Tamara van Donge

Physiological changes during pregnancy and neonatal life 25 2 Introduction The core goal of pediatric clinical pharmacology is to improve care through effective and safe use of drugs in fetuses, neonates, infants, children and adolescents. Studying the effectiveness and safety of drugs in pregnant women and children by conducting clinical trials is less straightforward as compared to performing these in adults due to practical and ethical concerns. This review will present an overview of the physiological changes in pregnant women, their fetuses and (pre)term neonates with the integration of pharmacometrics in pediatric clinical pharmacology resulting in the development of evidence-based pharmacotherapy during pregnancy and neonatal life. Physiological changes during pregnancy can influence the disposition of various drugs. Inappropriate dosing in pregnant women can result in sub-therapeutic or even toxic effects, putting not only the pregnant woman but also her fetus at risk. 1 After birth, the newborn is as well subject to rapid physiological changes related to the transition from intrauterine to extrauterine life and maturational processes affecting the pharmacokinetics and pharmacodynamics of administered drugs. 2 Incorrect dosing in neonates results not only in short-term complications but can also have a negative impact on the long-term development of infants and children. 3 As a consequence, it is very important to characterize these physiological changes in pregnant women, investigate the placental transfer of drugs, and describe the physiological changes and corresponding consequences related to maturation in preterm and term newborns. Currently, there are various approaches to assess these challenges, such as pharmacometric and physiologically-based modeling together with model-based simulations, which can help us characterize relevant physiological changes and their effects on drug exposure and response during pregnancy and neonatal life. Although there are still challenges to overcome, such as the implementation of these approaches in daily clinical practice, a lot of progress has been made. Understanding the impact of physiological changes on pharmacotherapy during pregnancy and neonatal life In the next paragraphs, we will highlight the influence of physiological changes on the pharmacotherapy for the pregnant woman and her unborn fetus and for the newborn during the neonatal period.