by John Barton
After more than two decades of studying the complex relationships
between nutrition and childhood development, a team of scientific
investigators from the University of Michigan may finally be
on the verge of learning how iron deficiency affects the human
brain.
Betsy Lozoff, M.D., professor
of pediatrics and communicable diseases and director of
the Center for Human Growth and Development, photographed
in her North Ingalls Building office. In the background
is a life-size self-portrait, done as a kindergarten class
project, of Lozoff’s daughter, Claudia Brittenham,
now 23 and a museum curatorial assistant in Washington,
D.C. Photo
by D.C. Goings, BMC Media. |
"It’s exciting," says Betsy Lozoff, M.D., director
of the U-M Center for Human Growth and Development. "We
have finally gotten to the point where it is possible to ask
brain-behavior questions more directly. It used to be that I
could never say what’s happening with the brain. We just
had to put that aside.
"But now we can ask those questions, and it is very exciting
to know we are getting closer to the answers. There is a handful
of investigators who are looking at the basic science side of
iron and the developing brain. A number of them are now starting
to work together."
Iron is required for myelin (the fatty sheath surrounding axons,
which connects nerve cells and speeds nerve conduction). Iron
is also required for normal functioning of the neurotransmitter
dopamine. The hippocampus (a structure in the medial-temporal
lobe of the brain), which is involved in memory processes, also
seems to be particularly vulnerable to early iron deficiency.
"These new understandings of iron’s role in the developing
brain make it possible for the first time to design studies
to test for these effects and to understand some of the findings
in iron-deficient infants," Lozoff notes.
Dramatic new insights regarding iron’s critical role in
children’s development were recently revealed to Lozoff
and her research team in a long-term study of 191 lower middle-class
children in Costa Rica that began in 1981 in conjunction with
colleagues there at National Children’s Hospital in San
jose. The researchers discovered that infants with an iron deficiency
at the beginning of the project exhibited learning and behavior
problems as teen-agers — even though their original iron-deficiency
anemia was corrected to normal levels through treatment.
Lozoff says the results of the study suggest there are long-lasting
developmental effects among children who are afflicted with
iron deficiency as infants.
The Costa Rican project was recently given a prestigious boost
when Lozoff won a National Institutes of Health MERIT (Method
to Extend Research in Time) grant that will allow researchers
to continue studying the children after the current set of evaluations
is completed.
"It’s great to be able to continue the research,"
Lozoff says. "When I first started the project, I really
thought the children would improve with iron. The fact that
they didn’t has led to new ways of trying to understand
what’s going on.
"At 12 years of age more of them have repeated a grade
and have trouble with arithmetic and writing. These are problems
in doing basic fundamental things that are going to make life
harder for them as they go along. And then there is more anxiety
and depression. When I started the work, I would never have
predicted that."
Lozoff’s research
in Chile included a home-based intervention program to
attempt to counteract the effects of early iron deficiency
anemia. Here, one of the home visitors works with a mother
and her baby. |
In addition to the Costa Rica study, Lozoff and her colleagues
are involved with a similar study of more than 1,000 children
in Chile that began in 1990. In a joint project with the University
of Maryland, Lozoff is working with colleagues who recently
launched a new study in India that involves both iron and zinc
supplements.
"And," she continues, "we are seeking funding
for a program project grant to work on iron deficiency in the
developing human infant, the monkey infant and the developing
rodent. That’s a new phase of the project for us.
"I have to say that this research area is more intriguing
now than at any time in the 25 years I’ve been working
on it.There is still only a handful of people involved, but
for a long stretch there was barely anybody. With the advancements
in basic neuroscience and the ability to assess young children,
I can’t help but be excited about the direction our research
is taking."
Lozoff was born in Milwaukee, grew up in Kansas and graduated
from high school after her parents moved to the San Francisco
Bay area. She earned degrees in social relations and computer
applications at Radcliffe College in 1965, and wasn’t immediately
inspired to attend medical school.
Instead, she found herself involved with anthropology projects
that included summer fieldwork with the Otavaleno Indians of
Ecuador for Harvard University, a study of the Indians of Martinique,
and a stint in India for a project dealing with childhood diarrhea.
"By that time, I was particularly interested in children’s
behavior and development, and I was interested in situations
that were common from a world-wide perspective, not just in
the United States. I went into medical school thinking that
I wanted to be involved with developing-country issues in some
way or another. I didn’t know about pediatrics or behavior
and development, but somehow I knew I was going to have something
to do with developing countries."
She graduated from Case Western Reserve University in 1971,
then spent three years at nearby Rainbow Babies and Childrens
Hospital in Cleveland, Ohio, followed by nearly 20 years on
the faculty of Case Western. Lozoff came to the Department of
Pediatrics in the U-M Medical School in 1993, and was named,
later that year, director of the U-M Center for Human Growth
and Development, a multidisciplinary collaboration among biomedical,
behavioral and social scientists to further the understanding
of the complex processes by which human beings develop and grow.
The long-range goal of the Center is to optimize children’s
physical, cognitive and socioemotional development.
"It was in the 1970s," she recalls, "that I
had the chance to hear Frank Oski, who was a wonderful hematologist,
talk about his pilot study on iron deficiency. I listened to
him and told myself, ‘That’s it!’"
It has been estimated that 20 to 25 percent of children throughout
the world have anemia — a reduction in oxygen-carrying
hemoglobin in the blood — due to severe iron deficiency.
Although the problem is less common in this country, recent
estimates indicate about five percent of poor African-American
and 18 percent of Mexican-American infants and toddlers are
iron deficient.
"In the U.S. we put iron in baby formula and cereals,"
Lozoff explains. "We’ve also put ascorbic acid in
certain foods to help the body absorb iron, and we’ve encouraged
breast feeding. All of those things have helped reduce iron
deficiency in the United States.
"But there isn’t a good way to prevent iron deficiency
in most parts of the world. You’ve got areas where there
are no safe water supplies and that means you’re feeding
babies unsafe formula. You also see more iron deficiency in
European infants than we have in the United States because many
European countries have not endorsed the same iron supplementation
recommendations as we have in this country."
Lozoff says that as she began to become interested in iron
deficiency, she was attracted to Central and South America as
potential areas for research.
"I was looking for places where there was not generalized
malnutrition," she explains. "I wanted places where
there weren’t problems with abnormal hemoglobins on a genetic
basis, where there wasn’t malaria and where there weren’t
a lot of parasites.
"I wanted a place where I would be able to focus on iron
deficiency. That’s what took me into Central and South
America. There are countries there where they have very good
health and have wiped out generalized malnutrition. Lead and
parasites are not major problems."
The Costa Rican government made a national recommendation to
supplement children’s diets with iron as a result of the
findings of Lozoff and her research team.
"My colleagues in Chile," she says, "have also
moved toward a national fortification program. The initiatives
to try to reduce micronutrient deficiencies have taken off around
the world. At the World Bank and UNICEF, it’s not only
iron. It’s also zinc deficiency and vitamin A deficiency.
"It’s gratifying to be able to look back and say
there is certainly a very different level of attention being
paid to these issues than when we started."
The interdisciplinary research team participating in Betsy
Lozoff’s iron deficiency studies includes the following
U-M scientists and faculty:
ROSARIO CEBALLO, PH.D.: Assistant Professor, College
of Literature, Science and the Arts, Psychology Department and
Women’s Studies Program
BARBARA FELT, M.D.: Assistant Professor, Department
of Pediatrics and Communicable Diseases
JOHN HAGEN, PH.D.: Director of Academic Programs, Center
for Human Growth and Development
JOHN JONIDES, PH.D.: Professor, Psychology Department
Rosa Angulo-Kinzler, Ph.D.: Assistant Professor, Division
of Kinesiology
EILEEN MOLLEN, PH.D.: Clinical Psychologist and Assistant
Professor, Department of Pediatrics and Communicable Diseases
STEPHEN RAUDENBUSH, ED.D.: Senior Research Scientist,
Survey Research Center, and Professor, School of Education
ARNOLD SAMEROFF, PH.D.: Professor, College of Literature,
Science, and the Arts, Psychology Department; Director of the
Center for Development and Mental Health; and Senior Research
Scientist, Center for Human Growth and Development
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