Tamara van Donge

Physiological changes during pregnancy and neonatal life 31 2 than that of the newborn, since creatinine is easily transferred across the placenta. 41 At birth, which is known to be an accelerator for postnatal maturation of renal function, the vascular resistance decreases and an increase in cardiac output and renal blood flow is observed, which will alter the GFR. 28,42 The renal tubules are not yet structurally or functionally mature at birth and leads to an activity that is approximately 20% of the adult value. By seven to eight months the adult tubular secretion values will be attained. 27 Although creatinine clearance is currently the best way to determine the renal function, it is probably not the most accurate method to use in newborns. A new renal biomarker such as cystatin C, a protein which is freely filtered by the glomerulus may reflect the GFR more closely in preterm infants. 28 Beta-trace protein is another possible renal marker which does not cross the placental barrier and is subject to increased attention as new indicator of GFR and renal function. 28,41 Integrating pharmacological expertise combined with clinical knowledge on physiological changes provides a strong foundation for innovative and new evidence-based dosing recommendations which are highly necessary for neonates as they are being considered the last therapeutic orphans. If born prematurely, apnea is often observed due to immaturity of the central nervous system and is primarily treated with caffeine. Although this drug is commonly used across many neonatal intensive care units by a standard dosing regimen consisting of a loading dose (20 mg/kg) followed by a maintenance dose (5 mg/kg/day), not much is known about the effect of the increasing caffeine clearance after birth. Recent research has shown that a higher maintenance dose is required in preterm neonates with apnea to maintain caffeine concentrations above 15 mg/L after the first week of life. 43 Gentamicin, a widely-used antibiotic where the pharmacokinetic understanding has increased over the past years, can be used as another illustration. Despite the increased knowledge, this has resulted in considerable variability in dosing regimen recommendations with respect to dose, dosing interval and patient characteristics. Model-based simulations for this antibiotic treatment in neonates illustrated that in order to attain an effective peak concentration of 10 mg/L, a dose of 7.5 mg/kg should be administered using an extended dosing interval based on gestational and postnatal age to reduce the risk of renal toxicity. 44 During the first days after birth, newborns will lose body fluids and fat resulting in an initial weight loss. When this weight loss becomes excessive (> 10% of birth weight) the risk for serious clinical complications increase. 45 The use of weight monographs belongs to the current practice and if a newborn loses five percent of its body weight during the first day of life, this is seen as a critical sign. In 2016, a semi-mechanistic model characterized the