256 Chapter 8 This risk profile is indicative of the distress levels families are likely to experience during the treatment of their child,44 and may therefore prove useful to identify parents and patients who will benefit from interventions or more support early during treatment, to eventually improve child behavior. This may be a first step towards improved knowledge, identification and future intervention for children who are at risk of dexamethasone-induced neurobehavioral problems. Ultimately, the development of a risk prediction model, taking into account both child and parental factors, can lead towards targeted identification of children at risk of dexamethasone-induced neurobehavioral problems, and subsequent selection of a group that may benefit from interventions. Sleep problems When reviewing existing literature on steroid-induced sleep problems (Chapter 2), older age, higher steroid dose and the use of dexamethasone (as opposed to prednisone) were associated with increased sleep problems during glucocorticoids. In contrast, in our cohort, parenting and parental stress were the only significant determinants for sleep problems (Chapter 4). The association between child sleep problems and parenting stress has been shown in healthy children, as well as in children with psychological problems.45-49 The bidirectional association was previously proposed in a transactional model which also included other aspects such as infant and environmental factors, which may influence child sleep.50,51 Another factor which is associated with poor child’s sleep is poor parental sleep, as was shown previously in children with ALL.52 We did not evaluate parental sleep in our cohort, but since poor sleep is also associated with (parenting) stress,53 it is feasible that parental sleep has influenced both parenting stress and the reporting of child sleep in our cohort. Still, positive effects on child sleep may be expected when targeting parenting stress, as was previously suggested in children with behavioral sleep problems.54 It would be of value to measure parenting stress, parental and child sleep problems throughout the treatment of ALL to detect changes and to be able to timely intervene in one or more of these domains. In our center, sleep is assessed in clinical practice through the KLIK PROM portal and awareness during consultation with the treating physician is strongly advocated.55 Interestingly, there appear to be different associations between genetic and environmental factors and objective versus subjective sleep measurements.56 The fact that we did not find a genetic (rs4918 SNP) or pharmacokinetic risk factor for dexamethasone-induced sleep problems may be due to our use of subjective, parent-reported outcome measures. This endorses the recommendation to use both actigraphy combined with parent-reported outcomes, and combine this knowledge with previously described SNPs and other risk factors, such as parenting stress, to gain more insight in the mechanisms behind and risk factors of steroid-induced sleep problems.
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