A recent study published in JAMA Network Open examined the associations between leukotriene-receptor antagonists (LTRAs) use in pregnancy and neuropsychiatric events (NEs) risk in offspring.
LTRAs are used to treat allergic respiratory diseases, such as allergic rhinitis and asthma. The United States (US) Food and Drug Administration (FDA) has monitored post-marketing data over the years to assess the potential risk of NEs due to montelukast. In 2020, the FDA issued a boxed warning of severe NEs linked to the use of montelukast. Moreover, conflicting evidence exists regarding the use of LTRAs in the context of NE risk.
The study and findings
In the present study, researchers evaluated whether the use of LTRAs in pregnancy was associated with the risk of developing NEs in the offspring. They identified pregnant individuals and their children in Taiwan between 2009 and 2019 from the National Health Insurance Research Database. Eligibility criteria were pregnant individuals without multiple births who had asthma/allergic rhinitis and offspring without congenital conditions.
The researchers defined exposure as having prescriptions for LTRAs during pregnancy. They used propensity score matching to control for differences between LTRA users and non-users at baseline. The outcomes were diagnoses of Tourette syndrome, autism spectrum disorder (ASD), or attention-deficit/hyperactivity disorder (ADHD) in children.
Outcomes were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for 2009-15 and ICD-10-CM codes for 2016-19. The associations between prenatal LTRA use and NEs among children were estimated using Cox proportional hazards models. Additional associations between LTRA exposure duration (up to and more than four weeks), cumulative dose (up to and above 170 mg), and NEs were investigated.
Overall, 576,157 pairs of mothers and offspring were initially identified. After propensity score matching, 19,863 unexposed children and 1988 LTRA-exposed children were included. There were no significant associations between prenatal exposure to LTRAs and the outcomes (ADHD, Tourette syndrome, and ASD) among offspring. The duration of LTRA exposure and the cumulative dose were not associated with the outcomes among children.
In summary, the study was the first to examine associations between LTRA exposure in pregnancy and the risk of NEs among children. The authors noted that prenatal use of LTRAs was not associated with a higher risk of ASD, Tourette syndrome, and ADHD in children.
The limitations of the study were the non-randomized design and the inability to assess the risk beyond the first years of life. These findings may reassure clinicians that LTRAs prescribed during pregnancy do not elevate the risk of NEs among children. Nonetheless, further studies should confirm these findings.