130 Chapter 4 DISCUSSION Our prospective national cohort study in 105 pediatric ALL patients identified parenting stress as a significant determinant for both parent-reported dexamethasoneinduced neurobehavioral and sleep problems. We did not find an association between dexamethasone pharmacokinetics, genetic variation, patient and parent demographics, or disease and treatment characteristics and behavioral or sleep problems. Parents with higher levels of parenting stress during a dexamethasone course of their child, reported more dexamethasone-induced neurobehavioral and sleep problems in their children. In addition, parents with more stress before the start of a dexamethasone course, reported more sleep problems. The direction of these associations however, is unclear: parenting stress may lead to disruptive child behavior and perceived sleep problems, vice versa, or the association may be bidirectional. To strengthen our finding, the association between parenting stress and child problems during dexamethasone should be established in an independent cohort. Moderating factors such as other stressful life events could play a role in both parenting stress and child behavioral problems.38 Previous studies showed that children of parents with higher levels of parenting stress showed more behavioral adjustment problems after ALL diagnosis.39,40 Also, parental distress and child distress are more strongly linked in a pediatric cancer cohort compared to controls.38 Targeting parenting stress, in individual cases, may be a useful intervention to decrease behavioral and sleep problems in children. Fedele et al showed that a randomly allocated psychosocial intervention focusing on uncertainty, coping, communication, support and problem solving for mothers, reduced internalizing symptoms in children with cancer.41 Similarly, Williams et al. pursued a successful evidence-based parenting intervention for parents with a child in ALL maintenance treatment. Even though this study involved only 12 patients, it showed both an improvement in quantitative difficulties (SDQ) as well as qualitative behavioral improvement (indicated by parents).42 Parents of children with a higher SDQ or SDSC score at T1 reported less dexamethasoneinduced neurobehavioral and sleep problems, respectively. This could indicate that, when parents already notice more problems in their child, the change during dexamethasone may be less pronounced. Also, if a child has a higher score at T1, a rise of 5 (SDQ) or 7 (SDSC) points may be more difficult to achieve. Still, pre-existing problems and parents’ ways of managing these problems are important to take into account, since targeting these problems may be beneficial for both parents and their children. Even though we evaluated numerous and various determinants, there may still be other mechanisms contributing to behavioral problems. Muriel et al. found family psychiatric history as risk factor of steroid-induced affective symptoms in a cohort of 125 ALL
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