Fever Episodes Before Age 4 May Raise Risk of Childhood ADHD

Episodes of fever experienced during the first 4 years of life are associated with a higher rate of attention-deficit/hyperactivity disorder (ADHD) diagnosis during childhood and demonstrates a dose-response relationship. Results from the population-based case-control study were published in the Journal of Attention Disorders.

Previous studies have confirmed a relationship between ADHD development and inflammatory responses during pregnancy. The study authors built upon these previous insights to examine the effect of fever young in life that is not caused by a specific pathogen.

Researchers utilized data collected by the Leumit Health Services (LHS), comprising 204,871 children enrolled between 2002 and 2022. Children with ADHD (n=18,558) were matched with non-ADHD controls (n=37,116) in a 1:2 ratio based on demographics. Across the cases and matched controls, average age was 8.38 (SD, 2.71) years, 36.5% were girls, and 35.0% had a medium-high socioeconomic status.

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Fever data was available through electronic medical records and categorized into 5 thresholds of body temperature: 37.5°C, 38°C, 38.5°C, 39°C, and ³ 39.5°C. Study authors observed that the children with ADHD had experienced significantly more instances of fever in 4 of the 5 thresholds (37.5°C, P<.001; 38°C, P<.001; 38.5°C, P<.001; ³39.5°C, P<.001).                                                     

At the lowest threshold of 37.5°C, the investigators observed an elevated risk for ADHD with fevers lasting 3 or more days (odds ratio [OR], 1.253; 95% CI, 1.166-1.347; P <.0001), 2 days (OR, 1.174; 95% CI, 1.090-1.264; P <.0001), and 1 day (OR, 1.115; 95% CI, 1.064-1.168; P <.0001). In contrast, having no days with fever was protective against an ADHD diagnosis (OR, 0.834; 95% CI, 0.802-0.866; P <.0001). Similar trends were observed with higher fever thresholds. The greatest ADHD risk was observed for individuals with 3 or more days with a fever ≥39.5°C (OR, 2.135; 95% CI, 1.256-3.639; P =.0029).

“Elevated body temperature, either itself or as an attribute of inflammatory processes in infancy and early childhood, may play a role in the emergence of ADHD,” study authors concluded based on their findings.

The findings of this study may be limited by inclusion criteria; researchers evaluated only fever measured during outpatient visits.

References

Israel A, Merzon E, Krone B, et al. The association between repeated measured febrile episodes during early childhood and attention deficit hyperactivity disorder: a large-scale population-based study. J Atten Disord. Published online January 28, 2024. doi:10.1177/10870547231215289

Nye J. Febrile episodes before 4 years of age linked to ADHD risk in childhood. Psychiatry Advisor. Published online February 26, 2024. Accessed March 1, 2024.