Iron Metabolism and Brain Development in Premature Infants

Overview

Journal Front Physiol

Date 2019 May 21

PMID 31105583

Citations 39

Authors

Yafeng Wang

Yanan Wu

Tao Li

Xiaoyang Wang

Changlian Zhu

Affiliations

Soon will be listed here.

Abstract

Iron is important for a remarkable array of essential functions during brain development, and it needs to be provided in adequate amounts, especially to preterm infants. In this review article, we provide an overview of iron metabolism and homeostasis at the cellular level, as well as its regulation at the mRNA translation level, and we emphasize the importance of iron for brain development in fetal and early life in preterm infants. We also review the risk factors for disrupted iron metabolism that lead to high risk of developing iron deficiency and subsequent adverse effects on neurodevelopment in preterm infants. At the other extreme, iron overload, which is usually caused by excess iron supplementation in iron-replete preterm infants, might negatively impact brain development or even induce brain injury. Maintaining the balance of iron during the fetal and neonatal periods is important, and thus iron status should be monitored routinely and evaluated thoroughly during the neonatal period or before discharge of preterm infants so that iron supplementation can be individualized.

Citing Articles

Role of iron in brain development, aging, and neurodegenerative diseases.

Gao Q, Zhou Y, Chen Y, Hu W, Jin W, Zhou C Ann Med. 2025; 57(1):2472871.

PMID: 40038870 PMC: 11884104. DOI: 10.1080/07853890.2025.2472871.

Brain iron deposition and cognitive decline in patients with cerebral small vessel disease : a quantitative susceptibility mapping study.

Gao Y, Liang C, Zhang Q, Zhuang H, Sui C, Zhang N Alzheimers Res Ther. 2025; 17(1):17.

PMID: 39789638 PMC: 11715900. DOI: 10.1186/s13195-024-01638-x.

Preterm Piglets Born by Cesarean Section as a Suitable Animal Model for the Study of Iron Metabolism in Premature Infants.

Wang X, Lenartowicz M, Mazgaj R, Ogluszka M, Szkopek D, Zaworski K Int J Mol Sci. 2024; 25(20).

PMID: 39456997 PMC: 11508764. DOI: 10.3390/ijms252011215.

A Study on the Effect of Umbilical Cord Milking Along With Delayed Cord Clamping on Hematological Parameters in Comparison to Delayed Cord Clamping Alone in Moderate-to-Late Preterm Newborns.

Dahiya P, Shweta , Parashar A, Lohakare T Cureus. 2024; 16(9):e69256.

PMID: 39403649 PMC: 11472205. DOI: 10.7759/cureus.69256.

Polysomnographically Defined Restless Sleep Disorder and Periodic Limb Movements during Sleep in Children Born Prematurely.

DelRosso L, Artinian H, Mogavero M, Bruni O, Witmans M, Tablizo M Children (Basel). 2024; 11(6).

PMID: 38929237 PMC: 11202265. DOI: 10.3390/children11060658.

References

Gazzolo D, Perrone S, Paffetti P, Longini M, Vezzosi P, Bruschettini M . Non protein bound iron concentrations in amniotic fluid. Clin Biochem. 2005; 38(7):674-7. DOI: 10.1016/j.clinbiochem.2005.03.010. View

Leong W, Bowlus C, Tallkvist J, Lonnerdal B . Iron supplementation during infancy--effects on expression of iron transporters, iron absorption, and iron utilization in rat pups. Am J Clin Nutr. 2003; 78(6):1203-11. DOI: 10.1093/ajcn/78.6.1203. View

MacQueen B, Christensen R, Ward D, Bennett S, OBrien E, Sheffield M . The iron status at birth of neonates with risk factors for developing iron deficiency: a pilot study. J Perinatol. 2016; 37(4):436-440. PMC: 5389916. DOI: 10.1038/jp.2016.234. View

Lozoff B, Castillo M, Clark K, Smith J, Sturza J . Iron supplementation in infancy contributes to more adaptive behavior at 10 years of age. J Nutr. 2014; 144(6):838-45. PMC: 4018948. DOI: 10.3945/jn.113.182048. 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

Ganaie M, Charoo B, Sofi R, Ahmed A, Bhat J . Maternal Overt Hypothyroidism and Neurobehavioral Outcome of Neonates: A Cohort Study from an Iodine-deficient Area of Northern India. Indian Pediatr. 2015; 52(10):864-6. DOI: 10.1007/s13312-015-0733-8. View

Langkammer C, Krebs N, Goessler W, Scheurer E, Ebner F, Yen K . Quantitative MR imaging of brain iron: a postmortem validation study. Radiology. 2010; 257(2):455-62. DOI: 10.1148/radiol.10100495. View

Jopling J, Henry E, Wiedmeier S, Christensen R . Reference ranges for hematocrit and blood hemoglobin concentration during the neonatal period: data from a multihospital health care system. Pediatrics. 2009; 123(2):e333-7. DOI: 10.1542/peds.2008-2654. View

Laptook A . Birth Asphyxia and Hypoxic-Ischemic Brain Injury in the Preterm Infant. Clin Perinatol. 2016; 43(3):529-45. DOI: 10.1016/j.clp.2016.04.010. View

10.

Beard J, Erikson K, Jones B . Neurobehavioral analysis of developmental iron deficiency in rats. Behav Brain Res. 2002; 134(1-2):517-24. DOI: 10.1016/s0166-4328(02)00092-x. View

11.

Xu Y, Wang H, Sun Y, Shang Q, Chen M, Li T . The association of apolipoprotein E gene polymorphisms with cerebral palsy in Chinese infants. Mol Genet Genomics. 2014; 289(3):411-6. DOI: 10.1007/s00438-014-0818-4. View

12.

Benton D . Micronutrient status, cognition and behavioral problems in childhood. Eur J Nutr. 2008; 47 Suppl 3:38-50. DOI: 10.1007/s00394-008-3004-9. View

13.

Stephenson E, Nathoo N, Mahjoub Y, Dunn J, Yong V . Iron in multiple sclerosis: roles in neurodegeneration and repair. Nat Rev Neurol. 2014; 10(8):459-68. DOI: 10.1038/nrneurol.2014.118. View

14.

Saito H . METABOLISM OF IRON STORES. Nagoya J Med Sci. 2015; 76(3-4):235-254. PMC: 4345694. View

15.

Shao J, Lou J, Rao R, Georgieff M, Kaciroti N, Felt B . Maternal serum ferritin concentration is positively associated with newborn iron stores in women with low ferritin status in late pregnancy. J Nutr. 2012; 142(11):2004-9. PMC: 3498973. DOI: 10.3945/jn.112.162362. View

16.

Christian E, Jin D, Attenello F, Wen T, Cen S, Mack W . Trends in hospitalization of preterm infants with intraventricular hemorrhage and hydrocephalus in the United States, 2000-2010. J Neurosurg Pediatr. 2015; 17(3):260-9. DOI: 10.3171/2015.7.PEDS15140. View

17.

McCarthy R, Kosman D . Iron transport across the blood-brain barrier: development, neurovascular regulation and cerebral amyloid angiopathy. Cell Mol Life Sci. 2014; 72(4):709-27. PMC: 4312246. DOI: 10.1007/s00018-014-1771-4. View

18.

Lonnerdal B, Georgieff M, Hernell O . Developmental Physiology of Iron Absorption, Homeostasis, and Metabolism in the Healthy Term Infant. J Pediatr. 2015; 167(4 Suppl):S8-14. PMC: 4634531. DOI: 10.1016/j.jpeds.2015.07.014. View

19.

Kc A, Rana N, Malqvist M, Ranneberg L, Subedi K, Andersson O . Effects of Delayed Umbilical Cord Clamping vs Early Clamping on Anemia in Infants at 8 and 12 Months: A Randomized Clinical Trial. JAMA Pediatr. 2017; 171(3):264-270. DOI: 10.1001/jamapediatrics.2016.3971. View

20.

Huo K, Sun Y, Li H, Du X, Wang X, Karlsson N . Lithium reduced neural progenitor apoptosis in the hippocampus and ameliorated functional deficits after irradiation to the immature mouse brain. Mol Cell Neurosci. 2012; 51(1-2):32-42. DOI: 10.1016/j.mcn.2012.07.002. View