Related Experiment Video
Updated: Jan 22, 2026
Quantitating Iron Transport Across the Mouse Placenta In Vivo Using Nonradioactive Iron Isotopes
Published on: May 10, 2022
Randomized Controlled Trial of Iron-Fortified versus Low-Iron Infant Formula: Developmental Outcomes at 16 Years
Sheila Gahagan1, Erin Delker2, Estela Blanco3
1Department of Pediatrics, Division of Child Development and Community Health, University of California, San Diego, La Jolla, CA; Center for Human Growth and Development and Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI.
Insights
Infants given iron-fortified formula experienced poorer cognitive development in adolescence. This highlights the importance of iron for infant brain development, though optimal levels remain uncertain.
Area of Science:
- Pediatric Nutrition
- Developmental Neuroscience
- Public Health
Background:
- Iron deficiency anemia (IDA) is a significant public health concern in infancy, potentially impacting neurodevelopment.
- Previous research suggests a link between early iron status and long-term cognitive outcomes.
- Understanding the optimal iron supplementation levels during infancy is crucial for preventing IDA without adverse effects.
Purpose of the Study:
- To evaluate the long-term cognitive outcomes in adolescents who were randomly assigned to receive either iron-fortified or low-iron formula in infancy.
- To investigate the impact of early infant formula iron content on various cognitive domains assessed in adolescence.
Main Methods:
- A randomized controlled trial involving 405 infants from Santiago, Chile, aged 6 months.
- Participants were assigned to receive either iron-fortified (12 mg/L) or low-iron (2.3 mg/L) formula for six months.
- Cognitive abilities, including visual memory, arithmetic, and reading comprehension, were assessed at 16 years of age.
Main Results:
- Adolescents who received iron-fortified formula as infants showed significantly lower scores in visual memory, arithmetic, and reading comprehension compared to the low-iron group.
- An interaction effect was observed for visual motor integration, where the iron-fortified group performed better with low baseline hemoglobin and worse with high baseline hemoglobin.
- These findings suggest a potential negative impact of higher iron fortification levels on certain cognitive functions.
Conclusions:
- Higher iron fortification levels in infant formula, as recommended in some regions, may be associated with poorer adolescent cognitive outcomes.
- While preventing iron deficiency anemia is vital for infant brain development, the optimal iron intake requires further investigation.
- The study underscores the complexity of iron supplementation and its long-term neurodevelopmental implications.
Objectives:
To test differences in cognitive outcomes among adolescents randomly assigned previously as infants to iron-fortified formula or low-iron formula as part of an iron deficiency anemia prevention trial.
Study Design:
Infants were recruited from community clinics in low- to middle-income neighborhoods in Santiago, Chile. Entrance criteria included term, singleton infants; birth weight of ≥3.0 kg; and no major congenital anomalies, perinatal complications, phototherapy, hospitalization >5 days, chronic illness, or iron deficiency anemia at 6 months. Six-month-old infants were randomized to iron-fortified (12 mg/L) or low-iron (2.3 mg/L) formula for 6 months. At 16 years of age, cognitive ability, visual perceptual ability, visual memory, and achievement in math, vocabulary, and comprehension were assessed, using standardized measures. We compared differences in developmental test scores according to randomization group.
Results:
At the follow-up assessment, the 405 participants averaged 16.2 years of age and 46% were male. Those randomized to iron-fortified formula had lower scores than those randomized to low-iron formula for visual memory, arithmetic achievement, and reading comprehension achievement. For visual motor integration, there was an interaction with baseline infancy hemoglobin, such that the iron-fortified group outperformed the low-iron group when 6-month hemoglobin was low and underperformed when 6-month hemoglobin was high.
Conclusions:
Adolescents who received iron-fortified formula as infants from 6 to 12 months of age at levels recommended in the US had poorer cognitive outcomes compared with those who received a low-iron formula. The prevention of iron deficiency anemia in infancy is important for brain development. However, the optimal level of iron supplementation in infancy is unclear.
Trial Registration:
Clinicaltrials.gov: NCT01166451.
Related Concept Videos
03:34Ionic Compounds: Formulas and Nomenclature
02:52Chemical Formulas
03:10Molecular Compounds: Formulas and Nomenclature
02:37Experimental Determination of Chemical Formula
02:56Formula Mass and Mole Concepts of Compounds
01:24Cattell's 16 Personality Factors
In contrast, source traits are the...