Associations of High Serum Ferritin Concentrations with Learning Disability and Attention Deficit/Hyperactivity Disorder among Children and Adolescents.

Abstract

Background: Associations of iron deficit with learning disability (LD) and attention deficit/hyperactivity disorder (ADHD) have been fully investigated. However, the association of high body iron levels with LD and ADHD in children and adolescents has seldom been investigated.

Objective: This study aimed to examine the association of serum ferritin concentrations, a biomarker of body iron status, with LD and ADHD in a large population-based cross-sectional study.

Design: This study utilized a cross-sectional study design.

Participants/setting: This study used data from the 1999 to 2002 National Health and Nutrition Examination Survey, which is a nationwide, population-based, cross-sectional survey in the United States. Participants with missing data on serum ferritin concentration, or LD and ADHD diagnosis, as well as those with anemia, were removed, and data of 4520 children and adolescents aged 4 to 15 years were included in the final analyses.

Main outcome measures: Outcome variables were LD and ADHD diagnoses, which were reported by the children's parents.

Statistical analyses performed: The characteristics of the participants according to quartiles of serum ferritin concentrations were calculated. Analysis of variance and Rao-Scott χ² tests were used to compare differences in continuous variables and categorical variables, respectively. Multivariable logistic regression was used to estimate the odds ratio (OR) and 95% CI of LD and ADHD according to quartiles of serum ferritin concentration. Several covariates were adjusted for in the models, including age, sex, race/ethnicity, family poverty-to-income ratio, cotinine concentration (tobacco exposure marker), total energy intake, body mass index, and serum C-reactive protein concentration.

Results: Higher serum ferritin concentrations were associated with a higher odds of LD in US children and adolescents. The adjusted OR for LD across increasing quartiles of serum ferritin levels was 1.00 (reference), 1.61 (95% CI, 1.11 to 2.32), 1.47 (95% CI, 0.93 to 2.32), and 1.89 (95% CI, 1.13 to 3.13), respectively (P for trend < .05). Each 10 ng/mL increase of serum ferritin level (to convert ng/mL to pmol/L, multiply by 2.247) was associated with a 13% higher odds of LD (adjusted OR, 1.13; 95% CI, 1.01 to 1.24). In addition, no significant association between serum ferritin levels and ADHD prevalence was found, and the adjusted ORs for ADHD across increasing quartiles of serum ferritin levels were 1.00 (reference), 1.16 (OR, 0.66 to 2.01), 1.04 (95% CI, 0.64 to 1.70), and 1.63 (OR, 0.95 to 2.82), respectively (P for trend was .08). Stratified analyses found that significant associations between serum ferritin level and LD prevalence were only found in boys with the highest quartile of serum ferritin (adjusted OR, 2.21; 95% CI, 1.05 to 4.67), and in children and adolescents whose race/ethnicity was non-Hispanic White with serum ferritin levels in quartile 2 (adjusted OR 1.73; 95% CI, 1.05 to 2.85) and quartile 4 (adjusted OR, 2.29; 95% CI, 1.08 to 4.88). In addition, the association between serum ferritin concentration and prevalence of ADHD was only significant for the highest quartile in boys, with an adjusted OR of 2.06 (95% CI, 1.01 to 4.20).

Conclusions: In a nationally representative, multiracial/ethnic population of US children and adolescents, high serum ferritin levels were found to be significantly associated with higher odds of LD, and when the serum ferritin level was ≥43 ng/mL, increased odds of LD and ADHD were both observed in boys.