Iron Deficiency’s Long - Term Effects
Abstract: Betsy Lozoff is among the world’s leading experts on iron deficiency and its effects on infant brain development and behavior. Iron deficiency is the most common single nutrient disorder in the world, affecting more than half of the world’s infants and young children. Research by Lozoff and others has shown that there are long-lasting developmental disadvantages among children who experienced severe, chronic iron deficiency as infants—disadvantages that are not corrected by giving iron later.
Council Member Betsy Lozoff a developmental-behavioral pediatrician, is a professor of pediatrics in the Department of Pediatrics and Communicable Diseases at the University of Michigan Medical School and former director of the University’s Center for Human Growth and Development. Her research focuses on iron deficiency anemia and infant behavior, primarily in developing countries, and the health and development of children who grow up in poverty in the U.S. Her recent research seeks to relate behavioral changes to the effects of iron deficiency on the developing brain. She has served on several review panels for the National Institutes of Health and the National Institute of Child Health and Human Development, as well as on the Executive Council of the Society for Developmental and Behavioral Pediatrics. She was a member of the Committee on Integrating the Science of Early Childhood Development for the Institute of Medicine and the National Research Council of the National Academy of Sciences.
For many years, you have studied the link between iron deficiency in children and their long-term health and development. What can you tell us about that connection and how it affects the growing brain’s architecture?
We know that the human body needs iron to perform some of the most basic and essential functions. It needs iron to manufacture hemoglobin—the protein in red blood cells that carries oxygen throughout the body. It needs iron for proper muscle function, too. And—most relevant to this discussion—the body needs iron to carry out many critical processes in our brain and central nervous system.
When it comes to the growing brain, we’re learning pretty definitively that the right level of iron is required for healthy neurotransmission, or the way the brain sends and receives “signals” from one area to another. Iron is essential for myelination—the process by which the brain produces a fatty insulation around the nerves. The insulation helps speed transmission of electrical signals. Based on studies of lab animals, we know iron has clear effects on the function of dopamine and probably serotonin, two brain chemicals that help send and receive signals (neurotransmitters) and have many roles in the brain. When iron deficiency anemia occurs in the young animal, important changes in both myelin and neurotransmitters persist to adulthood, despite iron therapy in infancy. We have to make a bit of a leap, but we can say that the behavioral changes we see in children who had iron deficiency in infancy are consistent with the brain effects we’re finding in animals. Children who suffered iron-deficiency anemia as infants have evidence of brain differences 10 years later.
Iron-deficiency anemia is considered the most common nutritional disorder in the world today, but we’ve managed to dramatically reduce its incidence among infants in the United States. What are some proven solutions?
In the U.S. and most economically developed countries, we have dramatically reduced anemia and iron deficiency through a few widespread interventions. From a clinical standpoint, this is a problem that can be solved if the community makes it a priority.
As late as the 1970s, we in the U.S. had levels of iron deficiency in infants on a par with much of the developing world. Federal government programs like Food Stamps and WIC (supplemental nutrition for Women, Infants and Children) started to make a big difference. In addition, baby formula companies started producing and marketing iron-fortified formula, prompted largely by calls from the American Academy of Pediatrics. Major cereal companies began adding iron to baby cereals. More vitamin C (also known as ascorbic acid, which enhances the body’s ability to absorb iron from the intestines) was added to infant foods. There was a big effort to encourage breast feeding; the iron in breast milk is easily absorbed. Another solution for infants and children at greater risk of iron deficiency is the use of iron-fortified drops, also readily available. Together, these interventions have worked well for U.S. children.
Your work with children in Costa Rica and Chile has yielded very important findings.
We’ve now been following our research group of children in Costa Rica for more than 20 years. All those who had iron deficiency in infancy were treated with a closely supervised full course of iron therapy, which corrected all cases of iron-deficiency anemia.
And here’s what we’ve been learning. When it comes to their motor development, children who had chronic, severe iron deficiency in infancy started with lower motor functioning and stayed lower over time; there’s no evidence they catch up with their peers. In terms of social-emotional functioning, in early adolescence their parents and teachers rated them as showing significant symptoms of anxiety, depression, and inattention. At ages 11 to 14, the proportion repeating a grade in school was twice that of children who had good iron status in infancy. In terms of cognitive skills, the evidence is especially troubling: the gap in test scores actually increased over time. By late adolescence, the gap was bigger, regardless of whether they started with low or high scores as babies. The cognitive gap was also worse for those children from the most disadvantaged families who also had chronic, severe iron deficiency in infancy.
By failing to solve this problem for millions of youngsters around the globe, aren’t we risking that they won’t meet their full potential?
In Chile, we’re finding that even after treatment for a year with iron drops, children who suffered iron-deficiency anemia as infants have evidence of brain differences 10 years later. Using electrophysiologic tests, we’ve been able to “look” into their brains and find that electrical signals move more slowly through their auditory and visual systems. Both the Costa Rican adolescents at 19 years and the Chilean children at 10 years who were treated for severe, chronic iron deficiency in infancy do worse on higher-level cognitive tests shown by functional magnetic resonance imaging (fMRI) to involve specific neural circuits where dopamine is the major neurotransmitter.
These long-term effects make us even more worried about how they’ll do in adulthood. So we are looking at how the consequences of early iron deficiency might impact the kinds of jobs the Costa Rican subjects get as young adults, how much money they earn, and what kinds of relationships they establish. We hope to do the same for the Chile sample.
So clearly the implications are quite serious.
The evidence is certainly accumulating: There are effects of iron deficiency that are not reversed with iron therapy. It’s very important to prevent the brain from being iron deficient in the first place—during its most sensitive time of development, in early childhood.
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