Chesley's Hypertensive Disorders in Pregnancy

Chesley's Hypertensive Disorders in Pregnancy

5th Edition - December 7, 2021

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  • Editors: Robert Taylor, Kirk Conrad, Sandra Davidge, Anne Staff, James Roberts
  • eBook ISBN: 9780128184189
  • Paperback ISBN: 9780128184172

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Leon Chesley’s Hypertensive Disorders in Pregnancy was initially published in 1978. Four decades later, hypertension complications in pregnancy are still a major cause of fetal and maternal morbidity and death, especially in less developed nations. It is also a leading cause of preterm birth now known to be a risk factor in remote cardiovascular disease. Despite this, hypertensive disorders remain marginally studied and management is often controversial. Chesley’s Hypertensive Disorders in Pregnancy, Fifth Edition continues its tradition as one of the beacons to guide the field of preeclampsia research, recognized for its uniqueness and utility. This revision focuses on prediction, prevention, and management for clinicians, and is an essential reference text for clinical and basic investigators alike. It provides a superb analysis of the multiple topics that relate to hypertension in pregnancy, especially of preeclampsia.

Key Features

  • Summarizes the most relevant basic and clinical studies on hypertensive disorders of pregnancy, helping researchers and students stay up-to-date
  • Discusses the roles of metabolic syndrome and obesity and the increasing incidence of preeclampsia
  • Widely acclaimed as an essential scholastic resource and enthusiastically endorsed by clinicians and scientists


Researchers and clinicians in OB/GYN, nephrology, and cardiology; as well as graduate students and post-doctoral fellows in physiology, renal, cardiovascular, and hypertension research

Table of Contents

  • Cover image
  • Title page
  • Table of Contents
  • Copyright
  • List of Contributors
  • About the Editors
  • Prefaces
  • Chapter 1. The Spectrum of Hypertensive Disorders in Pregnancy: Dr. Leon Chesley's Legacy
  • Introduction
  • History (by Leon Chesley) (Fig. 1.1)
  • Signs
  • Proteinuria
  • Hypertension
  • Hypotheses and Rational Management
  • Prophylaxis
  • Classification of the Hypertensive Disorders in Pregnancy
  • Denouement
  • False Steps in the Study of Preeclampsia (Banquet Commentary by Leon Chesley, 1975)
  • Chapter 2. Epidemiology of Hypertensive Disorders in Pregnancy
  • Introduction
  • Diagnostic Criteria and Research Definitions for Hypertensive Disorders of Pregnancy
  • Discussion of Differential Frequency Estimates
  • Risk Factors
  • Family History and Heritability
  • Clinical Predictors
  • First Birth and Other Placental Factors
  • Natural History
  • Recurrence of Preeclampsia in Subsequent Pregnancies
  • Impact on Children
  • Remote Impact of Preeclampsia on Women and Their Infants
  • Critique of Studies
  • Conclusion
  • Chapter 3. Genetic Factors in the Etiology of Preeclampsia/Eclampsia
  • Dedication
  • Introduction
  • Biological Pathways of Preeclampsia
  • Fetal/Placental Components of Preeclampsia
  • Immunogenetic Factors and Placentation (See Also Chapters 5 and 7)
  • Types of Genetic Studies Conducted
  • Twin Studies
  • Segregation Analyses
  • Linkage Analyses
  • Association Studies
  • Summary of Candidate Genes Most Frequently Studied
  • Genome-Wide Association Studies (GWAS)
  • Next-Generation Sequencing
  • A Genomics Approach to Preeclampsia
  • Essential Variables Make Preeclampsia a Challenging Subject
  • Interacting Genomes
  • Subgroup Ascertainment
  • Genomic Ancestry
  • Population Size
  • Gene–Gene Interactions
  • Epigenetics
  • Gene–Environment Interactions
  • Confounding Variables
  • High-Dimensional Biology
  • A Predictive Genetic Test
  • Integrated Polygenic Risk Score
  • Pharmacogenomics
  • The Future of Preeclampsia Genetic Research
  • Conclusions
  • Chapter 4. Preconceptional and Periconceptional Pathways to Preeclampsia
  • Evidence for Corpus Luteal and Endometrial Origins of Preeclampsia
  • Maternal Prepregnancy Cardiovascular and Metabolic Origins of Preeclampsia
  • Nutritional Contribution to the Genesis of Preeclampsia
  • Conclusions
  • Chapter 5. Placentation and Placental Function in Normal and Preeclamptic Pregnancies
  • Introduction
  • Early Placental Development
  • The Cytotrophoblastic Shell
  • The Trophoblast–Endometrial Gland Dialogue During Early Pregnancy
  • The Switch to Hemotrophic Nutrition
  • The Uteroplacental Vasculature in Normal Pregnancy
  • The Consequences of Deficient Remodeling for Placental Hemodynamics
  • Placental Oxidative Stress
  • Endoplasmic Reticulum Stress
  • Mitochondrial Stress
  • From Placental Stress to Preeclampsia
  • Overview
  • Chapter 6. Unbiased Approaches for Addressing the Complexities of the Placenta's Role in the Preeclampsia Syndrome
  • Introduction
  • Gestational Age-dependent Changes in Gene Expression at the Maternal Fetal Interface: 14–24 Weeks Versus Term
  • Gene Expression at the Maternal Fetal Interface: Preeclampsia Versus Noninfected Preterm Birth
  • The Effects of preeclampsia on cytotrophoblast Gene Expression Profiles
  • Preeclampsia-Associated Transcriptional Landscape of Trophoblasts in Situ
  • Preeclampsia-Associated Placental and Cytotrophoblast Chromatin Landscapes
  • Chapter 7. The Immunology of Preeclampsia
  • Introduction
  • The Scope of this Chapter
  • Placentation, Trophoblast, and Human Leukocyte Antigen
  • Where and when is Paternally Inherited Fetal Human Leukocyte Antigen Exposed to the Maternal Immune System?
  • Decidual Natural Killer Cells and Placentation
  • T Cells, Treg Cells, and Placentation
  • Effects of T Cells on Placental and Fetal Tissues
  • Maternal T Cell Responses in Preeclampsia: Regulated or Dysregulated?
  • Conclusions and Summary
  • Chapter 8. Trophoblast Extracellular Vesicles in Preeclampsia
  • Overview
  • Definition and Heterogeneity
  • Terminology and Size
  • STBEV Cargo
  • Summary
  • Chapter 9. Angiogenesis and Preeclampsia
  • Introduction
  • Placental Vascular Development in Health
  • Angiogenic Imbalance in Preeclampsia
  • Perspectives
  • Chapter 10. Vascular Endothelial Cell Dysfunction in Preeclampsia
  • Introduction
  • Part I: Endothelial Cell Dysfunction and Preeclampsia
  • Part II: Circulating Factors Induce Endothelial Cell Dysfunction
  • Part III: Oxidative Stress: a Point of Convergence for Endothelial Cell Dysfunction
  • Part IV: Clinical Trials
  • Part V: Summary, Speculations, and Directions of Future Investigations
  • Chapter 11. Cardiovascular Alterations in Normal and Preeclamptic Pregnancy
  • Introduction
  • Hemodynamics and Cardiac Function in Normal Pregnancy
  • Hemodynamics and Cardiac Function in Preeclampsia
  • Factors that May Explain Vascular Changes in Pregnancy
  • Pregnancy-Associated Responses and the Assessment of Cardiovascular Disease Risk Later in Life
  • Summary
  • Chapter 12. Cardiometabolic Antecedents of Preeclampsia
  • Introduction
  • Placental and Maternal Aspects of Preeclampsia
  • Pregnancy Profile—an Early Informer of Cardiometabolic Risk
  • Do Prepregnancy Cardiometabolic Risk Factors Foreshadow Preeclampsia?
  • Potential Pathways by Which Cardiometabolic Antecedents Contribute to Preeclampsia
  • Summary Thoughts on Cardiometabolic Antecedents
  • Chapter 13. Cerebrovascular Pathophysiology in Preeclampsia and Eclampsia
  • Introduction
  • Neuropathological Findings with Eclampsia
  • Neuroimaging Findings in Eclampsia
  • Pathogenesis of Cerebral Manifestations in Preeclampsia–Eclampsia
  • Eclampsia and Posterior Reversible Encephalopathy Syndrome (PRES)
  • Cerebral Blood Flow Autoregulation
  • Human Studies on Cerebral Hemodynamics in Preeclampsia-Eclampsia
  • Mechanisms of Seizure During Pregnancy and Preeclampsia
  • Role of Circulating Factors in Eclampsia
  • Blood–Brain Barrier
  • Effect of Magnesium Sulfate Treatment
  • Stroke in Pregnancy and Preeclampsia
  • Cortical Blindness
  • Visual Functioning
  • Future Cerebrovascular Health Following Preeclampsia and Eclampsia
  • Conclusion
  • Chapter 14. The Kidney in Normal Pregnancy and Preeclampsia
  • Introduction
  • Renal Hemodynamics and Glomerular Filtration Rate During Normal Pregnancy
  • Proteins
  • Osmoregulation
  • Uric Acid
  • Preeclampsia and the Kidney
  • Renal Morphology in Pregnancy and Preeclampsia
  • Superimposed Preeclampsia in Women with Kidney Disease
  • Summary
  • Chapter 15. Salt, Aldosterone, and the Renin–Angiotensin System in Pregnancy
  • Introduction
  • Body Fluid Volumes
  • Preeclampsia
  • “Normal Fill” or Resetting of the “Volumestat”
  • Primary Arterial Vasodilatation (“Underfill”)
  • Excessive Expansion or “Overfill”
  • Plasma Volume in Normal Pregnancy and Preeclampsia
  • Novel Salt Hypothesis
  • Mineralocorticoids and the Renin–Angiotensin–Aldosterone Axis
  • Antinaturetic Peptides
  • Renin–Angiotensin–Aldosterone System
  • Agonistic Anti-AT1 Receptor Antibodies in Preeclampsia (AT1-AA)
  • Signal Transduction and Pathophysiological Role of AT1-AA
  • AT1-AA in Animal Models of Hypertension During Pregnancy (See also Chapter 20)
  • AT1-AA Induced Hypertension
  • Interaction Between ATI-AA and sFlt-I, ET-1, and ROS
  • Inhibition of AT1-AA in the RUPP Rat Model
  • AT1-AA, Preeclampsia, and Lasting Effects
  • Presence of AT1-AA in Other Diseases
  • Concluding Perspectives
  • Chapter 16. Platelets, Coagulation, and the Liver
  • Introduction
  • Platelets
  • Platelets in Normal Pregnancies and with Preeclampsia
  • HELLP Syndrome
  • Platelet Activation and Platelet Function
  • Aspirin, an Antiplatelet Agent to Prevent Preeclampsia
  • Aspirin Nonresponsiveness
  • Expression of Platelet Receptors in Pregnancy and Preeclampsia
  • Platelet Second Messengers
  • Platelet Angiotensin II-Binding Sites
  • Coagulation
  • Coagulation Cascade Factors
  • Regulatory Proteins and Thrombophilia
  • Antithrombin III
  • Protein S
  • Protein C
  • Factor V Leiden (Activated Protein C Resistance)
  • Prothrombin G20210A
  • Antiphospholipid Syndrome
  • Fibrinolytic System
  • Fibrinolysis in Normal Pregnancy
  • Fibrinolysis in Preeclampsia
  • The Liver in Preeclampsia
  • Clinical Aspects of Liver Involvement
  • The Liver in HELLP Syndrome
  • Corticosteroid Therapy for HELLP Syndrome
  • Chapter 17. Clinical Management and Antihypertensive Treatment of Hypertensive Disorders of Pregnancy
  • Introduction
  • Diagnosis
  • Identifying Women with Hypertensive Disorders
  • Assessment for Preeclampsia
  • Antihypertensive Therapy—Its Goals
  • General Principles in the Choice of Antihypertensive Agents
  • Fetal Safety and Drug Use in Pregnant Women
  • Choice of an Antihypertensive Drug for Use in Pregnancy
  • Sympathetic Nervous System Inhibition
  • Centrally Acting α2-Adrenergic Agonists
  • Peripherally Acting Adrenergic-Receptor Antagonists
  • Diuretics
  • Calcium-Channel Antagonists
  • Direct Vasodilators
  • Modulators of the Renin–Angiotensin–Aldosterone Axis
  • Evidence for Antihypertensive Treatment in Severe Hypertension
  • Management of Severe Hypertension
  • Conclusion—Use of Antihypertensive Treatment in Pregnancy
  • Antihypertensive Drug Use While Breastfeeding
  • Treatment of Severe Forms of Preeclampsia
  • Prevention and Treatment of Eclampsia
  • Corticosteroids to Ameliorate HELLP Syndrome
  • Fluid Therapy
  • Pulmonary Edema
  • Plasma Volume Expansion
  • Glucocorticoids for Fetal Lung Maturation
  • Delivery—Hypertensive Disorders
  • Indications for Delivery
  • Risks Versus Benefits—Recommendations for Expectant Management
  • Blood Loss at Delivery
  • Analgesia and Anesthesia
  • Persistent Severe Postpartum Hypertension
  • In Summary: Clinical Handling of Hypertensive Pregnancies
  • Chapter 18. Prediction and Prevention of Preeclampsia
  • Introduction
  • Routine antenatal screening for preeclampsia
  • Early preeclampsia risk stratification for primary prophylaxis
  • Preeclampsia prevention modalities
  • Recommended areas of further research for preeclampsia prediction and prevention
  • Chapter 19. Long-Term Effects of Preeclampsia on Mothers and Offspring
  • Introduction
  • Long-Term Maternal Consequences of Hypertensive Disorders of Pregnancy
  • Long-Term Consequences of Hypertensive Disorders of Pregnancy in Offspring
  • Translating Current Knowledge into Optimal Follow-up and Preventive Strategies for Mothers and Children After Preeclampsia
  • Chapter 20. Animal Models Used for Investigating Pathophysiology of Preeclampsia and Identifying Therapeutic Targets
  • Introduction
  • Models Used to Study the Relationship Between Placental Ischemia and the Maternal Syndrome
  • Models Used to Investigate the Role of Immune Mechanisms in Preeclampsia
  • Model Used to Study Role of Vasopressin in Preeclampsia
  • Conclusion
  • Chapter 21. Harmonization of Data and Biobanks for Preeclampsia Research
  • Introduction: Why Do We Need to Harmonize?
  • Challenges of Dealing With Conditions Defined by Syndromes
  • What Has Hindered Our Ability to Unravel the Complexity of Preeclampsia?
  • Impediments to Collaboration and Data and Biosample
  • Meeting the Challenges
  • The Way Forward
  • Index

Product details

  • No. of pages: 486
  • Language: English
  • Copyright: © Academic Press 2021
  • Published: December 7, 2021
  • Imprint: Academic Press
  • eBook ISBN: 9780128184189
  • Paperback ISBN: 9780128184172

About the Editors

Robert Taylor

Robert Taylor
Robert N. Taylor, MD, PhD is Professor of Obstetrics and Gynecology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY. Previously, he was Professor of Obstetrics and Gynecology at The University of Utah, Wake Forest School of Medicine, Emory University, and Director of the Center for Reproductive Sciences at the University of California, San Francisco. Taylor received his undergraduate education at Stanford University and the combined MD-PhD at Baylor College of Medicine. He is a board-certified obstetrician-gynecologist and reproductive endocrinologist whose major research foci have included the role of placental angiogenesis and endothelial cell activation in preeclampsia, and the molecular actions of estrogen and progesterone on endometrial differentiation and neuroangiogenesis as they relate to endometriosis. Dr. Taylor served on executive committees of the American Board of Obstetrics and Gynecology, NIH Reproductive Scientist Development Program, the World Endometriosis Society and the California Institute for Regenerative Medicine.

Affiliations and Expertise

Professor of Obstetrics and Gynecology and Assistant Dean for Student and Academic Affairs, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA

Kirk Conrad

Dr. Conrad has had a longstanding research interest in the hormonal, cellular and molecular mechanisms underlying maternal renal and systemic vasodilation, and increased arterial compliance during normal pregnancy with emphasis on the ovarian hormone, relaxin. More recently, he has been PD/PI of a NIH Program Project Grant designed to explore maternal pregnancy physiology and outcome in women conceiving through in vitro fertilization with focus on the contribution of the corpus luteum. Finally, Dr. Conrad has been exploring a role for dysregulated (pre)decidualization in the genesis of preeclampsia, and in the larger context of “endometrium spectrum disorders”. Dr. Conrad has combined preclinical and clinical research throughout his career to translate findings in animal models, tissues and cells to humans or vice versa. The main disease focus of his pregnancy research has been preeclampsia—a hypertensive syndrome peculiar to human pregnancy.

Affiliations and Expertise

Professor of Physiology, Department of Physiology and Functional Genomics / Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, FL, USA

Sandra Davidge

Dr. Davidge is a Distinguished University Professor in the Faculty of Medicine & Dentistry at the University of Alberta and Executive Director of the Women and Children’s Health Research Institute, Edmonton, Alberta, Canada. Davidge received her PhD from the University of Vermont and completed her postdoctoral fellowship training at the Magee Womens Research Institute in Pittsburgh, PA, USA. Davidge’s research program is focused on understanding mechanisms for vascular dysfunction in pregnancy complications, particularly preeclampsia, and subsequent impact on later-life cardiovascular health. Her fundamental studies are currently focused on developing early intervention strategies for improving pregnancy outcomes to enhance life-long maternal and offspring cardiovascular health. Davidge is a Fellow in the Canadian Academy of Health Science and a past president of Society for Reproductive Investigation (2017-2018).

Affiliations and Expertise

Executive Director, Women and Children's Health Research Institute; Distinguished University Professor, University of Alberta, Canada

Anne Staff

Anne Cathrine (Annetine) Staff, MD, PhD, is a full-time Professor of Obstetrics and Gynaceology at the Faculty of Medicine, University of Oslo, Norway. She is also Head of Research at the Division of Obstetrics and Gynaecology at Oslo University Hospital, Norway. She obtained her Medical Degree in 1987 at The University of Oslo, where she also did her PhD in 2000 on “Preeclampsia and uteroplacental tissues: lipids, oxidative stress, and trophoblast invasion”. She is a board certified specialist in Gynecology and Obstetrics since 1996, and have worked clinically in the field since 1989. Dr. Staff is head of a research group in Oslo, where one main research area is within molecular understanding of pregnancy complications associated with placental dysfunction, including preeclampsia, and its relation to future maternal cardiovascular health. Dr. Staff was previously the EPG (European Placenta Group) Spokesperson 2011-17 and the Vice-President of the ISSHP (International Society for the Study of Hypertension in Pregnancy) 2012-16, and is currently an ISSHP Executive Committee member and part of the Global Pregnancy Collaboration team.

Affiliations and Expertise

Division of Obstetrics and Gynaecology, Oslo University Hospital; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway

James Roberts

James Roberts
Dr. Roberts’ research is interdisciplinary and involves fundamental, clinical, behavioral and epidemiological studies. He has been involved in several seminal studies of preeclampsia including the recognition of preeclampsia as involving endothelial dysfunction and being more than hypertension in pregnancy. He currently is involved in global health research as part of the Global Pregnancy Collaboration, a consortium of 40 centers world-wide that facilitates collaborative research. He is a co-investigator on studies in Brazil and South Africa. He chaired the ACOG Hypertension Task Force and was co-chair of the NHLBI NIH workshop on research on pregnancy hypertension.

Affiliations and Expertise

Senior Scientist, Magee Women’s Research Institute, Professor, Obstetrics, Gynecology, Reproductive Sciences, Epidemiology, and Clinical and Translational ResearchUniversity of Pittsburgh, Pittsburgh, PA, USA

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