University of Minnesota Alumni Association


The Iron Range

Researchers at the U of M are making significant advances in understanding the link between early iron deficiency and long-term mental health risks.

Illustration Credit: Dawn Yang

Although iron is a powerhouse nutrient that builds and supports strong bodies, it can be challenging to get enough of—especially if you’re pregnant.

U of M researchers have discovered that getting enough iron during pregnancy is more important than previously recognized. In fact, iron deficiency during fetal development is linked to a higher risk of certain long-term mental health outcomes.

Michael Georgieff, M.D., codirector of the new Masonic Institute for the Developing Brain and executive vice chair and professor at the Department of Pediatrics at the U of M, has spent the majority of his career studying the mechanisms by which iron deficiency affects the brain, particularly in young children.

A recent recipient of the Agnes Higgins Award from the March of Dimes Foundation, Georgieff and his research colleagues found that getting enough iron to the fetus throughout pregnancy is critical to brain development.

“Unfortunately, pregnancy is an irondeficiency state just waiting to happen,” Georgieff says. “A pregnant woman needs a lot more iron because she’s not only feeding her own needs, she’s also satisfying the needs of the fetus.”

Most obstetricians prescribe iron, and it’s found in most prenatal vitamins, but the problem is that iron levels are not routinely measured in expectant mothers. And they should be. “You need iron in order to support structural growth of the brain,” Georgieff says. “We’re talking about the ability of the brain to first build itself and also to change with activity, for example, making synapses. In the case of an iron-deficient person, the brain is more simply built and therefore doesn’t have the capacity that an iron-sufficient person would have. We see that evidenced in the region of the brain called the hippocampus.”

The hippocampus essentially learns how to learn, memorizes information, and processes spatial detail. It’s this area that needs iron to establish a structure that the brain will use throughout a lifetime. Without proper iron levels to support that development, which occurs in hyperdrive during third trimester, the brain is at risk for certain neurocognitive conditions.

And in terms of mental health outcomes, timing of iron deficiency during pregnancy can impact the risk of specific conditions later. Research links iron deficiency during the first trimester to a heightened risk of autism; during second trimester with risk of schizophrenia; and during third trimester with risk for depression.

Emphasis here on “risk:” Iron deficiency is not deterministic of mental health problems, but it likely predisposes those affected with a higher risk for some mental health conditions. The work that the U of M has done to advance this research on mental health pinpoints a direct correlation and specific biological mechanisms between access to iron in utero and brain development.

“The fetus’s brain develops throughout pregnancy and during third trimester, it grows exponentially,” says researcher Phu Tran, assistant professor in the Department of Pediatrics. “That kind of activity requires a lot of energy, and iron is one of the core elements that produces energy for the brain to develop. If you are deficient, you can imagine how growth would be compromised. It can lead to long-term consequences as the child enters adulthood.”

Tran’s research reveals that iron deficiency induces epigenetic changes to DNA, or how genes are expressed. Without sufficient iron, genes that give the brain plasticity—the ability to learn—are suppressed. Tran describes gene expression like a faucet turning on and off: For some genes to be expressed, like water turning on full blast, they require a specific protein to come in right on cue.

So why not simply prescribe more iron during pregnancy? The problem is complex: Not all pregnant women have access to good maternal care, and of those who do, many aren’t checked for their iron status, so it’s impossible to know how much iron to prescribe. Moreover, many people dislike taking iron supplements, so compliance is low.

Combine these factors with conditions like high blood pressure or diabetes—which inhibit the ability of mothers to get iron to the fetus—and it adds up to nearly half a million infants at risk for iron deficiency in the U.S.

U of M researchers are also exploring how the nutrient choline might partially reverse the negative effects caused by iron deficiency on the developing brain. “Iron is fundamental, but are there any workarounds?” Georgieff asks. “We’re concentrating on epigenetic effects and looking at how, if you notice iron deficiency late, you might [prescribe] iron plus choline [for the expectant mother]. It’s an unproven hypothesis, but it looks positive in the lab.”

While research continues, it’s clear that identifiable risks to a lifetime of brain health all tie back to early development in the womb. If iron deficiency can be detected and treated early on, before a crucial window of brain development closes, it may even be possible to prevent some long-term mental health problems later.

Kelli Billstein is a freelance writer in the Twin Cities.

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