 1998;69:24–36.

    Article  CAS  Google Scholar 

  6. Lozoff B, Jimenez E, Hagen J, Mollen E, Wolf AW . Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics 2000;105:E51.

    Article  CAS  Google Scholar 

  7. Angulo-Kinzler RM, Peirano P, Lin E, Algarin C, Garrido M, Lozoff B . Twenty-four-hour motor activity in human infants with and without iron deficiency anemia. Early Hum Dev 2002;70:85–101.

    Article  CAS  Google Scholar 

  8. Lozoff B, De Andraca I, Castillo M, Smith JB, Walter T, Pino P . Behavioral and developmental effects of preventing iron-deficiency anemia in healthy full-term infants. Pediatr 2003;112:846–854.

    Google Scholar 

  9. Yehuda S, Youdin MBH . Brain iron: a lesson from animal models. Am J Clin Nutr 1989;50:618–629.

    Article  CAS  Google Scholar 

  10. Yehuda S . Neurochemical basis of behavioural effects of brain iron deficiency in anemia In Dobbing J, editor. Brain, Behaviour, and Iron in the Infant Diet. London: Springer-Verlag, 1990 p. 63–81.

    Chapter  Google Scholar 

  11. Beard JL, Connor JD, Jones BC . Brain iron: Location and function. Prog Food Nutr Sci 1993;17:183–221.

    CAS  PubMed  Google Scholar 

  12. Beard JL, Erikson KM, Jones BC . Neonatal iron deficiency results in irreversible changes in dopamine function in rats. J Nutr 2003;133:1174–1179.

    Article  CAS  Google Scholar 

  13. Yu GSM, Steinkirchner TM, Rao GA, Larkin EC . Effect of prenatal iron deficiency on myelination in rat pups. Am J Pathol 1986;125:620–624.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Larkin EC, Rao GA . Importance of fetal and neonatal iron: adequacy for normal development of central nervous system In Dobbing J, editor. Brain, Behaviour and Iron in the Infant Diet. London: Springer-Verlag, 1990 p. 43–62.

    Chapter  Google Scholar 

  15. Connor JR, Menzies SL . Relationship of iron to oligodendrocytes and myelination. Glia 1996;17:83–93.

    Article  CAS  Google Scholar 

  16. deUngria M, Rao R, Wobken JD, Luciana M, Nelson CA, Georgieff MK . Perinatal iron deficiency decreases cytochrome c oxidase (CytOx) activity in selected regions of neonatal rat brain. Pediatr Res 2000;48:169–176.

    Article  CAS  Google Scholar 

  17. Rao R, Tkac I, Townsend EL, Gruetter R, Georgieff MK . Perinatal iron deficiency alters the neurochemical profile of the developing rat hippocampus. J Nutr 2003;133:3215–3221.

    Article  CAS  Google Scholar 

  18. Jorgenson LA, Wobken JD, Georgieff MK . Perinatal iron deficiency alters apical dendritic growth in hippocampal CA1 pyramidal neurons. Dev Neurosci 2003;25:412–420.

    Article  CAS  Google Scholar 

  19. Tamura T, Goldenberg RL, Hoe J, et al. Cord serum ferritin concentrations and mental and psychomotor development of children at five years of age. J Pediatr 2002;140:165–170.

    Article  CAS  Google Scholar 

  20. Fleming RE . Cord serum ferritin levels, fetal iron status, and neurodevelopmental outcomes: correlations and confounding variables. J Pediatr 2002;140:145–148.

    Article  CAS  Google Scholar 

  21. Beard JL, Connor JR . Iron status and neural functioning. Annu Rev Nutr 2003;23:41–58.

    Article  CAS  Google Scholar 

  22. Siddappa AM, Georgieff MK, Wewerka S, Worka C, Nelson CA, deRegnier RA . Iron deficiency alters auditory recognition memory in newborn infants of diabetic mothers. Pediatr Res 2004;55:1034–1041.

    Article  CAS  Google Scholar 

  23. Rao R, Georgieff MK . Neonatal iron nutrition. Semin Neonatol 2001;6:425–435.

    Article  CAS  Google Scholar 

  24. Rao R, Georgieff MK . Perinatal aspects of iron metabolism. Acta Paediatr Suppl 2002;91:124–129.

    Article  CAS  Google Scholar 

  25. Kling PJ, Winzerling JJ . Iron status and the treatment of the anemia of prematurity. Clin Perinatol 2002;29:283–294.

    Article  CAS  Google Scholar 

  26. Plessler JL, Hepworth JT . Newborn neurologic screening using NBAS reflexes. Neonatal Netw 1997;16:33–46.

    Google Scholar 

  27. Zafeiriou DI, Tsikoulas IG, Kremenopoulos GM . Prospective follow-up of primitive reflex profile in high-risk infants: clues to an early diagnosis of cerebral palsy. Pediatr Neurol 1995;13:148–152.

    Article  CAS  Google Scholar 

  28. Als H, Lester BM, Tronick EC, Brazelton B . Toward a research instrument for the assessment of preterm infants' behavior In: Fitzgerald HE, Lester BM, Yogman MW, editors. Theory and Research in Behavioral Pediatrics. New York: Plenum, 1982 p. 35–63.

    Chapter  Google Scholar 

  29. Datta-Bhutada S, Johnson HL, Rosen TS . Intrauterine cocaine and crack exposure: neonatal outcomes. J Perinatol 1998;18:183–188.

    CAS  PubMed  Google Scholar 

  30. Coles CD, Smith IE, Falek A . Prenatal alcohol exposure and infant behavior: immediate effects and implications for later development. Adv Alcohol Subst Abuse 1987;6:87–104.

    Article  CAS  Google Scholar 

  31. Raga WJ, Gladen BC, McKinney JD, et al. Neonatal effects of transplacental exposure to PCB and DDE. J Pediatr 1986;109:335–341.

    Article  Google Scholar 

  32. Georgieff MK, Wewerkw SW, Nelson CA, deRegnier RA . Iron status at 9 months of infants with low iron stores at birth. J Pediatr 2002;141:405–409.

    Article  CAS  Google Scholar 

  33. Ohls RK, Ehrenkranz RA, Wright LL, et al. Effects of early erythropoietin on the transfusion requirements of preterm infants below 1250 grams birth weight: A multicenter, randomized, controlled trial. Pediatrics 2001;108:934–942.

    Article  CAS  Google Scholar 

  34. Maier RF, Obladen M, Muller-Hansen I, et al. Early treatment with erythropoietin β ameliorates anemia and reduced transfusion requirements in infants with birth weight below 1000 g. J Pediatr 2002;141:8–15.

    Article  CAS  Google Scholar 

  35. International Neonatal Network. The CRIB (clinical risk index for babies) score: a tool for assessing initial neonatal risk and comparing performance of neonatal intensive care units. Lancet 1993;342:193–198.

  36. Richardson DK, Corcoran JD, Escobar GJ, Lee SK . SNAP-II and SNAPPE-II: simplified newborn illness severity and mortality risk score. J Pediatr 2001;138:92–100.

    Article  CAS  Google Scholar 

  37. Lago P, Freato F, Bettiol T, Chiandetti L, Vianello A, Zaramella P . Is the CRIB score (clinical risk index for babies) a valid tool in predicting neurodevelopmental outcome in extremely low birth weight infants? Biol Neonate 1999;76:220–227.

    Article  CAS  Google Scholar 

  38. Mattia FR, deRegnier RA . Chronic physiologic instability is associated with neurodevelopmental morbidity at one and two years in extremely premature infants. Pediatrics 1998;102:E35.

    Article  CAS  Google Scholar 

  39. Roncagliolo M, Garrido M, Walter T, Peirano P, Lozoff B . Evidence of altered central nervous system development in infants with iron deficiency anemia at 6 mo: delayed maturation of auditory brainstem responses. Am J Clin Nutr 1998;68:683–690.

    Article  CAS  Google Scholar 

  40. Algarin C, Peirano P, Garrido M, Pizarro F, Lozoff B . Iron deficiency anemia in infancy: long-lasting effects on auditory and visual system functioning. Pediatr Res 2003;53:217–223.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Shaare-Zedek Medical Center, Jerusalem, Israel

    Rinat Armony-Sivan PhD & Arthur I Eidelman MD

  2. Hebrew University School of Medicine, Jerusalem

    Arthur I Eidelman MD

  3. Biochemistry Department, Bnai-Zion Medical Center, Haifa, Israel

    Amos Lanir PhD

  4. The Interdisciplinary Department of Social Sciences, Bar-Ilan University, Ramat Gan, Israel

    Devora Sredni PhD

  5. Department of Psychology, Bar-Ilan University, Ramat Gan, Israel

    Shlomo Yehuda PhD

Authors
  1. Rinat Armony-Sivan PhD
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  2. Arthur I Eidelman MD
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  3. Amos Lanir PhD
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  4. Devora Sredni PhD
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  5. Shlomo Yehuda PhD
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Supported in part by the Irving Harris Early Development Educational Program of the Shaare-Zedek Medical Center, Jerusalem, Israel.

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Armony-Sivan, R., Eidelman, A., Lanir, A. et al. Iron Status and Neurobehavioral Development of Premature Infants. J Perinatol 24, 757–762 (2004). https://doi.org/10.1038/sj.jp.7211178

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