Neonatal pain score after use of paracetamol: Is there a relationship with serum trough concentration at steady state in preterm and term neonates?

OBJECTIVE: An easy to establish and patient-friendly biomarker to guide dosing of paracetamol in neonates is currently not available. The aim of this study was to determine the potential association between the serum trough concentration and area under the curve (AUC) of paracetamol at steady state and differences in pain scores in preterm and term neonates. MATERIALS AND METHODS: A retrospective observational study was performed, using an academic hospital database to identify neonates treated with intravenous or rectal paracetamol for at least 48 hours. At steady state, serum trough concentrations and the 24-hour AUC were determined. Pain was measured by COMFORTneo scores, before the 1st and 6th dose. Linear regression was performed to assess the association between serum trough concentration and 24-hour AUC and differences in pain scores. Subgroup analyses were performed for patients who received paracetamol due to a COMFORTneo score ≥ 14 (group 1) or who received prophylactic paracetamol because of upcoming surgery (group 2). RESULTS: 21 neonates were included. The median (interquartile range (IQR)) serum trough concentration of paracetamol before the 6th dose was 4.5 mg/L (2.7 - 8.5 mg/L). In subgroup 1, the median (IQR) COMFORTneo scores before the 1st and 6th dose were 17 (16.5 - 20) and 12 (11 - 16.5), respectively. In subgroup 2, the median (IQR) scores were 9 (8 - 10) and 11 (9 - 12), respectively. The serum trough concentration and 24-hour AUC were not associated with reduced pain scores (p = 0.12 and p = 0.67, respectively). CONCLUSION: No association was found between the serum trough concentration and 24-hour AUC of paracetamol at steady state and differences in pain scores in preterm and term neonates. Future research is needed to prospectively determine a patient-friendly biomarker to optimize the treatment with paracetamol.

Executive function training in very preterm children: a randomized controlled trial.

Objective of the current study was to assess whether game-formatted executive function (EF) training, is effective in improving attention, EF and academic performance in very preterm and/or extremely low birthweight children aged 8-12 years. A multi-center, double-blind, placebo- and waitlist controlled randomized trial (NTR5365) in two academic hospitals in The Netherlands was performed. Eighty-five very preterm children with parent-rated attention problems on the Child Behavior Checklist were randomized to one of three treatment conditions: EF training, placebo training or waitlist condition. EF or placebo training was completed at home (6 weeks, 25 sessions of 30-45 min each). At baseline, 2 weeks after training or being on the waitlist, and five months after first follow-up visit, children underwent assessments of primary outcomes (parent and teacher ratings of attention) and secondary outcomes (parent and teacher ratings of daily-life EF, computerized EF tasks and academic performance). Linear mixed model analyses were performed for all outcome measures. There were no significant differences in improvement over time on parent- and teacher ratings of attention, parent- and teacher ratings of daily-life EF, computerized EF tasks, and academic performance (arithmetic and reading) between the EF training, placebo training and waitlist condition. In conclusion, game-formatted EF training does not improve attention, EF or academic performance in very preterm children with parent-rated attention problems.

Effects of Executive Function Training on Attentional, Behavioral and Emotional Functioning and Self-Perceived Competence in Very Preterm Children: A Randomized Controlled Trial.

OBJECTIVE: Very preterm children have poorer attentional, behavioral and emotional functioning than term-born children. Problems on these domains have been linked to poorer executive function (EF). This study examined effects of a game-formatted, comprehensive EF training on attentional, behavioral and emotional functioning and self-perceived competence in very preterm children. STUDY DESIGN: Eighty-five children participated in a multi-center, double-blind, placebo and waitlist-controlled randomized trial. Children were recruited from neonatal follow-up units of two academic medical centers in The Netherlands. Eligible for inclusion were 8-12 year old children born very preterm (<30 weeks of gestation) and/or with extremely low birthweight (<1000 g) with parent reported attention problems. Children were randomly assigned to one of three treatment arms: EF training, placebo training or waitlist. The EF and placebo training involved a 6 weeks, 25 (30-45 min) sessions training program. Attentional functioning (Attention Network Test), behavioral and emotional functioning (parent and teacher Strengths and Difficulties questionnaire) and self-perceived competence (Self-Perception Profile for Children) were assessed at baseline, at the end of the training program and 5 months after the training was finished. Data analyses involved linear mixed model analyses. RESULTS: Children in the EF training arm significantly improved on all training tasks over the course of the EF training program. Despite these improvements on the EF training tasks, there were no significant differences over time on any of the outcome measures between the three treatment arms, indicating that this computerized EF training program had no beneficial effects. CONCLUSION: Although there were significant improvements in the EF training tasks, there was no generalization of these improvements to any of the outcome measures. Thus, our findings do not support the use of computerized EF training programs. Future research should investigate effectivity of more ecologically valid, real-world like EF training programs.