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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
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. sthiesen@liv.ac.uk.
Signe
S
Thiesen
Elizabeth J
EJ
Conroy
Jennifer R
JR
Bellis
Louise E
LE
Bracken
Helena L
HL
Mannix
Kim A
KA
Bird
Jennifer C
JC
Duncan
Lynne
L
Cresswell
Jamie J
JJ
Kirkham
Matthew
M
Peak
Paula R
PR
Williamson
Anthony J
AJ
Nunn
Mark A
MA
Turner
Munir
M
Pirmohamed
Rosalind L
RL
Smyth
D000293:Adolescent; D000704:Analysis of Variance; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D011446:Prospective Studies; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology