First-generation antihistamine prescriptions were linked to a 22% higher seizure risk in young children, especially those aged 6 to 24 months, according to recent findings.
Findings from a study published in JAMA Network Open demonstrated and reinforced the importance of using caution with first-generation antihistamine prescriptions in young children, as these prescriptions were associated with a 22%-higher seizure risk.
According to the study authors, there is widespread use of antihistamines in children for the treatment of common cold symptoms. With the treatment comes the affect on the central nervous system such as drowsiness. This is what underscores the importance of awareness related to the associated risks of antihistamines.
The investigative team, led by Ju Hee Kim, MD, Department of Pediatrics, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Korea, sought to assess these associations between prescriptions of first-generation antihistamines and seizures in children.
In a retrospective cohort design, the investigators used representative data from the National Health Insurance Service (NHIS) database in Korea. "Data for individuals born in Korea between January 1, 2002, and December 31, 2005, and followed up until December 31, 2019, or until participants became ineligible for health care insurance were considered," stated the investigators.
A case-crossover design was used, which assessed the risk of seizure events associated with first-generation antihistamine prescriptions. This design analyzed short-term exposure effects on acute events. "We chose this design because antihistamines are typically used for short periods, and seizures are considered their immediate health impacts," said Kim and colleagues. "In the case-crossover design, each participant acts as their own control. This approach inherently eliminates confounding factors that remain constant among individuals."
The primary endpoint was an index seizure events, with odds ratios (ORs) for seizure events estimated by a conditional logistic regression model that compared first-generation antihistamine prescription 1 to 15 days before seizure, defined as the hazard period, with the control period (31-45 days before event), and control period 2 (61-75 days before the event) using the same period windows.
In all, data from 3178 individuals (55.9% males) had been prescribed antihistamines during the hazard or control period, but not both. Seizure events were observed in children aged 6 to 24 months (31%) and aged 25 months to 6 years (45.5%). In the hazard period, there were 1476 first-generation prescriptions were recorded, which differed from 1239 and 1278 prescriptions during control periods 1 and 2, respectively.
Following multiple confounder adjustments, first-generation antihistamine prescription was associated with an increased seizure event risk during the hazard period (adjusted OR, 1.22 [95% CI, 1.13-1.31]). Stratified subgroup analyses demonstrated that children aged 6 to 24 months who were prescribed first-generation antihistamines had a higher risk (AOR, 1.49 [95% CI, 1.31-1.70]) compared to children aged 25 months to 6 years ((AOR, 1.11 [95% CI, 1.00-1.24]; P = .04 for interaction).
"Furthermore," the authors noted, "sensitivity analyses, including adjustment for exposure window periods, evaluation of new first-generation antihistamine prescriptions, comparison of control points from the same period 1 year prior, and exclusion of individuals using combination drugs, confirmed a similarly high risk."
First-generation antihistamine prescriptions were associated with a 22% higher seizure risk in children, primarily in those aged 6 to 24 months. In conclusion, the authors stated the results demonstrated in this study highlight the need for further research to "elucidate associations between antihistamine prescriptions and seizure risk."
Reference:
Kim JH, Ha EK, Han B, et al. First-Generation Antihistamines and Seizures in Young Children. JAMA Netw Open. 2024;7(8):e2429654. doi:10.1001/jamanetworkopen.2024.29654
