What is the relationship between iron deficiency and autism, and how is it treated?

Iron Deficiency and Autism: Relationship and Treatment Approach

Iron deficiency is associated with developmental delays and behavioral disturbances in children with autism spectrum disorder (ASD) and should be routinely screened for and treated with iron supplementation at 3 mg/kg per day in children with ASD who show evidence of iron deficiency. 1, 2

Relationship Between Iron Deficiency and Autism

• Iron deficiency is common in children with autism spectrum disorder, with studies showing prevalence rates of 24.1% for iron deficiency and 15.5% for iron deficiency anemia 3
• Iron plays a crucial role in brain metabolism, and deficiency can cause changes in neurotransmitter homeostasis, decreased myelin production, impaired synaptogenesis, and declined function of the basal ganglia 4
• Children with ASD have significantly lower ferritin levels compared to children with other neurodevelopmental disorders, suggesting an altered iron status specific to ASD 5
• Iron deficiency in children results in developmental delays and behavioral disturbances, including decreased motor activity, social interaction, and attention to tasks 1, 2
• These developmental delays may persist beyond school age (after 5 years) if iron deficiency is not fully reversed 1, 2

Clinical Manifestations and Impact

• Iron deficiency hampers the body's ability to produce hemoglobin, leading to increased fatigue, shortened attention span, and impaired intellectual performance 6
• Children with iron deficiency often experience irritability, difficulty concentrating, low energy, and reduced resistance to infection 6
• Lower hemoglobin levels have been associated with more severe autism symptoms, and there is a significant negative correlation between hematocrit levels and autism severity scores 7
• Iron deficiency increases the gastrointestinal tract's ability to absorb heavy metals, including lead, which can further impact neurodevelopment 1
• Children with ASD who have iron deficiency tend to experience poor appetite, which can worsen their overall health and nutritional status 6

Screening Recommendations

• Screen all children with ASD for iron deficiency as part of routine investigation 3
• For high-risk populations (including children with special healthcare needs like ASD), screen for anemia between ages 9-12 months, 6 months later, and annually from ages 2-5 years 1
• For children aged 2-5 years with risk factors (including special healthcare needs like ASD), conduct annual screening for iron-deficiency anemia 1
• Laboratory evaluation should include serum ferritin, iron, hemoglobin, hematocrit, mean corpuscular volume (MCV), and red cell distribution width (RDW) 3, 7
• Consider iron deficiency when ferritin levels are <10 ng/mL for preschoolers (<6 years) and <12 ng/mL for school-aged (>6 years) children 7

Treatment Approach

• Treat presumptive iron-deficiency anemia by prescribing 3 mg/kg per day of iron drops to be administered between meals 1
• Counsel parents or guardians about adequate diet to correct the underlying problem of low iron intake 1
• Repeat anemia screening in 4 weeks; an increase in hemoglobin concentration of ≥1 g/dL or in hematocrit of ≥3% confirms the diagnosis of iron-deficiency anemia 1
• If iron-deficiency anemia is confirmed, reinforce dietary counseling, continue iron treatment for 2 more months, then recheck hemoglobin or hematocrit 1
• Consider that oral iron supplementation may be less effective than intravenous iron for replenishing iron stores in severe deficiency cases, especially in children with ASD who may have feeding difficulties 2, 8

Dietary Recommendations

• Encourage consumption of foods rich in heme iron (meat, poultry, fish) which has higher bioavailability (15-35%) 6
• Encourage consumption of foods rich in non-heme iron (vegetables, beans, fortified cereals) with vitamin C to enhance absorption 6
• Suggest introducing plain, pureed meats after age 6 months or when the infant is developmentally ready to consume such food 1
• Encourage one feeding per day of foods rich in vitamin C (e.g., fruits, vegetables, or juice) to improve iron absorption, preferably with meals 1
• Avoid consuming iron supplements or iron-rich foods with calcium, phytates, or polyphenols, which can reduce iron absorption 6

Special Considerations for Children with ASD

• Children with ASD often have feeding problems due to behavioral issues and food aversions, making dietary management of iron deficiency challenging 8
• Iron deficiency in children with ASD might be associated with intellectual disability, with studies showing significantly lower hemoglobin and hematocrit levels in ASD patients with intellectual disability 7
• Consider that iron deficiency often coexists with other factors that may independently affect child development (low birthweight, general undernutrition, poverty) 1, 6
• Iron supplementation should be approached with caution in iron-replete children, as excessive iron may have negative effects on growth and gut microbiota 6
• If after 4 weeks the anemia does not respond to iron treatment despite compliance, further evaluate the anemia using additional laboratory tests, including MCV, RDW, and serum ferritin concentration 1