Neonatal critical illness and development: white matter and hippocampus alterations in school-age neonatal extracorporeal membrane oxygenation survivors.

Aim: To examine the neurobiology of long-term neuropsychological deficits after neonatal extracorporeal membrane oxygenation (ECMO).

Method: This cross-sectional study assessed white matter integrity and hippocampal volume of ECMO survivors (8-15y) and healthy children (8-17y) using diffusion tensor imaging (DTI) and structural magnetic resonance imaging (MRI) respectively. Neuropsychological outcome was evaluated in ECMO survivors.

The vulnerable microcirculation in the critically ill pediatric patient.

In neonates, cardiovascular system development does not stop after the transition from intra-uterine to extra-uterine life and is not limited to the macrocirculation. The microcirculation (MC), which is essential for oxygen, nutrient, and drug delivery to tissues and cells, also develops. Developmental changes in the microcirculatory structure continue to occur during the initial weeks of life in healthy neonates.

Paracetamol and morphine for infant and neonatal pain; still a long way to go?

Pharmacologic pain management in newborns and infants is often based on limited scientific data. To close the knowledge gap, drug-related research in this population is increasingly supported by the authorities, but remains very challenging. This review summarizes the challenges of analgesic studies in newborns and infants on morphine and paracetamol (acetaminophen).

Genetic variants associated with thermal pain sensitivity in a paediatric population.

Pain sensitivity is an inherited factor that varies strongly between individuals. We investigated whether genetic polymorphisms in the candidate genes COMT, OPRM1, OPRD1, TAOK3, TRPA1, TRPV1, and SCN9A are contributing to experimental pain variability between children. Our study included 136 children and adolescents (8-18 years).

Short-Term Health-Related Quality of Life of Critically Ill Children Following Daily Sedation Interruption.

Objective: Our earlier pediatric daily sedation interruption trial showed that daily sedation interruption in addition to protocolized sedation in critically ill children does not reduce duration of mechanical ventilation, length of stay, or amounts of sedative drugs administered when compared with protocolized sedation only, but undersedation was more frequent in the daily sedation interruption + protocolized sedation group. We now report the preplanned analysis comparing short-term health-related quality of life and posttraumatic stress symptoms between the two groups.

Design: Preplanned prospective part of a randomized controlled trial.

Nationwide Evaluation of Congenital Hypothyroidism Screening during Neonatal Extracorporeal Membrane Oxygenation.

Background: Thyroid hormone concentrations may deviate from normal values during critical illness. This condition is known as nonthyroidal illness syndrome (NTIS), and it can influence the results of screening for congenital hypothyroidism (CH) during neonatal extracorporeal membrane oxygenation (ECMO).

Objectives: To determine the incidence of aberrant CH screening results in ECMO-treated neonates, to identify possible determinants, and to follow up patients with abnormal thyroid hormone concentrations.

Developmental problems in patients with oesophageal atresia: a longitudinal follow-up study.

Objective: To longitudinally evaluate motor development and predictive factors in school-age children with oesophageal atresia.

Design: Cohort study with prospective longitudinal follow-up.

Setting: Outpatient clinic of a tertiary university paediatric hospital.

Pharmacological sedation management in the paediatric intensive care unit.

Objective: This review addresses sedation management on paediatric intensive care units and possible gaps in the knowledge of optimal sedation strategies. We present an overview of the commonly used sedatives and their pharmacokinetic and pharmacodynamic considerations in children, as well as the ongoing studies in this field. Also, sedation guidelines and current sedation strategies and assessment methods are addressed.

Clinically relevant timing of antenatal sildenafil treatment reduces pulmonary vascular remodeling in congenital diaphragmatic hernia.

Patients with congenital diaphragmatic hernia (CDH) suffer from severe pulmonary hypertension attributable to altered development of the pulmonary vasculature, which is often resistant to vasodilator therapy. Present treatment starts postnatally even though significant differences in the pulmonary vasculature are already present early during pregnancy. We examined the effects of prenatal treatment with the phosphodiesterase-5 inhibitor sildenafil on pulmonary vascular development in experimental CDH starting at a clinically relevant time.

Pharmacodynamics and Pharmacokinetics of Morphine After Cardiac Surgery in Children With and Without Down Syndrome.

Objective: To compare the pharmacodynamics and pharmacokinetics of IV morphine after cardiac surgery in two groups of children-those with and without Down syndrome.

Design: Prospective, single-center observational trial.

Setting: PICU in a university-affiliated pediatric teaching hospital.

Allometric Scaling of Clearance in Paediatric Patients: When Does the Magic of 0.75 Fade?

Allometric scaling on the basis of bodyweight raised to the power of 0.75 (AS0.75) is frequently used to scale size-related changes in plasma clearance (CL) from adults to children.

Prevalence and Implications of Abnormal Laboratory Results in Patients in the Terminal Phase of Life.

Background: Pathophysiological changes at the end of life may affect pharmacokinetics of drugs. However, caregivers typically do not extensively monitor patients' laboratory parameters at the end of life.

Objective: Our aim was to describe laboratory parameters of hospice patients in the week before death.

Copy number variations in 375 patients with oesophageal atresia and/or tracheoesophageal fistula.

Oesophageal atresia (OA) with or without tracheoesophageal fistula (TOF) are rare anatomical congenital malformations whose cause is unknown in over 90% of patients. A genetic background is suggested, and among the reported genetic defects are copy number variations (CNVs). We hypothesized that CNVs contribute to OA/TOF development.

Children in clinical trials: towards evidence-based pediatric pharmacotherapy using pharmacokinetic-pharmacodynamic modeling.

Introduction: In pediatric pharmacotherapy, many drugs are still used off-label, and their efficacy and safety is not well characterized. Different efficacy and safety profiles in children of varying ages may be anticipated, due to developmental changes occurring across pediatric life.

Areas Covered: Beside pharmacokinetic (PK) studies, pharmacodynamic (PD) studies are urgently needed.

Bispectral Index Monitoring in Terminally Ill Patients: A Validation Study.

Context: If regular therapies cannot relieve symptoms sufficiently in the last days of life, continuous palliative sedation may serve to reduce consciousness. Sedation level can be measured with EEG monitoring with the bispectral index (BIS) monitor.

Objectives: To determine the feasibility and validity of BIS monitoring in terminally ill patients.

Infants Operated on for Necrotizing Enterocolitis: Towards Evidence-Based Pain Guidelines.

Background: Necrotizing enterocolitis (NEC) is known as an extremely painful childhood condition.

Objectives: The objective of this study was to explore pain management around NEC-related surgery in our neonatal intensive care unit (NICU) from a chart review of prospectively collected data on 60 operated NEC patients admitted between 2008 and 2013 with a median (IQR) gestational age of 28.3 (25.

Cardiac arrest in infants, children, and adolescents: long-term emotional and behavioral functioning.

Unlabelled: Very little is known about the psychological consequences of a cardiac arrest (CA) during childhood. Our aim was to assess long-term emotional and behavioral functioning, and its predictors, in survivors of CA in childhood. This long-term follow-up study involved all consecutive infants, children, and adolescents surviving CA in a tertiary-care university children's hospital between January 2002 and December 2011.

Sphingolipids in Congenital Diaphragmatic Hernia; Results from an International Multicenter Study.

Background: Congenital diaphragmatic hernia is a severe congenital anomaly with significant mortality and morbidity, for instance chronic lung disease. Sphingolipids have shown to be involved in lung injury, but their role in the pathophysiology of chronic lung disease has not been explored. We hypothesized that sphingolipid profiles in tracheal aspirates could play a role in predicting the mortality/ development of chronic lung disease in congenital diaphragmatic hernia patients.

Score for Neonatal Acute Physiology-II Predicts Outcome in Congenital Diaphragmatic Hernia Patients.

Objective: Accurate and validated predictors of outcome for infants with congenital diaphragmatic hernia are needed. Score for Neonatal Acute Physiology-II has been validated to predict mortality in newborns. We investigated whether Score for Neonatal Acute Physiology-II scores in congenital diaphragmatic hernia could predict mortality, need for extracorporeal membrane oxygenation (in patients born in a center with extracorporeal membrane oxygenation availability), and development of bronchopulmonary dysplasia (oxygen dependency beyond 28 d after birth) in survivors.

Proteomic Analysis of the Developmental Trajectory of Human Hepatic Membrane Transporter Proteins in the First Three Months of Life.

Human hepatic membrane-embedded transporter proteins are involved in trafficking endogenous and exogenous substrates. Even though impact of transporters on pharmacokinetics is recognized, little is known on maturation of transporter protein expression levels, especially during early life. We aimed to study the protein expression of 10 transporters in liver tissue from fetuses, infants, and adults.

Clinical recommendations for pain, sedation, withdrawal and delirium assessment in critically ill infants and children: an ESPNIC position statement for healthcare professionals.

Background: This position statement provides clinical recommendations for the assessment of pain, level of sedation, iatrogenic withdrawal syndrome and delirium in critically ill infants and children. Admission to a neonatal or paediatric intensive care unit (NICU, PICU) exposes a child to a series of painful and stressful events. Accurate assessment of the presence of pain and non-pain-related distress (adequacy of sedation, iatrogenic withdrawal syndrome and delirium) is essential to good clinical management and to monitoring the effectiveness of interventions to relieve or prevent pain and distress in the individual patient.

SLC22A1/OCT1 Genotype Affects O-desmethyltramadol Exposure in Newborn Infants.

Background: This study determined whether the SLC22A1 [encoding the organic cation transporter 1 (OCT1)] genotype could explain, in addition to the postmenstrual age (referring to gestational plus postnatal age) and CYP2D6 genotype, the tramadol (M) pharmacokinetic variability in early infancy.

Methods: Fifty infants, median postmenstrual age 39.5 (interquartile range: 36.