Association of iron deficiency and iron-deficiency anemia with behavioral problems in children with autism: a cross-sectional study.

Purpose: Iron deficiency (ID) and iron deficiency anemia (IDA) are common in children with autism spectrum disorder (ASD) and may contribute to behavioral problems. We examined their association with internalizing and externalizing behavioral problems. Methods: This cross-sectional study (October 2023 to March 2025) was conducted at a tertiary hospital in India. Of 179 children aged 2 to 18 years with newly diagnosed ASD (DSM-5 criteria), 173 were analyzed after six exclusions for missing data. ID and IDA were defined using age-specific World Health Organization thresholds and modeled as a three-category variable with normal iron status as the reference. The Child Behavior Checklist was used to assess internalizing and externalizing problems (T-score > 63). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs), controlling for age, sex, maternal education and family type; ferritin and hemoglobin were modeled using restricted cubic splines. Bonferroni correction was applied across the six adjusted comparisons. Results: Among 173 children (median age 4.0 years [IQR 3.0-5.0]; 79.8% male), 19.7% had ID, 22.5% had IDA and 42.2% had either; internalizing and externalizing problems occurred in 39.9% and 35.8% of the children, respectively. Compared with normal iron status, both ID and IDA were associated with higher odds of internalizing problems (ID aOR 3.03, 95% confidence interval [CI] 1.34-6.86; IDA aOR 2.73, 95% CI 1.23-6.05) and externalizing problems (ID aOR 3.71, 95% CI 1.63-8.46; IDA aOR 3.24, 95% CI 1.45-7.24), corresponding to prevalence differences of 25 to 29 percentage points. An interquartile increase in ferritin (9.2 to 21.4 µg/L) was associated with lower odds of both outcomes (internalizing aOR 0.23, 95% CI 0.11-0.46; externalizing aOR 0.30, 95% CI 0.15-0.60). Five of six associations survived Bonferroni correction; IDA with internalizing problems did not. Hemoglobin was not consistently associated with either outcome. Conclusions: ID and IDA are prevalent in Indian children with ASD and are associated with clinically significant behavioral problems, with higher serum ferritin inversely associated with both outcomes. Routine iron screening may be considered during initial ASD evaluation, particularly in high-burden settings, although randomized trials are needed to determine whether correcting deficiency improves behavioral outcomes.