Infants with high levels of hemoglobin who were given iron fortified infant formula were found to have poorer long-term developmental outcomes ten years later, researchers from the University of Michigan, Ann Arbor reported in Archives of Pediatrics & Adolescent Medicine.

The researchers explained as background information:

"The high prevalence of iron deficiency in infancy has led to routine iron fortification of infant formula and foods in many countries," the authors write as background information in the study. "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."

Betsy Lozoff, M.D., and team set out to determine what the long-term developmental outcomes might be after ten years for infants who were given iron-fortified formula. The ten-year old kids had been part of a randomized controlled trial and had either been given iron-fortified or a low iron formula as infants. 835 full-term healthy infants at community clinics from the urban areas around Santiago, Chile, were randomly selected to receive formula either with or without iron.

56.5% (473) of the children were followed up for ten years. Researchers gathered data on their IQ, arithmetic skills, VMI (visual-motor integration), motor functioning, visual perception and spatial memory.

244 children in the iron-fortified group and 229 in the low-iron group were reassessed at the ten-year follow-up. At the age of ten the researchers detected no significant differences in the iron status in the children of both groups. 4.1% (9) of the infants and 6.9% (17) of the ten-year-olds were diagnosed with iron deficiency in the iron-fortified group.

The children in the iron-fortified group scored lower in every outcome measured at ten years, with statistically significantly lower scores in spatial memory and VMI, compared to those in the non-iron group. They showed suggestive trends that did not reach statistical significance in arithmetic skills, motor coordination, visual perception and IQ.

The lowest ten year follow-up scores were found among the infants with the highest hemoglobin scores who had been given iron-fortified formula. However, the highest scores were among the iron-fortified formula infants whose hemoglobin levels at six months of age were the lowest.

The authors wrote:

"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. Optimal amounts of iron in infant formula warrant further study."

Accompanying Editorial - Iron in infancy and link to long-term development

Parul Christian, Dr.P.H., M.Sc., of the Johns Hopkins Bloomberg School of Public Health, Baltimore, wrote:

(the importance of this study) "..lies in its evaluation of the long-term developmental outcomes of an early-infancy iron intervention.

The relationship between iron deficiency and iron deficiency anemia and developmental outcomes in children has been controversial, and clear causal evidence for a link found lacking when existing trials have been carefully evaluated. Lozoff et al have made significant contributions to establishing this link and demonstrated in longitudinal observational studies that iron deficiency in early life can result in cognitive and motor impairments that may be irreversible.

(However) Caution is needed in generalizing the results of the follow-up study by Lozoff et al, which stands, as yet, alone in showing small-sized negative consequences on developmental outcomes among iron-sufficient children exposed to iron-fortified vs low-iron formula during infancy.

(Conclusion) Whether iron deficiency in infancy, manifest largely due to deficiency in utero, can be overcome with supplementation during infancy for improving central nervous system development and function needs to be further examined in rigorous studies of short and long duration."

Written by Christian Nordqvist