Adverse Drug Reactions in Children—A Systematic Review

Abstract

BackgroundAdverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided.Methods and FindingsWe searched nineteen electronic databases using a comprehensive search strategy. In total, 102 studies were included. The primary outcome was any clinical event described as an adverse drug reaction to one or more drugs. Additional information relating to the ADR was collected: associated drug classification; clinical presentation; associated risk factors; methods used for assessing causality, severity, and avoidability. Seventy one percent (72/102) of studies assessed causality, and thirty four percent (34/102) performed a severity assessment. Only nineteen studies (19%) assessed avoidability. Incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children (pooled estimate of 2.9% (2.6%, 3.1%)) and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. Anti-infectives and anti-epileptics were the most frequently reported therapeutic class associated with ADRs in children admitted to hospital (17 studies; 12 studies respectively) and children in hospital (24 studies; 14 studies respectively), while anti-infectives and non-steroidal anti-inflammatory drugs (NSAIDs) were frequently reported as associated with ADRs in outpatient children (13 studies; 6 studies respectively). Fourteen studies reported rates ranging from 7%–98% of ADRs being either definitely/possibly avoidable.ConclusionsThere is extensive literature which investigates ADRs in children. Although these studies provide estimates of incidence in different settings and some indication of the therapeutic classes most frequently associated with ADRs, further work is needed to address how such ADRs may be prevented.

Adverse drug reactions in paediatric patients in a tertiary care hospital in India: a prospective observational single centre study

“…Few studies found female preponderance while certain others, no such correlation. 1,3,6,13,14 In our study, however, there was male The commonest ADRs were local site reactions (Table 1) which is in concordance with previous studies. According to a study done in Shanghai 1 and a systematic review by Smyth et al large proportion of ADRs were local site reactions and mostly due to vaccines.…”

“…According to a study done in Shanghai 1 and a systematic review by Smyth et al large proportion of ADRs were local site reactions and mostly due to vaccines. 3 Vaccine related studies by Choe et al in Korea and Aagard et al in Danish children reported the same. 19,20 Skin is the most common organ involved in hypersensitivity to drugs and biological substances.…”

“…1,3,6 Vaccines (55.9%) contributed to a large extent followed by antimicrobials (22.9%). 1,3,6,12,18 Drug classes according to ATC classification are divided into high-risk drugs (analgesics, antiepileptics, antibacterials, immunosuppressants, antimycotics and corticosteroids for systemic use) and low-risk drugs (others). 13 In the present study, anti-infectives and antiepileptics were among the most common classes of drugs causing ADRs suggesting caution during prescription.…”

“…21 Most common vaccines causing ADRs are: DT, hepatitis B vaccine (HBV), BCG, mumps measles rubella (MMR), DPT+HiB, pneumococcal vaccine, meningococcal C conjugate, human papilloma virus (HPV), DPT+IPV+HiB, DPT-IPV, OPV. 1,3,12,18,21,22 Most common ADRs seen with vaccines are pain, inflammation and infection at injection site, urticaria, angioedema, fever, vomiting, diarrhoea, irritability, rhinitis, cough and refusal of food among others. 22 In our study, all 66 (100%) children who received DPT+HepB+HiB developed injection site pain, local redness, injection site warmth and injection site swelling whereas only 60 (90.9%) developed fever and 54 (81.8%) excessive crying and refusal to feed.…”

Comparación de dos métodos de evaluación de causalidad de sospechas de reacciones adversas a medicamentos (RAM): 2003-2009

“…Una revisión sistemática de 102 estudios prospec-tivos 9 de RAM en niños, encontró gran variación cuando se compararon las tasas de incidencia reportadas desde estudios observacionales; entre los estudios, 36 estimaron una tasa de incidencia para RAM durante la hospitalización desde 0,6% a 16,8% de los pacientes; considerando que una de las principales dificultades, cuando se comparan tasas de incidencia para RAM, es que los estudios difieren en la calidad metodológica, escenario clínico, características de la población y duración del estudio.…”