Objective: To assess the safety of botulinum toxin type A for children with cerebral palsy using data from randomized clinical trials.
Data sources: A search was conducted of MEDLINE database for the period January 1990 to February 2008. A complementary search was carried out of references from previous reviews. From 122 articles, 20 randomized clinical trials were selected for the review.
Review methods: Two authors independently assessed eligibility of the studies and methodological quality of those according to CONSORT guidelines. For each adverse effect, relative risk was calculated, and when more than one study reported adverse effects, a meta-analysis was carried out. Sensitivity analyses with different continuity corrections factors were performed when zero cases were reported in a study arm.
Results: There were 882 participants in the 20 studies included in the meta-analysis. Six studies reported zero adverse effects. Thirty-five different adverse events were reported. Botulinum toxin type A use was related to respiratory tract infection, bronchitis, pharyngytis, asthma, muscle weakness, urinary incontinence, falls, seizures, fever and unspecified pain. Two deaths were reported in the study with higher person-time follow-up (relative risk (RR) 4.69, 95% confidence interval (CI) 0.23-95).
Conclusions: Botulinum toxin type A has a good safety profile during the first months of use. However the occurrence of adverse events is more frequent among children with cerebral palsy than individuals with other conditions. Severe adverse events are potentially related with the use of botulinum toxin type A, but data are sparse and additional study is required to clarify the causal relation.