1. After accounting for parental genetic factors, prenatal benzodiazepine exposure was not associated with an increased risk of autism spectrum or attention-deficit and hyperactivity disorders in children.
Evidence Rating Level: 2 (Good)
Benzodiazepine agents are often used to help improve symptoms of depression and anxiety during pregnancy. However, prenatal exposure to benzodiazepines is thought to be associated with neurodevelopmental disorders in children but research investigating autism spectrum (ASD) and attention-deficit and hyperactivity disorders (ADHD) has been scarce. In this retrospective cohort study, 1 547 702 participants in Taiwan who were exposed and unexposed to benzodiazepines were followed from birth to diagnoses of ADHD, ASD, or death, until 2017. These diagnoses were ascertained based on the International Classification of Diseases Ninth Revision (ICD-9) and International Statistical Classification of Diseases and Related Health Problems Tenth Revision (ICD-10). The unadjusted results showed that there was a higher risk of ASD and ADHD in all three trimesters among children exposed to benzodiazepines. The highest risk of ASD was related to third trimester exposure (HR 1.21, 95%CI 1.00-1.47), and the highest risk of ADHD was related to second trimester exposure (HR 1.27, 95%CI 1.21-1.34). However, there were no differences in neurodevelopmental outcomes and risk in unexposed sibling controls. In conclusion, this retrospective cohort study was the first of its kind to explore the association between benzodiazepine exposure during pregnancy and onset of neurodevelopmental disorders such as ASD and ADHD in children. After adjusting for potential confounders, benzodiazepine exposure during pregnancy was not associated with an increased risk of neurodevelopmental disorders. However, there are several limitations in this study that should be noted. For instance, there may be other psychological conditions the mothers included in this study may have, which may present with poorer neurodevelopmental outcomes in their offspring. Additionally, as this study was conducted only in Taiwan, its generalizability to other countries is limited. As such, conducting multicenter studies in various countries investigating this interaction between prenatal benzodiazepine exposure and neurodevelopmental outcomes among children can be valuable.
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