A database of pediatric drug effects to evaluate ontogenic mechanisms from child growth and development.

Background: Adverse drug effects (ADEs) in children are common and may result in disability and death, necessitating post-marketing monitoring of their use. Evaluating drug safety is especially challenging in children due to the processes of growth and maturation, which can alter how children respond to treatment. Current drug safety-signal-detection methods do not account for these dynamics.

Methods: We recently developed a method called disproportionality generalized additive models (dGAMs) to better identify safety signals for drugs across child-development stages.

Findings: We used dGAMs on a database of 264,453 pediatric adverse-event reports and found 19,438 ADEs signals associated with development and validated these signals against a small reference set of pediatric ADEs. Using our approach, we can hypothesize on the ontogenic dynamics of ADE signals, such as that montelukast-induced psychiatric disorders appear most significant in the second year of life. Additionally, we integrated pediatric enzyme expression data and found that pharmacogenes with dynamic childhood expression, such as CYP2C18 and CYP27B1, are associated with pediatric ADEs.

Conclusions: We curated KidSIDES, a database of pediatric drug safety signals, for the research community and developed the Pediatric Drug Safety portal (PDSportal) to facilitate evaluation of drug safety signals across childhood growth and development.

Funding: This study was supported by grants from the National Institutes of Health (NIH).