Nov. 25, 2025
Iron deficiency is the most common cause of anemia worldwide. However, recognizing iron deficiency as its own disease entity is essential. It can adversely affect physical endurance, cognitive performance, neurodevelopment, immune function and growth in pediatric patients — before anemia develops.
Current recommendations call for anemia screening in children and teens. However, anemia is a late marker of iron deficiency, and emerging research suggests current thresholds may be too low. Screening and diagnosis of iron deficiency before it becomes severe may help avoid irreversible cognitive and developmental issues associated with iron deficiency.
"There is growing evidence that even without having anemia, iron deficiency can be symptomatic, and patients will greatly benefit from repleting their iron stores," says Ahmad H. Al-Huniti, M.D., a pediatric hematologist and oncologist at Mayo Clinic Children's in Rochester, Minnesota. "I think this is where the field has been changing, and I don't think everyone in the medical world has caught up with these changes."
Dr. Al-Huniti is not alone in his view. Dana B. Steien, M.D., a pediatric gastroenterologist and nutrition specialist at Mayo Clinic Children's in Rochester, says there is room for improvement in all phases of pediatric iron deficiency, including:
- Screening.
- Lab interpretation and current thresholds.
- Treatment.
- Follow-up.
"There is growing evidence that even without having anemia, iron deficiency can be symptomatic, and patients will greatly benefit from repleting their iron stores. I think this is where the field has been changing, and I don't think everyone in the medical world has caught up with these changes."
Proactively screening for iron deficiency in at-risk pediatric patients
The American Academy of Pediatrics (AAP) recommends screening for anemia — not iron deficiency — using:
- Risk assessment performed at age 4 months and every well-child visit after age 12 months.
- Laboratory testing performed at age 12 months, suggesting a venous hemoglobin (Hgb) test instead of the previously recommended capillary test.
"The challenge is that iron deficiency anemia (IDA) does not occur until the deficiency is severe, and hemoglobin is the last lab to change when iron deficiency occurs," says Dr. Steien. "Pediatric populations that have risk factors and mild or no symptoms are often missed. Healthcare professionals should consider adjusting their screening practices for those patients."
The most at-risk pediatric patients include:
- Toddlers ages 12 months to 2 years.
- Teenage females, who have a 40% risk of developing iron deficiency following menarche.
- Adolescent athletes, who may experience increased iron loss during training.
Beyond taking a thorough health and family history, pediatric physicians should ask questions specific to iron intake, absorption and loss, such as:
- How much cow's milk is being consumed? (Calcium can inhibit iron absorption.)
- Does the child's daily diet include iron-rich foods, such as meat, legumes and dark green, leafy vegetables?
- Has the child been taking an iron supplement or a multivitamin that contains iron?
- What does the teen's physical activity entail?
- Have periods begun?
"Screening for iron deficiency is complex and needs to be thorough," says Dr. Al-Huniti. "I recommend checking serum ferritin if anemia screening is done through a venous sample. This pragmatic approach avoids missing iron deficiency without anemia."
Rethinking the interpretation of iron deficiency tests
Measuring iron stores, called serum ferritin, provides an overview of a child's iron stores that can help physicians identify iron deficiency early. Current guidelines put forth by the World Health Organization (WHO) set serum ferritin thresholds for iron deficiency as:
- Infants and children under 5 years of age: < 12 µg/L.
- Children and teens ages 5 and older: < 15 µg/L.
However, research published in The Lancet Global Health in 2025 suggests that those thresholds should be higher. Using a threshold of < 22 µg/L for children ages 6 to 59 months, the prevalence of iron deficiency reached 34%, compared with 16% prevalence using the recommended WHO threshold.
The American Society of Hematology agrees and is in the process of publishing new guidelines based on a systematic review of available evidence. Those anticipated guidelines may include the following recommendations:
- Young children (9 months to 4 years). Use a serum ferritin threshold of ≤ 20 µg/L for the diagnosis of iron deficiency. This cutoff is for children without known or suspected inflammation. A higher ferritin threshold may be required for children with inflammation.
- Menstruating individuals. Use a serum ferritin threshold of ≤ 30 µg/L for the diagnosis of iron deficiency. For people with heavy menstrual bleeding and symptoms or risk factors for iron deficiency, serum ferritin ≤ 50 µg/L may be used for diagnosis and treatment decisions.
Dr. Al-Huniti and Dr. Steien agree with the proposed higher threshold, reminding physicians that:
- Current iron deficiency thresholds may be set too low. Symptoms should be considered when making a decision about iron supplementation.
- Iron deficiency should not be ruled out if serum ferritin levels are higher than the threshold.
"The treatment goal should be to fully replenish iron stores, so repeated lab studies are critical. In children with IDA, correcting anemia is only the first step."
Treating pediatric iron deficiency aggressively
Left untreated, iron deficiency leads to IDA. The first line of treatment for iron deficiency is oral iron — typically 3 to 6 mg/kg of body weight. However, there are two significant challenges when treating iron deficiency orally:
- Low absorption, with oral iron having a rate of 20% absorption or less.
- Poor compliance, often due to gastrointestinal side effects.
If those challenges hinder repletion or the iron deficiency is severe, Dr. Al-Huniti says physicians should not hesitate to consider intravenous (IV) iron, which has an absorption rate of 100%.
"In severe cases, or if the child is not compliant or not responding to oral iron, one IV treatment can help fill iron stores quickly," says Dr. Al-Huniti. "Some studies suggest this approach may be more cost-efficient, and new IV iron formulations are much safer than in the past."
Recognizing the significance of early follow-up for iron deficiency
Following up with children and teens diagnosed with iron deficiency or IDA is critical for managing poor adherence, addressing side effects and identifying underlying absorption issues.
"A child's brain and body are growing, and we know iron is essential for that process," says Dr. Al-Huniti. "If they are not completely repleting their iron, it can cause long-term implications for their health."
Dr. Steien recommends follow-up timelines depending on the treatment pathway:
Oral iron treatment
In children and teens with IDA, follow-up lab studies should be done within one month.
"Hemoglobin will correct first, and improvement in hemoglobin is reassurance that the treatment is working," says Dr. Steien. "Depending on the severity of iron deficiency, ferritin may not increase at all or may even decrease after one month of oral iron treatment."
Iron administration should continue until iron stores are fully replenished, which may take three months or longer. Ongoing monitoring is critical to ensure iron treatment produces expected or sustained improvements in laboratory studies and symptoms. If it does not, further evaluation, referral or both to a pediatric hematologist or gastroenterologist is appropriate.
"The treatment goal should be to fully replenish iron stores, so repeated lab studies are critical," says Dr. Steien. "In children with IDA, correcting anemia is only the first step."
IV iron treatment
Following IV iron administration, hemoglobin will increase in 1 to 2 weeks and peak at 4 to 8 weeks. Serum ferritin levels will often peak (above normal range) soon after IV iron administration and then trend down to a steady state by 8 to 12 weeks. Dr. Steien says it is appropriate to obtain a CBC, ferritin with or without CRP 8 to 12 weeks after IV iron administration.
"In high-risk individuals, such as those with ongoing active bleeding, evaluating the patient sooner is appropriate," says Dr. Al-Huniti.
Practical clinical approaches to address iron deficiency in pediatric populations
Diagnosing and treating pediatric patients with iron deficiency can be challenging. Dr. Steien and Dr. Al-Huniti recommend a clinical approach that includes:
Reassess serum ferritin thresholds
Iron deficiency may still be present even when serum ferritin levels exceed traditional cutoffs. When treating with oral iron for iron deficiency without anemia, Dr. Steien recommends repeating labs in 2 to 3 months after beginning oral iron treatment. Repeat labs approximately every three months until iron stores are repleted. Consider clinical context and symptoms alongside lab values.
"There are many reasons, such as recent illness, that serum ferritin may be high, even when iron deficiency occurs," says Dr. Steien. "That's why I often also check complete blood count. If the patient has had any inflammation or illness within the last month, I add a C-reactive protein test."
Implement strategies to enhance oral iron absorption
Certain treatment choices support better absorption of prescribed oral iron. Recommendations to improve outcomes associated with oral iron include:
- Choose heme iron. With approximately 30% bioavailability, heme iron is more efficiently absorbed and better tolerated than non-heme or synthetic forms (approximately 10%).
- Specify dosing time. Administer iron supplements at least 2 to 4 hours apart from calcium (for example, milk), bran, grains, tea, coffee and antacids to avoid absorption interference.
- Consider alternate-day dosing in patients with mild iron-storage deficiency and no anemia. Regimens such as Monday, Wednesday and Friday may improve uptake and reduce gastrointestinal side effects, but it will take longer to replete iron stores.
Consider IV iron
IV iron is appropriate for severe deficiency, poor tolerance or response to oral iron, malabsorptive conditions, or when rapid repletion is clinically indicated.
"Low molecular weight iron dextran has become the most commonly used IV iron infusion," says Dr. Al-Huniti. "It can effectively replenish iron deficiency with just one infusion and has a reasonable safety profile."
Iron sucrose — another commonly used formulation — typically requires multiple infusions to fully address the iron deficit, making it less cost-effective. There also are other formulations that are used less frequently.
The dosing of IV iron depends on whether you are treating iron deficiency or IDA.
"I calculate the total iron deficit to determine the appropriate amount of iron needed," says Dr. Al-Huniti. "For treating iron deficiency without anemia, I usually opt for iron dextran at a dosage of 15 mg/kg in a single infusion, with a maximum limit of 1,000 mg."
For more information
Addo O, et al. Physiologically based serum ferritin thresholds for iron deficiency among women and children from Africa, Asia, Europe, and central America: A multinational comparative study. The Lancet Global Health. 2025;13:e831.
Refer a patient to Mayo Clinic.