Effects of Latent Iron Deficiency on Auditory Neural Maturation in Infants


Nutrition is critical for the normal development of the central nervous system (CNS) and is particularly important throughout pregnancy and childhood. These are essential time periods for brain growth and for establishing adequate cognitive, motor, and psychosocial development in childhood, as well as in adulthood. Thus, nutritional deficiencies during these periods have the potential to impair cognition, behavior, and productivity in school years and adulthood. Among the nutritional deficiencies, iron deficiency occupies a prominent place.

Iron plays a fundamental role in neural development, participating in the myelination and synaptogenesis processes. Regarding embryonic life, the importance of iron in the first three months is mostly related to the embryogenesis of the nervous system, whereas in the last trimester of pregnancy the fetus needs to form its own iron stores. Studies suggest that the peak of iron uptake in the CNS coincides with the myelination peak, especially in the late fetal and early postnatal stages.

Iron deficiency (ID) is the most common nutritional deficiency in the world, affecting about a quarter of the world population, and these numbers increase even more during pregnancy, reaching 59%. In addition, some maternal and fetal pathologies may affect the newborn's (NB) iron stores, such as hypertension, diabetes mellitus, intrauterine fetal growth restriction, smoking during pregnancy, and premature birth, making the perinatal period especially susceptible to nutritional deficiency of this element.

ID anemia has well-known impacts on CNS, such as reduced nerve conduction velocity and cognitive-behavioral changes. Iron deficiency without anemia, which has a prevalence 3-5 times higher than that of iron deficiency anemia, can also harm the CNS. Oligodendrocytes, the cells responsible for myelin production, are particularly sensitive to iron deficiency and it has been shown that NBs submitted to intrauterine iron deficiency presented long-term CNS damage, reaching lower language scores and motor development at 5 years of age compared to those born with normal iron stocks.

Being part of the CNS, the developing auditory system is particularly vulnerable to nutritional changes during early fetal and postnatal life, especially due to the accelerated process of neuronal growth and development, myelination, and establishment of the synaptic network. Neural maturation of the auditory system progresses in the caudal rostral direction and myelination of the auditory nerve pathway is considered an index of cerebral myelination.

Brainstem evoked response audiometry (BERA) consists of recording the electrical stimulus from the inner ear to the brainstem in response to an acoustic stimulus. This test evaluates the electrophysiological activity of the auditory system at the level of the brainstem from the cochlear nerve, cochlear nuclei, superior olivary complex, and the bridge to the inferior-mesencephalic colliculus.

The waves evaluated by BERA comprise three larger waves (I, III, and V) that can be reliably measured in newborns with a gestational age of more than 34 weeks. The absolute latencies for each of the waves and their intervals, as determined by BERA, are influenced by the degree of myelination, neuronal development, synaptic function, and axonal growth of the auditory nervous system; they are a measure of the nerve conduction velocity at different levels of the auditory pathway. As the relationship between these latencies and myelination is negative, less latency means greater (better) myelination and vice versa.

Although data from the literature show the close relationship between the development of the auditory system and iron homeostasis, the changes that ID without anemia cause, also called latent iron deficiency (LID), are still not completely clear.

Considering the possible negative repercussions of LID on the CNS myelination process, this study aimed to analyze the relationship between LID through serum ferritin of the umbilical cord, and myelination of the auditory nerve through BERA in NBs of gestational age (GA) equal to or greater than 37 weeks.