| Pre-eclampsia | |
|---|---|
| Other names | Pre-eclampsia toxaemia (PET), pre-eclampsia |
 | |
| A micrograph showing hypertrophic decidual vasculopathy, a finding seen in gestational hypertension and pre-eclampsia. H&E stain. | |
| Specialty | Obstetrics |
| Symptoms | High blood pressure, protein in the urine |
| Complications | Red blood cell breakdown, low blood platelet count, impaired liver function, kidney problems, swelling, shortness of breath due to fluid in the lungs, eclampsia |
| Usual onset | After 20 weeks of pregnancy |
| Risk factors | Obesity, prior hypertension, older age, diabetes mellitus |
| Diagnostic method | BP > 140 mmHg systolic or 90 mmHg diastolic at two separate times |
| Prevention | Aspirin, calcium supplementation, treatment of prior hypertension |
| Treatment | Delivery, medications |
| Medication | Labetalol, methyldopa, magnesium sulfate |
| Frequency | 2–8% of pregnancies |
| Deaths | 46,900 hypertensive disorders in pregnancy (2015) |
Pre-eclampsia (PE) is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe disease there may be red blood cell breakdown, a low blood platelet count, impaired liver function, kidney dysfunction, swelling, shortness of breath due to fluid in the lungs, or visual disturbances. Pre-eclampsia increases the risk of poor outcomes for both the mother and the baby. If left untreated, it may result in seizures at which point it is known as eclampsia.
Risk factors for pre-eclampsia include obesity, prior hypertension, older age, and diabetes mellitus. It is also more frequent in a woman's first pregnancy and if she is carrying twins. The underlying mechanism involves abnormal formation of blood vessels in the placenta amongst other factors. Most cases are diagnosed before delivery. 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 or 90 mmHg diastolic 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.
Recommendations for prevention include: aspirin in those at high risk, calcium supplementation in areas with low intake, and treatment of prior hypertension with medications. In those with pre-eclampsia delivery of the baby and placenta is an effective treatment. When delivery becomes recommended depends on how severe the pre-eclampsia and how far along in pregnancy a woman is. Blood pressure medication, such as labetalol and methyldopa, may be used to improve the mother's condition before delivery. 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 (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 and stroke later in life. The word "eclampsia" is from the Greek term for lightning. The first known description of the condition was by Hippocrates in the 5th century BC.
Signs and symptoms
Swelling
(especially in the hands and face) was originally considered an
important sign for a diagnosis of pre-eclampsia. However, because
swelling is a common occurrence in pregnancy, its utility as a
distinguishing factor in pre-eclampsia is not high. Pitting edema
(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. Diagnosis, therefore, depends on
finding a coincidence of several pre-eclamptic features, the final proof
being their regression 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 (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, obesity, antiphospholipid antibody syndrome, and those with 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 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 cell injury, altered vascular reactivity, oxidative stress, imbalance among vasoactive substances, decreased intravascular volume, and disseminated intravascular coagulation.
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 dysfunction. The abnormal implantation may stem from the maternal immune system'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.
Risk factors
Known risk factors for pre-eclampsia include:
- Having never previously given birth
- Diabetes mellitus
- Kidney disease
- Chronic hypertension
- Prior history of pre-eclampsia
- Family history of pre-eclampsia
- Advanced maternal age (more than 35 years)
- Obesity
- Antiphospholipid antibody syndrome
- Multiple gestation
- Having donated a kidney.
- Having sub-clinical hypothyroidism or 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. Implicit in this generalized endothelial dysfunction may be an imbalance of angiogenic and anti-angiogenic 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 (VEGF) and placental growth factor (PIGF), both of which are proangiogenic factors. Soluble endoglin
(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
(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 and insufficiency of gestational immune tolerance 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 cells of the uterus, the placental dendritic cells modulating responses of T helper cells, alterations in synthesis of or response to regulatory molecules, or changes in the function of regulatory T cells 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 as well as cell-free fetal DNA
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 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 paternal
donor, as determined by repeated semen exposure of the paternal donor
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 paternal donor had a reduced
risk of pre-eclampsia while subsequent pregnancies by a different
paternal donor 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
| Pre-eclampsia laboratory values | |
|---|---|
| Medical diagnostics | |
Shorthand for laboratory values commonly used in pre-eclampsia. LDH=Lactate dehydrogenase, Uric acid=Uric acid, AST=Aspartate aminotransferase, ALT=Alanine aminotransferase, Plt=Platelets, Cr=Creatinine.
| |
| Reference range | LDH: 105–333 IU/L Uric Acid: 2.4–6.0 mg/dL AST: 5–40 U/L ALT: 7–56 U/L Plt: 140–450 x 109/L Cr: 0.6–1.2 mg/dL |
| MeSH | D007770 |
| LOINC | Codes for pre-eclampsia |
Testing for pre-eclampsia is recommended throughout 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 ≥ 0.3 grams (300 mg) 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 (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, elevated creatinine levels)
- Impaired liver function (noted by liver function tests)
- Thrombocytopenia (platelet count less than100,000/microliter)
- 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 more than 5g
in a 24-hour period is also indicative of severe pre-eclampsia. Clinically, individuals with severe pre-eclampsia may also present epigastric/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
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 dysfunction, and oxidative stress. Examples of notable tests include:
- Doppler ultrasonography 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) 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) are likely due to reduced uric acid clearance secondary to impaired kidney function.
- Angiogenic proteins such as vascular endothelial growth factor (VEGF) and placental growth factor (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 sufficient to recommend a clinical use for these markers.
- Recent studies have shown that looking for podocytes (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, antiphospholipid syndrome 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 are present. Women with acute fatty liver of pregnancy
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, 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 intake has an effect.
Supplementation with antioxidants 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
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. Low selenium status is associated with higher incidence of pre-eclampsia.
Aspirin
Taking 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
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 recommends a low-dose regimen for women at high risk beginning in the 12th week. Benefits are less if started after 16 weeks.
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
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.
Treatment
The
definitive treatment for pre-eclampsia is the delivery of the baby and
placenta. 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 induction of labor or Caesarean section,
in addition to medications. Important in management is the assessment
of the mothers 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 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 hypertension in pregnancy. ACE inhibitors and 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. 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, obesity, diabetes, autoimmune diseases such as lupus, various inherited thrombophilias such as Factor V Leiden, 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, the development of HELLP syndrome, hemorrhagic or ischemic 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 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 cause.
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. 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
There
is also an increased risk for cardiovascular complications, including
hypertension and ischemic heart disease, and kidney disease. Other risks include stroke and venous thromboembolism. It 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 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 that 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 in the 5th century BC.
An outdated medical term for pre-eclampsia is toxemia of pregnancy, a term that originated in the mistaken belief that the condition was caused by toxins.
Research
Some studies have suggested the importance of a woman's 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.
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 has also investigated to see if men who have fathered pregnancies which have ended in miscarriage or pre-eclampsia had low seminal levels of critical immune modulating factors such as TGF-beta.
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.
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
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.
A Congo Red Dot Paper Test is being studied for the rapid identification of preeclampsia.
