Differential Analysis of Neonatal Adverse Drug Events from Intrauterine and Extrauterine Exposure: Insights into Administration Routes Using the FAERS Database

Abstract

Objective

This study aimed to systematically characterize the features and drug distribution of neonatal adverse drug reactions using data from the FAERS, with a focus on exposure-specific patterns and stratified analyses by sex and clinical outcomes.

Methods

Reports submitted to FAERS from the first quarter of 2004 to the fourth quarter of 2024 were utilized. Patients experienced the ADR at an age of no more than 28 days. Four quantitative disproportionality analysis methods, including ROR, PRR, BCPNN, and MGPS, were used to detect signals of adverse drug events.

Results

A total of 15,456 neonatal cases exposed to the target drugs were included, yielding 60,611 adverse event reports, 95.45% of which were classified as serious. The median time to onset of ADRs was 264 days for intrauterine drug exposure, compared to 1–3 days for extrauterine exposure. The most affected SOCs were injury and procedural complications (19.53%), congenital disorders (15.96%), and pregnancy/perinatal conditions (8.65%). Transplacental exposure accounted for the highest proportion (52.47%), followed by intravenous (9.34%), oral (6.77%), breastfeeding (1.80%), intramuscular (1.48%), and inhalation (1.29%). The top maternal exposure drugs included venlafaxine, sertraline, quetiapine, lamotrigine, and levetiracetam. For intravenous use, levetiracetam, zidovudine, indomethacin, ibuprofen, and vancomycin were most common. Female neonates had higher risks of microcephaly, ventricular septal defect, and growth restriction, while male neonates were more prone to hypospadias, cryptorchidism, and agitation. Serious AEs were mainly linked to maternal drug exposure during pregnancy.

Conclusion

These results showed that the use of antidepressants, antiepileptics, and antivirals during pregnancy represents a significant risk factor for neonatal adverse reactions, particularly congenital malformations. Consequently, it is imperative to implement precise prevention strategies tailored to specific exposure stages and to advocate for the establishment of an international pharmacovigilance network for neonates.

Keywords

Neonates - Adverse event report - Drug exposure routes - Pharmacovigilance - FAERS

Publication History

Received: 23 July 2025

Accepted after revision: 20 November 2025

Article published online:
22 December 2025

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