History ( 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.

This portrait of Francois Mauriceau inaugurated the “History” chapter in the first edition of this text.

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 is 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 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 whatever.

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 it if were, 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 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 Be), 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 ad 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. 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 male 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 dealing with the subject. 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 the 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 might cause convulsions. His assigning 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 words 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 Ecclampsia 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 Leipsig, 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 3 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

Hypotheses and Rational Management

Zuspan and Ward wrote that in the treatment of the eclamptic patient, “she has been blistered, bled, purged, packed, lavaged, irrigated, punctured, starved, sedated, anesthetized, paralyzed, tranquilized, rendered hypotensive, drowned, been given diuretics, had mammectomy, been dehydrated, forcibly delivered, and neglected.” Many procedures could be added to the list. Aside from the great variety of medications, surgical approaches have included ureteral catheterization, implantation of the ureters in the colon, renal decapsulation, drainage of spinal fluid, cisternal puncture, trepanation, ventral suspension of the uterus, postpartum curettage, oophorectomy, and so on. I do not rehearse the list in any spirit of levity, for it is important to remember that each of the treatments was rational in the light of some hypothesis as to the cause or nature of eclampsia. That is more than we can say for our present management, which is purely empiric, perhaps too often symptomatic, and in some respects based upon imitative magic.

Eclampsia was not differentiated from epilepsy until 1739, and the distinction was not generally accepted for another century. Merriman discussed dystocia convulsiva and wrote: “The cases alone deserving the appellation of puerperal convulsions, which have fallen under my observation, have borne a very exact resemblance to the epilepsy.” Ryan, in his Manual of Midwifery (1831), recognized eclampsia as an entity, but 25 years later his countryman Churchill, in his Theory and Practice of Midwifery (1856), classified gestational convulsions as hysteric, epileptic, and apoplectic. By the time the differentiation from epilepsy was generally accepted, eclampsia had been confused with uremic Bright’s disease, and the proliferation of hypotheses as to its cause was delayed until late in the 19th century.

Hippocrates, in his Aphorisms, Section VI, No. 39, wrote: “Convulsions take place either from repletion or depletion” (translated by Adams). Hippocrates referred to convulsions generally, as did Galen, who iterated his view (Vol. 18, pt. I, p. 61, Kühn [ed]: 1829). Accordingly, obstetricians divided on the question of which factor accounted for convulsions in childbirth. Mauriceau recommended bloodletting, except in the convulsions associated with severe hemorrhage. According to Gutsch, who did not give a reference, van Swieten wrote that depletion was the cause and attributed the convulsions to collapse of the cerebral blood vessels. Gutsch was completely wrong, but virtually every history of eclampsia has perpetuated his error. Van Swieten, in commenting on Boerhaave’s Aphorism No. 1322, was in agreement with the concept that the sudden reduction in intraabdominal pressure at delivery might lead to a pooling of blood diverted from the brain and thus account for weakness and syncope. Van Swieten went on to say that if the uterus did not contract, “then lying-in women run with blood, and, by the sudden inanition of the (cerebral) vessels, die in convulsions; pretty nearly in the same manner that the strongest animals, when their arteries are cut open by the butcher, their blood being entirely exhausted, are seized with violent convulsions before they die” (English translation of 1776). Clearly, van Swieten was not referring to eclamptic convulsions. In his comments on Aphorisms Nos. 1010, 1295, and 1302, van Swieten indicated unequivocally that cerebral congestion is the cause of what we now call eclamptic convulsions. He attributed the cerebral repletion to compression of the abdominal organs by the large uterus, to blockage of the aorta by the uterus, and to the violent expulsive efforts at delivery, all of which diverted blood to the brain. Accordingly, he wrote: “no one can doubt but the letting of blood must prove of the greatest service, especially if these symptoms (including edema) happen near the time of delivery; for then by the violent efforts of labour, the blood may be forcibly thrown into the vessels of the encephalon, and all its functions thereby suppressed; or even a fatal apoplexy may ensue from a rupture of the vessels; convulsions too may often follow” (comment on Aphorism No. 1302).

In addition to the factors specified by van Swieten as leading to repletion, other writers had suggested reflex effects arising from stimulation of the uterine nerves and suppression of the menses during pregnancy. The opposite hypothesis, that the convulsions were caused by depletion or cerebral anemia, had its proponents and still lingers on in terms of cerebral vasospasm and edema.

Old-time physicians and barber-surgeons resorted to bloodletting in the treatment of many disorders and they noted the extraordinary tolerance of pregnant women for hemorrhage. By the end of the 18th century the “plethora of pregnancy” was a widely accepted concept that seems to have tipped the scales in favor of repletion and cerebral congestion as the cause of gestational convulsions. Phlebotomy and purgation, which were the sheet anchors in the management of eclampsia one and two centuries ago, probably were of late origin. Section V of Hippocrates’s Aphorisms specified contraindications to those measures. No. 29: “Women in state of pregnancy may be purged, if there be any urgent necessity, from the fourth to seventh month, but less so in the latter case. In the first and last periods it must be avoided.” No. 31: “If a woman with child be bled, she will have an abortion, and this will be the more likely to happen, the larger the foetus” (translated by ). Galen agreed (Vol. 17, pt. II, pp. 652, 821, Kühn [ed]: 1829).

Although Celsus, in the first century ad , disputed the adverse effect of bleeding, the doctrine persisted (Bk. II, Chapter 10, translated by Lee). In the 6th century, Aetios reiterated the deleterious effect of phlebotomy; he cited Hippocrates when he recommended bleeding as a means of inducing abortion (Chapter 18, translated by Ricci). Avicenna, in the 11th century, advised against both bleeding and purgation during pregnancy (translated by Krueger). Maimonides, in the 12th century, seems to have contradicted himself. His 12th Treatise, Aphorism 5 is: “The conditions and complications that mitigate [sic] against bloodletting, although signs of filling may be apparent, are as follows: Convulsive disorders …” But Aphorism 22 says: “Venesection is an utmost necessity at the very onset: (in) patients suffering from … convulsions …” (translated by Rosner and Muntner).

The prime object of phlebotomy was to decrease cerebral congestion and to that end, some physicians preferred bleeding from the temporal artery or jugular vein. Leeches and cups were applied to the scalp, neck, and even face to draw blood away from the brain. Blisters and sinapisms were placed in various areas for the same purpose, and the scalp was shaved for the closer application of cold packs. Sometimes the physician recognized that repeated phlebotomies had so weakened the woman that another would be hazardous, so that rather than subject her to another general hemorrhage, he placed leeches or cups on the head for the local diversion of blood from the brain. Ryan, who attributed eclampsia to cerebral congestion, wrote: “In these kingdoms, copious depletion with camphor mixture, ether, etc, are chiefly employed,” along with repeated bleeding. Ether, which was popular in France, was given in mixtures by mouth or subcutaneously.

Those who believed that the convulsions were caused by irritation of the uterus also used sinapisms, blistering, and the like as counterirritants, and they bled patients from veins in the feet, which they believed to be a revulsive measure.

Later, when a circulating toxin was postulated as the cause of eclampsia, phlebotomy was retained as a rational treatment because it directly removed the noxious substance. To the same end, all of the emunctories were stimulated and the use of diuretic, purgative, emetic, and sudorific drugs became popular. High colonic irrigation and gastric lavage were used for the same purpose. Tincture or extract of jaborandi was used to induce intense sweating and when its most active alkaloid was identified as pilocarpine, that drug came into use. It was tried for a time in Edinburgh, but abandoned when it was found to have doubled the maternal mortality from 30 or 35% to 67%; the women drowned in their own secretions (Hirst). A parallel situation exists today in the common use of potent diuretic drugs, which probably do no real good and are dangerous, though not so dramatically as in the case of pilocarpine.

The concept of eclampsia as a toxemia is more than a century old. The earliest reference that I have found is by William Tyler Smith, who wrote: “It deserves to be borne in mind, that the depurgatory functions ought, in order to preserve health, to be increased during gestation, as the debris of the foetal, as well as the maternal system, have to be eliminated by the organs of the mother. Besides these forms of toxaemia, the state of the blood which obtains during fevers, or during the excitement of the first secretion of milk, may excite the convulsive disorder.” He used the word toxaemia so casually as to suggest that it might have been a current concept. Murphy, in his Lectures on the Principles and Practice of Midwifery , wrote 13 years later: “Predisposing causes of convulsions are hyperaemia, anaemia, and toxaemia” and “ The direct proximate cause of convulsions is impure blood” (his italics). Mahomed, explaining the hypertension that he thought to be present in all pregnant women, wrote: “The blood of the mother is overcharged with effete material, for she has to discharge the excrementitious matters of the fetus by her own excretory organs; her blood is therefore in a measure poisoned …” and “Thus puerperal eclampsia and albuminuria were accounted for ….” The later controversy as to whether Fehling or van der Hoeven had priority in suggesting fetal waste products as the cause of eclampsia was obviously an exercise in futility.

Actually, Mauriceau had attributed convulsions in many cases to decompositional products of the dead fetus.

In the symposium on eclampsia, held in Giessen in 1901, the almost unanimous opinion was that the disease is caused by a toxin, but there was no agreement as to its source. The uremic hypothesis had not yet succumbed, and some writers held out renal insufficiency, either intrinsic or secondary to uterine compression of the renal veins or ureters, as the cause. As previously mentioned, a variant explanation was renal vascular spasm arising as a reflex from nervous stimulation in the uterus. Other hypotheses included fetal catabolic products, bacterial toxins, autointoxication by noxious substances absorbed from the gut, toxins from the placenta released directly or by lytic antibodies against it. Several French investigators, of whom Delore was probably the first, suggested bacterial infection. Gerdes attributed eclampsia to a bacillus that was later identified as Proteus vulgaris and Favre alleged the same role for Micrococcus eclampsia . That hypothesis was quickly overthrown, but the idea that bacterial toxins released in focal infections had a role was advocated for another half century. Proponents of autointoxication as the cause of eclampsia pointed to the predominance of the hepatic lesion in the periportal areas of the hepatic lobules, which receive most of the blood draining the gut.

Rosenstein, adopting Traube’s explanation of uremic convulsions, suggested that the proteinuria depleted the plasma proteins and that the combination of watery blood and hypertension led to cerebral edema, convulsions, and coma. Munk tested Traube’s hypothesis by ligating the ureters and jugular veins of dogs and injecting water through the carotid artery, thereby evoking convulsions and coma that he regarded as uremia. A modern clinical counterpart is the water intoxication produced in an occasional patient by the injudicious and prolonged infusion of oxytocin in large volumes of dextrose solution.

An enormous amount of work was expended in trying to identify the toxin. Frerichs, who equated eclampsia with uremic convulsions, postulated an enzyme that converted urea to ammonium carbonate. Some thought that a precursor of urea, carbamic acid, was the toxin. Other substances “identified” as the toxin included creatine, creatinine, xanthine, acetone, lactic acid, urobilin, leucomaines akin to ptomaines, globulins, and water.

Then, as now, new hypotheses were introduced with supporting observations or experiments that either could not be confirmed or were interpreted differently by other investigators. Many examples could be cited. The French school developed the concept that pregnant women excreted less than normal amounts of endogenous toxins, which therefore accumulated in the bloodstream. In support of their hypothesis, they reported that the urine of eclamptic women was less toxic and the serum more toxic than the same fluids from normal pregnant and nonpregnant subjects. Volhard and Schumacher reviewed their work critically, repeated their experiments, and demolished their conclusions. Dixon and Taylor reported pressor activity in alcoholic extracts of placenta, but Rosenheim showed that bacterial contamination accounted for the effect. More recently, the many reports of antidiuretic activity in blood, urine, and cerebrospinal fluid of women with preeclampsia–eclampsia have been called into question for the same reason (Krieger, Butler, and Kilvington). The earlier reports of the lethal effect of placental extracts, press juices, and autolysates given intravenously or their production of proteinuria when injected into the abdominal cavity were largely explained by Lichtenstein. He found (1) that extracts of other organs are equally toxic, (2) that the particulate matter in the preparations blocked the pulmonary capillaries, (3) that the lethal effect and intravascular coagulation could be duplicated by the injection of inorganic particles suspended in saline solution, (4) that the proteinuria could be duplicated by the injection of other foreign proteins, and (5) that filtered extracts were innocuous. Schneider identified the “toxin” in placental extracts free of particles as thromboplastin, which causes intravascular coagulation.

Prophylaxis

Mauriceau recommended two or three phlebotomies during the course of pregnancy as prophylaxis against eclampsia, but he disparaged a colleague who had bled one woman 48 times and another 90 times.

Dietary taboos originated in the superstitions of antiquity and have persisted, with modifications, to the present day. Meat, especially red meat, has had a bad name and has been forbidden or restricted in the dietary treatment of many disorders, including preeclampsia–eclampsia. Thus Miquel, in discussing prophylaxis against convulsions in pregnancy, recommended a farinaceous vegetable diet in the form of a slop or, preferably, one of milk products together with avoidance of spices. De Wees attributed to overeating the one case of eclampsia that he mentioned in his Treatise on the Diseases of Females . Prenatal care was unusual in the first half of the 19th century, but some physicians did see private patients before labor. Johns wrote that every physician should see his obstetric patients at intervals during the latter months of pregnancy. He described edema of the hands and face, headache, giddiness, ringing in the ears, loss of vision, pain in the stomach, and a flushed face as denoting an increased risk of convulsions. He wrote that the risk was converted to certainty if (1) the women were pregnant for the first time or had had convulsions in a previous pregnancy; (2) if the head of the child presented, or (3) if the women were of full and plethoric habit. (In passing, it was widely believed at that time that convulsions occurred only in association with vertex presentations.) To prevent convulsions, Johns advocated a diet of fruits, vegetables, and milk, as well as laxatives or purgatives, diuretics, moderate exercise and plenty of fresh air, phlebotomy, and, if the signs and symptoms were marked, emetics. Meigs boasted that although he had seen a good many cases of eclampsia, he was very sure that he had prevented a far greater number.

Sinclair and Johnston wrote that admittances of women to the Dublin Lying-in Hospital, in all cases except dire emergencies, were by arrangement made before the end of pregnancy. Each woman was given a ticket to be signed by a priest or by a respectable citizen, which she then took to the Dispensary for the countersignature of a physician. The physician checked on her signs and symptoms, and if she had edema, headaches, dizziness, or proteinuria, she was either admitted to the hospital or seen regularly in the Dispensary. She was purged freely and repeatedly, kept in bed, and allowed nothing but the mildest and lightest nutriment. The authors stated: “Very often have convulsions been most certainly warded off altogether.” When convulsions had not been prevented, they thought that the severity of the disease had been decreased by their treatment.

After Lever’s discovery of proteinuria in eclamptic and preeclamptic women, more and more physicians recommended periodic urinalyses in the latter months of pregnancy. When proteinuria was found, they prescribed dietary restrictions along with laxative and diuretic agents and, often, phlebotomy. The diet usually was limited to fruits, vegetables, and milk and was low in protein. Low protein diets were advocated for an ever-increasing number of reasons. They were thought to be more easily digestible and to minimize gastric irritation; nervous stimuli from the uterus and gastrointestinal tract were long thought to cause cerebral repletion (or depletion) and thus to trigger convulsions. Another objective was to lessen the “plethora of pregnancy.” When eclampsia came to be regarded as uremic Bright’s disease, the diets seemed rational because they reduced the load of nitrogenous catabolites and supposed toxins to be excreted by the kidney. Still later, the Dublin school, especially, argued that incompletely digested fragments of the protein molecule were absorbed from the intestine and had a toxic effect. The bodily defenses against the so-called split proteins were normally adequate but during pregnancy the fetus and placenta represented an additional source of such noxious substances. When the combined invasions overwhelmed the defenses, toxemia and eclampsia resulted. Another hypothesis was that the amino acids from the digested proteins were decarboxylated but not deaminated, with the production of toxic amines.

One of the circumstantial evidences for the efficacy of low protein diets was the observation that eclampsia was predominantly a disease of middle- and upperclass women. That widely held opinion may have been influenced by the fact that many physicians who published had private practices, but Fitzgibbon, who saw all classes in Dublin’s Rotunda, wrote: “Toxaemia is unquestionably a disease of the well-to-do classes of society.” Ruiz-Contreras, of Barcelona, reported that the incidences of proteinuria and eclampsia were far greater in his private patients than in the charity patients he managed in the clinic. When the nutrition improved and the dietary intake of protein increased among the masses, the incidences of proteinuria and eclampsia rose.

During World War I the incidence of eclampsia decreased significantly in Germany and rose again after the Armistice. Germans are reputed to eat heavily, and the nutritionists reasoned that in good times they eat too much. During the war years they might have eaten less protein and benefited by a relative immunity to eclampsia. An editorial (1917) in the Journal of the American Medical Association stated: “The conclusion seems inevitable that restrictions of fat and meat tend to ward off eclampsia.” That interpretation had an effect that persists to the present day. As late as 1945, Stander, in the ninth edition of Williams’ Obstetrics , advocated the dietary restriction of protein in the treatment of hypertensive disorders in pregnancy. Many obstetricians prescribed such diets for all of their patients as prophylaxis against preeclampsia. The current practice of nearly all American obstetricians in limiting weight gain during pregnancy to 15 or 20 lbs stems from the same source.

Classification of the Hypertensive Disorders in Pregnancy

Classifications are of relatively recent origin. Women with prodromal signs of gestational or puerperal convulsions were designated as having threatening or imminent eclampsia, but a specific name of the condition was long delayed. During much of the latter half of the 19th century, eclampsia was thought to be uremic Bright’s disease and women with proteinuria and edema were thought to have nephritis, although a few authors simply called it “albuminuria,” a term that persisted for many years in England.

Leyden described “the kidney of pregnancy” (Schwangerschaftsniere) and, in 1886, pointed out that the renal changes in eclampsia are similar (Chesley referred to his own Chapter 4, [our ref. ]; his other citations are our refs ). He reviewed the meager literature, citing several authors who had suggested that prolonged duration of the kidney of pregnancy sometimes leads to chronic nephritis and wrote that he had seen several such cases. Probably the most vigorous proponent of that view was Schroeder, who thought that what we call preeclampsia was acute nephritis. He wrote that prompt termination of pregnancy would prevent the progression to chronic nephritis, whereas delay would favor it. Needless to say, the kidneys of survivors were not examined during pregnancy and the differential diagnosis was highly uncertain.

As a result of Leyden’s work, nonconvulsive hypertensive disorders in pregnancy were called “kidney of pregnancy” or “nephropathy,” and later, “nephritic toxemia.” Some of those terms still persist. In the United States, just after 1900, the most common designation was “the toxemia of pregnancy.” Webster, in his Textbook of Obstetrics , referred to the “pre-eclamptic state” and Bar introduced the word “eclampsisme” as meaning eclampsia without convulsions or threatening eclampsia.

Once the concept of circulating toxins gained acceptance at the turn of the century, many disorders of obscure origin came to be classified as toxemias of pregnancy. Included were such diverse conditions as hyperemesis, acute yellow atrophy of the liver, ptyalism, gingivitis, pruritus, herpes, severe dermatitides, neuritis, psychosis, chorea, anemia, abruptio placentae, and all forms of hypertension. We see a comparable situation today, when so many physicians attribute almost any disorder of unknown origin, or even malaise, to “a virus.”

The unitarians thought that a single toxin might be responsible for the array of effects and suggested that hyperemesis protected a woman from eclampsia because she vomited out much of the noxious substance. Williams, in the third edition of his Obstetrics , wrote that the unitarians were impeding progress and that investigators should look for toxins specific for each disorder. His classification of the “toxemias of pregnancy” was: pernicious vomiting, acute yellow atrophy of the liver, nephritic toxemia, preeclamptic toxemia, eclampsia, presumable toxemia (under which he included most of the diverse array just cited).

The many classifications proposed before 1940 were essentially variations on Williams’ theme, although there was a progressive disappearance of the presumable toxemias. Some writers differentiated hepatic eclampsia from renal eclampsia.

In 1940, the American Committee on Maternal Welfare (Bell et al.) proposed the following classification:

• Group A.
  

  Diseases not peculiar to pregnancy

  
  
  
  
  • I.
    

    Hypertensive disease (hypertensive cardiovascular disease) – benign, mild, severe, or malignant

    
    
  • II.
    

    Renal diseases

    
    
    
    
    • a.
      

      Chronic vascular nephritis (nephrosclerosis)

      
      
    • b.
      

      Glomerulonephritis, acute or chronic

      
      
    • c.
      

      Nephrosis, acute or chronic

      
      
    • d.
      

      Other forms of renal disease

    
    

  
  
  
  
• Group B.
  

  Disease dependent on or peculiar to pregnancy

  
  
  
  
  • I.
    

    Preeclampsia, mild or severe

    
    
  • II.
    

    Eclampsia

    
    
    
    
    • a.
      

      Convulsive

      
      
    • b.
      

      Nonconvulsive (coma with findings at necropsy typical of eclampsia)

    
    

  
  
  
  
• Group C.
  

  Vomiting of pregnancy

  
  
• Group D.
  

  Unclassified toxemia, in which the above categories cannot be separated for want of information.

Acute yellow atrophy was dropped, but vomiting was retained “because of precedent.” Mild hypertensive disease was defined by the absence of marked vascular changes and blood pressures below 160/100; no lower limit of blood pressure was specified. Mild preeclampsia was defined by the appearance after the 24th week of blood pressures of 140 to 160 systolic and 90 to 100 diastolic, proteinuria of less than 6 g/L, and slight or no edema.

In 1952, another subcommittee of the American Committee on Maternal Welfare (Eastman et al.) revised the classification. They dropped vomiting as unrelated to the hypertensive disorders and deleted renal diseases in the mistaken belief that they are easily differentiable from essential hypertension and preeclampsia. Two new categories were added: preeclampsia or eclampsia superimposed upon chronic hypertension, and recurrent toxemias. Clumsy diction inadvertently permitted the diagnosis of preeclampsia on the basis of any one of the three cardinal signs, even persistent edema or rapid weight gain alone.

Obstetricians in Aberdeen, and in some other areas, follow Nelson’s definition of preeclampsia. Edema is ignored and the diagnosis is made if the diastolic pressure rises to 90 mm Hg or more after the 25th week and is found on at least 2 days. In the absence of proteinuria, the disorder is called mild; if proteinuria appears, it is called severe preeclampsia. The mildly preeclamptic group, thus classified, must include many women with latent hypertension brought to light by pregnancy, as well as chronic hypertensive women whose blood pressures have abated during midgestation. The severe group would include many cases that would be called mild in other classifications.

Various schemes of classification have been published within the past few years in Gynaecologia . They have been compared by Rippmann, who has compiled a list of more than 60 names in English and more than 40 in German that have been applied to the hypertensive disorders in pregnancy. ( Dr Chesley’s original chapter ends here. )