Open Access Research article

Incidence, characteristics and risk factors of adverse drug reactions in hospitalized children – a prospective observational cohort study of 6,601 admissions

Signe Thiesen1*, Elizabeth J Conroy2, Jennifer R Bellis3, Louise E Bracken3, Helena L Mannix3, Kim A Bird4, Jennifer C Duncan3, Lynne Cresswell5, Jamie J Kirkham2, Matthew Peak3, Paula R Williamson2, Anthony J Nunn1, Mark A Turner6, Munir Pirmohamed7 and Rosalind L Smyth8

Author Affiliations

1 Department of Women’s and Children’s Health, Institute of Translational Medicine (Child Health), University of Liverpool, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool L12 2AP, UK

2 Department of Biostatistics, University of Liverpool, Shelley’s Cottage, Brownlow Street, Liverpool L69 3GS, UK

3 Research and Development, Alder Hey Children’s NHS Foundation Trust, Eaton Road, Liverpool L12 2AP, UK

4 Oncology Unit, Alder Hey Children’s NHS Foundation Trust, Eaton Road, Liverpool L12 2AP, UK

5 MRC Biostatistics Unit, Institute of Public Health, University Forvie Site, Robinson Way, Cambridge CB2 0SR, UK

6 Department of Women’s and Children’s Health, University of Liverpool, First Floor, Liverpool Women’s Hospital, Crown Street, Liverpool L8 7SS, Uk

7 The Wolfson Centre for Personalised Medicine, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Block A: Waterhouse Building, 1-5 Brownlow Street, Liverpool L69 3G, UK

8 Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK

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BMC Medicine 2013, 11:237  doi:10.1186/1741-7015-11-237

Published: 7 November 2013



Adverse drug reactions (ADRs) are an important cause of harm in children. Current data are incomplete due to methodological differences between studies: only half of all studies provide drug data, incidence rates vary (0.6% to 16.8%) and very few studies provide data on causality, severity and risk factors of pediatric ADRs. We aimed to determine the incidence of ADRs in hospitalized children, to characterize these ADRs in terms of type, drug etiology, causality and severity and to identify risk factors.


We undertook a year-long, prospective observational cohort study of admissions to a single UK pediatric medical and surgical secondary and tertiary referral center (Alder Hey, Liverpool, UK). Children between 0 and 16 years 11 months old and admitted for more than 48 hours were included. Observed outcomes were occurrence of ADR and time to first ADR for the risk factor analysis.


A total of 5,118 children (6,601 admissions) were included, 17.7% of whom experienced at least one ADR. Opiate analgesics and drugs used in general anesthesia (GA) accounted for more than 50% of all drugs implicated in ADRs. Of these ADRs, 0.9% caused permanent harm or required admission to a higher level of care. Children who underwent GA were at more than six times the risk of developing an ADR than children without a GA (hazard ratio (HR) 6.40; 95% confidence interval (CI) 5.30 to 7.70). Other factors increasing the risk of an ADR were increasing age (HR 1.06 for each year; 95% CI 1.04 to 1.07), increasing number of drugs (HR 1.25 for each additional drug; 95% CI 1.22 to 1.28) and oncological treatment (HR 1.90; 95% CI 1.40 to 2.60).


ADRs are common in hospitalized children and children who had undergone a GA had more than six times the risk of developing an ADR. GA agents and opiate analgesics are a significant cause of ADRs and have been underrepresented in previous studies. This is a concern in view of the increasing number of pediatric short-stay surgeries.

Adverse drug reactions; Drug safety; Hospitalized children; Risk factors; General anesthesia; Peri- and post-operative pain management