Pre-eclampsia

Prevention, Prediction and Possibilities

Pankaj Desai

• Publisher: CRC Press
• Year: 2020
• Print ISBN: 9780367135072
• eBook ISBN: 9780429662829
• Topic: Business
• Subtopic: Meetings & Presentations
• Index: Business

Pre-eclampsia, a complication of pregnancy characterized by hypertension and/or edema and/or proteinuria, can have profound effects on the mother as well as the unborn fetus and even threaten their lives. Pre-eclampsia: Prevention, Prediction and Possibilities discusses the possible causes of the condition, its effects on various body systems, current methods of prediction, prevention, and treatment. What makes this book unique is its coverage of the deep intricacies of what causes Pre-eclampsia from examining the role of genetics and exosomes to lipids and their denaturation to endothelial denaturation and reperfusion damage. These extremely complex processes are thoroughly examined and then explained in a simplified way to enhance understanding. The latest concepts in color Doppler in prediction and current measures of prevention and treatment are explained at length. Overall, Pre-eclampsia will provide an updated resource for practicing obstetricians, research scientists, students and professionals involved in the care of pregnant subjects.

Key Features

• Presents the etiopathology of Pre-eclampsia with recent research updates
• Establishes the link between Pre-eclampsia and other obstetric vasculopathies
• Covers individual systemic effects of the condition
• Explores the latest approach in prediction, prevention and treatment of Pre-eclampsia

About the Author

Dr. Pankaj Desai is a Consultant Obstetrics and Gynecology Specialist at Janani Maternity Hospital, Baroda, India. A prolific writer, he has contributed 43 chapters to different textbooks internationally and nationally. His outstanding academic contributions in the subject have been acknowledged and honored with 7 gold medals and 60 orations.

PART 1

General aspects of pre-eclampsia

1

Introduction

GENERAL ASPECTS OF PRE-ECLAMPSIA

Of all systems in the human body, the reproductive system is probably the last on the priority list of nature. With any life-threatening crisis looming on the horizon, the first to be shut down is the reproductive system. As if by magic, it takes hardly any time for the process of physiology to get deranged and diseased. During the course of my journey through the science of obstetrics, adverse outcomes always intrigued me. Three questions have been the greatest drivers in all sciences. Right from the definition of time and space by Aristotle to his scientific investigations into the same by Isaac Newton and over to the astounding precepts by Albert Einstein, all progress in science has been driven by these three questions: Why? What if? and How? These questions permeate through all progress in science, including the most complex obstetric derangement of obstetric vasculopathies.

As a junior resident pursuing my post-MBBS studies in the labour ward, I once received two mothers with PIH one after another in quick succession. The first was a full-term pregnant woman, who had a blood pressure of 150/100 mmHg, had oedema and trace of albuminuria. The second subject had only a mid-trimester pregnancy of about 22 weeks, a blood pressure of 160/110 mmHg, oedema and very high albuminuria. The first subject went on to deliver vaginally a 2.9-kg child who was healthy and alive. The second woman with the same disease had to be induced because her blood pressure progressively got more dangerous. The baby could not be saved, and the mother took a long time to get her blood pressure back to a normal state. She stayed in the hospital for nearly 3 months. Many such patients came and went, and each time I got challenged, “Why did she have this outcome? Why not the others?”

As a couple of years rolled by, I saw these same mothers for subsequent obstetric services. In her next pregnancy, the first mother who had a milder form of the disease did not have PIH or any other high-risk factor. She delivered vaginally uneventfully and left. The second mother (who had a severe form of the disease and that early in pregnancy) came in at her next pregnancy, which resulted in a foetal demise at 10 weeks. Her third pregnancy in which I attended to her, she had an IUGR with accidental haemorrhage. Incidentally, she managed to reach 34 weeks, but she had to be sectioned out by a lower segment caesarean section (LSCS) and went home after nearly a month in the hospital. Her blood pressure had shot up nearing delivery, and it took nearly a month for it to reach a normal state again. Concurrently, her baby was admitted to the neonatal intensive care unit (NICU), but the silver lining was that this time, the pregnancy resulted in a live neonate.

Seemingly diverse obstetric conditions: severe PIH remote from term, IUGR, accidental haemorrhage and foetal demise all occurred in the same mother in different pregnancies. Are those interlinked conditions? If yes, in what way they are interlinked? What binds them together? Do they have some long-term effects? Above all, what causes them? How does one treat these conditions?

Those were the early years of the 1980s. The institution where I worked did not have any facilities for ultrasound or a colour Doppler then. Using aspirin was still scoffed at. We had just begun to use magnesium sulphate to treat eclampsia. There were no computers to manage the data, and at best, we had calculators to calculate statistical indices. Our first study on this matter titled, “Preeclampsia remote from term” was presented at the All India Conference of Obstetrics & Gynaecology at Jaipur. The study showed interesting results; and it was the harbinger of more than two decades of diligent and dedicated study of these conditions which are now known as “Obstetric Vasculopathies”.

WHAT IS PRE-ECLAMPSIA?

Pre-eclampsia is a pregnancy complication characterised by high blood pressure and signs of damage to another organ system, most often the liver and kidneys. It may be accompanied by albuminuria or oedema. It usually begins after 20 weeks of pregnancy in women whose blood pressure has been normal. This is the standard definition of pre-eclampsia.

There have been many attempts to produce animal models that mimic the hypertensive disorders of pregnancy, especially pre-eclampsia, but most are incomplete when compared to the full spectrum of the human disease. It also remains to be properly investigated as to whether pre-eclampsia is one disease or a similar manifestation of many disease conditions. This intrigue is fuelled by the two different types of pre-eclampsia: that before 34 weeks and that at or after 34 weeks. Both of these types are completely different: the former has a stormy course that can potentially kill the foetus and mother, whereas the second one seems to be less devastating. Also, their origins seem to be different. Although the former has a placental origin, the latter is genetic in origin. There was a brief period when it was thought that both had nearly same aetiology, and therefore, there was no need to group them separately. However, thankfully, this thinking did not last long. The former is accepted as an obstetric vasculopathy, whereas the latter is not. This brings us to the concept of obstetric vasculopathies.

WHAT IS OBSTETRIC VASCULOPATHY?

In simplest terms, obstetric vasculopathy means a disease of vessels resulting from an obstetric event. Though this is the first step to the understanding of obstetric vasculopathies, it is the most preliminary step. From here, the complexity of this science begins, and it is this complexity that makes it beautiful but challenging, intriguing and inviting for keen students to decode its mysteries.

Obstetric vasculopathy is not to be confused with vasculitis that occurs in the maternal vascular system. It is the vasculopathy that occurs at the foetomaternal interface. It is, therefore, also known as “placental vasculopathy”. Inherited probably by an amorphous genetic propensity at the foetomaternal system, there occurs a series of changes at this interface that invites seemingly totally diverse and apparently unrelated conditions.

In early understandings, it was perceived that one condition led to the other. But as advances in understanding were made, it became clear that these were not cause-and-effect relationships but rather were fruits of the same pathology. In the initial years, only a few conditions were attributed to obstetric vasculopathy, namely:

•  Recurrent spontaneous miscarriages (RSA),

•  Intrauterine growth restriction (IUGR),

•  Pre-eclampsia and pre-eclampsia remote from term,

•  Accidental haemorrhage and

•  Chorea gravidarum.

However, with scientific research of these conditions, more specifics and complexities added up. Currently, obstetric vasculopathies include:

•  RSAs of late first trimesters and second trimesters;

•  Accidental haemorrhage with an association of IUGR or pre-eclampsia remote from term and

•  Foetal demise of non-anomalous pregnancies with association of any one of the preceding conditions.

Additions to this list also continued to be made and include hyperhomocysteinemia. Systemic lupus erythematosus (SLE)-associated pregnancies are a special class because they have a magnified manifestation of vasculopathy, thereby enabling a closer look at this miraculous but mysterious phenomenon. I am reminded of a thought-provoking incident that took place in 1980. It was during my internship in internal medicine that I witnessed a postgraduate clinical case presentation. A guest faculty visiting the institution was also present during the case presentation of SLE. This subject was not pregnant and the professor in internal medicine remarked that this was a rare case. The visiting faculty did not agree. He said that he wanted to visit the clinical wards. Much to our surprise, he pointed out many admissions that could have lupus in association (or as I understand it now, an immunological basis). I do not know if any further investigations were done or if it was merely pointed out. But I, too, had completely forgotten this incident until nearly a decade later when I suddenly recollected the event because more and more diverse obstetric conditions started being associated with obstetric vasculopathy. Lest I misunderstood, I wish to clarify that all obstetric vasculopathies are not SLE, but SLE does produce obstetric vasculopathy. I would, however, like to highlight that immunology and its disturbances have a big role to play in obstetric vasculopathy.

PART 2

Possibilities in aetiology of pre-eclampsia

2

Immunology of pre-eclampsia

IMMUNE TOLERANCE AND PRE-ECLAMPSIA

Obstetric vasculopathies in general and pre-eclampsia, in particular have a strong immunological basis. The foetus is an allograft with half of its immunological component derived from its mother and the other half from the father. The maternal component is her innate, so the mother tolerates it, but the component coming from the father is immunologically distinct, and the maternal system will try to reject it. The conceptus, therefore, needs perpetual protection from the rejection system of the mother. This protection is provided by the paternal immunological component, which seems paradoxical. If the father is immunologically similar to the mother, then his donated organs will be tolerated by the mother, but his foetus will be rejected by her. On the other hand, if he is immunologically different from the mother, his foetus will be well tolerated by the mother, but the organs donated by him will be rejected by the mother. Besides many other protective systems in the mother for the conceptus, syncytiotrophoblasts play an important role as protectors of the conceptus.

In pregnancies where the immune tolerance is suboptimal, a series of effects take place. The premier effect is a defective trophoblastic invasion and this results in clinical conditions known as obstetric vasculopathies. An excessive maternal inflammatory response, directed against foreign foetal antigens results in a chain of events, including shallow trophoblast invasion, defective spiral artery remodelling, placental infarction and release of pro-inflammatory cytokines and placental fragments in the systemic circulation. During a normal pregnancy, trophoblasts interact in the decidua with the unique uterine natural killer (NK) cells, modifying their cytokine repertoire and regulating adhesion molecules and matrix metalloproteinases. The inability of trophoblasts to accomplish these changes might be a critical factor for the onset of pre-eclampsia.¹

Complete failure of this mechanism can cause miscarriage, and partial failure can cause poor placentation, dysfunctional uteroplacental perfusion and resultant clinical manifestation of obstetric vasculopathies like pre-eclampsia, intrauterine growth restriction (IUGR), and accidental haemorrhage.

TYPES OF PRE-ECLAMPSIA BASED ON IMMUNOLOGY

Pre-eclampsia appears to be two types of diseases:

1. Pre-eclampsia of onset after 34 weeks: This type of pre-eclampsia is often indistinguishable from normotensive controls as regards foetomaternal outcomes. In this type of pre-eclampsia, placental malperfusion appears to be minimal. Maternal protective systems that sense the foetus as foreign are kept at bay in normotensive pregnancies that do not register any rise in blood pressure during pregnancy. It does not, however, mean that the maternal systems were not out to eliminate the foetus. But the protective systems successfully thwart its onslaught by the protecting and nourishing mechanisms. It is postulated that if human pregnancies continue at or beyond 55 weeks, all of them will eventually develop pre-eclampsia. This type of pre-eclampsia has a distinct but amorphous genetic predisposition.

2. Early onset pre-eclampsia (or pre-eclampsia remote from term): This type of pre-eclampsia manifests clinically at or before 34 weeks of pregnancy. It is, therefore, labelled as early-onset p...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Table of Contents
• Preface
• Acknowledgements
• Author
• Part 1 General aspects of pre-eclampsia
• Part 2 Possibilities in Aetiology of pre-eclampsia
• Part 3 Prediction
• Part 4 Prevention
• Part 5 Systemic Manifestations
• Part 6 Clinical features of pre-eclampsia
• Part 7 Treatment of pre-eclampsia
• Index