Preeclampsia: History and Discovery

Few conditions in medicine have a longer or more humbling history than preeclampsia and its convulsive endpoint, eclampsia. The terrifying seizures of late pregnancy were recorded in antiquity — in Egyptian, Indian, Chinese, and Greek texts — long before anyone understood the placenta, blood pressure, or the kidney. For centuries the disorder was blamed on a circulating "poison," giving it the name toxemia of pregnancy — a theory that turned out to be wrong: no such toxin was ever found. The real story is one of patient, accumulating observation: protein in the urine (1843), a rising blood pressure (after 1896), a diseased placenta whose only cure is delivery, and, in our own century, the discovery of the placental anti-angiogenic factors that finally gave this ancient enemy a chemical address.

Eclampsia in Antiquity: A Disease Known to the Ancients
Naming the Lightning: Coining "Eclampsia"
The Toxemia Theory — and Why It Was Wrong
Protein in the Urine: Lever, Rayer, and 1843
Measuring the Pressure: Riva-Rocci and Modern Signs
The Placenta and the Cure of Delivery
Stopping the Seizures: Magnesium Sulfate and MAGPIE
The Modern Breakthrough: sFlt-1, PlGF, and Aspirin
Legacy: From Mystery to Mechanism
Research Papers and References
Connections

Eclampsia in Antiquity: A Disease Known to the Ancients

The convulsions of late pregnancy are dramatic and unmistakable — a previously well woman, near her due date, suddenly seized by violent fits — so it is no surprise that the condition was recognized in the earliest written medicine. References that scholars read as eclampsia appear across the ancient world: in the Egyptian medical papyri (the Kahun gynaecological papyrus, dating to roughly 2000–2200 BCE, is among the oldest documents on women's health), in the Indian Ayurvedic tradition (the Atharva Veda and the works of Sushruta), in classical Chinese medicine, and in the Greek writings associated with Hippocrates around 400 BCE, who described headache, heaviness, and convulsions in pregnancy. Celsus and Galen later noted the same association of seizures with the gravid state.

To the ancients the spectacle of a pregnant woman convulsing, losing consciousness, and then — if she survived — remembering nothing of the attack often suggested demonic possession or witchcraft rather than disease. What unified these scattered observations was a single, hard-won clinical insight that the fits were somehow bound up with pregnancy itself and frequently ended with the birth. The mechanism was entirely unknown, and would remain so for millennia, but the recognition of eclampsia as a distinct calamity of childbearing is genuinely ancient. For accessibility these works are named here as historical primary sources rather than as modern citations.

It is worth being precise about terms. What antiquity could see was eclampsia — the seizures themselves. The idea of a warning stage that precedes the convulsions (what we now call preeclampsia) required tools the ancient world did not possess: a way to find protein in the urine and a way to measure blood pressure. Those discoveries lay more than two thousand years in the future.

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Naming the Lightning: Coining "Eclampsia"

The word eclampsia comes from the Ancient Greek eklampsis (ἔκλαμψις), meaning "a shining forth" or "a sudden flashing," from ek- ("out") and lampein ("to shine"). The sense the term was meant to capture is the abruptness of onset — the way a seizure bursts upon a woman without warning, like a flash of lightning out of a clear sky. The popular gloss "lightning" is a fair shorthand for that meaning, though the literal root is the flashing-forth of brightness, not the bolt itself.

The term was introduced into medicine by the French physician and disease-classifier François Boissier de Sauvages de Lacroix (1706–1767), generally credited with first applying "eclampsia" to these pregnancy convulsions around 1739 in his work on the taxonomy of disease. His crucial contribution was conceptual as much as linguistic: he distinguished eclampsia from epilepsy, observing that the pregnancy seizures were acute, self-limited, and resolved once the precipitating condition (the pregnancy) was over — unlike the chronic, recurring fits of true epilepsy. This separation of a transient, pregnancy-bound convulsion from a lifelong seizure disorder was a real diagnostic advance, even though the underlying cause stayed completely obscure.

That distinction took roughly another century to be widely accepted, and the deeper term preeclampsia — literally the stage before (pre-) the seizures — is much more recent, entering common usage in the twentieth century as physicians learned to identify the warning signs (rising blood pressure, protein in the urine, swelling) that so often precede an eclamptic fit. Naming the warning stage was only possible once those signs could actually be detected.

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The Toxemia Theory — and Why It Was Wrong

For a long stretch of the nineteenth and early twentieth centuries, the dominant explanation for eclampsia was that pregnancy generated a circulating poison — a toxin in the blood that acted on the nervous system to provoke seizures. This belief was so entrenched that it gave the whole family of disorders its enduring name: toxemia of pregnancy (literally "toxins in the blood"). Various sources were proposed for the supposed poison: metabolic waste products of the fetus, the mother, or the placenta (an idea of self-poisoning, or "autointoxication"), and even bacteria — one investigator, Gerdes, went so far as to propose a specific germ he named Bacillus eclampsiae. In 1905 the obstetrician Joseph DeLee captured the confusion of the era by calling eclampsia "the disease of theories."

It is important to state plainly, because the old name still circulates: the toxemia theory is wrong. Despite decades of intensive searching, no such circulating toxin was ever identified, and no "eclampsia bacillus" exists. By the middle of the twentieth century the accumulating evidence pointed not to a poison but to the blood vessels, the kidneys, and above all the placenta as the true seat of the disorder. The term "toxemia of pregnancy" is now regarded by historians and clinicians as a misnomer — a relic that survives in older textbooks and lay speech but no longer reflects any real understanding of the disease.

This correction matters for anyone reading about preeclampsia today. If you encounter the phrase "toxemia," understand that it describes a historical hypothesis, not a fact: there is no toxin to flush out, no poison to detoxify, and remedies that promise to "cleanse" such a toxin rest on a discredited idea. The modern picture — abnormal placental blood vessels releasing signaling proteins that injure the mother's circulation — is described in the sections that follow.

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Protein in the Urine: Lever, Rayer, and 1843

The first decisive crack in the mystery came not from theory but from a simple bedside test. In the early 1840s, physicians noticed that the urine of women with eclampsia, when heated, clouded and coagulated — the sign of albumin (protein) spilling from the kidney, the same phenomenon already known in Bright's disease of the kidney. The French physician Pierre Rayer is generally credited with first noting proteinuria in eclamptic women around 1840. But the landmark observation is usually dated to 1843 and attributed to John Charles Weaver Lever (1811–1859) at Guy's Hospital in London.

Lever's achievement was to show that the proteinuria was specific to eclampsia rather than a coincidence. The story, recorded in the historical literature, is that he found albumin almost by accident, initially suspecting ordinary kidney disease; but as he tested patient after patient he found albumin in nearly every eclamptic woman (by one account, all but one), and he noticed the protein faded after delivery. He published his findings in Guy's Hospital Reports. The Scottish obstetrician James Young Simpson — later famous for introducing chloroform in childbirth — reported the same association independently within about a month, lending the discovery immediate weight.

The significance is hard to overstate. For the first time, eclampsia could be linked to a measurable, internal organ sign — protein from the kidney — rather than to an invisible poison. Just as importantly, proteinuria could be detected before the convulsions struck, which opened the door, decades later, to the very concept of preeclampsia: a warning state that could be caught and watched. Proteinuria remained a core diagnostic criterion for more than a century and a half (modern guidelines now recognize that severe preeclampsia can occur even without it, but its historical role was foundational).

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Measuring the Pressure: Riva-Rocci and Modern Signs

The second cardinal sign of preeclampsia — high blood pressure — could not even be measured at the bedside until the very end of the nineteenth century. The breakthrough instrument was the practical mercury sphygmomanometer with an inflatable arm cuff, devised by the Italian physician Scipione Riva-Rocci and presented in 1896. (The auscultatory method of listening for the Korotkoff sounds, which made diastolic pressure readable, followed from the Russian surgeon Nikolai Korotkoff in 1905.) For the first time, clinicians could put a number on the pressure inside a patient's arteries.

Applied to pregnancy, the cuff revealed what the toxemia theorists had missed: eclamptic and pre-eclamptic women were hypertensive. Once blood pressure could be tracked through pregnancy, a recognizable triad emerged — rising blood pressure, protein in the urine, and oedema (swelling) — that allowed physicians to identify the dangerous pre-convulsive stage and to act before a seizure occurred. This is the clinical definition that crystallized in the first half of the twentieth century and gave the warning stage its modern name, preeclampsia: hypertension with proteinuria or other signs of maternal organ involvement, arising in the second half of pregnancy.

Over time, understanding deepened beyond the simple triad. Swelling alone proved unreliable (many healthy pregnancies swell), and the field came to recognize that preeclampsia is a multi-system disorder — it can injure the liver (as in HELLP syndrome), the brain, the clotting system, and the placenta's blood supply, not just raise the pressure and spill protein. But the core insight that preeclampsia is fundamentally a hypertensive disorder of pregnancy, made measurable by Riva-Rocci's cuff, remains the bedrock of diagnosis to this day.

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The Placenta and the Cure of Delivery

Running like a thread through the entire history of preeclampsia is one stubborn clinical fact that observant physicians noticed centuries before they could explain it: the disease resolves after the baby and placenta are delivered. Eclamptic seizures, soaring blood pressure, and spilled protein typically settle in the days following birth. This pointed unmistakably to the conclusion, now universally accepted, that the placenta is the central organ of the disease — and that, to this day, the only definitive cure for preeclampsia is delivery. Everything else (blood-pressure control, magnesium to prevent seizures, bed rest, monitoring) buys time; only ending the pregnancy ends the disorder.

The mechanistic understanding of why the placenta is at fault came together in the twentieth century. A pivotal step was the work of Ian Brosens and colleagues, who in 1972 described defective remodeling of the uterine spiral arteries in preeclampsia. In a healthy pregnancy, specialized placental cells (trophoblasts) invade and transform these small arteries into wide, slack channels that deliver a generous, low-resistance blood supply to the placenta. In preeclampsia this transformation is incomplete: the spiral arteries stay narrow and muscular, the placenta is under-perfused, and the resulting placental ischemia (poor blood flow) is thought to trigger the release of factors that damage the mother's blood vessels throughout her body.

This "two-stage" model — poor placentation first, maternal illness second — reframed preeclampsia as a disorder rooted in the placental bed rather than in any mysterious circulating poison. It explained the old observations beautifully: why delivery cures the disease (it removes the offending placenta), why the disorder clusters in first pregnancies and in conditions that stress the placenta, and why preeclampsia and fetal growth restriction so often travel together. The remaining question — exactly what the ischemic placenta releases to make the mother ill — would be answered at the turn of the twenty-first century.

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Stopping the Seizures: Magnesium Sulfate and MAGPIE

While the causes of preeclampsia were being unraveled, a parallel story unfolded in treatment — specifically, in how to stop the life-threatening eclamptic convulsions. The drug that proved decisive was an old and unglamorous one: magnesium sulfate (often called "mag"). Intravenous and intramuscular magnesium sulfate came into obstetric use in the early twentieth century, and across the 1920s onward it accumulated a strong clinical reputation, particularly in American obstetrics, for both treating eclamptic seizures and preventing them in women with severe preeclampsia.

For decades, however, magnesium's superiority was disputed — rival anticonvulsants such as diazepam and phenytoin were widely used, and good comparative evidence was lacking. The question was settled by large randomized trials. The Collaborative Eclampsia Trial (1995) showed magnesium sulfate was clearly better than diazepam or phenytoin at preventing recurrent seizures in women who had already had an eclamptic fit. Then the landmark MAGPIE trial, published in The Lancet in 2002, enrolled more than 10,000 women with preeclampsia across 33 countries and demonstrated that magnesium sulfate roughly halved the risk of eclampsia (about a 58% reduction) compared with placebo, with a trend toward lower maternal mortality and no major harm to mothers or babies.

MAGPIE was a turning point in global maternal health. It established magnesium sulfate as the worldwide standard of care for preventing and treating eclamptic seizures — a cheap, off-patent medicine, available even in low-resource settings, that prevents one of the deadliest complications of pregnancy. It remains one of the clearest examples in obstetrics of a simple intervention, validated by rigorous evidence, saving large numbers of women's lives. (Magnesium controls the seizures; it does not cure the underlying preeclampsia, for which delivery is still required.)

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The Modern Breakthrough: sFlt-1, PlGF, and Aspirin

The deepest insight into preeclampsia arrived in the early 2000s, when researchers finally identified the placental signals that make the mother ill — not a toxin, but an imbalance in the proteins that govern blood-vessel health. The pivotal molecule is soluble fms-like tyrosine kinase-1, abbreviated sFlt-1 (also written sVEGFR-1). A landmark 2003 study by Maynard and colleagues (published in the Journal of Clinical Investigation) showed that the preeclamptic placenta over-produces sFlt-1, which floods the mother's circulation. sFlt-1 is a decoy receptor: it mops up two crucial pro-growth proteins, vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), that normally keep blood vessels healthy. With VEGF and PlGF neutralized, the mother's endothelium (the lining of her blood vessels), including the delicate filtering vessels of the kidney, is injured — producing exactly the hypertension, proteinuria, and organ damage that define the disease. Injecting sFlt-1 into pregnant rats reproduced the full syndrome.

This is an anti-angiogenic state — too little of the growth factors that build and maintain vessels, too much of the decoy that blocks them. A 2004 study by Levine and colleagues in the New England Journal of Medicine showed the imbalance is detectable in maternal blood weeks before symptoms appear. Measuring the sFlt-1/PlGF ratio in a blood sample is now used clinically to help predict and rule out preeclampsia — a biochemical window into the placenta the toxemia theorists could only have dreamed of. (The signal clears within a day or two of delivery, again confirming the placenta as the source.)

On the prevention side, the modern era is defined by a remarkably ordinary drug: low-dose aspirin. Building on the two-stage placental model, researchers reasoned that an agent improving placental blood flow, taken early enough, might head off the disease. The landmark ASPRE trial, published in the New England Journal of Medicine in 2017, randomized high-risk women (identified by first-trimester screening) to 150 mg of aspirin nightly or placebo from about 11–14 weeks until 36 weeks, and found roughly a 60% reduction in preterm preeclampsia — with even greater benefit in women who took it faithfully. Low-dose aspirin prophylaxis for high-risk pregnancies is now recommended by major obstetric bodies worldwide. It does not abolish the disease, but for an ancient and dreaded disorder, a cheap daily tablet that meaningfully lowers the risk is a genuine triumph of modern, mechanism-driven medicine.

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Legacy: From Mystery to Mechanism

The history of preeclampsia is, in miniature, the history of scientific medicine itself — the slow replacement of a frightening mystery with a chain of testable mechanisms. The ancients saw only the seizures and called them lightning. The early-modern era separated those seizures from epilepsy and, fatefully, blamed an imaginary poison. The nineteenth century found the first real sign — protein in the urine — and its close gave us the means to measure blood pressure. The twentieth century traced the disorder to the placenta and proved magnesium could prevent the convulsions. The twenty-first named the molecules and offered a tablet to lower the risk.

Two honest cautions run through this whole story and deserve repeating. First, the toxemia / toxin theory was simply wrong — there is no poison to detoxify, and any product that claims to "cleanse" pregnancy of a toxin is selling a discredited idea. Second, despite all the progress, preeclampsia is still not preventable in every case and still has only one definitive cure: delivery. It remains a leading cause of maternal and infant illness and death worldwide, which is precisely why the lineage of discoveries described here — from Lever's test tube to the sFlt-1/PlGF ratio — matters so much.

For the practical, present-day picture — what the warning signs are, how the condition is monitored and treated, the role of aspirin and magnesium, and what it means for mother and baby — see the main Preeclampsia article. The arc of this history is ultimately hopeful: a disorder that killed silently for thousands of years is, at last, one that medicine can predict, monitor, partly prevent, and manage — even if the final answers are still being written.

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Research Papers and References

The references below combine key peer-reviewed papers on the history and mechanism of preeclampsia with curated PubMed topic-search links into the historical and clinical literature. Historical primary texts (the Egyptian and Indian medical writings, the Hippocratic corpus, and the works of Boissier de Sauvages, Rayer, Lever, and Simpson) are named in the article as historical sources rather than as modern citations. Each link opens in a new tab.

Bell MJ. A historical overview of preeclampsia-eclampsia. Journal of Obstetric, Gynecologic & Neonatal Nursing. 2010;39(5):510-518. — doi:10.1111/j.1552-6909.2010.01172.x
Maynard SE, Min JY, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. Journal of Clinical Investigation. 2003;111(5):649-658. — doi:10.1172/JCI17189
Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. New England Journal of Medicine. 2004;350(7):672-683. — doi:10.1056/NEJMoa031884
Altman D, Carroli G, Duley L, et al. (MAGPIE Trial Collaborative Group). Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. The Lancet. 2002;359(9321):1877-1890. — doi:10.1016/S0140-6736(02)08778-0
Rolnik DL, Wright D, Poon LC, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia (ASPRE). New England Journal of Medicine. 2017;377(7):613-622. — doi:10.1056/NEJMoa1704559
Roberts JM, Hubel CA. The two stage model of preeclampsia: variations on the theme. Placenta. 2009;30 Suppl A:S32-S37. — doi:10.1016/j.placenta.2008.11.009
Chesley LC. A short history of eclampsia. Obstetrics & Gynecology. 1974;43(4):599-602. — PubMed: Chesley, A short history of eclampsia
Lindheimer MD, Taler SJ, Cunningham FG. Hypertension in pregnancy. — PubMed: history of eclampsia, preeclampsia and "toxemia"
Eclampsia in antiquity and early medicine (Hippocrates, Egyptian and Indian texts) — PubMed: eclampsia history antiquity Hippocrates
John Lever, proteinuria and the 1843 discovery in eclampsia — PubMed: Lever proteinuria eclampsia history
Brosens I, et al. Spiral artery remodeling, trophoblast invasion and the placental bed in preeclampsia — PubMed: Brosens spiral artery remodeling preeclampsia
The sFlt-1/PlGF ratio in the prediction and diagnosis of preeclampsia — PubMed: sFlt-1/PlGF ratio preeclampsia
Low-dose aspirin for the prevention of preeclampsia — PubMed: low-dose aspirin prevention of preeclampsia
Magnesium sulfate for the prevention and treatment of eclampsia (MAGPIE and Collaborative Eclampsia Trial) — PubMed: magnesium sulfate eclampsia MAGPIE

External Authoritative Resources

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