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Iron consumption in infants and youth shapes early development.
As infants grow up, they take in nutrients to build the foundation for their social, motor and cognitive development. Formula milk and weaning foods, among other nutrient sources, are fortified with micronutrients to support this process. Iron, among other micronutrients, is critical for neural development, a rapidly-occurring process during the first three years of life.
According to the World Health Organization, over one billion people are affected by anemia, a condition where blood cells are not able to properly carry oxygen and nutrients through the body. Over a half million of the affected individuals are children.
During pregnancy, a mother’s blood volume increases to meet supply demands for growing fetuses. An increased blood volume needs an accompanying increased iron consumption as iron is used by hemoglobin proteins — oxygen-carrying proteins — in red blood cells. The World Health Organization recommends iron and folic acid intake during pregnancy to promote fetal and infant development and reduce the risk of the child developing anemia.
“Iron supplementation is recommended for undernourished populations, but it is universally practiced,” said Peng Ji, an assistant professor in the UC Davis Department of Nutrition. “In the United States, formula milk is iron fortified, containing about 10mg of iron per liter.”
Another source of iron and iron-carrying proteins is found in breast milk. Breastfed infants also have lower rates of diabetes and obesity compared to formula-fed infants. Pregnant women frequently take prenatal multivitamins containing iron.
“Too much iron during pregnancy creates oxidative stress,” said Elizabeth Prado, an assistant professor in the UC Davis Department of Nutrition. “It leads to low birth weight babies and impaired brain development.”
Breast milk contains proteins supporting infant development, including lactoferrin — an iron-binding protein.
“Lactoferrin serves as an antibacterial defense and promotes immune system development,” said Bo Lönnerdal, a distinguished professor emeritus of the UC Davis Department of Nutrition and Department of Internal Medicine. “It perforates harmful bacterial membranes to promote the growth of good bacteria inside infants. It also turns down inflammatory cytokines, which control fever response, while increasing anti-inflammatory cytokines. It helps guide immune development and responses when infants get sick.”
Lactoferrin remains intact throughout the digestive tract, latching onto lactoferrin-specific binding receptors residing in the small intestine or in excrement.
Lönnerdal’s previous research in Chilean infants suggests formula milk that contains high iron supplementation may lead to cognitive impairment.
Ji’s research found similar results in a nursing piglet model. Piglets have a similar brain development pattern as human infants and come with a shorter growth spurt. Two years in infant brain development equates to 24 weeks in piglets, allowing piglets to serve as a functional model for human infants in their development response to iron and excess iron. Additionally, the swine industry provides iron supplementation during early development. Iron injections accumulate iron in the liver for use by other organs in the body. However, piglets have difficulty regulating iron absorption during their early lives.
“When there is excess iron in the human body, there are mechanisms to regulate iron absorption,” Lönnerdal said. “You absorb less iron. Infants, however, lack this mechanism.”
Ji conducted a social novelty experiment with piglets and stranger piglets, finding that excess iron in nursing piglets impaired their cognitive, motor and social development. Piglets have a social and cognitive behavior to explore the unknown and meet new strangers.
In the first phase of the experiment, piglets befriended a new piglet. When introduced to a new piglet and a befriended piglet, the piglet’s social novelty behavior would encourage them to spend more time befriending the stranger piglet. In the experimental groups that were supplemented with iron, the excess iron negatively impacted the piglets’ behavior to discern the two piglets and engage in social novelty behavior.
“The control piglet groups met stranger piglets, but moderate and high iron dosage piglet groups would move between both the stranger and friend piglet,” Ji said.
Ji also conducted a bioinformatic assessment of metabolism in the piglet hippocampus – a region of the brain involved in learning and memory.
“Purine metabolism was altered by excessive iron supplementation,” Ji said.
Purine can be either salvaged or completely degraded during metabolism. Purine salvation provides energy for neuron cells in the piglet hippocampus to function. Purine degradation creates a reactive oxygen byproduct, which can create oxidative stress in the developing brain.
“We noticed there was a significant iron content in the developing hippocampus,” Ji said. “We found increased lipid peroxidation [in] the hippocampus in response to high iron supplementation.”
Lipid peroxidation also creates reactive oxygen and oxidative stress.
Though iron availability shapes the development of infants and piglets, too much iron may severely impact their development in life. A strategy to navigate iron supplementation may call for reflection by a mother on her child’s needs.
“If you’re getting too much iron in your diet, that could lead to toxicity,” Prado said. “If you are iron-deficient, then you should take supplements. A lot of people fall in that area of this range.”
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