47 Risk factors: a systematic review 2 Measurement outcome Risk factor Measurement risk factor Results Risk of bias: QUIPS domains SDSC - Cortisol - Dex PK - DST, CLIA - Trough levels Cortisol: Baseline and AUC not correlated with sleep. Cortisol suppression not correlated with sleep. Trough levels: no correlation with sleep 2/6 high PK: Pharmacokinetics, Pred: Prednisone, RCT: Randomized Controlled Trial, SD: Standard Deviation, SDSC: Sleep Disturbance Scale for Children, SNP: Single Nucleotide Polymorphism, SR: Standard Risk, WASO: Wake time After Sleep Onset. levels,4 dexamethasone pharmacokinetics,53 and neuronal cell destruction4 were studied but not confirmed as significant risk factors for APRs, possibly due to small sample sizes (n = 37 and n = 46). Sleep problems Risk factors for steroid-induced sleep problems were evaluated in seven studies of which three54-56 reported secondary analyses of the cohort originally collected by Hinds et al.13 Four papers used an objective measuring method: actigraphy.13,54-56 Three papers used (parent-reported) subjective methods: 28-day sleep diary,12 the Sleep Disturbance Scale for Children (SDSC) questionnaire,12,53 and a self-constructed item rating sleep disturbance.48 All studies measured sleep problems during maintenance phase of treatment. Overall, the quality of evidence regarding risk factors for sleep problems was very low to low (Table 4), mostly due to the limited amount of studies conducted in this area. Sociodemographic factors (age and sex) The influence of age on sleep problems was investigated in three studies (two cohorts). A higher quality study found that age was associated with sleep duration. Older children were in bed less during dexamethasone treatment and older age was also associated with less total daily sleep minutes, however other sleep parameters did not differ significantly between age groups.13 In the same cohort, Rogers et al. reports no difference in age on actigraphic circadian parameters,54 in coherence with Drigan et al. who also did not find a difference in age on sleep disturbances.48 However, this is a low quality evidence paper, using subjective measurement for sleep. Evidence for age as a risk factor is limited to
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