The Spectrum of Hypertensive Disorders in Pregnancy: Dr. Leon Chesley’s Legacy

Introduction

The fifth edition of Chesley's Hypertensive Disorders of Pregnancy represents the most recent revision of the previous three, multiauthored editions. The fact that five editors and an additional 39 co-authors contributed to the current edition is a testament to Leon Chesley's remarkable solo accomplishment, published in 1978. Emphasized will be knowledge accrued during the 43 years following Chesley's epic first edition—keeping apace of the information that seems to have increased exponentially over the past four decades or so. The many advances that are chronicled in the chapters that follow, stress the giant strides in basic research leading to new insights regarding the pathophysiology of preeclampsia, some made with cutting-edge tools in areas such as genetics, cell imaging, immunology, molecular biology, -omics and bioinformatics.

These advances in the basic science are a true reflection of Leon Chesley, who as previously mentioned was a scientist—a Ph.D. who did not practice medicine—but the goals of his studies were always designed with the object to improve pregnancy outcomes as a common denominator. To this end, he espoused the application of scientific observations in the clinic, the hospital, the labor and delivery unit, and importantly, to long-term follow-up of women found to be hypertensive during pregnancy. What follows is a legacy of that keen scientific application of new knowledge to improve the practice of clinical medicine that Dr. Chesley so well communicated in his words and deeds. Just as the other editions since Dr. Chesley's original book, the fifth edition aims to be a leading reference text, multiauthored by active investigators in the field. Our stated goal of the previous editions, that this text will do scholarly justice to Dr. Chesley's own 1978 tour de force , remains the raison d’être for the fifth edition.

Unable to improve on his encyclopedic perspective of the field, we reproduce Dr. Chesley's original chapter entitled “History” in its entirety (with minor edits for clarity). Our introductory chapter then concludes by republishing Dr. Chesley's 1975 banquet address titled “False Steps in the Study of Preeclampsia.” That workshop meeting stimulated establishment of the International Society for the Study of Hypertension in Pregnancy in 1976, an organization that remains committed “to stimulate research in the field of hypertension in pregnancy, disseminate the useful results of such research, and advance education in the field.” That presentation also was published by Lindheimer, Katz and Zuspan in Hypertension in Pregnancy in 1976. Dr. Chesley's messages about how to study preeclampsia remain entirely valid today.

History (by Leon Chesley) ( Fig. 1.1 )

Several German authors, such as von Siebold, Knapp, Kossmann, Fasbender, Fischer, and Bernhart, have written on the history of eclampsia, but all too often they did not document their sources and made errors that live on in second-, third-, and n th-hand reviews.

Bernhart wrote that eclampsia was mentioned in the ancient Egyptian, Chinese, Indian, and Greek medical literature. One of the oldest sources that he cited, without specific reference, was the Kahun (Petrie) papyrus dating from about 2200 BC. His source was likely to have been Menascha. Griffith had translated Prescription No. 33, on the third page of the papyrus, as: “To prevent (the uterus) of a woman from itching (?) auit pound—upon her jaws the day of birth. It cures itching of the womb excellent truly millions of times.” Menascha cited Griffith's paper but rendered the translation (in German) as: “To prevent a woman from biting her tongue auit pound—upon her jaws the day of birth. It is a cure of biting excellent truly millions of times.” He suggested that the untranslated word “auit” means “small wooden stick.” In a later book on the Kahun papyrus, Griffith changed his translation to: “To prevent a woman from biting (her tongue?) beans, pound—upon her jaws the day of birth.” ^, Curiously, Menascha did not cite Griffith's later translation and he included the word “ auit ” from the first version. Possibly the ancient scribe had eclampsia (preeclampsia with grand mal seizures) in mind, but that interpretation is tenuous at best.

Bernhart also wrote, again without references, that both the Indian Atharva Veda and the Sushruta, of old but unknown dates, mention eclampsia. He said that the Atharva Veda described an amulet to be worn in late pregnancy for warding off convulsions during childbirth. There are several references to pregnancy in the Atharva Veda (translated by Whitney ). One is a description of a protective amulet to be put on in the 8th month of gestation (Bk. VIII, 6, pp. 493–498), but there is not the remotest indication of any specific disorder such as convulsions. The ceremonial verses are clearly directed toward protecting the woman's genital organs against demons and rapists, who are characterized by such epithets as “after-snuffling,” “fore-feeling,” and “much licking” (to name the milder ones).

There are two possible references to eclampsia in the Sushruta (English translation edited by Bhishagratna). In Volume II, Chapter 8, p. 58: “A child, moving in the womb of a dead mother, who had just expired (from convulsions etc.)” should be delivered by cesarean section. The parenthetic “from convulsions etc.” was supplied by the editor and comparison with the Latin translation (Hessler) indicates that it probably was not in the original text. In Chapter 1, p. 11 of Volume II: “An attack of Apatànkah due to excessive hemorrhage, or following closely upon an abortion or miscarriage at pregnancy (difficult labor) or which is incidental to an external blow or injury (traumatic) should be regarded as incurable.” Again, the parenthetic words are editorial explanations and the “Apatànkah” (convulsions) might well be those associated with severe hemorrhage. By comparison with the Latin translation, the English version seems to have been embellished, for the Latin version specifies only abortion and hemorrhage. An editorial note (pp. 58–60, Vol. II) asserts that the ancient Indians delivered living eclamptic women by cesarean section, but the editor provided no documentation whatsoever.

Bernhart's reference to the old Chinese literature was to Wang Dui Me, whose work was translated into German by Lo. The work, originally published in 1832 AD, was thought to be free of any influence of Western medicine, but even if it was, there is no indication that it recorded only ancient observations. In several respects, it seems to have been contemporary; the author described what Lo translated as “Eklampsie” and wrote: “I use recipe No. 232 ….”

Several of the German authors cite Hippocrates as commenting on the susceptibility of pregnant women to convulsions and on their prognosis. None of the quotations appears in The Genuine Works of Hippocrates as translated by Adams, or in any of the half-dozen other translations that I have seen. Some of the quotations can be found in other Greek sources. Earlier translators, for instance, had attributed the Coacae Praenotiones to Hippocrates, but most scholars agree that it was written before Hippocrates's time. One such understated quotation, appearing in several German papers is: “In pregnancy, drowsiness and headache accompanied by heaviness and convulsions, is generally bad.” It comes from the Coacae Praenotiones ( Coan Prognosis ), XXXI, No. 507. The Greeks of that time recognized preeclampsia, for in the Coan Prognosis , XXXI, No. 523, we find: “In pregnancy, the onset of drowsy headaches with heaviness is bad; such cases are perhaps liable to some sort of fits at the same time” (translated by Chadwick and Mann). Hippocrates (4th century BC), in his Aphorisms (Sec. VI, No. 30), wrote: “It proves fatal to a woman in a state of pregnancy, if she be seized with any of the acute diseases.” Galen, in the 2nd century had commented that epilepsy, apoplexy, convulsions, and tetanus are especially lethal (Vol. 17, pt. II, p. 820, Kühn [ed]). It may be significant that Galen specified convulsive disorders and perhaps he had in mind what we now call eclampsia, which was not to be differentiated from epilepsy for another 1600 years.

Celsus, in the first century AD, mentioned often fatal convulsions in association with the extraction of dead fetuses (Bk. VII, Chapter 29, translated by Lee). In the same connection, Aetios, in the 6th century AD, wrote: “Those who are seriously ill are oppressed by a stuporous condition …,” “Some are subject to convulsions …,” and “The pulse is strong and swollen” (translated by Ricci).

There is a possible reference to eclampsia in Rösslin's Der Swangern Frawen und Hebammen Rosengarten , a book that was the standard text of midwifery in Europe and England for almost two centuries. In discussing the maternal prognosis in difficult labor with fetal death, Rösslin listed among the ominous signs, unconsciousness and convulsions (Bk. I, Chapter 9, p. 67). The book was largely based upon the older classics, and the relevant section is reminiscent of Celsus, Aetios, and, especially, Paul of Aegina (translated by Adams). The book was translated into English from a Latin version of what probably was the second edition and appeared in 1540 as The Byrth of Mankinde . Raynalde revised and amplified the second edition of 1545, and the text was little altered thereafter. Ballantyne's quotation of the relevant paragraph in Book II, Chapter 9, from the edition of 1560 is virtually identical with that published 53 years later (Raynalde), except for the variable and carefree spelling of the times. ^,

Gaebelkhouern (variously, Gabelchoverus, Gabelkover) distinguished four sorts of epilepsy in relation to the seats of their causes, which he placed in the head, the stomach, the uterus, and chilled extremities. He further specified that only the pregnant uterus causes convulsions, particularly if it carries a malformed fetus. “The mothers feel a biting and gnawing in the uterus and diaphragm that leads them to think that something is gnawing on their hearts (epigastric pain?).” The description of that symptom is usually credited to Chaussier, 1824, 228 years later.

Although eclampsia is dramatic, it is not astonishing that there are so few references to it in the older writings, which covered the whole field of medicine. Eclampsia had not been differentiated from epilepsy, and obstetrics was largely in the hands of midwives, who at that time did not typically write and publish their clinical observations. Even some relatively modern textbooks of obstetrics have barely noticed eclampsia, and those of Burton and Exton made no mention whatever of convulsions. ^, In the first edition of Mauriceau's book, the only comment on convulsions relates to those associated with severe hemorrhage, of which his sister died. The literature of eclampsia, for practical purposes, began in France because it was there that physicians first took up the practice of obstetrics on a significant scale. Viardel, Portal, Peu, and de la Motte each published notable books in the late 17th and early 18th centuries.

In later editions of his book, Mauriceau devoted more and more attention to what we now call eclampsia. Hugh Chamberlen published purported translations of Mauriceau's later editions, but they seem to have been impostures and really were reissues of the translation of the first edition. Such fraud befits a family that kept so important an invention as the forceps secret through three generations for personal profit, and befits the man who sold the secret. In the edition of 1694, and possibly earlier, Mauriceau set forth several aphorisms (their numbers are provided in parentheses, below) dealing with the subject. Still highly relevant among them were (No. 228): The mortal danger to mother and fetus is greater when the mother does not recover consciousness between convulsions; (No. 229): Primigravidas are at far greater risk of convulsions than are multiparas; (No. 230): Convulsions during pregnancy are more dangerous than those beginning after delivery; (No. 231): Convulsions are more dangerous if the fetus is dead than if it is alive. He attributed convulsions to an excess of heated blood rising from the uterus and stimulating the nervous system and thought that irritation of the cervix would aggravate the situation. He also believed that if the fetus were dead, malignant vapors arising from its decomposition would exacerbate convulsions. His attribution of convulsions to such specific causes carries the implication that he had distinguished eclampsia from epilepsy.

Kossmann wrote that in 1760, before he had bought (gekauft hatte) his title “de Sauvages,” Bossier first introduced the word eclampsia . He said that de Sauvages was a typical Frenchman in that he took it badly whenever his title was omitted, that he had mistaken the meaning of the Greek word from which he derived eclampsia, that none of the supporting references that he cited was correct, and that we owe the word to de Sauvages's slovenly scholarship.

Kossmann was in error. De Sauvages published under that name at least as early as 1739, and there is no indication in the Biographisches Lexikon (Hirsch ) that he had not been born as de Sauvages. He did acquire the title “de Lacroix” later. De Sauvages differentiated eclampsia from epilepsy in his Pathologia Methodica , the three editions of which were forerunners of his Nosologia that Kossmann cited. He indicated that epilepsy is chronic and that the fits recur over long periods of time; all convulsions of acute causation de Sauvages called eclampsia , spelled with one c in the first and second editions and with two in later publications. ^, He attributed the source of the word to Hippocrates, in the sense of Epilepsia puerilis , which Kossmann considered to be erroneous. In later editions, he cited de Gorris's Definitionem Medicarum , Hippocrates, and the Coan Prognosis , in none of which the word occurs, according to Kossmann.

Part of the discrepancy is explained by the questionable authorship of many writings that have been attributed to Hippocrates. ^{, ,} Most scholars do not accept the sixth book of Epidemics as being his, but in Section I, No.5, the word does appear and has been translated as “epilepsy,” both before and after de Sauvages's time. Galen (Vol. 17, pt. I, p. 824, Kühn [ed]: 1829) translated εχλαμψιεζ as “fulgores” (lightning, shining, brilliance) but after four half-pages of discussion as to its significance, concluded that here it means epilepsy. Nearly a century after de Sauvages, Grimm translated the word as “Fallsucht” (epilepsy). The word does not appear in the edition of de Gorris's definitions that I have seen, but it may be in others. Perhaps de Sauvages cited the wrong dictionary, for he is vindicated by another one. Castelli, in his Lexicon Medicum , defined eclampsis as brightness, lightning, effulgence, or shining forth, as in a flashing glance (“splendorum, fulgorum, effulgescentium et emicationem, qualis ex oculis aliquando prodeunt”). He cited several writings attributed to Hippocrates in which the word was used metaphorically to mean the shining vital flame in puberty and the vigorous years of life (“emicatione flamme vitalis in pubertate et aetatis vigora”). Under Effulgescentia he wrote “vide eclampsis.” In an earlier edition (1651), eclampsis did not appear, but effulgescentia had several definitions, the first of which is a disorder characteristic of boys, the most familiar being epilepsy (“quas Graeci εχλαμψιαζ vocant Hipp. praesertim significant morbum puerorum proprium, aut certe perquam familiarissimum, id est, Epilepsium”). Castelli, who followed Galen's discussion just mentioned, wrote that to some the word denoted the temperamental change to warmth, or the effulgent vital flame of youth and early manhood. Others considered the interpretation to be the bodily development and perfection during early adulthood.

Blancard (variously Blancardo, Blankaard) in his Lexicon Medicum , defined eclampsis as “effulgio” and wrote that some authors had called the circulation eclampsis because they thought that a flashing principle in the heart (“luminoso principe in corde”) impelled the blood. The word disappeared from his later editions.

In the third edition (1759) of Pathologia Methodica , de Sauvages listed several species of eclampsia in relation to such acute causes as severe hemorrhage, various sources of pain, vermicular infestations, and other such factors as had been noted by Hippocrates. One species was Eclampsia parturientium and de Sauvages indicated that Mauriceau had described the disease.

Vogel, Cullen, and Sagar, in their classifications of diseases, adopted de Sauvages's Eclampsia parturientium , but dropped one of the two C s. Interestingly, the taxonomists defined both Convulsio gravidarum and Eclampsia parturientium (or parturientes ) as different genera and without cross-reference between the two.

Gutsch, a student of J. C. Gehler in Leipzig, may have been the first German obstetrician to take up the word, and for a generation the German use of it seems to have been confined to that center. Kossmann wrote that the word reappeared in France in 1844, but Ryan said that it was generally used there in his time. ^, That is confirmed by the listing of publications in the Index-Catalogue of the Library of the Surgeon General's Office (1890), where the word eclampsia appears in the titles of 31 books or monographs from six European countries before 1845; there were many from France.

Ryan recognized the specificity of what he called dystocia convulsiva: He gave as synonyms “labor with convulsions,” “convulsio apoplectica,” “apoplexia hysterica,” “apoplexia lactusa,” “apoplexia sympathetica,” and “eclampsia.” When consciousness returned between fits, Ryan called them epileptiform; when coma or stertor supervened, he called them apoplectic or eclamptic convulsions. He wrote that the convulsions may occur during the last three months of pregnancy, in labor, or after delivery and that the prognosis is unfavorable “as a third of those afflicted are destroyed.” Postpartum eclampsia is less dangerous, he said.

Bossier de Sauvages's use of the word eclampsia as a generic term for convulsions having an acute cause persisted for more than 200 years. Stedman's Medical Dictionary (1957) defined eclampsia as “convulsions of an epileptoid character” and listed several varieties. Puerperal eclampsia was defined as “convulsions of uremic or other origin, occurring in the latter part of pregnancy or during labor”; there was no mention of the puerperium. The 20th edition, in 1961, discarded all but the obstetric definition; “Coma and convulsions that may develop during or immediately after pregnancy, related to proteinuria, edema, and hypertension.” Puerperal eclampsia was described as following delivery, which is technically correct, but a misleading guide to interpretation of much of the literature of the 19th century.

Signs