Association Between Neonatal Iron Overload and Early Human Brain Development in Premature Infants

Overview

Journal Early Hum Dev

Publisher Elsevier

Specialties Gynecology & Obstetrics
Pediatrics
Reproductive Medicine

Date 2012 Feb 22

PMID 22349188

Citations 11

Authors

Sanjiv B Amin

Gary Myers

Hongyue Wang

Affiliations

Soon will be listed here.

Abstract

Background: Emerging evidence suggests that excess iron may be detrimental for brain development. However, little is known regarding the association between neonatal iron overload and subsequent neurodevelopment during infancy in vulnerable premature infants.

Aims: To evaluate the association between neonatal iron overload and neurodevelopment in premature infants.

Study Design: Prospective cohort study.

Subjects: 24-32 weeks gestational age infants who had serum ferritin (SF) measured at 34-35 weeks post-menstrual age (PMA) and did not meet exclusion criteria: SF<76 ng/ml, toxoplasmosis, syphilis, rubella, cytomegalovirus, herpes infections, chromosomal disorders, or craniofacial anomalies were eligible. In addition, infants with sepsis or elevated C-reactive protein within 10 days before their SF measurement were excluded.

Outcome Measures: Infants were evaluated for neurodevelopmental outcome at 8-12 months of age and were deemed to have neurodevelopmental impairment if they had one or more of the following: mental developmental index<70, abnormal neurological examination, bilateral blindness, bilateral deafness, or required occupational, physical, or speech therapy.

Results: 95 infants were studied. 70 had normal iron status (SF 76-400 ng/ml) while 25 were deemed to have iron overload (SF >400 ng/ml) at 34-35 weeks PMA. There was a marginal increase in neurodevelopmental impairment among infants with iron overload compared to infants with normal iron status (64% vs. 41%, p=0.05). However, after controlling for confounders, iron overload was not associated with neurodevelopmental impairment (Adjusted OR 0.71, 95% CI, 0.21-2.5).

Conclusion: Modest neonatal iron overload is not associated with neurodevelopmental impairment during infancy in premature infants.

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References

Kontoghiorghes G, Pattichi K, Hadjigavriel M, Kolnagou A . Transfusional iron overload and chelation therapy with deferoxamine and deferiprone (L1). Transfus Sci. 2000; 23(3):211-23. DOI: 10.1016/s0955-3886(00)00089-8. View

Rao R, Georgieff M . Iron therapy for preterm infants. Clin Perinatol. 2009; 36(1):27-42. PMC: 2657918. DOI: 10.1016/j.clp.2008.09.013. View

Breuer W, Hershko C, Cabantchik Z . The importance of non-transferrin bound iron in disorders of iron metabolism. Transfus Sci. 2000; 23(3):185-92. DOI: 10.1016/s0955-3886(00)00087-4. View

Berg D, Youdim M . Role of iron in neurodegenerative disorders. Top Magn Reson Imaging. 2006; 17(1):5-17. DOI: 10.1097/01.rmr.0000245461.90406.ad. View

Vohr B, Wright L, Poole W, McDonald S . Neurodevelopmental outcomes of extremely low birth weight infants <32 weeks' gestation between 1993 and 1998. Pediatrics. 2005; 116(3):635-43. DOI: 10.1542/peds.2004-2247. View

Buonocore G, Perrone S, Bracci R . Free radicals and brain damage in the newborn. Biol Neonate. 2001; 79(3-4):180-6. DOI: 10.1159/000047088. View

Burns Y, OCallaghan M, Tudehope D . Early identification of cerebral palsy in high risk infants. Aust Paediatr J. 1989; 25(4):215-9. DOI: 10.1111/j.1440-1754.1989.tb01459.x. View

Ozment C, Turi J . Iron overload following red blood cell transfusion and its impact on disease severity. Biochim Biophys Acta. 2008; 1790(7):694-701. DOI: 10.1016/j.bbagen.2008.09.010. View

Murthy J, Hicks J, Soldin S . Evaluation of the Technicon Immuno I random access immunoassay analyzer and calculation of pediatric reference ranges for endocrine tests, T-uptake, and ferritin. Clin Biochem. 1995; 28(2):181-5. DOI: 10.1016/0009-9120(94)00080-f. View

10.

Frisone M, Mercuri E, Laroche S, Foglia C, Maalouf E, Haataja L . Prognostic value of the neurologic optimality score at 9 and 18 months in preterm infants born before 31 weeks' gestation. J Pediatr. 2002; 140(1):57-60. DOI: 10.1067/mpd.2002.119626. View

11.

Stoltzfus R . Research needed to strengthen science and programs for the control of iron deficiency and its consequences in young children. J Nutr. 2008; 138(12):2542-6. DOI: 10.3945/jn.108.094888. View

12.

Bell E, Strauss R, Widness J, Mahoney L, Mock D, Seward V . Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants. Pediatrics. 2005; 115(6):1685-91. PMC: 2866196. DOI: 10.1542/peds.2004-1884. View

13.

Papanikolaou G, Pantopoulos K . Iron metabolism and toxicity. Toxicol Appl Pharmacol. 2005; 202(2):199-211. DOI: 10.1016/j.taap.2004.06.021. View

14.

. American Academy of Pediatrics Committee on Nutrition: Nutritional needs of low-birth-weight infants. Pediatrics. 1985; 75(5):976-86. View

15.

Siegel L . Correction for prematurity and its consequences for the assessment of the very low birth weight infant. Child Dev. 1983; 54(5):1176-88. View

16.

Ng P, Lam C, Lee C, To K, Fok T, Chan I . Hepatic iron storage in very low birthweight infants after multiple blood transfusions. Arch Dis Child Fetal Neonatal Ed. 2001; 84(2):F101-5. PMC: 1721227. DOI: 10.1136/fn.84.2.f101. View

17.

Morrison E, Brandhagen D, Phatak P, Barton J, Krawitt E, El-Serag H . Serum ferritin level predicts advanced hepatic fibrosis among U.S. patients with phenotypic hemochromatosis. Ann Intern Med. 2003; 138(8):627-33. DOI: 10.7326/0003-4819-138-8-200304150-00008. View

18.

Braekke K, Bechensteen A, Halvorsen B, Blomhoff R, Haaland K, Staff A . Oxidative stress markers and antioxidant status after oral iron supplementation to very low birth weight infants. J Pediatr. 2007; 151(1):23-8. DOI: 10.1016/j.jpeds.2007.02.016. View

19.

Hirano K, Morinobu T, Kim H, Hiroi M, Ban R, Ogawa S . Blood transfusion increases radical promoting non-transferrin bound iron in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2001; 84(3):F188-93. PMC: 1721242. DOI: 10.1136/fn.84.3.f188. View

20.

Kaur C, Ling E . Periventricular white matter damage in the hypoxic neonatal brain: role of microglial cells. Prog Neurobiol. 2009; 87(4):264-80. DOI: 10.1016/j.pneurobio.2009.01.003. View