SEARCHNARRATIVE_REVIEWpediatrics, obstetrics and gynecology

narrative_review·pediatrics, obstetrics and gynecology, neurology, nutrition, micronutrients·PMC10490173

The Interaction between Psychological Stress and Iron Status on Early-Life Neurodevelopmental Outcomes

Nutrients · 2 authors, 3 centres

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This narrative review examines how psychological stress and iron deficiency may interact to influence early-life neurodevelopment, focusing on shared pathways including hypothalamic–pituitary–adrenocortical (HPA) axis dysregulation, proinflammatory cytokine elevation, and hepcidin-mediated iron metabolism disruption. A central proposed mechanism is that chronic psychological stress elevates IL-6 and CRP, which in turn activates hepcidin and may disrupt iron absorption and utilization even with adequate intake. The review highlights that no prior study has simultaneously examined both exposures' combined contributions to neurodevelopment.

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narrative_review

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pediatrics

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ORIGINAL PAPER

PMC10490173

The Interaction between Psychological Stress and Iron Status on Early-Life Neurodevelopmental Outcomes

Nutrients

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ABSTRACT

Abstract This review presents evidence from animal and human studies demonstrating the possible connection and significant impact of poor iron status and psychological distress on neurocognitive development during pregnancy and the neonatal period, with implications for long-term cognition. Stress and iron deficiency are independently prevalent and thus are frequently comorbid. While iron deficiency and early-life stress independently contribute to long-term neurodevelopmental alterations, their combined effects remain underexplored. Psychological stress responses may engage similar pathways as infectious stress, which alters fundamental iron metabolism processes and cause functional tissue-level iron deficiency. Psychological stress, analogous to but to a lesser degree than infectious stress, activates the hypothalamic–pituitary–adrenocortical (HPA) axis and increases proinflammatory cytokines. Chronic or severe stress is associated with dysregulated HPA axis functioning and a proinflammatory state. This dysregulation may disrupt iron absorption and utilization, likely mediated by the IL-6 activation of hepcidin, a molecule that impedes iron absorption and redistributes total body iron. This narrative review highlights suggestive studies investigating the relationship between psychological stress and iron status and outlines hypothesized mechanistic pathways connecting psychological stress exposure and iron metabolism. We examine findings regarding the overlapping impacts of early stress exposure to iron deficiency and children’s neurocognitive development. We propose that studying the influence of psychological stress on iron metabolism is crucial for comprehending neurocognitive development in children exposed to prenatal and early postnatal stressors and for children at risk of early iron insufficiency. We recommend future directions for dual-exposure studies exploring iron as a potential mediating pathway between early stress and offspring neurodevelopment, offering opportunities for targeted interventions. Keywords: psychological stress, pregnancy, infancy, iron status, inflammation, neurodevelopment

CITATION EXPORT

Brie M Reid, Michael K Georgieff. The Interaction between Psychological Stress and Iron Status on Early-Life Neurodevelopmental Outcomes. Nutrients. (2023). https://doi.org/10.3390/nu15173798

AUTHORS

2 · 3 CENTRES

Brie M Reid, Michael K Georgieff

1Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA
2Center for Behavioral and Preventive Medicine, The Miriam Hospital, Providence, RI 02906, USA
3Division of Neonatology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA; [email protected]