Association between maternal iron deficiency and delayed neonatal auditory maturation and altered cochlear synaptic energy metabolism: analysis from a mother-infant observational study, mouse models, and cochlear explants.

Authors

Yi Zhao, Rui Hou, Wei Song, Wei Shao, Lifeng Zhang, Fei Yu, Shuai Hao

Published in

Frontiers in nutrition. Volume 13. Pages 1842147. Epub Jun 19, 2026.

Abstract

Iron is a key nutrient for the development of the fetal auditory system. However, the potential impact of non-anemic prenatal iron deficiency (ID) on neonatal auditory function remains unclear. This study aimed to systematically explore the potential mechanisms by which maternal ID may affect auditory maturation of offspring.
We analyzed population data from 696 mother-infant pairs, established ID mouse models (C57BL/6 J) during pregnancy, and conducted cellular experiments.
In the human cohort, maternal serum ferritin (SF) and hemoglobin (Hb) were significantly negatively associated with the latency (ms) of auditory brainstem response (ABR) waves I, III, and V, as well as intervals (ms) of waves I-III, III-V, and I-V and summating potential/action potential ratios (%). Neonatal SF partially mediated the association between maternal iron status and auditory function, with mediation effects ranging from 28.57 to 76.32%. In mouse models, prenatal ID was associated with decreased wave I amplitude and extended latency in offspring, along with reduced ribbon synapses in inner hair cells, mitochondrial damage, and decreased enzyme activity in supporting cells. A metabolomics analysis revealed significant downregulation of pyruvate levels in the ID group, and exogenous supplementation with sodium pyruvate partially restored ribbon synaptic function. Collectively, prenatal ID may reduce fetal iron reserves, impair energy metabolism of cochlear supporting cells, inhibit ribbon synaptic maturation, and potentially contribute to auditory dysfunction.
Our findings suggest that non-anemic maternal ID may be associated with delayed neonatal auditory maturation, highlighting the potential importance of iron intervention during pregnancy for improving neonatal auditory outcomes; however, causal relationships cannot be established from the observational human data, and the animal/cellular findings should be interpreted as supportive evidence requiring further validation.

PMID:
42404160
Bibliographic data and abstract were imported from PubMed on 12 Sep 2026.

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