Iron supplementation given to nonanemic infants: neurocognitive functioning at 16 years

ABSTRACT

Objective

There is concern that high iron uptake during the critical period of early brain development carries potential risks, especially for nonanemic infants. This study examined the neurocognitive functioning of 16-year-olds who were nonanemic as infants and received iron supplementation.

Methods

We studied 562 Chilean adolescents (M 16.2 years; 52.7% female) who participated in a randomized controlled iron supplementation trial in infancy. Between 6 and 12 months, 346 consumed an iron-fortified formula (12.7 Fe mg/L) or, if primarily breastfed, liquid vitamins with 15 mg elemental iron as ferrous sulfate, and 216 consumed unmodified cow milk without iron or liquid vitamins without iron if primarily breastfed.

Results

Compared to adolescents in the no-added iron condition in infancy, those in the iron-supplemented condition had poorer visual-motor integration, quantitative reasoning skills, and incurred more errors on neurocognitive tasks. Consuming larger amounts of iron-fortified formula in infancy was associated with lower arithmetic achievement. Of adolescents who had high hemoglobin at 6 months (Hb ≥ 125 g/L), those in the iron supplemented condition had poorer performance on arithmetic, quantitative reasoning, and response inhibition tests than those in the no-added iron condition. Of adolescents who had marginally low 6-month hemoglobin (Hb > 100 and < 110 g/L), those who received no-added iron incurred more errors on a visual searching task than those in the iron-supplemented condition.

Conclusion

The physiologic need for iron during the period of rapid and critical brain development in young infants should be considered vis-à-vis the risks associated with supplementing nonanemic infants with high levels of iron.

Clinical Trials number: NCT01166451

KEYWORDS:

• Iron supplementation
• excess iron
• iron deficiency
• neurocognition
• executive function
• cognitive flexibility
• adolescents
• Chile

Data availability statement (DAS)

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R03-HD097295, R01-HD033487), and the National Heart, Lung, and Blood Institute (R01-HL-088530).

Notes on contributors

Patricia L. East

Patricia L. East received her PhD in child and adolescent development from Penn State University. Her research interests include the cognitive and behavioral effects of early-life iron deficiency and iron excess. She is a Full Research Scientist in the Department of Pediatrics at the University of California, San Diego.

Brie Reid

Brie Reid earned her PhD in developmental psychology from the University of Minnesota's Institute of Child Development with a doctoral minor in Epidemiology from the University of Minnesota School of Public Health. Her research focuses on nutritional adversity, stress neurobiology, and factors that influence health disparities. She is a Postdoctoral Research Fellow in the Department of Psychiatry and Human Behavior at the Warren Alpert Medical School of Brown University.

Estela Blanco

Estela Blanco received her PhD in public health from the University of Chile. Her research interests include the importance of early life (first 1000 days) for long-term health outcomes, causal inference, and other epidemiological methods. She is a Postdoctoral Fellow at the Pontifical Catholic University of Chile.

Raquel Burrows

Raquel Burrows is a pediatrician and child endocrinologist. Her research is related to the impact of malnutrition either due to deficit or excess on future health. One of these lines studies the impact of iron deficiency and iron excess on cardiometabolic and cognitive health. Dr. Burrows is a Full Professor at the University of Chile and Head of the Public Nutrition Unit within the Institute of Nutrition and Food Technology.

Betsy Lozoff

Betsy Lozoff received her MD from Case Western Reserve University and is Professor Emeritus at the University of Michigan. Dr. Lozoff has investigated the developmental and behavioral effects of iron deficiency in infancy in several U.S. and international contexts, including Detroit, Michigan, Chile, Costa Rica, Guatemala, China, and New Delhi, India.

Sheila Gahagan

Sheila Gahagan received her MD degree from Michigan State University and her MPH from the University of Michigan. She is Professor of Clinical Pediatrics at the University of California, San Diego. Her research focuses on early-life exposures related to later life health and mental health outcomes. She is the PI of the Santiago Longitudinal Study.