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Unraveling Dexamethasone-Induced Neurobehavioral and Sleep Problems in Children With ALL: Which Determinants Are
Annelienke M van Hulst1, Martha A Grootenhuis1, Emma J Verwaaijen1
1Pediatric Oncology, Princess Máxima Center, Utrecht, the Netherlands.
Insights
Parenting stress significantly contributes to neurobehavioral and sleep problems in children undergoing dexamethasone treatment for acute lymphoblastic leukemia (ALL). Addressing parental stress may help mitigate these common side effects in pediatric ALL patients.
Area of Science:
- Pediatric Oncology
- Clinical Pharmacology
- Child Psychology
Background:
- Dexamethasone is a crucial corticosteroid in treating pediatric acute lymphoblastic leukemia (ALL).
- However, dexamethasone use is associated with significant neurobehavioral and sleep disturbances in children.
- High interpatient variability exists in the occurrence and severity of these adverse effects.
Purpose of the Study:
- To identify key determinants of parent-reported neurobehavioral and sleep problems induced by dexamethasone in pediatric ALL patients.
- To investigate the influence of patient/parent demographics, disease/treatment factors, parenting stress, dexamethasone pharmacokinetics, and genetic variations.
Main Methods:
- A prospective study involving 105 pediatric ALL patients during maintenance treatment.
- Parent-reported neurobehavioral and sleep problems were assessed using validated questionnaires (Strengths and Difficulties Questionnaire, Sleep Disturbance Scale for Children).
- Multivariable logistic regression analyses were employed to identify significant determinants, including parenting stress, pharmacokinetics, and genetic markers (rs41423247, rs4918).
Main Results:
- Clinically relevant neurobehavioral and sleep problems were reported in 67% and 59% of patients, respectively.
- Parenting stress emerged as a significant determinant for both neurobehavioral (OR, 1.16) and sleep problems (OR, 1.06).
- Higher parental stress prior to dexamethasone administration correlated with increased sleep problems in children (OR, 1.16).
Conclusions:
- Parenting stress, rather than pharmacokinetic or genetic factors, is a significant determinant of dexamethasone-induced neurobehavioral and sleep issues in pediatric ALL.
- Parenting stress represents a potentially modifiable target for interventions aimed at reducing these adverse effects.
- Further research should explore strategies to alleviate parenting stress to improve treatment outcomes and quality of life for children with ALL.
Purpose:
Dexamethasone, the preferred corticosteroid in most treatment protocols for pediatric acute lymphoblastic leukemia (ALL), can induce undesirable side effects. Neurobehavioral and sleep problems are frequently reported, but the interpatient variability is high. We therefore aimed to identify determinants for parent-reported dexamethasone-induced neurobehavioral and sleep problems in pediatric ALL.
Methods:
Our prospective study included patients with medium-risk ALL and their parents during maintenance treatment. Patients were assessed before and after one 5-day dexamethasone course. Primary end points were parent-reported dexamethasone-induced neurobehavioral and sleep problems, measured with the Strengths and Difficulties Questionnaire and Sleep Disturbance Scale for Children, respectively. Analyzed determinants included patient and parent demographics, disease and treatment characteristics, parenting stress (Parenting Stress Index and Distress Thermometer for Parents), dexamethasone pharmacokinetics, and genetic variation (candidate single-nucleotide polymorphisms rs41423247 and rs4918). Statistically significant determinants identified in univariable logistic regression analyses were incorporated in a multivariable model.
Results:
We included 105 patients: median age was 5.4 years (range, 3.0-18.8) and 61% were boys. Clinically relevant dexamethasone-induced neurobehavioral and sleep problems were reported by parents in 70 (67%) and 61 (59%) patients, respectively. In our multivariable regression models, we identified parenting stress as a significant determinant for parent-reported neurobehavioral (odds ratio [OR], 1.16; 95% CI, 1.07 to 1.26) and sleep problems (OR, 1.06; 95% CI, 1.02 to 1.10). Furthermore, parents who experienced more stress before start of a dexamethasone course reported more sleep problems in their child (OR, 1.16; 95% CI, 1.02 to 1.32).
Conclusion:
We identified parenting stress, and not dexamethasone pharmacokinetics, genetic variation, patient/parent demographics, or disease/treatment characteristics, as a significant determinant for parent-reported dexamethasone-induced neurobehavioral and sleep problems. Parenting stress may be a modifiable target to reduce these problems.
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