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Perinatal iron deficiency and neurocognitive development
Open accessAbstract
Iron deficiency is the most common form of nutrient deficiency worldwide. It is highly prevalent due to the limited availability of high quality food in developing countries and poor dietary habits in industrialized countries. According to the World Health Organization, it affects nearly 2 billion people and up to 50% of women who are pregnant. Maternal anemia during pregnancy is especially burdensome to healthy neurodevelopment in the fetus because iron is needed for proper neurogenesis, development, and myelination. Maternal anemia also increases the risk of low birth weight, either due to premature birth or fetal growth restriction, which is associated with delayed neurocognitive development and even psychiatric illness. As rapid neurodevelopment continues after birth infants that received sufficient iron in utero, but that receive a low iron diet after 6 months of age, also show deficits in neurocognitive development, including impairments in learning and memory. Unfortunately, the neurocognitive complications of iron deficiency during critical pre- and postnatal periods of brain development are difficult to remedy, persisting into adulthood. Thus, preventing iron deficiency in the pre- and postnatal periods is critical as is devising new means to recapture cognitive function in individuals who experienced early iron deficiency. This review will discuss the prevalence of pre- and postnatal iron deficiency, the mechanism, and effects of iron deficiency on brain and cognitive development.
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“the neurocognitive damage elicited by iron deficiency during this period is irreversible and will persist into adulthood [176].”
From Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence (2020) · cites this paper as [176]
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“There is a wide consensus regarding the critical importance of appropriate iron supply during neurodevelopment from birth, and even before, up to the first years of life”
From Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence (2020) · cites this paper as [176]
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InfluentialIron Metabolism and Ferroptosis in Physiological and Pathological Pregnancy
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Hassan, N. E., Boville, B. M., Reischmann, D., Ndika, A. N., Sterken, D. J., & Kovey, K. (2017) · Annals of Pharmacotherapy · doi:10.1177/1060028017699429 · Cited by 36
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“Consequently, its deficiency during childhood has been associated with short- and longterm deficiencies in cognitive, motor, socio-emotional, and behavioral development (105, 106).”
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“Iron is one of the key minerals in human nutrition because of its physiological functions including oxygen transport, synthesis of enzymes, energy production, and regulation of immune functions (Radlowski and Johnson, 2013).”
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“Iron is also known to play a crucial role in brain development and maintenance of neuronal activity and networks [2,3].”
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Auerbach, M., James, S. E., Nicoletti, M., Lenowitz, S., London, N., Bahrain, H., Derman, R. J., & Smith, S. L. (2017) · The American Journal of Medicine · doi:10.1016/j.amjmed.2017.06.025 · Cited by 32
Teng, X., Shan, Z., Li, C., Yu, X., Mao, J., Wang, W., Xie, X., Du, J., ShaoWei, Z., Gao, Z., et al. (2018) · Thyroid · doi:10.1089/thy.2017.0491 · Cited by 32
Nicklas, T. A., O’Neil, C. E., & Fulgoni, V. L. I. (2020) · AIMS Public Health · doi:10.3934/publichealth.2020012 · Cited by 32
“Therefore, iron deficiency remains a public health concern for infants, particularly because iron is a critical nutrient for neurodevelopment [15,16].”
BackgroundAssociation of Maternal and Child Anemia With Brain Structure in Early Life in South Africa
Wedderburn, C. J., Ringshaw, J. E., Donald, K. A., Joshi, S. H., Subramoney, S., Fouché, J., Stadler, J. A. M., Barnett, W., Rehman, A. M., Hoffman, N., et al. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.44772 · Cited by 31
“3% (46 of 147; median [IQR] gestation of measurement: 13 [9-20] weeks).”
Meeting iron needs for infants and children
Berglund, S. K., & Domellöf, M. (2014) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000043 · Cited by 31
Defining peri‐operative anaemia in pregnant women – challenging the status quo
Ferguson, M., & Dennis, A. T. (2018) · Anaesthesia · doi:10.1111/anae.14468 · Cited by 31
“Maternal ferritin levels correlate with neonatal ferritin levels, and iron-dependent neurogenesis is maximum during the third trimester and in early neonatal life [15, 16].”
BackgroundNyachoti, S., Adebayo, S., & Godebo, T. R. (2020) · Journal of Food Composition and Analysis · doi:10.1016/j.jfca.2020.103660 · Cited by 31
Mudd, A. T., Fil, J. E., Knight, L., Lam, F., Liang, Z., & Dilger, R. N. (2018) · Nutrients · doi:10.3390/nu10020135 · Cited by 34
Ashish, K. C., Målqvist, M., Rana, N., Ranneberg, L. J., & Andersson, O. (2016) · BMC Pediatrics · doi:10.1186/s12887-016-0576-z · Cited by 31
“As ID in infants even without anaemia has been associated with impaired development [15, 16], delayed cord clamping seems to benefit full term infants even in regions with a relatively low prevalence of ID anaemia [12].”
BackgroundIglesias‐Vázquez, L., Arija, V., Aranda, N., Aparicio, E., Serrat, N., Fargas, F., Ruiz, F., Pallejà-Millán, M., Coronel, P., Gimeno, M., et al. (2019) · Nutrients · doi:10.3390/nu11102418 · Cited by 29
Paving the way for adequate myelination: The contribution of galectin‐3, transferrin and iron
Franco, P. G., Pasquini, L. A., Pérez, M. J., Rosato‐Siri, M. V., Silvestroff, L., & Pasquini, J. M. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.08.001 · Cited by 29
Maternal and Cord Blood Hepcidin Concentrations in Severe Iron Deficiency Anemia
Basu, S., Kumar, N., Srivastava, R., & Kumar, A. (2016) · Pediatrics & Neonatology · doi:10.1016/j.pedneo.2015.09.012 · Cited by 28
Kim, S., Yadav, D., Kim, S., Kim, J., & Cho, K. (2017) · Nutrients · doi:10.3390/nu9070690 · Cited by 28
Abbas, M., Hayirli, Z., Drakesmith, H., Andrews, S. C., & Lewis, M. C. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.927754 · Cited by 32
“Poor efficiency of iron transfer through the placenta is an important contributing factor for the relatively low maternal iron endowment received prior to birth in both humans (130) and pigs (131).”
BackgroundElalfy, M. S., El-Farrash, R. A., Taha, H., Ismail, E. A. R., & Mokhtar, N. A. (2018) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767058.2018.1533940 · Cited by 26
“This finding supports earlier studies [2,5,7].”
BackgroundFactors associated with timing of umbilical cord clamping in tertiary hospital of Nepal
Nelin, V., Ashish, K. C., Andersson, O., Rana, N., & Målqvist, M. (2018) · BMC Research Notes · doi:10.1186/s13104-018-3198-8 · Cited by 26
Marcewicz, L. H., Anderson, B. L., Byams, V. R., Grant, A. M., & Schulkin, J. A. (2017) · Maternal and Child Health Journal · doi:10.1007/s10995-016-2252-1 · Cited by 25
“IDA in pregnancy may also contribute to poorer cognitive development and IDA among children (Radlowski and Johnson 2013), and has been implicated in the development of post-partum depression (Albacar et al. 2011).”
Backgroundde Lauzon‐Guillain, B., Marques, C., Kadawathagedara, M., Bernard, J. Y., Tafflet, M., Lioret, S., & Charles, M.-A. A. (2022) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqac206 · Cited by 26
Lucas, E. S., & Watkins, A. J. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-62414-3_8 · Cited by 26
Rapid diagnostics for point-of-care quantification of soluble transferrin receptor
Srinivasan, B., Finkelstein, J. L., O’Dell, D., Erickson, D., & Mehta, S. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.03.017 · Cited by 25
“Iron is the most common nutritional deficiency among infants and children, with an estimated prevalence of 3–80% [1], and is associated with long-term detrimental effects on neurodevelopment [2,3] which may be irreversible.”
BackgroundSchoolchildren with Learning Difficulties Have Low Iron Status and High Anemia Prevalence
Arcanjo, F. P. N., Arcanjo, C. P. C., & Santos, P. R. (2016) · Journal of Nutrition and Metabolism · doi:10.1155/2016/7357136 · Cited by 27
“According to Radlowski and Johnson [17] ID delays learning and motor and emotional development; individuals exposed to ID during the perinatal period are at high risk for not reaching educational standards later in life.”
BackgroundTrace elements during primordial plexiform network formation in human cerebral organoids
Sartore, R., Cardoso, S. C., Lages, Y., Paraguassu, J. M., Stelling, M. P., da Costa, R. M., Guimarães, M. Z. P., Perez, C. A., & Rehen, S. K. (2017) · PeerJ · doi:10.7717/peerj.2927 · Cited by 24
“While less understood, abnormalities in the levels of essential minerals potentially 69 begin in utero (Radlowski & Johnson, 2013; Golub & Hogrefe, 2015).”
BackgroundSpectrum of anemia after kidney transplantation: pathophysiology and therapeutic implications
Bamgbola, O. F. (2016) · Clinical Transplantation · doi:10.1111/ctr.12813 · Cited by 24
“Children may sustain irreparable neurodevelopmental loss (115).”
BackgroundMohammed, N. I., Wason, J. M. S., Mendy, T., Nass, S. A., Ofordile, O., Camara, F., Baldeh, B., Sanyang, C., Jallow, A. T., Hossain, I. M., et al. (2023) · EClinicalMedicine · doi:10.1016/j.eclinm.2023.101853 · Cited by 23
Moos, T., Skjørringe, T., & Thomsen, L. (2018) · Reproductive Health · doi:10.1186/s12978-018-0537-0 · Cited by 19
Iron Deficiency Affects Seizure Susceptibility in a Time- and Sex-Specific Manner
Rudy, M. J., & Mayer‐Pröschel, M. (2017) · ASN NEURO · doi:10.1177/1759091417746521 · Cited by 22
“Its effect on developing children is particularly devastating since iron supplementation later in life cannot remedy the learning difficulties, behavioral problems, and psychiatric disorders that are associated with early life ID (Lozoff et al., 2000; Chen et al., 2013; Lozoff et al., 2013; Radlowski and Johnson, 2013…”
BackgroundKangalgil, M., Şahinler, A., Kırkbir, İ. B., & Özçelik, A. Ö. (2021) · Journal of Gynecology Obstetrics and Human Reproduction · doi:10.1016/j.jogoh.2021.102137 · Cited by 22
Overview of iron deficiency and iron deficiency anemia in women and girls of reproductive age
Derman, R. J., & Patted, A. (2023) · International Journal of Gynecology & Obstetrics · doi:10.1002/ijgo.14950 · Cited by 22
Iron overload induces hypogonadism in male mice via extrahypothalamic mechanisms
Macchi, C., Steffani, L., Oleari, R., Lettieri, A., Valenti, L. V. C., Dongiovanni, P., Romero‐Ruíz, A., Tena‐Sempere, M., Cariboni, A. M., Magni, P., et al. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.06.019 · Cited by 22
“It is also required for proper brain development during embryogenesis, and for brain function in the early neonatal period and adult age (Radlowski and Johnson, 2013).”
BackgroundMudd, A. T., Fil, J. E., Knight, L. C., & Dilger, R. N. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2017.00735 · Cited by 27
German, K. R., Vu, P. T., Irvine, J. D., & Juul, S. E. (2019) · Journal of Perinatology · doi:10.1038/s41372-019-0434-6 · Cited by 21
Sandri, B. J., Lubach, G. R., Lock, E. F., Georgieff, M., Kling, P. J., Coe, C. L., & Rao, R. (2019) · Journal of Nutrition · doi:10.1093/jn/nxz274 · Cited by 22
Pathophysiology of Iron Homeostasis during Inflammatory States
Cherayil, B. J. (2015) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2015.07.015 · Cited by 24
“neurocognitive development, an issue of particular importance in infants and young children (4).”
Background
Metadata
- Authors
- Radlowski, E. C., & Johnson, R. W.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Johnson, Rodney W.
- ORCID
- Johnson, Rodney W.
- Venue
- Frontiers in Human Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 7
- Pages
- 585-585
- ISSN
- 1662-5161 (ISSN-L)
- PMC
- PMC3779843
- OpenAlex
- W1980560945
- Cited by
- 315
- References
- 104
- Citations by year
- 2026: 16 · 2025: 27 · 2024: 17 · 2023: 32 · 2022: 34 · 2021: 25 · 2020: 23 · 2019: 23 · 2018: 29 · 2017: 33 · 2016: 20 · 2015: 21 · 2014: 13 · 2013: 1
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Human Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Aging (R01AG016710)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD069899)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Nursing › Nutrition and Dietetics › Child Nutrition and Water Access
- Keywords
- iron deficiency, neurocognitive development, low birth weight, fetal growth restriction, preterm birth, brain development, neurogenesis, myelination, learning and memory impairment, cognitive recovery, iron deficiency prevention
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