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Prenatal leukotriene receptor antagonist use does not increase neuropsychiatric events in offspring

Prenatal leukotriene receptor antagonist use has been found to not increase the risk of adverse neuropsychiatric events in their children

Prenatal leukotriene receptor antagonist use does not appear to significantly elevate the risk of developing neuropsychiatric events among their offspring according to the findings of a study by Taiwanese researchers.

The leukotriene-receptor antagonists have demonstrated favourable anti-asthmatic activity over a wide spectrum of disease severity either alone or in combination with inhaled corticosteroids but also as an effective treatment for allergic rhinitis. But despite the value of these drugs, in the US, the FDA issued warnings about the risk of neuropsychiatric side effects (NSE)-related to the use of one leukotriene antagonist, montelukast and which often occurred within the first 10 days of use and were most common in 4 – 6 year old children. Moreover, other evidence also hints at such an association with a 2022 study of patients initiated on montelukast observing an increased odds of adverse neuropsychiatric outcomes among those starting the drug. Nevertheless, whether prenatal leukotriene receptor antagonist use could pose a risk by increasing the incidence of NSE in children is currently unclear.

In the current study researchers identified a group of women and their offspring, where the mother had been dispensed any prescription for a leukotriene receptor antagonist during her pregnancy. They set the outcome as a primary diagnosis of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) or Tourette syndrome (TS) in the offspring of these mothers and propensity matched these mothers with non-exposed control children.

Prenatal leukotriene receptor antagonist use and neuropsychiatric outcomes

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After propensity score matching, a total of 1,988 leukotriene receptor antagonist exposed children and 19,863 non-exposed children with included in the analysis.

Among the offspring, there was no significant association observed between prenatal leukotriene receptor antagonist exposure and ADHD (adjusted hazard ratio, aHR = 1.03, 95% CI 0.79 – 1.35, p = 0.82), ASD (aHR = 1.01, 95% CI 0.65 – 1.59, p = 0.96) and TS (aHR = 0.63, 95% CI 0.29 – 1.36, p = 0.24). This association remained non-significant when the prenatal leukotriene receptor antagonist use was categorised as either 1 – 4 weeks or > 4 weeks and where the cumulative dose ranged from 1 – 170 mg or > 170 mg, for each of the three outcomes.

The authors concluded that there was no significant risk of neuropsychiatric events in children following prenatal leukotriene receptor antagonist use, although they called for further work to confirm these findings.

Tsai HJ et al. Use of Leukotriene-Receptor Antagonists During Pregnancy and Risk of Neuropsychiatric Events in Offspring. JAMA Netw Open 2023

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