Prematurely born neonates require, amongst others, pharmaceutical therapy. Dosing guidelines for these therapies are often based on data from term born neonates or older infants, while these are... Show morePrematurely born neonates require, amongst others, pharmaceutical therapy. Dosing guidelines for these therapies are often based on data from term born neonates or older infants, while these are not necessarily similar to prematurely born neonates. When suboptimal dosing guidelines are applied the neonates are at risk for under- or overdosing. In this thesis the pharmacokinetics and pharmacodynamics of a variety of drugs frequently used in preterm neonates were characterized, ultimately to optimize treatment. Specifically, caffeine, ibuprofen and fluconazole were studied which are drugs to treat apnea of prematurity, to close a patent ductus arteriosus and to treat or prevent infections with Candida in newborns, respectively. These drugs were introduced and used in clinical practice without sufficient knowledge, especially on appropriate dosing for this subpopulation. For caffeine and ibuprofen we found that the clearance rapidly increases with postnatal age, while for fluconazole clearance is better reflected by body weight and serum creatinine. For these drugs dosing guidelines were proposed based on identified covariates for their pharmacokinetics. Ibuprofen therapy was further investigated by examining the course of spontaneous closure of the ductus arteriosus, and evaluating the effects of ibuprofen exposure and patient characteristics simultaneously. Show less
Respiratory distress syndrome (RDS) care pathways evolve slowly as new evidence emerges. We report the sixth version of "European Guidelines for the Management of RDS " by a panel of experienced... Show moreRespiratory distress syndrome (RDS) care pathways evolve slowly as new evidence emerges. We report the sixth version of "European Guidelines for the Management of RDS " by a panel of experienced European neonatologists and an expert perinatal obstetrician based on available literature up to end of 2022. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, appropriate maternal transfer to a perinatal centre, and appropriate and timely use of antenatal steroids. Evidence-based lung-protective management includes initiation of non-invasive respiratory support from birth, judicious use of oxygen, early surfactant administration, caffeine therapy, and avoidance of intubation and mechanical ventilation where possible. Methods of ongoing non-invasive respiratory support have been further refined and may help reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation by targeted use of postnatal corticosteroids remains essential. The general care of infants with RDS is also reviewed, including emphasis on appropriate cardiovascular support and judicious use of antibiotics as being important determinants of best outcome. We would like to dedicate this guideline to the memory of Professor Henry Halliday who died on November 12(,) 2022.These updated guidelines contain evidence from recent Cochrane reviews and medical literature since 2019. Strength of evidence supporting recommendations has been evaluated using the GRADE system. There are changes to some of the previous recommendations as well as some changes to the strength of evidence supporting recommendations that have not changed. This guideline has been endorsed by the European Society for Paediatric Research (ESPR) and the Union of European Neonatal and Perinatal Societies (UENPS). Show less
Sweet, D.G.; Carnielli, V.; Greisen, G.; Hallman, M.; Ozek, E.; Pas, A. te; ... ; Halliday, H.L. 2019
