122 Chapter 4 ‘resting’). If a response which was not predefined was noted more than five times, this was also highlighted (e.g. ‘lax parenting’). The highlighted keywords were totaled. At T2, one question regarding received support during the dexamethasone course was included. Parenting stress To measure parenting stress at T1 and T2 we used the NOSI-K (Nijmeegse Ouderlijke Stress Index Korte versie),30 an adapted version of the PSI (Parenting Stress Index).31 This validated 25-item questionnaire measures stress experienced within the parenting role. A higher score reflects higher stress levels (range 25-150). We also used the Distress Thermometer for parents (DT-P).32 This validated questionnaire consists of three parts: 1) a thermometer (visual analogue scale) ranging from 0 (no distress) to 10 (extreme distress), 2) a total score based on a problem list about everyday problems and 3) additional questions concerning support, lack of understanding, and parental chronic illness. The total questionnaire and thermometer were completed by parents at T1, the thermometer at T2. Dexamethasone pharmacokinetics At T1, a peripheral blood sample was obtained approximately two hours after the first dexamethasone dose on day 1 (peak level). The exact time of intake and blood sampling was registered. For the measurement at T2 (trough level), parents were asked to document the exact time of the last dexamethasone administration the evening before. The moment of T2 blood sampling was registered. To calculate area under the curve (AUC) of dexamethasone, we selected patients with both a peak and trough measurement concentration value within 24 hours after dexamethasone administration. We calculated slope and intercept values of the concentration and time after dose (0-24h) plots for each patient using a linear regression method. We then used these values to get the extrapolated intercept on both x-axis and y-axis and calculated the triangle area as the AUC in each patient (Equation 1). Equation 1: = ! ∗ " 2 Candidate SNP assessment We used a candidate SNP approach, analyzing whether Bcl1 (rs41423247 G>C, GR gene) and rs4918 C>G (AHSG gene) polymorphisms were associated with dexamethasone-induced neurobehavioral or sleep problems, respectively.17-19 We analyzed both dominant models (e.g. CC vs. CG+GG: heterozygous carrier status) and recessive models (e.g. CC+CG vs. GG: homozygous carrier status). Details about the methodology are available in the Supplement.
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