17 General introduction 1 Psychosocial and environmental factors It has been previously shown that the child’s distress during procedures in childhood cancer treatment is associated with parental distress and parental stress on its own is associated with behavioral problems in children.44,45 Moreover, parents of a child with cancer appear to have higher stress levels than parents of children with physical disabilities.46 Overall, the degree of parental stress may be a factor in the occurrence of dexamethasone induced behavioral or sleep problems.47 Besides parenting stress, other family or environmental risk factors such as familial predisposition,48 parenting strategies,49-51 or psychosocial support may affect parents’ perceptions of the side effects which occur during dexamethasone. Genetic and pharmacokinetic factors Genetic variation may contribute to the differences in dexamethasone-induced side effects as well, therefore studying single nucleotide polymorphisms (SNPs) which may contribute to differences in neurobehavioral and sleep problems would be of value. Two previous studies suggest an association between the Bcl-1 polymorphism (NR3C1 gene) and depressive symptoms.52,53 The rs4918 polymorphism (Alpha2-HS glycoprotein (AHSG) gene) was suggested to be associated with impaired sleep during dexamethasone treatment in pediatric ALL patients.54 However, replication of these results is still pending. Genetic variants that have been shown to be associated with psychopathology or sleep problems, may give further insight in the pathophysiology and risk of these side effects caused by dexamethasone. In addition, dexamethasone pharmacokinetics may play a role in the occurrence of neurobehavioral side effects. Dexamethasone clearance is higher in younger children, so there may be an inter-patient variability in dexamethasone levels during maintenance phase, which may explain the differences in side effects.55 In summary, many different factors may contribute to the inter-patient variability of both dexamethasone-induced neurobehavioral and sleep problems. Some of these factors have been described before, however, findings are often conflicting or focus on only one possible determinant or outcome. It would be of interest to review the complete literature regarding risk factors for dexamethasone-induced neurobehavioral and sleep problems and to prospectively study these possible determinants. Somatic side effects Somatic side effects of glucocorticoids include increased risk of infections, osteonecrosis, osteopenia and consequent fractures, thromboembolisms, metabolic changes such as hyperglycemia, hyperlipidemia, weight gain, hypertension and myopathy.11,26,56-58 Previous research in children with ALL showed that merely four or five days of dexamethasone
RkJQdWJsaXNoZXIy MTk4NDMw