A NHANES analysis suggests a ferritin cutoff below 24 μg/L may identify more iron deficiency in children aged 5 to 14 years.
A new analysis of US survey data suggests that iron deficiency in school-aged children may be substantially underrecognized when clinicians rely on ferritin thresholds currently used in public health guidance.
The study, published in Blood Red Cells & Iron and summarized by the American Society of Hematology, found that a ferritin cutoff of less than 24 μg/L identified iron deficiency in approximately 30% of children aged 5 to 14 years in the study sample, compared with 9% when older thresholds of about 15 μg/L were applied.<sup>1</sup> “Identifying the ferritin level in blood needed to support a child’s physical growth and learning is important because low iron levels can lead to serious health issues such as difficulties with concentration and learning, fatigue, and reduced physical performance,” Yaw Addo, PhD, lead author and epidemiologist in the CDC’s Division of Nutrition, Physical Activity, and Obesity.1
The findings do not establish a new clinical guideline, but they add to ongoing debate over whether ferritin cutoffs used to define iron deficiency detect the condition only after iron stores are already substantially depleted. Current CDC and WHO guidance has generally used ferritin concentrations near 15 μg/L to identify iron deficiency in children and other populations, while recognizing that ferritin interpretation is complicated by inflammation and other conditions that can elevate ferritin independent of iron status.2,3
The investigators analyzed data from 3765 otherwise healthy children aged 5 to 14 years who participated in NHANES III, conducted from 1988 to 1994. Participants had physical examinations and blood testing, including ferritin, hemoglobin, and zinc protoporphyrin (ZPP), a red blood cell marker that can rise when tissue iron supply is inadequate. Children were excluded if they had evidence of infection, inflammation, liver-related abnormalities, or missing key laboratory data.1
Key Facts
Using a method intended to detect earlier changes in erythropoiesis, the researchers estimated that ferritin concentrations below 24 μg/L may be insufficient to support normal red blood cell production in this age group. They reported that the higher threshold was consistent across age and sex strata, although iron deficiency was more common among girls aged 12 to 14 years, likely reflecting menstrual blood loss.1
The clinical relevance is that iron deficiency can occur with or without anemia. Screening strategies that depend primarily on hemoglobin may therefore miss children with depleted or declining iron stores before anemia develops. Pediatric iron deficiency has been associated with impaired cognitive and behavioral development, fatigue, reduced exercise tolerance, and poorer school performance, although the degree to which earlier ferritin-based detection improves long-term outcomes in school-aged children remains an important question for prospective study.4
The new analysis is also consistent with concerns raised in public health guidance that ferritin is a useful but imperfect biomarker. Ferritin reflects iron stores, but concentrations can rise during inflammation, infection, liver disease, and other conditions. The study attempted to address this by excluding children with evidence of inflammatory or liver-related abnormalities, but the analysis remains dependent on available NHANES measures.1-3
To assess whether findings from older NHANES data remained applicable, the researchers performed supplemental analyses using more recent NHANES data from 2017 to 2023. Those analyses used soluble transferrin receptor rather than ZPP and yielded a ferritin threshold consistent with the NHANES III estimate, according to the study summary.1
The authors noted several limitations, including reliance on NHANES III data collected approximately 3 decades ago and inability to account for pubertal stage in boys or girls or onset of menstruation in girls. Those factors are clinically important because iron requirements increase during rapid growth and, in menstruating adolescents, with blood loss.1
For clinicians, the study may support a lower threshold for considering iron deficiency in symptomatic children or those at nutritional risk, even when hemoglobin is normal. However, treatment decisions still require clinical context, assessment of dietary intake and blood loss, and consideration of conditions that may alter ferritin interpretation. CDC researchers are continuing to examine how revised thresholds might be used in practice, according to Maria Elena Jefferds, PhD, a study coauthor and team lead in the CDC division.1
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