For Healthcare Professionals only

Role of Iron in Brain Development of Infants
By - Danone Nutricia Academy

Iron is an essential nutrient for the developing foetus, neonate, infant, and child. Its requirements are high during early years of life because it is critically important for the production of new red blood cells, muscle cells as well as for brain development . For brain development the first 1000 days of life, from conception to two years of age, are recognised as the most critical period 2.

Role of Iron in brain development 1,3

  • Development and proliferation of cells: Iron helps in development and proliferation of brain cells.
  • Growth and development of the central nervous system: During fetal development, iron plays a profound role in organ development, particularly the brain.
  • Myelination: Iron is directly involved in myelin production as an essential co-factor for cholesterol and lipid biosynthesis and indirectly because of its requirement for oxidative metabolism (which compared to other brain cells occurs at a higher rate in the oligodendrocytes)4.
  • Monoamine neurotransmitter function: Iron affects synthesis and signaling of the neurotransmitters dopamine, noradrenalin, adrenaline and 5-hydroxytryptamine, which are involved in emotion, attention, reward, movement, and various other functions5.
  • Neuronal and glial energy metabolism: It participates in energy metabolism through its role as a catalytic component of mitochondrial proteins6.
  • Hippocampal dendritogenesis: Helps especially neuronal maturation (i.e. axon/dendrite branching, growth and spine/synapse formation) 7.

Iron in Neonates and Early childhood.

Full-term infants usually have high to normal hemoglobin concentrations (15–17 g/dl) at birth and then remain iron replete till 6 months of age. Children of mothers having Iron Deficiency Anemia (IDA) are at increased risk of iron deficiency (ID), but this deficiency develops at 4–6 months and is not apparent at birth. Premature babies have greater iron requirements than healthy full-term babies (Table 1). They also have lower iron stores than full-term infants and are at increased risk of developing ID and IDA1

Table 1

Daily iron requirements during childhood1

Age

Recommended dietary amount

Full-term (0-1 year old)

1 mg/kg

Premature (0-1 year old)

2 – 4 mg/kg

1- to 3-year-olds

7 mg

Iron Absorption and Availability1,3

  • Iron is available to new born babies, infants, and children from dietary sources including human milk (lactoferrin) and heme- and non-heme-containing foods. Iron in breast milk has high bioavailability (upto 50%)
  • Heme iron is the most bioavailable form of iron and is easily absorbed from meat, eggs, and fish.
  • Non-heme iron is available from vegetables [especially dark green leafy vegetables, lentils, beans, whole grain cereals and millets like finger millet(ragi), pearl millet(bajra)]
  • Absorption of non-heme iron is increased when consumed with foods rich in vitamin C (oranges, sweet lime, lemon, strawberry, kiwi, amla, tomatoes) and decreased by phytate (in bran, oats), polyphenols (in coffee, tea and cocoa), dietary calcium, and soy proteins.
  • Calcium hinders the absorption of iron by as much as 60% and thus there is a risk of ID in children who drink more than 700 mL of cow’s milk per day.
  • Iron absorption is highly dependent on the individual's iron status too. If a child is iron deficient, absorption percentage will be more.

Effects of Iron Deficiency on Brain

ID in children below two years of age can have irreversible and crirical effects on brain development 8. Infants with ID can have various symptoms that are associated with reduced myelination, impaired hippocampal function, altered dopamine metabolism and altered temperament. For example, iron-deficient infants can have decreased attention and memory1. Children with IDA also have been shown to have long-lasting behavioural problems, including wariness, hesitance, externalizing and internalizing problems and poor motor development3.

Iron is critical in the process of neurodevelopment which is most rapid during the first years of life. IDA in infancy is associated with long-lasting poor cognitive and behavioural performance. It can be prevented by ensuring adequate iron intake in early life.

For Healthcare Professionals use only, not for distribution to general public.

References:

  1. Cerami C. (2017). Iron Nutriture of the Fetus, Neonate, Infant, and Child. Annals of nutrition & metabolism, 71 Suppl 3(Suppl 3), 8–14. https://doi.org/10.1159/000481447
  2. McCann, S., Perapoch Amadó, M., & Moore, S. E. (2020). The Role of Iron in Brain Development: A Systematic Review. Nutrients, 12(7), 2001. https://doi.org/10.3390/nu12072 001
  3. Domellöf, M., Braegger, C., Campoy, C., Colomb, V., Decsi, T., Fewtrell, M., Hojsak, I., Mihatsch, W., Molgaard, C., Shamir, R., Turck, D., van Goudoever, J., & ESPGHAN Committee on Nutrition (2014). Iron requirements of infants and toddlers. Journal of pediatric gastroenterology and nutrition, 58(1), 119–129. https://doi.org/10.1097/MPG.0000
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  4. Connor, J. R., & Menzies, S. L. (1996). Relationship of iron to oligodendrocytes and myelination. Glia, 17(2), 83–93. https://doi.org/10.1002/(SICI)1098-1136(199606)17:2<83::AID-GLIA1>3.0.CO;2-7
  5. Dominic Hare, Scott Ayton, Ashley Bush & Peng Lei (2013). A delicate balance: iron metabolism and diseases of the brain. Front. Aging Neurosci. https://doi.org/10.3389/fnagi.2013. 00034
  6. Bastian, T. W., Rao, R., Tran, P. V., & Georgieff, M. K. (2020). The Effects of Early-Life Iron Deficiency on Brain Energy Metabolism. Neuroscience insights, 15, 2633105520935104. https://doi.org/10.1177/26331055 209
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  7. Bastian, T. W., von Hohenberg, W. C., Mickelson, D. J., Lanier, L. M., & Georgieff, M. K. (2016). Iron Deficiency Impairs Developing Hippocampal Neuron Gene Expression, Energy Metabolism, and Dendrite Complexity. Developmental neuroscience, 38(4), 264–276. https://doi.org/10.1159/000448514
  8. WHO guidance helps detect iron deficiency and protect brain development Available from : https://www.who.int/news/item/20-04-2020-who-guidance-helps-detect-iron-deficiency-and-protect-brain-development

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