Routine iron fortification of infant formula linked to poor development

A long-term study examining iron-fortified vs. low-iron infant formula suggests that infants with high hemoglobin levels who received iron fortified infant formula have poorer developmental outcomes.

The study, conducted in Santiago, Chile, was published online ahead of print in the Archives of Pediatrics & Adolescent Medicine, and raises questions about the optimal amount of iron in infant formula.

“The high prevalence of iron deficiency in infancy has led to routine iron fortification of infant formula and foods in many countries,” says lead study author Dr. Betsy Lozoff, a behavioral pediatrician at the U-M Health System and research professor at the Center for Human Growth and Development.

“These interventions help reduce iron-deficiency anemia and iron deficiency without anemia. However, the optimal amount of iron in such products, especially infant formula, is debated,” she says.

Iron deficiency affects roughly 25 percent of the world’s babies. Some have iron deficiency anemia, in which a lack of iron causes problems with hemoglobin — the compound that red blood cells use to transport oxygen through the bloodstream.

Lozoff has conducted award-winning research on functional development and iron deficiencies for more than 25 years in India, Costa Rica and Chile. Iron deficiency is the single most common nutrient deficiency.

The recent study provides a follow-up on 835 healthy, full-term infants living in urban areas around Santiago. They were randomized in the trial at 6 months of age to receive formula with or without iron.

The 10-year assessment included 473 children and researchers measured IQ, spatial memory, arithmetic achievement, visual-motor integration, visual perception and motor functioning.

Compared to the low-iron group, the iron-fortified group scored lower on every 10-year outcome measured.

Of the seven tests administered at the 10-year follow-up, two (spatial memory and VMI) showed statistically significant lower scores in the iron-fortified group compared to the low-iron group, and four (IQ, visual perception, motor coordination and arithmetic achievement) showed suggestive trends that did not reach statistical significance.

No statistically significant differences were found in iron status at 10 years, and only one child had iron-deficiency anemia.

Less than 10 percent of infants in the iron-fortified group met criteria for iron deficiency.

The authors also found that children with the highest hemoglobin levels at 6 months of age had lower 10-year scores if they had received the iron-fortified formula, but those with the lowest 6-month hemoglobin levels had higher scores.

“In conclusion, this study indicates poorer long-term developmental outcome in infants with high hemoglobin concentrations who received formula fortified with iron at levels currently used in the United States,” the study authors write. “Optimal amounts of iron in infant formula warrant further study.”

An additional U-M author is Katy Clark, Center for Growth and Human Development.

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