34 CHAPTER 1 for the first injection. This is relatively high compared to: (1) treatment success (53–70%) of previous studies at the same centre using similar definitions and (2) treatment success of the second and third injections in the current cohort.4,5,29,30 Two studies, however, evaluated the effect of onabotulinumneurotoxin A in children who received an average of 1.6 to 2.3 previous injections whereas our success rate is calculated solely based on the first injection.4,5 As our inclusion criteria only allowed children with repeated injections, survivor bias may have caused a higher treatment success rate for the first injection. In addition, non-ambulant children show better subjective effect compared to ambulant children, but were treated with fewer injections. Reasons for discontinuation of treatment, despite satisfactory response rates, could include the practical burden of repeated hospital visits for wheelchair-bound children. Age was negatively correlated with treatment effect: older children respond less. This is in contrast to a recent study in which age (more mature) was considered a predictor for successful two-duct ligation treatment of anterior drooling.15 We cannot fully explain this, but one theory is that older children hadmore exposition to previous onabotulinum neurotoxin A which could have induced NAb. Alternatively, expectations of carers may be higher after repeated injections. However, this may not be the only reason as the objective measure is also negatively correlated with age. The main strengths of the study were the number of children included, the standardized subjective and objective measurements, and the homogeneity of treatment characteristics. There are, however, also some limitations to the study. First, as this study was done retrospectively, treatment was clinically driven. Children with a good response to onabotulinum neurotoxin A will most likely continue with the same treatment, potentially leading to survivor bias. This may result in an overestimation of the effect of the second and third injection. Second, there was a relatively small number of children included with three injections, which means that the study had relatively little statistical power to address the effect of the
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