Anatomical and physiological alterations of pregnancy

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REVIEW PAPER

Anatomical and physiological alterations of pregnancy Jamil M. Kazma1 • John van den Anker2,3 Homa K. Ahmadzia1



Karel Allegaert4,5



Andre´ Dallmann6



Received: 8 October 2019 / Accepted: 28 January 2020 Ó Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract The extensive metabolic demands of pregnancy require specific physiological and anatomical changes. These changes affect almost all organ systems, including the cardiovascular, respiratory, renal, gastrointestinal, and hematologic system. The placenta adds another layer of complexity. These changes make it challenging for clinicians to understand presenting signs and symptoms, or to interpret laboratory and radiological tests. Furthermore, these physiological alterations can affect the pharmacokinetics and pharmacodynamics of drugs. Drug safety in lactation is only supported by limited evidence. In addition, the teratogenic effects of medications are often extrapolated from animals, which further adds uncertainties. Unfortunately, pregnant women are only rarely included in clinical drug trials, while doses, regimens, and side effects are often extrapolated from studies conducted in non-pregnant populations. In this comprehensive review, we present the changes occurring in each system with its effects on the pharmacokinetic variables. Understanding these physiological changes throughout normal pregnancy helps clinicians to optimize the health of pregnant women and their fetuses. Furthermore, the information on pregnancy-related physiology is also critical to guide study design in this vulnerable ‘orphan’ population, and provides a framework to explore pregnancy-related pathophysiology such as pre-eclampsia. Keywords Pregnancy  Physiology  Pharmacokinetics  Pharmacology  Anatomy

Introduction

& Homa K. Ahmadzia [email protected] 1

Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

2

Division of Clinical Pharmacology, Children’s National Hospital, Washington, DC, USA

3

Pediatric Pharmacology and Pharmacometrics, University of Basel Children’s Hospital, Basel, Switzerland

4

Department of Development and Regeneration, and Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium

5

Department of Clinical Pharmacy, Erasmus MC, Rotterdam, The Netherlands

6

Clinical Pharmacometrics, Research & Development, Pharmaceuticals, Bayer AG, Leverkusen, Germany

The amount of drug prescriptions and herbal medicine use in pregnancy has substantially increased during recent decades. This change has been more evident during the first trimester, where the average drug usage has increased by 62.5% between 1976 and 2008 [1–4]. The risks of pharmacotherapy in pregnancy are twofold: for the pregnant woman and her fetus; altered pharmacokinetics and pharmacodynamics may lead to inadequate therapeutic response or maternal toxicity, and maternal–fetal transmission may impair fetal organ form