Higher ferritin threshold could detect childhood iron deficiency much earlier

Many cases of iron deficiency in school-aged children could be diagnosed earlier, according to a new study published in Blood Red Cells & Iron, a journal of the American Society of Hematology (ASH). By applying a higher ferritin threshold than used in current guidelines, researchers found that iron deficiency in U.S. children 5 to 14 years may be more common than previously thought and could be diagnosed earlier in many cases. 

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, Division of Nutrition, Physical Activity, and Obesity, Centers for Disease Control and Prevention (CDC)

Researchers developed a new method to identify the ferritin cutoff level among U.S. school-age children. This new method detects early stages of iron deficiency by looking at changes in red blood cells and how the body makes them. Using this updated approach, about 1 in 3 (30%) children 5 to 14 years included in the study's sample were identified as having iron deficiency, a substantial increase from the 9% identified in the same sample using previous methods. 

Ferritin is a protein that stores iron in cells and releases it when needed. Iron is then used to make hemoglobin, the protein in red blood cells that carries oxygen to organs and tissues. When a child's ferritin is low, they develop iron deficiency, which can impair brain development, learning, and growth. It is possible to have iron deficiency with anemia (e.g. low hemoglobin) or without anemia. 

The study included data from 3,765 otherwise healthy children 5 to 14 years (10.3 years on average) who participated in NHANES III, a 1988-1994 national survey by CDC, and underwent a physical exam 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 were 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 CDC and the World Health Organization (WHO) identify iron deficiency at a ferritin threshold around 15 μg/L. However, the researchers' findings suggest iron levels may already be insufficient to sustain normal red blood cell production when a child's ferritin level is less than 24 μg/L. This finding adds to growing evidence that current CDC and WHO thresholds across the lifecycle tend to detect iron deficiency at more advanced stages, when iron levels may already be low and depleted. Iron deficiency begins at a hemoglobin level that is higher than the level used to diagnose anemia. Because screening often relies on anemia, it can miss earlier, treatable iron deficiency. 

"This study applied a new methodology to identify iron deficiency and found that iron can already be low and possibly start to affect children's health when ferritin is less than 24 μg/L. The findings of this study might help identify earlier stages of iron deficiency than the previously recommended cutoff," said Maria Elena Jefferds, PhD, coauthor and team lead in CDC's Division of Nutrition, Physical Activity, and Obesity. "CDC is continuing to examine how these thresholds can be used by healthcare providers to improve detection of iron deficiency in children 5 to 14 years." 

The increased demand and need for iron nutrition during this life stage was similar between boys and girls, all of whom are actively growing and need iron for skeletal growth and development. However, iron deficiency was higher among older girls (12-14 years), likely due to blood loss from menstruation. Still, the ferritin threshold was consistently higher than current cutoffs across ages and sexes. 

Because the study is based on 30-year-old NHANES III data, researchers performed supplemental analyses using more recent NHANES data (2017-2023) that included soluble transferrin receptor instead of ZPP, and the ferritin threshold identified was consistent with the NHANES III study, further validating the findings. The researchers said one limitation of the study is that they were unable to account for puberty for boys and girls or the start of menstruation for girls. 

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