High ferritin thresholds allow early detection of iron deficiency in childhood

Many cases of iron deficiency in school-going children may be diagnosed earlier, according to a new study published in blood red cells and ironA journal of the American Society of Hematology (ASH). By applying a higher ferritin threshold than used in current guidelines, the researchers found that iron deficiency in American children ages 5 to 14 may be more common than previously thought and in many cases may be diagnosed earlier.

It is important to identify ferritin levels in the blood needed to support a child’s physical development and learning as low iron levels can lead to serious health problems such as difficulty in concentration and learning, fatigue and reduced physical performance.”

Yaw Addo, PhD, lead author and epidemiologist, Division of Nutrition, Physical Activity, and Obesity, Centers for Disease Control and Prevention (CDC)

Researchers developed a new method to identify ferritin cutoff levels in American school-aged children. This new method detects the early stages of iron deficiency by looking at changes in red blood cells and how the body makes them. Using this updated approach, nearly 1 in 3 (30%) children ages 5 to 14 included in the study sample were identified as iron deficient, significantly higher than the 9% identified in the same sample using previous methods.

Ferritin is a protein that stores iron in cells and releases it when needed. The iron is then used to make hemoglobin, the protein in red blood cells that carries oxygen to organs and tissues. When a child has low ferritin, they may become iron deficient, which can impair brain development, learning, and growth. It is possible to have iron deficiency with anemia (such as low hemoglobin) or without anemia.

The study included data from 3,765 healthy children ages 5 to 14 (average 10.3 years) who participated in NHANES III, a 1988–1994 national survey conducted by the CDC and had physical examinations and blood draws. Children were excluded from the analysis if they had evidence of infection, inflammation, or liver-related issues — all of which can affect ferritin — or if they had missing data on ferritin, hemoglobin, or zinc protoporphyrin (ZPP, a red blood cell compound that increases when tissue iron needs increase during iron deficiency).

Current guidelines from the CDC and the World Health Organization (WHO) identify iron deficiency at a ferritin threshold around 15 μg/L. However, the researchers’ findings suggest that when a child’s ferritin level is below 24 μg/L, iron levels may already be insufficient to maintain normal red blood cell production. This finding reinforces the growing evidence that current CDC and WHO limitations detect iron deficiency throughout the life cycle at more advanced stages, when iron levels may already be low and eliminated. Iron deficiency begins with hemoglobin levels that exceed those used to diagnose anemia. Because screening often depends on anemia, it may lead to premature, treatable iron deficiency.

“This study applied a new method to identify iron deficiency and found that iron may already be low and possibly begin to affect children’s health when ferritin is below 24 μg/L. The findings of this study may help identify earlier stages of iron deficiency compared to previously recommended cutoffs,” said Maria Elena Jeffords, PhD, coauthor and team lead in CDC’s Division of Nutrition, Physical Activity, and Obesity. “CDC is continuing to investigate how these ranges can be used by health care providers to improve the detection of iron deficiency in children ages 5 to 14.”

The increased demand and need for iron nutrition during this stage of life was similar between boys and girls, all of whom are actively growing and require iron for skeletal growth and development. However, iron deficiency was higher in older girls (12–14 years), possibly due to blood loss during menstruation. Nevertheless, ferritin ranges depending on age and sex were consistently higher than the current cutoff.

Because the study is based on 30-year-old NHANES III data, researchers conducted supplemental analyzes using more recent NHANES data (2017-2023) that included soluble transferrin receptors instead of ZPP, and the identified ferritin thresholds were consistent with those in the NHANES III study, further validating the findings. The researchers said a limitation of the study is that they were unable to account for the onset of puberty in boys and girls or the onset of menstruation in girls.

Researchers hope these data will improve detection of iron deficiency in children aged 5 to 14 years.