Iron deficiency (ID) is the world?s leading nutrient deficiency, affecting more than 2 billion people worldwide, including approximately 115 million children. Iron deficiency anemia (IDA) during infancy is of significant concern due to the vulnerability of the developing brain. Iron is a critical nutrient for normal brain development, yet iron homeostasis exists within a relatively narrow optimal range, with risks associated with both deficiency and excess. While there are known adverse effects of IDA during infancy, overexposure to iron of any duration within the 6-24-month critical window of rapid brain development is also suspected to cause harm. Scientists speculate that the onset of impairments emerge well after the neuropathological insult caused by high-iron supplementation. This research will examine the long-term effects of 2 exposures: 1) IDA that occurred during infancy and, 2) high-iron supplementation given to nonanemic infants. For each condition, we will investigate whether new neurocognitive impairments emerge in early adulthood, and whether known deficits worsen with age, persist, or perhaps improve. We will also investigate the presence of cascade effects, or effects that emerge as by-products of earlier deficits. To examine effects, we use data from a large longitudinal cohort of Chilean infants studied for more than 2 decades who had high rates of IDA and participated in a double-blind randomized- controlled IDA preventive trial that involved 3 iron supplementation conditions: high-iron, low-iron, and no-added iron. Comprehensive assessments of neurocognitive, socioemotional, and physiologic functioning were obtained every 5 years from 6m to 21y. The RCT design, coupled with longitudinal follow-up, allows us to address across- time differential decline (divergence) by iron supplementation group and infant iron status.
Aim 1 will investigate whether high-dose iron supplementation in infancy has adverse effects on cognitive and executive functioning at young adulthood, interrogating new emerging effects, intraindividual change (worsening, improvement, lingering), differential decline by iron supplementation condition, and cascade-indirect effects.
Aim 2 will identify the long-term cognitive effects of infant IDA at young adulthood (emerging effects, intraindividual change, differential decline by infant iron status, cascade effects), involving learning, memory, planning, IQ, inhibitory control, attention, and mental processing.
Aim 3 will examine the long-term psychosocial effects associated with infant IDA (emerging, intraindividual change, differential decline, cascade), involving affect, social functioning, and mental health. We will also identify who is most at risk for long-term harm using neuro- physiologic, intraindividual, and contextual characteristics measured throughout development. There is no other study that combines randomized iron supplementation, extensive neurocognitive and mental health assessments, and long-term follow-up to young adulthood. Findings could have significant impact on public health policy given the global prevalence of IDA, questions about the persistence of neuropsychosocial deficits associated with IDA, and concerns about possible adverse effects resulting from high-iron supplementation.

Public Health Relevance

Iron deficiency is the world?s leading nutrient deficiency affecting more than 1.5 million U.S. children, including approximately 15% of 1-2-year-olds. Although iron is a critical nutrient for normal brain development, iron homeostasis exists within a relatively narrow optimal range, with risks associated with both deficiency and excess. This research will examine the long-term effects of two exposures: 1) IDA that occurred during infancy and, 2) high-iron supplementation given to nonanemic infants as part of a randomized-controlled iron- deficiency anemia preventive trial delivered to a large cohort of children studied from infancy to 21 years.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD097295-02
Application #
9990573
Study Section
National Institute of Child Health and Human Development Initial Review Group (CHHD)
Program Officer
Raiten, Daniel J
Project Start
2019-08-11
Project End
2021-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Pediatrics
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093