Correcting iron deficiency after birth may not be enough to reverse its effects on the developing brain, according to new research from the University of Rochester. Scientists found that insufficient iron during pregnancy can trigger lasting changes in brain chemistry, gene activity and communication between nerve cells, even after iron levels in the blood return to normal.

Published in The Journal of Nutrition, the study highlights the importance of adequate iron during early pregnancy, when the foundations of the brain are being established. Previous population studies have linked low maternal iron levels during the first trimester with an increased risk of neurodevelopmental conditions, including autism, attention-deficit/hyperactivity disorder (ADHD) and learning disabilities.

“Pregnancy is a critical window for iron-dependent brain development, and current clinical measures may underestimate the long-term impact of prenatal iron deficiency,” said Dr Margot Mayer-Proschel, professor of Biomedical Genetics and Neuroscience at the University of Rochester School of Medicine & Dentistry and lead author of the study.

To investigate these effects, researchers used a mouse model, feeding animals either iron-rich or iron-deficient diets before conception and throughout pregnancy. After birth, all mice received adequate iron to determine whether the effects of prenatal deficiency could be reversed. Although blood iron levels eventually returned to normal, the researchers discovered that iron remained unevenly distributed throughout the brain. Some regions continued to experience deficiencies, while others accumulated excessive amounts.

The disruption extended beyond iron. Researchers identified imbalances in several other essential minerals, including calcium, magnesium, manganese, copper and zinc, all of which contribute to healthy brain development and function. These abnormalities were considerably more pronounced in brain tissue than in blood, suggesting that routine blood tests may fail to detect persistent neurological effects.

Further analysis revealed long-term alterations in gene networks responsible for brain development and communication between nerve cells. Among the affected processes was myelin formation, which creates the protective insulation surrounding nerve fibres and enables electrical signals to travel efficiently. Disruptions to this process could interfere with normal communication between neurons.

The researchers also identified altered activity in genes associated with neurodevelopment and autism spectrum disorder. The changes differed across brain regions, with reduced gene activity in the cortex, hippocampus and thalamus, but increased activity in the posterior cortex. Particularly extensive changes appeared in the superior colliculus, a region involved in sensory processing and attention.

The findings suggest that restoring normal blood iron levels may not guarantee recovery of the developing brain. Although the research was conducted in mice and its implications for humans require further investigation, it raises important questions about how prenatal iron deficiency is detected and managed. Mayer-Proschel emphasised the need for brain-specific biomarkers that could identify hidden developmental changes and support earlier interventions to protect children’s long-term neurological health.

More information: Janine Cubello et al, Postnatal Iron Supplementation Fails to Fully Rescue Brain Metal and Transcriptional Defects Caused by Nutrition-Based Gestational Iron Deficiency, The Journal of Nutrition. DOI: 10.1016/j.tjnut.2026.101730

Journal information: The Journal of Nutrition Provided by University of Rochester Medical Center