P2.E096: Adverse Drug Reactions in Neonates: comprehensive analyses of the FDA Adverse Event Reporting System

Background: Drug trials in neonates are scarce and consequently, up to 90% of treatments in neonates are off-label, raising concerns about the risks of unknown adverse drug reactions (ADRs) in neonates. Given the limited clinical testing in neonates, spontaneous ADR reporting is an important tool to expand our knowledge and increase drug safety in neonates; however, it’s well known that the applicability of the currently collected data is undermined by underreporting. Also, data on prenatal and postnatal exposure is often combined in registers.
Accordingly, this comprehensive study aims to explore the quality of the current neonatal ADR reports in the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) database and to explore the most commonly reported drugs leading to ADRs in the neonatal departments.

Methods: An observational cross-sectional study focused on neonates, using publicly available data on spontaneous reports extracted from the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) from Q3 2014 until December 2022. Only primary suspect drugs given to age < 30 days were included in the analysis and categorized by active substances and furthermore stratified by intrauterine and extrauterine exposure. We defined intrauterine exposure as ADR reports of i) transplacental administration route, ii) indication as maternal/fetal exposure, or iii) listed as having a congenital anomaly as an outcome. To distinguish between neonatal ADR through maternal/fetal exposure and direct neonatal exposure, we specifically investigated the most frequently administrated drugs in the US neonatal intensive care units.

Results: Spontaneous reports from 13 million patients of all ages, totaling 50 million adverse drug reactions (ADRs), were evaluated. Information regarding age was missing in 40% of the reports, and data on 43,737 neonates with 948 different suspect drugs were identified and included in the analyses. Table 1 presents the drugs most frequently reported alongside suspected patient outcomes. We also report frequency of spontaneous ADR reports in the FAERS database for the ten most frequently administrated drugs at the US neonatal intensive care units (table 2).

Conclusion: Our results illustrate an overall significant underreporting of adverse events in neonates, which supports the findings of previous studies. According to data from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) database, approximately 9.3% of newborns in the U.S. are admitted to a neonatal department equivalent to 3 million neonates in the study period. For perspective, as little as 1.5% of hospitalized neonates were estimated to have ADRs reported during the study period, assuming that all reported ADRs were observed during hospitalization. Underreporting of ADRs may origin in the inherent difficulty in identifying ADRs in the newborn due to immature organ systems, but also to a general lack attention to ADRs and shortage of allocated resources.