Up to one in three children aged five to 14 years may have iron deficiency, with new US research suggesting current ferritin thresholds identify the condition too late.
Many cases of iron deficiency in school-aged children may be going undetected until relatively late in the disease process, with new research suggesting that current ferritin thresholds miss a substantial proportion of children with early, potentially treatable deficiency.
A study published in the journal Blood Red Cells & Iron found that raising the ferritin threshold used to define iron deficiency from the current 15 μg/L to 24 μg/L identified around 30% of US children aged five to 14 years as iron deficient, compared with just 9% under existing criteria.
The findings add to growing concerns that reliance on low ferritin levels and anaemia-based screening may delay diagnosis until iron stores are already significantly depleted.
“Iron levels can already be low and possibly start to affect children’s health when ferritin is less than 24 μg/L,” said lead author Dr Yaw Addo, an epidemiologist in the nutrition division of the US Centers for Disease Control and Prevention.
“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.”
Ferritin is the primary storage protein for iron and is widely used to assess iron status. Current thresholds recommended by the CDC and the World Health Organization define iron deficiency at approximately 15 μg/L. However, the new analysis suggests that red blood cell production may already be affected before ferritin falls to that level.
“The original WHO ferritin thresholds for ID were formulated during National Health and Nutrition Examination Survey (NHANES) III in the 1990s, based on absent iron in bone marrow and not on physiologic aberration,” the researchers wrote.
“Since then, new evidence has indicated that physiological measures may be used to identify ferritin thresholds for the onset of iron depletion and ID erythropoiesis.
“The physiologic onset of ID is manifested by reduced levels of functional iron compounds, like haemoglobin (Hb) and myoglobin, concomitantly with an increase in markers of erythroid and tissue iron needs, such as soluble transferrin receptor and erythrocyte zinc protoporphyrin (ZPP).”
The researchers analysed data from 3765 otherwise healthy children aged five to 14 years who participated in the US National Health and Nutrition Examination Survey (NHANES III) between 1988 and 1994.
Children with evidence of infection, inflammation or liver disease were excluded because these conditions can alter ferritin concentrations.
The researchers examined the relationship between ferritin levels and biomarkers of erythropoiesis, including zinc protoporphyrin, which rises when tissue iron requirements increase.
They found evidence that iron availability for normal red blood cell production began to decline when ferritin dropped below 24 μg/L.
The researchers said that current thresholds may identify iron deficiency only at a more advanced stage, while earlier deficiency remained unrecognised.
Because haemoglobin levels often remain within the normal range during the initial phases of iron depletion, screening strategies focused on anaemia may fail to detect children who could benefit from intervention.
Co-author Dr Maria Elena Jefferds said the findings could help clinicians recognise iron deficiency before anaemia develops.
“The findings of this study might help identify earlier stages of iron deficiency than the previously recommended cutoff,” she said.
The higher ferritin threshold was observed across age groups and both sexes, although iron deficiency was more common among girls aged 12 to 14 years, likely reflecting menstrual blood loss.
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The researchers noted that the physiological demands of rapid growth during childhood and early adolescence increase iron requirements for both boys and girls.
To assess whether the findings remained relevant to contemporary populations, the researchers conducted supplementary analyses using NHANES data collected between 2017 and 2023.
Although a different biomarker was used, the ferritin threshold identified was similar, supporting the validity of the results.
The researchers acknowledged that the study could not account for pubertal status or the onset of menstruation, factors that may influence iron requirements and ferritin concentrations.
If confirmed in further research, they said the findings could prompt reconsideration of current diagnostic thresholds and support earlier identification and treatment of iron deficiency in children before the development of overt anaemia.
“Physiologically based ferritin thresholds for identifying the onset of ID were consistent by sex, age, iron analyte, and hematologic indices, and were higher than current CDC and WHO thresholds,” the researchers wrote.
“Prevalence of IDA was unchanged when using the physiologically based threshold compared to CDC or WHO thresholds, but iron deficiency prevalence increased, suggesting that anaemia alone is not an adequate proxy for ID screening.
“It might be important to consider using higher and functionally responsive ferritin thresholds for defining ID in US children aged 5-14 years.”
