Effectiveness and safety of interventions for fever-associated discomfort in children: A systematic review

Aims: Fever is one of the most frequent reasons for paediatric consultations. While traditionally managed by reducing body temperature, recent guidelines emphasize alleviating discomfort as the primary therapeutic goal. Although different interventions have been described to manage fever-associated discomfort in children, their effectiveness and safety has never been systematically analysed. The aim of this study was to review the evidence on the effectiveness and safety of pharmacological and nonpharmacological interventions for managing discomfort in febrile children. Methods: A systematic review was conducted following PRISMA guidelines (PROSPERO: CRD420250655721). PubMed, Embase and Cochrane Library were searched up to 31 January 2025, for studies involving children aged 29 days to 18 years that assessed interventions for fever-associated discomfort. Randomized controlled trials and observational studies were included. Risk of bias was assessed using Cochrane and STROBE tools. Results were synthesized narratively and grouped according to the type of intervention. Results: Eight studies (5 randomized controlled trials, 3 observational) involving 1877 children were included. Study designs, including dosage of antipyretics and quality varied across studies. Studies comparing ibuprofen and paracetamol provided conflicting results, while combination therapy (paracetamol + ibuprofen) appeared more effective than using a single drug in -one trial. Tepid sponging, despite reducing temperature, was associated with increased discomfort. No serious adverse events were reported. Conclusion: Pharmacological treatments appear effective and safe, whereas physical methods offer limited benefit. The available evidence is limited by the small number of studies, methodological heterogeneity, and concerns about risk of bias and outcome measurement inconsistency. New high-quality studies are needed to guide clinical practice for the management of fever-associated discomfort in children.