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Pre-eclampsia is a disorder of
pregnancy Pregnancy, also known as gestation, is the time during which one or more offspring In biology, offspring are the young creation of living organisms, produced either by a Asexual reproduction, single organism or, in the case of sexual repr ...

pregnancy
characterized by the onset of
high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term Long-Term Capital Management L.P. (LTCM) was a hedge fund''A financial History of the United States Volume II: 1970–2001'', Jerry W. Markham, Chapter 5: "Bank ...

high blood pressure
and often a significant amount of protein in the urine. When it arises, the condition begins after 20
weeks of pregnancy Gestational age is a measure of the age of a pregnancy which is taken from the beginning of the woman's Menstruation#Onset and frequency, last menstrual period (LMP), or the corresponding age of the gestation as estimated by a more accurate method i ...
. In severe cases of the disease there may be , a , impaired liver function, kidney dysfunction, , , or visual disturbances. Pre-eclampsia increases the risk of undesirable outcomes for both the mother and the fetus. If left untreated, it may result in
seizure An epileptic seizure, formally known as a seizure, is a period of symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temp ...
s at which point it is known as
eclampsia Eclampsia is the onset of seizures (convulsions) in a woman with pre-eclampsia. Pre-eclampsia is a disorder of pregnancy in which there is high blood pressure and either large amounts of protenuria, protein in the urine or other organ dysfunction ...
. Risk factors for pre-eclampsia include
obesity Obesity is a medical condition A disease is a particular abnormal condition that negatively affects the structure or function (biology), function of all or part of an organism, and that is not due to any immediate external injury. ...

obesity
, prior
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not ...

hypertension
, older age, and
diabetes mellitus Diabetes mellitus, commonly known as just diabetes, is a group of metabolic disorders characterized by a hyperglycemia, high blood sugar level over a prolonged period of time. Symptoms often include frequent urination, Polydipsia, increased th ...
. It is also more frequent in a woman's first pregnancy and if she is carrying twins. The underlying mechanism involves abnormal amongst other factors. Most cases are diagnosed before delivery. Commonly, pre-eclampsia continues into the period after delivery, then known as postpartum pre-eclampsia. Rarely, pre-eclampsia may begin in the period after delivery. While historically both high blood pressure and protein in the urine were required to make the diagnosis, some definitions also include those with hypertension and any associated organ dysfunction. Blood pressure is defined as high when it is greater than 140 mmHg
systolic to supply all body systems; 2) oxygen-depleted blood (blue arrow) in the right ventricle begins pulsing through the pulmonic (pulmonary) valve en route to the lungs for reoxygenation. depolarization is the start-point of the atrial stage of syst ...
or 90 mmHg
diastolic Image:Heart diastole.png, upright=1.5, Heart performance during ventricular diastole: early diastole is a suction mechanism that draws blood 'down' from the left atrium (pink) and right atrium (blue) into each of the two ventricles. Then, in late ve ...
at two separate times, more than four hours apart in a woman after twenty weeks of pregnancy. Pre-eclampsia is routinely screened for during
prenatal care Prenatal care, also known as antenatal care, is a type of preventive healthcare. It is provided in the form of medical checkups, consisting of recommendations on managing a healthy lifestyle and the provision of medical information such as materna ...
. Recommendations for prevention include:
aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a medication used to reduce pain, fever, or inflammation. Specific inflammatory conditions which aspirin is used to treat include Kawasaki disease, pericarditis, and rheumatic fever. Aspirin ...

aspirin
in those at high risk,
calcium supplementation Calcium supplements are salts of calcium Calcium is a chemical element with the Symbol (chemistry), symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed t ...
in areas with low intake, and treatment of prior hypertension with medications. In those with pre-eclampsia, delivery of the baby and
placenta The placenta is a temporary fetal organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. ...

placenta
is an effective treatment but full recovery can take days or weeks. When delivery becomes recommended depends on how severe the pre-eclampsia and how far along in pregnancy a woman is.
Blood pressure medicationAntihypertensives are a class of medication, drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence sugge ...
, such as
labetalol Labetalol is a medication used to treat high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elev ...

labetalol
and
methyldopa Methyldopa, sold under the brand name Aldomet among others, is a medication used for high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term Disease, medical condition in which the blood pressure ...

methyldopa
, may be used to improve the mother's condition before delivery.
Magnesium sulfate Magnesium sulfate or magnesium sulphate (in British English British English (BrE) is the standard dialect of the English language English is a West Germanic languages, West Germanic language first spoken in History of Anglo-Saxon E ...

Magnesium sulfate
may be used to prevent eclampsia in those with severe disease. Bedrest and salt intake have not been found to be useful for either treatment or prevention. Pre-eclampsia affects 2–8% of pregnancies worldwide.
Hypertensive disorders of pregnancy Hypertensive disease of pregnancy, also known as maternal hypertensive disorder, is a group of high blood pressure disorders that include preeclampsia, preeclampsia superimposed on chronic hypertension, gestational hypertension, and hypertension, c ...
(which include pre-eclampsia) are one of the most common causes of death due to pregnancy. They resulted in 46,900 deaths in 2015. Pre-eclampsia usually occurs after 32 weeks; however, if it occurs earlier it is associated with worse outcomes. Women who have had pre-eclampsia are at increased risk of
heart disease Cardiovascular disease (CVD) is a class of diseases that involve the heart The heart is a cardiac muscle, muscular Organ (biology), organ in most animals, which pumps blood through the blood vessels of the circulatory system. The pumped b ...
and
stroke A stroke is a medical condition A disease is a particular abnormal condition that negatively affects the structure or function (biology), function of all or part of an organism, and that is not due to any immediate external injury. Di ...

stroke
later in life. The word "eclampsia" is from the Greek term for lightning. The first known description of the condition was by
Hippocrates Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ε ...

Hippocrates
in the 5th century BC.


Signs and symptoms

Oedema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a ...

Oedema
(especially in the hands and face) was originally considered an important sign for a diagnosis of pre-eclampsia. However, because oedema is a common occurrence in pregnancy, its utility as a distinguishing factor in pre-eclampsia is not high.
Pitting edema Edema, also spelt oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight ...
(unusual swelling, particularly of the hands, feet, or face, notable by leaving an indentation when pressed on) can be significant, and should be reported to a health care provider. In general, none of the signs of pre-eclampsia are specific, and even convulsions in pregnancy are more likely to have causes other than eclampsia in modern practice. Further, a symptom such as epigastric pain may be misinterpreted as heartburn. Common features of pre-eclampsia which are screened for during pre-natal visits include elevated blood pressure and excess protein in the urine. Diagnosis depends on finding a coincidence of several pre-eclamptic features, the final proof being their regression within the days and weeks after delivery.


Causes

There is no definitive known cause of pre-eclampsia, though it is likely related to a number of factors. Some of these factors include: * Abnormal
placentation In biology, placentation refers to the formation, type and structure, or arrangement of the placenta The placenta is a temporary fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in faci ...

placentation
(formation and development of the placenta) * Immunologic factors * Prior or existing maternal pathology—pre-eclampsia is seen more at a higher incidence in individuals with pre-existing
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not ...

hypertension
, obesity, or antiphospholipid antibody syndrome or those with a history of pre-eclampsia * Dietary factors, e.g. calcium supplementation in areas where dietary calcium intake is low has been shown to reduce the risk of pre-eclampsia * Environmental factors, e.g. air pollution Those with long term
high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term Long-Term Capital Management L.P. (LTCM) was a hedge fund''A financial History of the United States Volume II: 1970–2001'', Jerry W. Markham, Chapter 5: "Bank ...

high blood pressure
have a risk 7 to 8 times higher than those without. Physiologically, research has linked pre-eclampsia to the following physiologic changes: alterations in the interaction between the maternal immune response and the placenta, placental injury,
endothelial Endothelium is a single layer of squamous Epithelium () is one of the four basic types of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingdom Animalia. With ...
cell injury, altered vascular reactivity, oxidative stress, imbalance among
vasoactive A vasoactive substance is an endogenous agent or pharmaceutical drug that has the effect of either increasing or decreasing blood pressure and/or heart rate through its vasoactivity, that is, vascular activity (effect on blood vessel The b ...
substances, decreased intravascular volume, and
disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking Microvessel, small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems mov ...
. While the exact cause of pre-eclampsia remains unclear, there is strong evidence that a major cause predisposing a susceptible woman to pre-eclampsia is an abnormally implanted placenta. This abnormally implanted placenta may result in poor uterine and placental perfusion, yielding a state of hypoxia and increased oxidative stress and the release of anti-angiogenic proteins along with inflammatory mediators into the maternal plasma. A major consequence of this sequence of events is generalized
endothelial Endothelium is a single layer of squamous Epithelium () is one of the four basic types of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingdom Animalia. With ...
dysfunction. The abnormal implantation may stem from the maternal
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as Tumor immunology, cancer cells and objects such ...
's response to the placenta, specifically a lack of established immunological tolerance in pregnancy. Endothelial dysfunction results in hypertension and many of the other symptoms and complications associated with pre-eclampsia. Those with pre-eclampsia may have a lower risk of breast cancer. Abnormal chromosome 19 microRNA cluster ( C19MC) impairs extravillus trophoblast cell invasion to the spiral arteries, causing high resistance, low blood flow, and low nutrient supply to the fetus.


Genetic factors

Despite a lack of knowledge on specific causal mechanisms of pre-eclampsia, there is strong evidence to suggest it results from both environmental and heritable factors. A 2005 study showed that women with a first-degree relative who had a pre-eclamptic birth are twice as likely to develop it themselves. Furthermore, men related to someone with affected birth have an increased risk of fathering a pre-eclamptic pregnancy. Fetuses affected by pre-eclampsia have a higher chance of later pregnancy complications including growth restriction, prematurity, and stillbirth. The onset of pre-eclampsia is thought to be caused by several complex interactions between genetics and environmental factors. Our current understanding of the specifically heritable cause involves an imbalance of angiogenic factors in the placenta.
Angiogenesis Angiogenesis is the physiological process through which new blood vessel The blood vessels are the components of the circulatory system The circulatory system, also called the cardiovascular system or the vascular system, is an organ sy ...

Angiogenesis
involves the growth of new blood vessels from existing vessels, and an imbalance during pregnancy can affect the vascularization, growth, and biological function of the fetus. The irregular expression of these factors is thought to be controlled by multiple loci on different chromosomes. Research on the topic has been limited because of the
heterogeneous Homogeneity and heterogeneity are concepts often used in the sciences Science () is a systematic enterprise that Scientific method, builds and organizes knowledge in the form of Testability, testable explanations and predictions about th ...
nature of the disease. Maternal, Paternal, and Fetal genotypes all play a role as well as complex epigenetic factors such as whether the parents smoke, maternal age, sexual cohabitation, and obesity (Phipps et al., 2019). Currently, there is very little understanding behind the mechanisms of these interactions. Due to the polygenic nature of pre-eclampsia, a majority of the studies that have been conducted thus far on the topic have utilized genome-wide association studies. One known effector of pre-eclampsia is the fetal loci FLT1. Located on chromosome 13 in the q12 region, FLT1 codes for Fms-like tyrosine kinase 1, an angiogenic factor expressed in fetal
trophoblasts Trophoblasts (from Greek 'trephein': to feed; and 'blastos': germinator) are cells that form the outer layer of a blastocyst, and are present four days post-fertilization in humans. They provide nutrients to the embryo An embryo is the early ...
. Angiogenic factors are crucial for vascular growth in the placenta. An FLT1 soluble isoform caused by a splice variant is sFLT1, which works as an antiangiogenic factor, reducing vascular growth in the placenta. A healthy, normotensive pregnancy is characterized by a balance between these factors. However, upregulation of this variant and overexpression of sFL1 can contribute to
endothelial dysfunction In vascular diseases, endothelial dysfunction is a systemic pathological state of the endothelium. Along with acting as a semi-permeable membrane, the endothelium is responsible for maintaining vascular tone and regulating oxidative stress ( ...
. Reduced vascular growth and endothelial dysfunction manifest primarily in maternal symptoms such as renal failure, edema, and seizures. However, these factors can also lead to inadequate oxygen, nutrient, or blood supply to the fetus. Furthermore, in this loci region, several single-nucleotide polymorphisms have been observed to impact the overexpression of sFL1. Specifically, SNPs rs12050029 and rs4769613’s risk alleles are linked with low red blood cell counts and carry an increased risk of late-onset pre-eclampsia.
Patau syndrome Patau syndrome is a syndrome caused by a chromosomal abnormality, in which some or all of the cells of the body contain extra genetic material from chromosome 13. The extra genetic material disrupts normal development, causing multiple and comp ...
, or Trisomy 13, is also associated with the upregulation of sFLT1 due to the extra copy of the 13th chromosome. Because of this upregulation of an antiangiogenic factor, women with trisomy 13 pregnancies often experience reduced placental vascularization and are at higher risk for developing pre-eclampsia. Beyond fetal loci, there have been some maternal loci identified as effectors of pre-eclampsia.
Alpha-ketoglutarate-dependent hydroxylase Alpha-ketoglutarate-dependent hydroxylases are a major class of non-heme iron protein In biochemistry, non-heme iron proteins describe families of enzymes that utilize iron at the active site but lack heme cofactors. Iron-sulfur proteins, including ...
expression on the 16th chromosome in the q12 region is also associated with pre-eclampsia. Specifically, allele rs1421085 heightens the risk of not just pre-eclampsia but also an increase in BMI and hypertension. This
pleiotropy Pleiotropy (from Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approxi ...
is one of the reasons why these traits are considered to be a risk factor. Furthermore, ZNF831 (zinc finger protein 831) and its loci on chromosome 20q13 were identified as another significant factor in pre-eclampsia. The risk allele rs259983 is also associated with both pre-eclampsia and hypertension, further evidence that the two traits are possibly linked. While the current understanding suggests that maternal alleles are the main hereditary cause of pre-eclampsia, paternal loci have also been implicated. In one study, paternal
DLX5 Homeobox A homeobox is a Nucleic acid sequence, DNA sequence, around 180 base pairs long, found within genes that are involved in the regulation of patterns of anatomical development (morphogenesis) in animals, fungus, fungi, plants, and numerous ...
(Distal-Less Homeobox 5) was identified as an . Located on chromosome 7 in the q21 region, DLX5 serves as a transcription factor often linked with the developmental growth of organs. When paternally inherited, DLX5 and its SNP rs73708843 are shown to play a role in trophoblast proliferation, affecting vascular growth and nutrient delivery. Besides specific loci, several important genetic regulatory factors contribute to the development of pre-eclampsia. Micro RNAs, or
miRNAs A microRNA (abbreviated miRNA) is a small single-stranded non-coding RNA A non-coding RNA (ncRNA) is an RNA Ribonucleic acid (RNA) is a polymer A polymer (; Greek '' poly-'', "many" + '' -mer'', "part") is a substance or materi ...
, are noncoding mRNAs that down-regulate posttranscriptional gene expression through RNA-induced silencing complexes. In the placenta, miRNAs are crucial for regulating cell growth, angiogenesis, cell proliferation, and metabolism. These placental-specific miRNAs are clustered in large groups, mainly on chromosomes 14 and 19, and irregular expression of either is associated with an increased risk of an affected pregnancy. For instance, miR-16 and miR-29 are vascular endothelial growth factors (VEGFs) and play a role in upregulating sFLT-1. In particular, the overexpression of miRNA miR-210 has been shown to induce hypoxia, which affects spiral artery remodeling, an important part of the pathogenesis of pre-eclampsia.


Risk factors

Known risk factors for pre-eclampsia include: * Having never previously given birth *
Diabetes mellitus Diabetes mellitus, commonly known as just diabetes, is a group of metabolic disorders characterized by a hyperglycemia, high blood sugar level over a prolonged period of time. Symptoms often include frequent urination, Polydipsia, increased th ...
*
Kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease A disease is a particular abnormal condition that negatively affects the structure A structure is an arrangement and organization of i ...
* Chronic hypertension * Prior history of pre-eclampsia * Family history of pre-eclampsia * Advanced maternal age (>35 years) * Obesity *
Antiphospholipid antibody syndrome Antiphospholipid syndrome, or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune Autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other body normal constituents. Any disease ...
*
Multiple gestation A multiple birth is the culmination of one multiple pregnancy, wherein the mother delivers two or more offspring. A term most applicable to vertebrate species, multiple births occur in most kinds of mammals, with varying frequencies. Such births a ...
* Having donated a kidney * Having sub-clinical
hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland The thyroid, or thyroid gland, is an endocrine gland in the neck consisting of two ...

hypothyroidism
or
thyroid The thyroid, or thyroid gland, is an endocrine gland Endocrine glands are ductless glands of the endocrine system The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organi ...

thyroid
antibodies * Placental abnormalities such as placental ischemia


Pathogenesis

Although much research into mechanism of pre-eclampsia has taken place, its exact pathogenesis remains uncertain. Pre-eclampsia is thought to result from an abnormal placenta, the removal of which ends the disease in most cases. During normal pregnancy, the placenta vascularizes to allow for the exchange of water, gases, and solutes, including nutrients and wastes, between maternal and fetal circulations. Abnormal development of the placenta leads to poor placental perfusion. The placenta of women with pre-eclampsia is abnormal and characterized by poor trophoblastic invasion. It is thought that this results in oxidative stress, hypoxia, and the release of factors that promote endothelial dysfunction, inflammation, and other possible reactions. The clinical manifestations of pre-eclampsia are associated with general endothelial dysfunction, including vasoconstriction and end-organ
ischemia Ischemia or ischaemia is a restriction in blood Blood is a body fluid in humans and other animals that delivers necessary substances such as nutrients and oxygen to the Cell (biology), cells and transports metabolic waste products away fr ...
. Implicit in this generalized endothelial dysfunction may be an imbalance of
angiogenic Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the circulatory system, vasculature by processes of sprou ...
and
anti-angiogenicAn angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through drugs, pharmaceutic ...
factors. Both circulating and placental levels of soluble fms-like tyrosine kinase-1 (sFlt-1) are higher in women with pre-eclampsia than in women with normal pregnancy. sFlt-1 is an anti-angiogenic protein that antagonizes
vascular endothelial growth factor Vascular endothelial growth factor (VEGF), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, t ...
(VEGF) and
placental growth factor Placental growth factor is a protein that in humans is encoded by the ''PGF'' gene. Placental growth factor (PGF) is a member of the VEGF (vascular endothelial growth factor) sub-family - a key molecule in angiogenesis and vasculogenesis, in parti ...
(PIGF), both of which are proangiogenic factors. Soluble
endoglin Endoglin (ENG) is a type I membrane glycoprotein located on cell (biology), cell surfaces and is part of the TGF beta receptor complex. It is also commonly referred to as CD105, END, FLJ41744, HHT1, ORW and ORW1. It has a crucial role in angiogenesi ...
(sEng) has also been shown to be elevated in women with pre-eclampsia and has anti-angiogenic properties, much like sFlt-1 does. Both sFlt-1 and sEng are upregulated in all pregnant women to some extent, supporting the idea that hypertensive disease in pregnancy is a normal pregnancy adaptation gone awry. As natural killer cells are intimately involved in placentation and placentation involves a degree of maternal immune tolerance for a foreign placenta, it is not surprising that the maternal immune system might respond more negatively to the arrival of some placentae under certain circumstances, such as a placenta which is more invasive than normal. Initial maternal rejection of the placental cytotrophoblasts may be the cause of the inadequately remodeled spiral arteries in those cases of pre-eclampsia associated with shallow implantation, leading to downstream hypoxia and the appearance of maternal symptoms in response to upregulated sFlt-1 and sEng. Oxidative stress may also play an important part in the pathogenesis of pre-eclampsia. The main source of reactive oxygen species (ROS) is the enzyme
xanthine oxidase Xanthine oxidase (XO, sometimes XAO) is a form of xanthine oxidoreductase, a type of enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may ...
(XO) and this enzyme mainly occurs in the liver. One hypothesis is that the increased purine catabolism from placental hypoxia results in increased ROS production in the maternal liver and release into the maternal circulation that causes endothelial cell damage. Abnormalities in the maternal
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as Tumor immunology, cancer cells and objects such ...
and insufficiency of
gestational immune toleranceImmune tolerance in pregnancy or maternal immune tolerance is the immune tolerance shown towards the fetus and placenta during pregnancy. This tolerance counters the immune response that would normally result in the transplant rejection, rejection of ...
seem to play major roles in pre-eclampsia. One of the main differences found in pre-eclampsia is a shift toward Th1 responses and the production of IFN-γ. The origin of IFN-γ is not clearly identified and could be the
natural killer cell Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic Cytotoxicity is the quality of being toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances c ...

natural killer cell
s of the uterus, the placental dendritic cells modulating responses of
T helper cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the immune system, particularly in the adaptive immune system. As their name suggests, they "help" the activity o ...
, alterations in synthesis of or response to regulatory molecules, or changes in the function of
regulatory T cell The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosu ...
s in pregnancy. Aberrant immune responses promoting pre-eclampsia may also be due to an altered fetal allorecognition or to inflammatory triggers. It has been documented that fetal cells such as fetal
erythroblasts A nucleated red blood cell (NRBC), also known by #Nomenclature, several other names, is a red blood cell that contains a cell nucleus. Almost all vertebrate organisms have hemoglobin-containing cells in their blood, and with the exception of mamma ...
as well as
cell-free fetal DNA Cell-free fetal DNA (cffDNA) is fetal A fetus American and British English spelling differences#ae and oe, or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic de ...
are increased in the maternal circulation in women who develop pre-eclampsia. These findings have given rise to the hypothesis that pre-eclampsia is a disease process by which a placental lesion such as hypoxia allows increased fetal material into the maternal circulation, that in turn leads to an
immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, Parasitism, parasites, and Fungus ...

immune response
and endothelial damage, and that ultimately results in pre-eclampsia and eclampsia. One hypothesis for vulnerability to pre-eclampsia is the maternal-fetal conflict between the maternal organism and fetus. After the first trimester trophoblasts enter the spiral arteries of the mother to alter the spiral arteries and thereby gain more access to maternal nutrients. Occasionally there is impaired trophoblast invasion that results in inadequate alterations to the uterine spiral arteries. It is hypothesized that the developing embryo releases biochemical signals that result in the woman developing hypertension and pre-eclampsia so that the fetus can benefit from a greater amount of maternal circulation of nutrients due to increased blood flow to the impaired placenta. This results in a conflict between maternal and fetal fitness and survival because the fetus is invested in only its survival and fitness while the mother is invested in this and subsequent pregnancies. Another evolutionary hypothesis for vulnerability to pre-eclampsia is the idea of ensuring pair-bonding between the mother and father and paternal investment in the fetus. Researchers posit that pre-eclampsia is an adaptation for the mother to terminate investment in a fetus that might have an unavailable father, as determined by repeated semen exposure of the father to the mother. Various studies have shown that women who frequently had exposure to partners' semen before conception had a reduced risk of pre-eclampsia. Also, subsequent pregnancies by the same father had a reduced risk of pre-eclampsia while subsequent pregnancies by a different father had a higher risk of developing pre-eclampsia. In normal early embryonic development, the outer epithelial layer contains cytotrophoblast cells, a stem cell type found in the trophoblast that later differentiates into the fetal placenta. These cells differentiate into many placental cells types, including extravillous trophoblast cells. Extravillous trophoblast cells are an invasive cell type which remodel the maternal spiral arteries by replacing the maternal epithelium and smooth muscle lining the spiral arteries causing artery dilation. This prevents maternal vasoconstriction in the spiral arteries and allows for continued blood and nutrient supply to the growing fetus with low resistance and high blood flow. In pre-eclampsia, abnormal expression of chromosome 19 microRNA cluster (C19MC) in placental cell lines reduces extravillus trophoblast migration. Specific microRNAs in this cluster which might cause abnormal spiral artery invasion include miR-520h, miR-520b, and 520c-3p. This impairs extravillus trophoblast cells invasion to the maternal spiral arteries, causing high resistance and low blood flow and low nutrient supply to the fetus. There is tentative evidence that vitamin supplementation can decrease the risk. Immune factors may also play a role.


Diagnosis

Testing for pre-eclampsia is recommended throughout
pregnancy Pregnancy, also known as gestation, is the time during which one or more offspring In biology, offspring are the young creation of living organisms, produced either by a Asexual reproduction, single organism or, in the case of sexual repr ...

pregnancy
via measuring a woman's blood pressure.


Diagnostic criteria

Pre-eclampsia is diagnosed when a pregnant woman develops: * Blood pressure ≥140 mmHg systolic or ≥90 mmHg diastolic on two separate readings taken at least four to six hours apart after 20 weeks' gestation in an individual with previously normal blood pressure. * In a woman with essential hypertension beginning before 20 weeks' gestational age, the diagnostic criteria are an increase in systolic blood pressure (SBP) of ≥30 mmHg or an increase in diastolic blood pressure (DBP) of ≥15 mmHg. *
Proteinuria Proteinuria is the presence of excess protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , providing and , and from one location to ano ...
≥ or more of protein in a 24-hour urine sample or a SPOT urinary protein to creatinine ratio ≥0.3 or a urine dipstick reading of 1+ or greater (dipstick reading should only be used if other quantitative methods are not available). Suspicion for pre-eclampsia should be maintained in any pregnancy complicated by elevated blood pressure, even in the absence of proteinuria. Ten percent of individuals with other signs and symptoms of pre-eclampsia and 20% of individuals diagnosed with eclampsia show no evidence of proteinuria. In the absence of proteinuria, the presence of new-onset
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not ...

hypertension
(elevated blood pressure) and the new onset of one or more of the following is suggestive of the diagnosis of pre-eclampsia: * Evidence of kidney dysfunction (
oliguria Oliguria or hypouresis is the low output of urine specifically more than 80 ml/day but less than 400ml/day.Boon et al, Davidson's Principles & Practice of Medicine (20th Ed), p475 The decreased output of urine may be a sign of dehydration, kidney f ...
, elevated
creatinine Creatinine ( or ; from el, κρέας, kreas, flesh) is a breakdown product of creatine phosphate Phosphocreatine, also known as creatine phosphate (CP) or PCr (Pcr), is a phosphorylated creatine molecule that serves as a rapidly mobilizable ...

creatinine
levels) * Impaired liver function (noted by
liver function tests Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated Partial Thromboplastin Ti ...
) *
Thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care units, intensive care patients and is seen in 20% of med ...

Thrombocytopenia
(platelet count <100,000/microliter) *
Pulmonary edema Pulmonary edema (PE), also known as pulmonary congestion, is liquid accumulation in the tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a specific function * ''Triphosa haesitata'', a ...

Pulmonary edema
* Ankle edema (pitting type) * Cerebral or visual disturbances Pre-eclampsia is a progressive disorder and these signs of organ dysfunction are indicative of severe pre-eclampsia. A systolic blood pressure ≥160 or diastolic blood pressure ≥110 and/or proteinuria >5g in a 24-hour period is also indicative of severe pre-eclampsia. Clinically, individuals with severe pre-eclampsia may also present
epigastric In anatomy Anatomy (Greek ''anatomē'', 'dissection') is the branch of biology concerned with the study of the structure of organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any ind ...
/right upper quadrant abdominal pain, headaches, and vomiting. Severe pre-eclampsia is a significant risk factor for intrauterine fetal death. A rise in baseline blood pressure (BP) of 30
mmHg A millimetre of mercury is a manometric unit of pressure Pressure (symbol: ''p'' or ''P'') is the force In physics, a force is an influence that can change the motion (physics), motion of an Physical object, object. A force can ca ...
systolic or 15 mmHg diastolic, while not meeting the absolute criteria of 140/90, is important to note but is not considered diagnostic.


Predictive tests

There have been many assessments of tests aimed at predicting pre-eclampsia, though no single biomarker is likely to be sufficiently predictive of the disorder. Predictive tests that have been assessed include those related to placental perfusion, vascular resistance, kidney dysfunction,
endothelial Endothelium is a single layer of squamous Epithelium () is one of the four basic types of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingdom Animalia. With ...
dysfunction, and oxidative stress. Examples of notable tests include: * Doppler
ultrasonography Ultrasound is sound wave In physics Physics (from grc, φυσική (ἐπιστήμη), physikḗ (epistḗmē), knowledge of nature, from ''phýsis'' 'nature'), , is the natural science that studies matter, its Motion (phys ...
of the uterine arteries to investigate for signs of inadequate placental perfusion. This test has a high negative predictive value among those individuals with a history of prior pre-eclampsia. * Elevations in serum uric acid (
hyperuricemia Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7&nbs ...
) is used by some to "define" pre-eclampsia, though it has been found to be a poor predictor of the disorder. Elevated levels in the blood (
hyperuricemia Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7&nbs ...
) are likely due to reduced uric acid clearance secondary to impaired kidney function. *
Angiogenic Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the circulatory system, vasculature by processes of sprou ...
proteins such as
vascular endothelial growth factor Vascular endothelial growth factor (VEGF), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, t ...
(VEGF) and
placental growth factor Placental growth factor is a protein that in humans is encoded by the ''PGF'' gene. Placental growth factor (PGF) is a member of the VEGF (vascular endothelial growth factor) sub-family - a key molecule in angiogenesis and vasculogenesis, in parti ...
(PIGF) and anti-angiogenic proteins such as soluble fms-like tyrosine kinase-1 (sFlt-1) have shown promise for potential clinical use in diagnosing pre-eclampsia, though evidence is unsufficient to recommend a clinical use for these markers. A recent study, ASPRE, known to be the largest multi-country prospective trial, has reported a significant performance in identifying pregnant women at high risk of pre-eclampsia yet during the first trimester of pregnancy. Utilizing a combination of maternal history, mean arterial blood pressure, intra-uterine Doppler and PlGF measurement, the study has shown a capacity to identify more than 75% of the women that will develop pre-eclampsia, allowing early intervention to prevent development of later symptoms. This approach is now officially recommended by the International Federation of Gynecologists & Obstetricians (FIGO) * Recent studies have shown that looking for
podocyte Podocytes are cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Closed spaces * Monastic cell, a small room, hut, or cave in which a monk or religious recluse lives * Prison cell, a ro ...
s (specialized cells of the kidney) in the urine has the potential to aid in the prediction of pre-eclampsia. Studies have demonstrated that finding podocytes in the urine may serve as an early marker of and diagnostic test for pre-eclampsia.


Differential diagnosis

Pre-eclampsia can mimic and be confused with many other diseases, including chronic hypertension, chronic renal disease, primary seizure disorders, gallbladder and pancreatic disease, immune or
thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that results in thrombi, blood clots forming in small blood vessels throughout the body. This results in a thrombocytopenia, low platelet count, hemolytic anemia, low red blood cells du ...
,
antiphospholipid syndrome Antiphospholipid syndrome, or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune Autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other body normal constituents. Any disease t ...
and hemolytic-uremic syndrome. It must be considered a possibility in any pregnant woman beyond 20 weeks of gestation. It is particularly difficult to diagnose when pre-existing conditions such as
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not ...

hypertension
are present. Women with
acute fatty liver of pregnancy Acute fatty liver of pregnancy is a rare life-threatening complication of pregnancy Pregnancy, also known as gestation, is the time during which one or more offspring develops inside a woman. A multiple birth, multiple pregnancy involves more ...
may also present with elevated blood pressure and protein in the urine, but differ by the extent of liver damage. Other disorders that can cause high blood pressure include
thyrotoxicosis Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormone File:Thyroid_system.svg, upright=1.5, The thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck ...
,
pheochromocytoma Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...

pheochromocytoma
, and drug misuse.


Prevention

Preventive measures against pre-eclampsia have been heavily studied. Because the pathogenesis of pre-eclampsia is not completely understood, prevention remains a complex issue. Below are some of the currently accepted recommendations.


Diet

Supplementation with a balanced protein and energy diet does not appear to reduce the risk of pre-eclampsia. Further, there is no evidence that changing
salt Salt is a mineral In geology and mineralogy, a mineral or mineral species is, broadly speaking, a solid chemical compound with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure fo ...

salt
intake has an effect. Supplementation with
antioxidant Antioxidants are compounds Compound may refer to: Architecture and built environments * Compound (enclosure), a cluster of buildings having a shared purpose, usually inside a fence or wall ** Compound (fortification), a version of the above ...

antioxidant
s such as vitamin C, D and E has no effect on pre-eclampsia incidence; therefore, supplementation with vitamins C, E, and D is not recommended for reducing the risk of pre-eclampsia.
Calcium Calcium is a chemical element In chemistry, an element is a pure Chemical substance, substance consisting only of atoms that all have the same numbers of protons in their atomic nucleus, nuclei. Unlike chemical compounds, chemical elem ...

Calcium
supplementation of at least 1 gram per day is recommended during pregnancy as it prevents pre-eclampsia where dietary calcium intake is low, especially for those at high risk. Higher
selenium Selenium is a chemical element upright=1.0, 500px, The chemical elements ordered by link=Periodic table In chemistry Chemistry is the science, scientific study of the properties and behavior of matter. It is a natural science that ...

selenium
level is associated with lower incidence of pre-eclampsia. Higher
cadmium Cadmium is a chemical element In chemistry, an element is a pure Chemical substance, substance consisting only of atoms that all have the same numbers of protons in their atomic nucleus, nuclei. Unlike chemical compounds, chemical eleme ...

cadmium
level is associated with higher incidence of pre-eclampsia.


Aspirin

Taking
aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a medication used to reduce pain, fever, or inflammation. Specific inflammatory conditions which aspirin is used to treat include Kawasaki disease, pericarditis, and rheumatic fever. Aspirin ...

aspirin
is associated with a 1 to 5% reduction in pre-eclampsia and a 1 to 5% reduction in premature births in women at high risk. The
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations United Nations Specialized Agencies are autonomous organizations working with the United Nations and each other through the co-ordinating machinery of the Unit ...
recommends low-dose aspirin for the prevention of pre-eclampsia in women at high risk and recommends it be started before 20 weeks of pregnancy. The
United States Preventive Services Task Force The United States Preventive Services Task Force (USPSTF) is "an independent panel of experts in primary care and prevention that systematically reviews the Evidence-based medicine, evidence of effectiveness and develops recommendations for clinic ...
recommends a low-dose regimen for women at high risk beginning in the 12th week. Benefits are less if started after 16 weeks. The more recent study ASPRE, beside its performance in identifying suspected women to develop pre-eclampsia, has also been able to demonstrate a strong drop in the rate of early pre-eclampsia (-82%) and preterm pre-eclampsia (-62%). Such efficacy of aspirin has been reached due to high performing screening to identify at high risk women, adjusted prophylaxis dosage (150 mg/day), timing of the intake (bedtime) and must start before week 16 of pregnancy.


Physical activity

There is insufficient evidence to recommend either exercise or strict bedrest as preventive measures of pre-eclampsia.


Smoking cessation

In low-risk pregnancies, the association between cigarette
smoking Smoking is a practice in which a substance is burned and the resulting smoke Smoke is a collection of airborne and es emitted when a material undergoes or , together with the quantity of air that is or otherwise mixed into the ma ...

smoking
and a reduced risk of pre-eclampsia has been consistent and reproducible across epidemiologic studies. High-risk pregnancies (those with pregestational diabetes, chronic hypertension, history of pre-eclampsia in a previous pregnancy, or multifetal gestation) showed no significant protective effect. The reason for this discrepancy is not definitively known; research supports speculation that the underlying pathology increases the risk of pre-eclampsia to such a degree that any measurable reduction of risk due to smoking is masked. However, the damaging effects of smoking on overall health and pregnancy outcomes outweighs the benefits in decreasing the incidence of pre-eclampsia. It is recommended that smoking be stopped prior to, during and after pregnancy.


Immune modulation

Some studies have suggested the importance of a woman's gestational immunological tolerance to her baby's father, as the baby and father share genetics. There is tentative evidence that ongoing exposure either by vaginal or oral sex to the same semen that resulted in the pregnancy decreases the risk of pre-eclampsia. As one early study described, "although pre-eclampsia is a disease of first pregnancies, the protective effect of multiparity is lost with change of partner". The study also concluded that although women with changing partners are strongly advised to use condoms to prevent sexually transmitted diseases, "a certain period of sperm exposure within a stable relation, when pregnancy is aimed for, is associated with protection against pre-eclampsia". Several other studies have since investigated the decreased incidence of pre-eclampsia in women who had received blood transfusions from their partner, those with long preceding histories of sex without barrier contraceptives, and in women who had been regularly performing
oral sex Oral sex, sometimes referred to as oral intercourse, is sexual activity Human sexual activity, human sexual practice or human sexual behaviour is the manner in which humans experience and express their sexuality Human sexuality is ...
. Having already noted the importance of a woman's immunological tolerance to her baby's paternal genes, several Dutch reproductive biologists decided to take their research a step further. Consistent with the fact that human immune systems tolerate things better when they enter the body via the mouth, the Dutch researchers conducted a series of studies that confirmed a surprisingly strong correlation between a diminished incidence of pre-eclampsia and a woman's practice of oral sex, and noted that the protective effects were strongest if she swallowed her partner's semen. A team from the
University of Adelaide The University of Adelaide (informally Adelaide University) is a public university A public university or public college is a university or college that is in state ownership or receives significant Government spending, public funds through a ...

University of Adelaide
has also investigated to see if men who have fathered pregnancies which have ended in
miscarriage Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the natural loss of an embryo An embryo is the early stage of development of a multicellular organism A multicellular organism is an organism ...
or pre-eclampsia had low seminal levels of critical immune modulating factors such as
TGF-beta Transforming growth factor beta (TGF-β) is a multifunctional cytokine Cytokines are a broad and loose category of small protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first ...
. The team has found that certain men, dubbed "dangerous males", are several times more likely to father pregnancies that would end in either pre-eclampsia or
miscarriage Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the natural loss of an embryo An embryo is the early stage of development of a multicellular organism A multicellular organism is an organism ...
. Among other things, most of the "dangerous males" seemed to lack sufficient levels of the seminal immune factors necessary to induce immunological tolerance in their partners. As the theory of immune intolerance as a cause of pre-eclampsia has become accepted, women who with repeated pre-eclampsia, miscarriages, or
in vitro fertilization In vitro fertilisation (IVF) is a process of fertilisation Fertilisation or fertilization (see American and British English spelling differences#-ise.2C -ize .28-isation.2C -ization.29, spelling differences), also known as generative ...
failures could potentially be administered key immune factors such as TGF-beta along with the father's foreign proteins, possibly either orally, as a sublingual spray, or as a vaginal gel to be applied onto the vaginal wall before intercourse.


Treatment

The definitive treatment for pre-eclampsia is the delivery of the baby and placenta, but danger to the mother persists after delivery, and full recovery can take days or weeks. The timing of delivery should balance the desire for optimal outcomes for the baby while reducing risks for the mother. The severity of disease and the maturity of the baby are primary considerations. These considerations are situation-specific and management will vary with situation, location, and institution. Treatment can range from expectant management to expedited delivery by Labor induction, induction of labor or Caesarean section, in addition to medications. Important in management is the assessment of the mother's organ systems, management of severe hypertension, and prevention and treatment of eclamptic seizures. Separate interventions directed at the baby may also be necessary. Bed rest has not been found to be useful and is thus not routinely recommended.


Blood pressure

The World Health Organization recommends that women with severe
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not ...

hypertension
during pregnancy should receive treatment with anti-hypertensive agents. Severe hypertension is generally considered systolic BP of at least 160 or diastolic BP of at least 110. Evidence does not support the use of one anti-hypertensive over another. The choice of which agent to use should be based on the prescribing clinician's experience with a particular agent, its cost, and its availability. Diuretics are not recommended for prevention of pre-eclampsia and its complications. Labetalol, hydralazine and nifedipine are commonly used antihypertensive agents for Hypertensive disease of pregnancy, hypertension in pregnancy. ACE inhibitors and Angiotensin II receptor blocker, angiotensin receptor blockers are contraindicated as they affect fetal development. The goal of treatment of severe hypertension in pregnancy is to prevent cardiovascular, kidney, and cerebrovascular complications. The target blood pressure has been proposed to be 140–160 mmHg systolic and 90–105 mmHg diastolic, although values are variable.


Prevention of eclampsia

The intrapartum and postpartum administration of magnesium sulfate is recommended in severe pre-eclampsia for the prevention of
eclampsia Eclampsia is the onset of seizures (convulsions) in a woman with pre-eclampsia. Pre-eclampsia is a disorder of pregnancy in which there is high blood pressure and either large amounts of protenuria, protein in the urine or other organ dysfunction ...
. Further, magnesium sulfate is recommended for the treatment of eclampsia over other anticonvulsants. Magnesium sulfate acts by interacting with NMDA receptors.


Epidemiology

Pre-eclampsia affects approximately 2–8% of all pregnancies worldwide. The incidence of pre-eclampsia has risen in the U.S. since the 1990s, possibly as a result of increased prevalence of predisposing disorders, such as chronic hypertension, diabetes, and obesity. Pre-eclampsia is one of the leading causes of maternal and perinatal morbidity and mortality worldwide. Nearly one-tenth of all maternal deaths in Africa and Asia and one-quarter in Latin America are associated with hypertensive diseases in pregnancy, a category that encompasses pre-eclampsia. Pre-eclampsia is much more common in women who are pregnant for the first time. Women who have previously been diagnosed with pre-eclampsia are also more likely to experience pre-eclampsia in subsequent pregnancies. Pre-eclampsia is also more common in women who have pre-existing
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not ...

hypertension
,
obesity Obesity is a medical condition A disease is a particular abnormal condition that negatively affects the structure or function (biology), function of all or part of an organism, and that is not due to any immediate external injury. ...

obesity
, diabetes, autoimmune diseases such as Lupus erythematosus, lupus, various inherited thrombophilias such as Factor V Leiden, chronic renal failure, renal disease, multiple gestation (twins or multiple birth), and advanced maternal age. Women who live at high altitude are also more likely to experience pre-eclampsia. Pre-eclampsia is also more common in some ethnic groups (e.g. African-Americans, Sub-Saharan Africans, Latin Americans, African Caribbeans, and Filipinos). Change of paternity in a subsequent pregnancy has been implicated as affecting risk, except in those with a family history of hypertensive pregnancy. Eclampsia is a major complication of pre-eclampsia. Eclampsia affects 0.56 per 1,000 pregnant women in developed countries and almost 10 to 30 times as many women in low-income countries as in developed countries.


Complications

Complications of pre-eclampsia can affect both the mother and the fetus. Acutely, pre-eclampsia can be complicated by
eclampsia Eclampsia is the onset of seizures (convulsions) in a woman with pre-eclampsia. Pre-eclampsia is a disorder of pregnancy in which there is high blood pressure and either large amounts of protenuria, protein in the urine or other organ dysfunction ...
, the development of HELLP syndrome, hemorrhagic or ischemic
stroke A stroke is a medical condition A disease is a particular abnormal condition that negatively affects the structure or function (biology), function of all or part of an organism, and that is not due to any immediate external injury. Di ...

stroke
, liver damage and dysfunction, acute kidney injury, and acute respiratory distress syndrome (ARDS). Pre-eclampsia is also associated with increased frequency of Caesarean section, Preterm birth, preterm delivery, and placental abruption. Furthermore, an elevation in blood pressure can occur in some individuals in the first week postpartum attributable to volume expansion and fluid mobilization. Fetal complications include fetal growth restriction and potential fetal or perinatal death. Long-term, an individual with pre-eclampsia is at increased risk for recurrence of pre-eclampsia in subsequent pregnancies.


Eclampsia

Eclampsia is the development of new convulsions in a pre-eclamptic patient that may not be attributed to other causes. It is a sign that the underlying pre-eclamptic condition is severe and is associated with high rates of perinatal and maternal morbidity and mortality. Warning symptoms for eclampsia in an individual with current pre-eclampsia may include headaches, visual disturbances, and right upper quadrant or epigastric abdominal pain, with a headache being the most consistent symptom. During pregnancy brisk or hyperactive reflexes are common, however ankle clonus is a sign of neuromuscular irritability that usually reflects severe pre-eclampsia and also can precede eclampsia.
Magnesium sulfate Magnesium sulfate or magnesium sulphate (in British English British English (BrE) is the standard dialect of the English language English is a West Germanic languages, West Germanic language first spoken in History of Anglo-Saxon E ...

Magnesium sulfate
is used to prevent convulsions in cases of severe pre-eclampsia.


HELLP Syndrome

HELLP syndrome is defined as hemolysis (microangiopathic), elevated liver enzymes (liver dysfunction), and low platelets (thrombocytopenia). This condition may occur in 10–20% of patients with severe pre-eclampsia and eclampsia and is associated with increased maternal and fetal morbidity and mortality. In 50% of instances, HELLP syndrome develops preterm, while 20% of cases develop in late gestation and 30% during the post-partum period.


Long term

Preeclampsia predisposes for future cardiovascular disease and a history of preeclampsia/eclampsia doubles the risk for cardiovascular mortality later in life. Other risks include
stroke A stroke is a medical condition A disease is a particular abnormal condition that negatively affects the structure or function (biology), function of all or part of an organism, and that is not due to any immediate external injury. Di ...

stroke
, Hypertension, chronic hypertension, kidney disease and Venous thrombosis, venous thromboembolism. Preeclampsia and cardiovascular disease share many risk factors such as age, elevated BMI, family history and certain chronic diseases. seems pre-eclampsia does not increase the risk of cancer. Lowered blood supply to the fetus in pre-eclampsia causes lowered nutrient supply, which could result in intrauterine growth restriction (IUGR) and low birth weight. The fetal origins hypothesis states that fetal undernutrition is linked with coronary heart disease later in adult life due to disproportionate growth. Because pre-eclampsia leads to a mismatch between the maternal energy supply and fetal energy demands, pre-eclampsia can lead to IUGR in the developing fetus. Infants suffering from IUGR are prone to suffer from poor neuronal development and in increased risk for adult disease according to the Barker hypothesis. Associated adult diseases of the fetus due to IUGR include, but are not limited to, coronary artery disease (CAD), Type 2 diabetes, type 2 diabetes mellitus (T2DM), cancer, osteoporosis, and various psychiatric illnesses. The risk of pre-eclampsia and development of placental dysfunction has also been shown to be recurrent cross-generationally on the maternal side and most likely on the paternal side. Fetuses born to mothers who were born small for gestational age (SGA) were 50% more likely to develop pre-eclampsia while fetuses born to both SGA parents were three-fold more likely to develop pre-eclampsia in future pregnancies.


History

The word "eclampsia" is from the Greek term for lightning. The first known description of the condition was by
Hippocrates Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ε ...

Hippocrates
in the 5th century BC. An outdated medical term for pre-eclampsia is wikt:toxemia, toxemia of pregnancy, a term that originated in the mistaken belief that the condition was caused by toxins.


References


External links

* * MedlinePlus]
entry on high blood pressure in pregnancy
* Mayo Clinic]
fact sheet on pre-eclampsia
{{Pathology of pregnancy, childbirth and the puerperium Health issues in pregnancy Medical emergencies Rare diseases Wikipedia medicine articles ready to translate Women's health