The association between infantile microcytic anemia and attention deficit hyperactivity disorder, a case-control study

Background: Microcytic anemia due to iron deficiency is the most common type of anemia in children in Israel and many parts of the world, and has been shown to have negative consequences for the cognitive performance. We aimed to examine the association between microcytic anemia at age 9-18 months and ADHD during childhood. Methods: This case-control study included healthy children aged 6-18 years at data collection (April 2020), insured by Clalit-Health-Services, and aged 9-18 months between June 2004 and December 2013, when a blood-count was performed. The study group included children diagnosed with ADHD based on the medical documentation of at least two consecutive stimulant prescriptions. A control group without any stimulant prescriptions was matched in a ratio of 1-3:1, by year of birth, sex and cultural background. Any microcytic anemia was defined as Hb < 10.5 g/dl and MCV 60-75 fl. Moderate microcytic anemia as Hb 7-9.9 g/dl. We performed a conditional-logistic-regression analysis, adjusted by socioeconomic status (SES) and year of birth. Sensitivity analysis examined this association stratified by sex, cultural background, SES and age at data collection quintiles. Results: Any microcytic anemia prevalence was lower in the ADHD group (n = 19,467) as compared to the controls (n = 39,004) (3.4 % and 4.0 %, respectively), adjusted-OR = 0.86 (95% CI: 0.78, 0.98). The prevalence of moderate microcytic anemia was similar (0.9 % vs. 1.0 %). Lower any microcytic anemia prevalence in the ADHD group was found in boys, seculartraditional Jews, and in the 4th quintile of age (12.1-13.5 years). Conclusions: We found a small inverse association between microcytic anemia at 9-18-months and ADHD during childhood, thus rejecting our hypothesis that microcytic anemia at infancy is associated with a higher prevalence of ADHD. Further studies are warranted, to examine the effects of ID and brain iron concentration on the development of ADHD in childhood.