The global extent of polypharmacy in neonatal intensive care: A systematic review

Aims Pharmaceutical treatment in the neonatal intensive care unit (NICU) is challenging, with neonates often receiving multiple drugs during hospitalization. Given their physiological immaturity, polypharmacy raises concerns about potential adverse effects, drug–drug interactions and the risk of supratherapeutic or subtherapeutic treatment. However, the extent and patterns of drug utilization in NICUs remain underexplored. Accordingly, this study aims to systematically summarise existing literature on polypharmacy in NICUs worldwide. Methods This systematic review, registered in PROSPERO, adhered to PRISMA guidelines. A structured search in EMBASE, Medline and CINAHL identified NICU drug utilization studies (2014–2024). Study selection followed a two‐step screening process using the PICO framework. Two reviewers independently screened articles, extracted data and assessed quality with the Newcastle‐Ottawa Scale. Results We included 40 studies across 17 countries, with India and Brazil most frequently represented. Cohorts varied widely, with sample sizes ranging from 41 to 799 016. Polypharmacy was prevalent, particularly among preterm neonates. Commonly prescribed drugs were anti‐infectives, respiratory agents and gastrointestinal/metabolic medications. Methodological inconsistencies and variability in medication classification complicated accurate quantification of polypharmacy. Conclusions This review highlights the widespread use of polypharmacy in NICUs globally, yet few studies comprehensively assess the full scope and impact of polypharmacy. The lack of detailed data on drug indications, dosages, treatment duration and adverse effects limits the ability to evaluate the safety and clinical consequences of polypharmacy. Data collection resulting in standardized methodologies are essential to advancing neonatal pharmacotherapy ensuring safer medication use in this vulnerable population.