Effects of iron-deficiency anemia in infants linger

April 29, 2001

BALTIMORE - Infants with iron-deficiency anemia may suffer long-lasting central nervous system effects even with early treatment, say researchers at the University of Michigan and the University of Chile.

Results of a new collaborative U-M study that will be presented April 28 at the 2001 Pediatric Academic Societies and American Academy of Pediatrics joint meeting found that 3- to 4-year-old children who were treated for iron-deficiency anemia in infancy show slower transmission of nerve impulses throughout the brain in both the auditory and visual systems.

"This is the most direct evidence to date that iron-deficiency anemia in infancy has long-lasting effects on the developing brain," says Betsy Lozoff, M.D., director of the U-M Center for Human Growth & Development and professor of pediatrics and communicable diseases.

Iron deficiency - a severe lack of iron in the blood - is the most common single nutrient deficiency in the world and infants are one of the age groups at highest risk, Lozoff says. In the U.S., iron fortification of infant formula was begun 30 years ago, and iron-deficiency anemia was drastically decreased. However, about 20 percent to 25 percent of all infants in the world have iron-deficiency anemia, and many more have iron deficiency that is not severe enough to cause anemia.

The investigators hypothesize that the differences in nerve conduction are due to problems in myelination, because iron is required for normal myelination. The myelin sheath, which acts like the casing of a sausage around the nerve, allows for more speedy transmission of signals from the brain to the rest of the body or from the periphery back to the brain. Without myelin, signals cannot be transmitted as efficiently. Much myelin formation takes place early in a child's life.

The collaborative U-M and University of Chile study examined 84 Chilean children - 41 who had iron-deficiency anemia as infants and were treated with iron, and 43 who were never anemic in infancy. All of the children were full-term babies weighing at least 6 pounds 12 ounces. All children were from similar communities.

Chile was chosen as the study site because it was one of the few places in the world where there was a very sophisticated infant neurophysiology laboratory, but also a high prevalence of iron deficiency in infants, Lozoff explains. In Chile, Cecilia Algarin, M.D., and Patricio Peirano, M.D., Ph.D., of the Laboratory for Sleep and Neurobiology at the Institute of Nutrition and Food Technology, University of Chile, headed the actual neurophysiologic studies.

Each child was given two tests that provide measures of the integrity of these sensory systems. To test the auditory system, electrodes were placed on the scalp and small clicks were made near the ear. This test measured the time it took for the signal, prompted by the click, to go along the auditory pathway from the ear to the brain. A second, similar test was preformed to measure visual evoked potentials - the time it took for the signal, prompted by a visual stimulus - to go from the eye to the brain.

"What we found is that there are differences in latencies," Lozoff says. "That means that there's slower transmission of the nervous impulse in both auditory and visual systems for children who had iron-deficiency anemia as infants."

Lozoff emphasizes that the differences in times, measured in milliseconds, appear small but in statistical terms are very significant. "The differences in absolute amount are tiny," Lozoff says. "In statistical terms, however, the differences are large."

Both the auditory and visual systems rapidly develop during infancy, when iron deficiency is most common. The changes in signal transmission could also mean that other aspects of brain function dependent on normal myelination are affected. Subtle disruptions in timing could affect broader systems of development. For instance, children who had early iron-deficiency anemia have been found to have lower IQ scores and motor skills at 5 years of age, poorer reading, writing and arithmetic at 12 years of age, and more symptoms of anxiety and depression.

Thus, "there is increasing evidence of subtle differences in behavior and development with early iron deficiency and that effects can be long-lasting," says Lozoff.

An important next step in the research program will be to determine the direct effects of iron on the developing brain in studies combining research in laboratory rats, non-human primates, and young infants. The team will also continue to follow the children in Chile to determine whether the effects on the auditory and visual system resolve or not.
Other researchers on the project were Marcelo Garrido, M.S. and Felipe Pizarro, M.S., Laboratory for Sleep and Functional Neurobiology, Institute of Nutrition and Food Technology, University of Chile.

Contact: Valerie Gliem, vgliem@umich.edu, or
Kara Gavin, kegavin@umich.edu

University of Michigan Health System

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