Preeclampsia

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Preeclampsia

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Blood pressure
Protein - urine
Diabetes
Hypertension
Kidney disease
Eclampsia
Premature infant

Preeclampsia is high blood pressure and protein in the urine that develops after the 20th week of
pregnancy.

Causes

The exact cause of preeclampsia is not known. Possible causes include:

• Autoimmune disorders
• Blood vessel problems
• Diet
• Genes

Preeclampsia occurs in a small percentage of pregnancies. Risk factors include:

• First pregnancy
• Multiple pregnancy (twins or more)
• Obesity
• Older than age 35
• Past history of diabetes, high blood pressure, or kidney disease

Symptoms

Symptoms of preeclampsia can include:

• Headaches
• Swelling of the hands and face (edema)
• Weight gain
 o More than 2 pounds per week
o Sudden weight gain over 1 - 2 days

Note: Some swelling of the feet and ankles is considered normal with pregnancy.

Other symptoms that can occur with this disease:

• Abdominal pain
• Agitation
• Decreased urine output
• Nausea and vomiting
• Vision changes

Exams and Tests

• Increase in blood pressure

• Higher than normal liver enzymes
• Platelet count less than 100,000 (thrombocytopenia)
• Protein in the urine (proteinuria)
• Swelling in the upper body
• Weight gain

Treatment

The only way to cure preeclampsia is to deliver the baby. However, if that delivery would be
very early (premature), the disease can be managed by bed rest, close monitoring, and delivery as
soon as the fetus has a good chance of surviving outside the womb. Sometimes, medicines are
prescribed to lower the mother's blood pressure.

The pregnant mother is usually admitted to the hospital, but some women may be allowed to stay
at home with careful monitoring of their blood pressure, urine, and weight, and the baby.

Ideally, the condition is managed until the baby can be delivered after the 37th week of
pregnancy.

Labor may be induced if any of the following occur:

• Abdominal pain
• Abnormal biophysical profile (a test to monitor the health of the fetus)
• Abnormal liver function tests
• Diastolic blood pressure greater than 100 mmHg consistently for a 24-hour period, or any
confirmed reading over 110 mmHg
• Eclampsia
• Failure of the fetus to grow
• Fluid in lungs (pulmonary edema)
• HELLP syndrome
 • Increase in the level of creatinine in the blood
• Low platelet count (thrombocytopenia)
• Low urine production or severe protein in the urine, suggesting decline in kidney function
• Persistent or severe headache

Delivery is the treatment of choice for women with severe preeclampsia who are between 34 - 40
weeks pregnant.

For those who are less than 24 weeks pregnant, inducing labor is recommended, although the
chance that the fetus will survive is very small.

Pregnancies between weeks 24 and 34 are considered a "gray zone." Prolonging a pregnancy has
been shown to lead to problems for the mother in most cases. Infant death also can occur. The
medical team and parents may decide to delay delivery to allow the fetus to develop.

Treatment during 24 - 34 weeks includes giving the mother steroid injections to help tspeed up
the development of the baby's organs (including the lungs). The mother and baby are closely
monitored for complications.

When labor and delivery are induced, the mother will be given medication to prevent seizures
and to keep blood pressure under control. The decision to have a vaginal delivery versus
cesarean section is based on the health of the mother, the baby's ability to tolerate labor, and
other factors.

Outlook (Prognosis)

Death of the mother from preeclampsia is rare in the U.S. The infant's risk of death generally
decreases as the pregnancy continues.

A woman with a history of preeclampsia is at risk for the condition again during future
pregnancies.

Women who have high blood pressure problems during more than one pregnancy have an
increased risk for high blood pressure when they get older.

Possible Complications

Preeclampsia can develop into eclampsia if the mother has seizures. Complications can occur if
the baby is delivered prematurely.

Severe preeclampsia may lead to HELLP syndrome.

When to Contact a Medical Professional

Call your health care provider if you have symptoms of preeclampsia during your pregnancy.
Prevention

Although there is no known way to prevent preeclampsia, it is important for all pregnant women
to start prenatal care early and continue it through the pregnancy. This allows the health care
provider to find and treat conditions such as preeclampsia early.

Alternative Names

Toxemia; Pregnancy-induced hypertension

Pregnancy-Induced Hypertension

What is pregnancy-induced hypertension?

Pregnancy-induced hypertension (PIH), which is also called toxemia or preeclampsia

(say "pre-ee-clamp-see-ah"), is a problem that occurs in some women during
pregnancy. It can happen during the second half of pregnancy. Your doctor will look
for the following signs of PIH: high blood pressure, swelling that doesn't go away
and large amounts of protein in your urine.

Return to top

Who is at risk for PIH?

PIH is more common in a woman's first pregnancy and in women whose mothers or
sisters had PIH. The risk of PIH is higher in women carrying multiple babies, in
teenage mothers and in women older than age 40. Other women at risk include
those who had high blood pressure or kidney disease before they became pregnant.
The cause of PIH isn't known.

Return to top

Does high blood pressure mean I have PIH?

Not necessarily. If your doctor sees that your blood pressure is high, he or she will
watch you closely for changes that could mean you have PIH. In addition to high
blood pressure, women who have PIH also have excessive swelling. They may also
have protein in their urine. Many women with high blood pressure during pregnancy
don't have protein in their urine or extreme swelling, and don't get PIH.

Return to top
Does swelling mean I have PIH?

Swelling alone doesn't necessarily mean you have PIH. Some swelling is normal
during pregnancy. For example, your rings or shoes might become too tight.
Swelling is more serious if it doesn't go away after resting, if it's very obvious in
your face and hands, or if it's a rapid weight gain of more than 5 pounds in a week.

Return to top

What tests can show if I have PIH?

No one test diagnoses PIH. Your blood pressure will be checked during each doctor's
visit. A big rise in your blood pressure can be an early sign that you might have PIH.
A urine test can tell if there is protein in your urine. Your doctor may order certain
blood tests, which may show if you have PIH. If you have signs of PIH, your doctor
may want to see you at least once a week and possibly every day.

Return to top

What are the risks of PIH to the baby and me?

PIH can prevent the placenta (which gives air and food to your baby) from getting
enough blood. If the placenta doesn't get enough blood, your baby gets less air and
food. This can cause low birth weight and other problems for the baby.

Most women who have PIH still deliver healthy babies. A few develop a condition
called eclampsia (PIH with seizures), which is very serious for the mother and baby,
or other serious problems. Fortunately, PIH is usually detected early in women who
get regular prenatal care, and most problems can be prevented.

Return to top

What is the treatment for PIH?

If you have PIH, delivery of the baby is the best way to protect both you and your
baby. This isn't always possible, because it may be too early for the baby to live
outside of the womb.

If delivery isn't possible because it's too early in your pregnancy, steps can be taken
to manage the PIH until the baby can be delivered. These steps include making your
blood pressure drop, with bed-rest or medicines, and keeping a close eye on you
and your baby. In some cases, hospitalization may be necessary.

One way to control high blood pressure when you're not pregnant is to cut the
amount of salt you eat. This isn't a good idea if you have high blood pressure
during pregnancy. Your body needs salt to keep up the flow of fluid in your body,
so you need a normal intake of salt. Your doctor will tell you how much salt to eat
each day and how much water you should drink each day.

Your doctor might tell you to take aspirin or extra calcium to prevent PIH. Your
doctor might also tell you to lie on your left side while you are resting. This will
improve blood flow and take weight off your large blood vessels. Many doctors give
magnesium sulfate to their patients during labor and for a few days afterward to
help prevent eclampsia. Talk to your doctor about these things.

Return to top

If my doctor decides to deliver the baby early, will I have to have a cesarean
section?

This is up to your doctor and you. A cesarean section (an operation to deliver the
baby) is more likely if your health or your baby's health is in danger. If things aren't
this serious, your doctor may use medicine (such as oxytocin) to start your labor,
and you can deliver your baby through a vaginal delivery.

Return to top

Symptoms of PIH

If you have any of these symptoms, call your doctor right away:

• Severe headaches
• Vomiting blood
• Excessive swelling of the feet and hands
• Smaller amounts of urine or no urine
• Blood in your urine
• Rapid heartbeat
• Dizziness
• Excessive nausea
• Ringing or buzzing sound in ears
• Excessive vomiting
• Drowsiness
• Fever
• Double vision
• Blurred vision
• Sudden blindness
• Pain in the abdomen (tummy)
Pre-eclampsia

From Wikipedia, the free encyclopedia

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Pre-eclampsia

Classification and external resources

ICD-10 O11., O13., O14.

ICD-9 642.4-642.7

DiseasesDB 10494

MedlinePlus 000898

eMedicine med/1905 ped/1885

MeSH [1]

Pre-eclampsia (US: preeclampsia) is a medical condition where hypertension arises in

pregnancy (pregnancy-induced hypertension) in association with significant amounts of protein
in the urine. Because pre-eclampsia refers to a set of symptoms rather than any causative factor,
it is established that there are many different causes for the syndrome. It also appears likely that
there is a substance or substances from the placenta that may cause endothelial dysfunction in the
maternal blood vessels of susceptible women.[1] While blood pressure elevation is the most
visible sign of the disease, it involves generalized damage to the maternal endothelium and
kidneys and liver, with the release of vasopressive factors only secondary to the original damage.

Pre-eclampsia may develop from 20 weeks gestation (it is considered early onset before 32
weeks, which is associated with increased morbidity) and its progress differs among patients;
most cases are diagnosed pre-term. Apart from Caesarean section, or induction of labor, and
therefore delivery of the placenta, there is no known cure. It may also occur up to six weeks post-
partum. It is the most common of the dangerous pregnancy complications; it may affect both the
mother and the fetus.[1]
Contents
[hide]

• 1 Diagnosis
• 2 Epidemiology
• 3 Causes
• 4 Pathogenesis
• 5 Differential diagnosis
• 6 Complications
• 7 Treatment and prevention
o 7.1 Magnesium sulfate
o 7.2 Dietary and nutritional factors
o 7.3 Aspirin supplementation
o 7.4 Exercise
o 7.5 Exposure to partner's semen
o 7.6 Administration of immune factors
• 8 References

• 9 External links

[edit] Diagnosis

Pre-eclampsia is diagnosed when a pregnant woman develops high blood pressure (two separate
readings taken at least 4 hours apart of 140/90 or more) and 300 mg of protein in a 24-hour urine
sample (proteinuria). A rise in baseline BP of 30 systolic or 15 diastolic, while not meeting the
absolute criteria of 140/90 is still considered important to note but no longer diagnostic.
Swelling, or edema, (especially in the hands and face) was originally considered an important
sign for a diagnosis of pre-eclampsia, but in current medical practice only hypertension and
proteinuria are necessary for a diagnosis. However, 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.

Pre-eclampsia may progress to eclampsia, characterized by the appearance of tonic-clonic

seizures. This happens only very rarely.

Although eclampsia is potentially fatal, pre-eclampsia is often asymptomatic, hence its detection
depends on signs or investigations. Nonetheless, one symptom is crucially important because it is
so often misinterpreted. The epigastric pain, which reflects hepatic involvement and is typical of
the HELLP syndrome, may easily be confused with heartburn, a very common problem of
pregnancy. However, it is not burning in quality, does not spread upwards towards the throat, is
associated with hepatic tenderness, may radiate through to the back, and is not relieved by giving
antacids. It is often very severe, described by sufferers as the worst pain that they have ever
experienced. Affected women are not uncommonly referred to general surgeons as suffering
from an acute abdomen, for example acute cholecystitis.
In general, none of the signs of pre-eclampsia is specific; even convulsions in pregnancy are
more likely to have causes other than eclampsia in modern practice. Diagnosis, therefore,
depends on finding a coincidence of several pre-eclamptic features, the final proof being their
regression after delivery.

Some women develop high blood pressure without the proteinuria (protein in urine); this is
called Pregnancy-induced hypertension (PIH) or gestational hypertension. Both pre-eclampsia
and PIH are regarded as very serious conditions and require careful monitoring of mother and
baby.

[edit] Epidemiology

Pre-eclampsia occurs in as many as 10% of pregnancies, usually in the second or third trimester,
and after the 32nd week. Some women will experience pre-eclampsia as early as 20 weeks,
though this is rare. It is much more common in women who are pregnant for the first time,[2] and
its frequency drops significantly in second pregnancies. While change of paternity in a
subsequent pregnancy is now thought to lower risk except in those with a family history of
hypertensive pregnancy,[3] since increasing maternal age raises risk[4] it has been difficult to
evaluate how significant paternity change actually is and studies are providing conflicting data
on this point.

Pre-eclampsia is also more common in women who have preexisting hypertension, diabetes,
autoimmune diseases like lupus, various inherited thrombophilias like Factor V Leiden, or renal
disease, in women with a family history of pre-eclampsia, obese women, and in women with a
multiple gestation (twins, triplets, and more). The single most significant risk for developing pre-
eclampsia is having had pre-eclampsia in a previous pregnancy.

Pre-eclampsia may also occur in the immediate post-partum period or up to 6–8 weeks post-
partum. This is referred to as "postpartum pre-eclampsia." The most dangerous time for the
mother is the 24–48 hours postpartum and careful attention should be paid to pre-eclampsia signs
and symptoms.[5]

[edit] Causes

The pre-eclampsia syndrome is thought in many cases to be caused by a shallowly implanted

placenta which becomes hypoxic, leading to an immune reaction characterized by secretion of
upregulated inflammatory mediators from the placenta, and acting on the vascular endothelium.
The shallow implantation is thought to stem from the maternal immune system's response to the
placenta. This theory emphasizes the role of the maternal immune system, and refers to evidence
suggesting a lack of established immunological tolerance in pregnancy, resulting in an immune
response against paternal antigens from the fetus and its placenta.[6] In some cases of pre-
eclampsia it is thought that the mother lacks the receptors for the proteins the placenta is using to
downregulate the maternal immune system's response to it.[7] This view is also consistent with
evidence showing many miscarriages to be an immunological disorder where the mother's
immune system "unleashes a destructive attack on the tissues of the developing fetus."[8]
In many cases of the pre-eclampsia syndrome, however, the maternal response to the placenta
appears to have allowed for normal implantation. It is possible that women with higher baseline
levels of inflammation stemming from underlying conditions such as chronic hypertension or
autoimmune disease may have less tolerance for the inflammatory burden of pregnancy.

If severe, preeclampsia progresses to fulminant pre-eclampsia, with headaches, visual

disturbances, and epigastric pain, and further to HELLP syndrome and eclampsia. Placental
abruption is associated with hypertensive pregnancies. These are life-threatening conditions for
both the developing baby and the mother.

Many theories have attempted to explain why preeclampsia arises, and have linked the syndrome
to the presence of the following:

• endothelial cell injury

• immune rejection of the placenta
• compromised placental perfusion
• altered vascular reactivity
• imbalance between prostacyclin and thromboxane
• decreased glomerular filtration rate with retention of salt and water
• decreased intravascular volume
• increased central nervous system irritability
• disseminated intravascular coagulation
• uterine muscle stretch (ischemia)
• dietary factors, including vitamin deficiency
• genetic factors[9]
• air pollution[10]

The current understanding of the syndrome is as a two-stage process, with a highly variable first
stage which predisposes the placenta to hypoxia, followed by the release of soluble factors which
result in many of the other observed phenomena. Many of the older theories can be subsumed
under this umbrella, as the soluble factors have been shown to cause, for example, endothelial
cell injury, altered vascular reactivity, the classic lesion of glomerular endotheliosis, decreased
intravascular volume, inflammation, etc. Underlying maternal susceptibility to the damage is
likely implicated as well.

[edit] Pathogenesis

Although much research into the etiology and mechanism of pre-eclampsia has taken place, its
exact pathogenesis remains uncertain. Some studies support notions of inadequate blood supply
to the placenta making it release particular hormones or chemical agents that, in mothers
predisposed to the condition, leads to damage of the endothelium (lining of blood vessels),
alterations in metabolism, inflammation, and other possible reactions.[1]

Some studies suggest that hypoxia resulting from inadequate perfusion upregulates sFlt-1, a
VEGF and PlGF antagonist, leading to a damaged maternal endothelium and restriction of
placental growth.[11] In addition, endoglin, a TGF-beta antagonist, is elevated in pregnant women
who develop preeclampsia.[12] Soluble endoglin is likely upregulated by the placenta in response
to an upregulation of cell-surface endoglin produced by the maternal immune system, although
there is also the potential that sEng is produced by the maternal endothelium. Levels of both sFlt-
1 and sEng increase as severity of disease increases, with levels of sEng surpassing levels of
sFlt-1 in HELLP syndrome cases. Recent data indicate that Gadd45a stress signaling regulates
elevated sFlt-1 expression in preeclampsia[13].

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 as placentation involves a degree of
maternal tolerance for a foreign placenta which requires maternal resources for its support, 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 preeclampsia associated with shallow
implantation, leading to downstream hypoxia and the appearance of maternal symptoms in
response to upregulated sFlt-1 and sEng. (See parent-offspring conflict.)

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 preeclampsia. These findings
have given rise to the hypothesis that preeclampsia is a disease process by which a placental
lesion such as hypoxia allows increased fetal material into maternal circulation that leads to an
immune response and endothelial damage ultimately resulting in preeclampsia and eclampsia.

[edit] Differential diagnosis

Preeclampsia-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 always be considered a possibility in any pregnant woman
beyond 20 weeks of gestation. It is particularly difficult to diagnose when preexisting disease
such as hypertension is present.[14]

[edit] Complications

Eclampsia can occur after the onset of pre-eclampsia. Eclampsia, which is a more serious
condition, complicates 1 in 2000 maternities in the United Kingdom and carries a maternal
mortality of 1.8 percent.[15] The HELLP syndrome is more common, probably about 1 in 500
maternities, but may be as dangerous as eclampsia itself. These two major maternal crises can
present unheralded by prodromal signs of pre-eclampsia.

Cerebral hemorrhage is a lesion that can kill women with pre-eclampsia or eclampsia. In that
cerebral hemorrhage is a known complication of severe hypertension in other contexts, it must be
assumed that this is a major predisposing factor in this situation, although this has not been
proved. Adult respiratory distress syndrome appears to have become more common, it is not
known whether this is a consequence of modern methods of respiratory support rather than of the
disease itself.
[edit] Treatment and prevention

The only known treatments for eclampsia or advancing pre-eclampsia are abortion or delivery,
either by induction or Caesarean section. However, post-partum pre-eclampsia may occur up to 6
weeks following delivery even if symptoms were not present during the pregnancy. Post-partum
pre-eclampsia is dangerous to the health of the mother since she may ignore or dismiss
symptoms as simple post-delivery headaches and edema. Hypertension can sometimes be
controlled with anti-hypertensive medication, but any effect this might have on the progress of
the underlying disease is unknown.

Many studies have also suggested the importance of a woman's immunological tolerance to her
baby's father, whose genes are present in the young fetus and its placenta and which may pose a
challenge to her immune system.[6][16] As the theory is further investigated,[17] researchers are
increasingly studying the importance of a woman's continued exposure to her partner's semen as
early as several years before conception. One study published in the American Journal of
Obstetrics and Gynecology involved several hundreds of women and found that "women with a
short period of cohabitation (less than 4 months) who used barrier methods for contraception had
a substantially elevated risk for the development of pre-eclampsia compared with women with
more than 12 months of cohabitation before conception."[18] However, the results from a study
conducted in 2004 show that the theory is still not conclusive. In that study, the researchers
found that after adjustment and stratification, the effect of barrier contraceptive use on the
development of pre-eclampsia had disappeared, with both arms having identical rates of pre-
eclampsia.[19] Although the study has since then been criticized for its subjective adjustment of
data, it remains important because it demonstrates that there is still some contention over the
degree to which failure of tolerance induction can be attributed to prior exposure to the partner's
sperm.

Women with underlying inflammatory disorders such as chronic hypertension or autoimmune

diseases would likely benefit from aggressive treatment of those conditions prior to conception,
tamping down the overactive immune system.

Thrombophilias may be weakly linked to pre-eclampsia. There are no high quality studies to
suggest that blood thinners will prevent pre-eclampsia in thrombophilic women[20].

[edit] Magnesium sulfate

In some cases, women with preeclampsia or eclampsia can be stabilized temporarily with
magnesium sulfate intravenously to forestall seizures while steroid injections are administered to
promote fetal lung maturation. Magnesium sulfate as a possible treatment was considered at least
as far back as 1955,[21] but only in recent years did its use in the UK replace the use of diazepam
or phenytoin.[22] Evidence for the use of magnesium sulfate came from the international
MAGPIE study.[23] When induced delivery needs to take place before 37 weeks gestation, it is
accepted that there are additional risks to the baby from premature birth that will require
additional monitoring and care.

[edit] Dietary and nutritional factors

Studies of protein/calorie supplementation have found no effect on preeclampsia rates, and
dietary protein restriction does not appear to increase preeclampsia rates. [24] No mechanism by
which protein or calorie intake would affect either placentation or inflammation has been
proposed.

Studies conducted on the effect of supplementation with antioxidants such as vitamin C and E
found no change in pre-eclampsia rates.[25] However, Drs. Padayatty and Levine with the NIH
criticized the studies for overlooking several key factors that would have been important to the
success of the supplementation. Because plasma ascorbate concentrations were not reported, they
were estimated from known data, and the placebo and treatment groups in the study probably had
similar plasma and tissue ascorbate concentrations. Some of the smaller doses of 1 g per day
would have had little effect on plasma or intracellular ascorbate concentrations,[26] so the studies
should have been conducted with higher dosages of vitamin C in order for there to have been
any beneficial effects.

Low levels of vitamin D may be a risk factor for preeclampsia,[27] and calcium supplementation
in women with low-calcium diets found no change in preeclampsia rates but did find a decrease
in the rate of severe preeclamptic complications.[28] Low selenium status is associated with higher
incidence of pre-eclampsia.[29][30] Some other vitamin may also play a role.[31]

The late Dr. Thomas Brewer, OBGYN, believed in the role that diet can play in contributing to
pre-eclampsia, especially HELLP syndrome. Although Dr. Brewer's approach has been seen as
unconventional by western medicine because there is no evidence for it,[original research?] some
pregnancy practitioners adhere religiously to his recommendations.[citation needed] Women who
previously had pre-eclampsia or HELLP present anecdotes claiming that following Dr. Brewer's
guidelines has allowed them to go on to have healthy pregnancies, even in cases where their
physicians believed their pre-eclampsia could reoccur.[citation needed] Subsequent pregnancies are
known to be at lower risk of pre-eclampsia.[citation needed] The Brewer dietary theory is over 40 years
old but lacks peer-reviewed support; modern research provides no role for diet in placentation or
in tolerance induction.[citation needed]

[edit] Aspirin supplementation

Aspirin supplementation is still being evaluated as to dosage, timing, and population and may
provide a slight preventative benefit in some women; however, significant research has been
done on aspirin and the results thus far are unimpressive.[32]

[edit] Exercise

There is insufficient evidence to recommend either exercise[33] or bedrest[34] as preventative

measures.

[edit] Exposure to partner's semen

Continued exposure to a partner's semen has a strong protective effect against pre-eclampsia,
largely due to the absorption of several immune modulating factors present in seminal fluid.[35]
[36]

Long periods of sexual cohabitation with the same partner fathering a woman's child
significantly decreased her chances of suffering pre-eclampsia.[18] [36] As one early study
described, "although preeclampsia is a disease of first pregnancies, the protective effect of
multiparity is lost with change of partner." [37] 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 preeclampsia."[37]

Several other studies have since investigated the strongly 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,[38][39] with one study concluding that "induction of allogeneic tolerance to the paternal
HLA molecules of the fetus may be crucial. Data collected strongly suggests that exposure, and
especially oral exposure to soluble HLA from semen can lead to transplantation tolerance."[39]

Other studies have investigated the roles of semen in the female reproductive tracts of mice,
showing that "insemination elicits inflammatory changes in female reproductive tissues,"[40]
concluding that the changes "likely lead to immunological priming to paternal antigens or
influence pregnancy outcomes." A similar series of studies confirmed the importance of immune
modulation in female mice through the absorption of specific immune factors in semen,
including TGF-Beta, lack of which is also being investigated as a cause of miscarriage in women
and infertility in men.

According to the theory, the fetus both contain "foreign" proteins from paternal genes, but
regular, preceding and coincident exposure to the father's semen may promote immune
acceptance and subsequent implantation, a process which is significantly supported by as many
as 93 currently identified immune regulating factors in seminal fluid.[6][16]

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.[39][38][41][42][43][44] The researchers concluded that while any exposure to a partner's
semen during sexual activity appears to decrease a woman's chances for the various
immunological disorders that can occur during pregnancy, immunological tolerance could be
most quickly established through oral introduction and gastrointestinal absorption of semen.[39][41]
Recognizing that some of the studies potentially included the presence of confounding factors,
such as the possibility that women who regularly perform oral sex and swallow semen also
engage in more frequent intercourse, the researchers also noted that, either way, "the data still
overwhelmingly supports the main theory" behind all their studies--that repeated exposure to
semen establishes the maternal immunological tolerance necessary for a safe and successful
pregnancy.[36][41]

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
preeclampsia or miscarriage.[36] 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. [45]

[edit] Administration of immune factors

As the theory of immune intolerance as a cause of pre-eclampsia has become accepted, women
who suffer 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.[36]

In 2006, researchers at the University of Adelaide developed a gel containing TGF-Beta for use
in human populations.[46] Later, GroPep, the company which was awarded the patent on a TGF-
Beta3 variant, conducted trials where the miscarriage rate was halved in the mice studied.
According to a GroPep news release later published, "a faulty immune response is implicated in
the etiology of as many as 50% of all miscarriages."[47] Their drug, PV903, was "targeted to treat
recurrent miscarriages caused by an abnormal immune response to the foetus, a condition for
which there is no current [drug] treatment." [47] Stage I clinical trials of their vaginal gel were
partly successful, succeeding in establishing the safety of the drug, but failing in their aim of
increasing the number of specific immune cells measured in circulation, the necessary condition
for affecting a desired immunological desensitization.[47][48] The trials were later criticized for
failing to recognize the synergistic effects of a large variety of immune factors naturally present
in seminal fluid, which, acting together and with the localized presence of the foreign paternal
proteins, modulate the female immune response so as to allow for implantation, and then the
subsequent immune acceptance of the (foreign) fetus throughout a successful pregnancy. GroPep
was later acquired by the biotechnology giant, Novozymes. The development of the PV903 drug
has since then been placed on hold.

Preeclampsia

Definition
By Mayo Clinic staff

Preeclampsia is a condition of pregnancy marked by high blood pressure and excess protein in
your urine after 20 weeks of pregnancy. Preeclampsia often causes only modest increases in
blood pressure. Left untreated, however, preeclampsia can lead to serious — even fatal —
complications for both you and your baby.

If you have preeclampsia, the only cure is delivery of your baby. If you're diagnosed with
preeclampsia too early in your pregnancy for delivery to be an option, you and your doctor need
to allow your baby more time to mature, without putting you or your baby at risk of serious
complications.

Symptoms
By Mayo Clinic staff

Preeclampsia can develop gradually but often attacks suddenly, after 20 weeks of pregnancy.
Preeclampsia may range from mild to severe. If your blood pressure was normal before your
pregnancy, signs and symptoms of preeclampsia may include:

• High blood pressure (hypertension) — 140/90 millimeters of mercury (mm

Hg) or greater — documented on two occasions, at least six hours but no
more than seven days apart
• Excess protein in your urine (proteinuria)
• Severe headaches
• Changes in vision, including temporary loss of vision, blurred vision or light
sensitivity
• Upper abdominal pain, usually under your ribs on the right side
• Nausea or vomiting
• Dizziness
• Decreased urine output
• Sudden weight gain, typically more than 2 pounds (.9 kilograms) a week

Swelling (edema), particularly in your face and hands, often accompanies preeclampsia.
Swelling isn't considered a reliable sign of preeclampsia, however, because it also occurs in
many normal pregnancies.

When to see a doctor

Contact your doctor immediately or go to an emergency room if you have severe headaches,
blurred vision or severe pain in your abdomen.

Because headaches, nausea, and aches and pains are common pregnancy complaints, it's difficult
to know when new symptoms are simply part of being pregnant and when they may indicate a
serious problem — especially if it's your first pregnancy. If you're concerned about your
symptoms, contact your doctor.

Causes
By Mayo Clinic staff
Preeclampsia used to be called toxemia because it was thought to be caused by a toxin in a
pregnant woman's bloodstream. This theory has been discarded, but researchers have yet to
determine what causes preeclampsia. Possible causes may include:

• Insufficient blood flow to the uterus

• Damage to the blood vessels
• A problem with the immune system
• Poor diet

Other high blood pressure disorders during pregnancy

Preeclampsia is classified as one of four high blood pressure disorders that can occur during
pregnancy. The other three are:

• Gestational hypertension. Women with gestational hypertension have

high blood pressure, but no excess protein in their urine. Some women with
gestational hypertension eventually develop preeclampsia.
• Chronic hypertension. Chronic hypertension is high blood pressure that
appears before 20 weeks of pregnancy or lasts more than 12 weeks after
delivery. Usually, chronic hypertension was present — but not detected —
before pregnancy.
• Preeclampsia superimposed on chronic hypertension. This term
describes women who have chronic high blood pressure before pregnancy
and then develop worsening high blood pressure and protein in the urine
during pregnancy.

Risk factors
By Mayo Clinic staff

Preeclampsia develops only during pregnancy. Risk factors include:

• History of preeclampsia. A personal or family history of preeclampsia

increases your risk of developing the condition.
• First pregnancy. The risk of developing preeclampsia is highest during your
first pregnancy or your first pregnancy with a new partner.
• Age. The risk of preeclampsia is higher for pregnant women younger than 20
and older than 40.
• Obesity. The risk of preeclampsia is higher if you're obese.
• Multiple pregnancy. Preeclampsia is more common in women who are
carrying twins, triplets or other multiples.
• Prolonged interval between pregnancies. This seems to increase the risk
of preeclampsia.
• Gestational diabetes. Women who develop gestational diabetes have a
higher risk of developing preeclampsia as the pregnancy progresses.
• History of certain conditions. Having certain conditions before you
become pregnant — such as chronic high blood pressure, migraine
headaches, diabetes, kidney disease, rheumatoid arthritis or lupus —
increases the risk of preeclampsia.
Other associated factors
Other factors that may be associated with a higher risk of preeclampsia include:

• Having other health conditions. There's some evidence that both urinary
tract infections and periodontal disease during pregnancy are associated with
an increased risk of preeclampsia, which may indicate that antibiotics could
play a role in prevention of preeclampsia. More study is needed.
• Vitamin D insufficiency. There's also some evidence that insufficient
vitamin D intake increases the risk of preeclampsia, and that vitamin D
supplements in early pregnancy could play a role in prevention. More study is
needed.
• High levels of certain proteins. Pregnant women who had high levels of
certain proteins in their blood or urine have been found to be more likely to
develop preeclampsia than are other women. These proteins interfere with
the growth and function of blood vessels — lending evidence to the theory
that preeclampsia is caused by abnormalities in the blood vessels feeding the
placenta. Although more research is needed, the discovery suggests that a
blood or urine test may one day serve as an effective screening tool for
preeclampsia.

Complications
By Mayo Clinic staff

Most women with preeclampsia deliver healthy babies. The more severe your preeclampsia and
the earlier it occurs in your pregnancy, however, the greater the risks for you and your baby.
Preeclampsia may require induced labor and delivery by Caesarian section. Complications of
preeclampsia may include:

• Lack of blood flow to the placenta. Preeclampsia affects the arteries

carrying blood to the placenta. If the placenta doesn't get enough blood, your
baby may receive less oxygen and fewer nutrients. This can lead to slow
growth, low birth weight, preterm birth and breathing difficulties for your
baby.
• Placental abruption. Preeclampsia increases your risk of placental
abruption, in which the placenta separates from the inner wall of your uterus
before delivery. Severe abruption can cause heavy bleeding, which can be
life-threatening for both you and your baby.
• HELLP syndrome. HELLP — which stands for hemolysis (the destruction of
red blood cells), elevated liver enzymes and low platelet count — syndrome
can rapidly become life-threatening for both you and your baby. Symptoms of
HELLP syndrome include nausea and vomiting, headache, and upper right
abdominal pain. HELLP syndrome is particularly dangerous because it can
occur before signs or symptoms of preeclampsia appear.
• Eclampsia. When preeclampsia isn't controlled, eclampsia — which is
essentially preeclampsia plus seizures — can develop. Symptoms of
eclampsia include upper right abdominal pain, severe headache, vision
problems and change in mental status, such as decreased alertness.
Eclampsia can permanently damage your vital organs, including your brain,
 liver and kidneys. Left untreated, eclampsia can cause coma, brain damage
and death for both you and your baby.
• Cardiovascular disease. Having preeclampsia may increase your risk of
future cardiovascular disease.

Tests and diagnosis

By Mayo Clinic staff

Preeclampsia usually shows up during a routine prenatal blood pressure check and urine test. The
diagnosis depends on the presence of high blood pressure and protein in your urine after 20
weeks of pregnancy. Certain markers in your blood and urine may be indications of
preeclampsia. That's why it's essential to seek early and regular prenatal care throughout your
pregnancy.

A blood pressure reading in excess of 140/90 mm Hg clearly is abnormal in pregnancy.

However, a single high blood pressure reading doesn't mean you have preeclampsia. If you have
one reading in the abnormal range — or a reading that's substantially higher than your usual
blood pressure — your doctor will closely observe your numbers. You may also be asked to
come in for additional blood pressure readings and urinary protein measurements.

Additional tests
If you're diagnosed with preeclampsia, your doctor may recommend additional tests, including:

• Blood tests. These can determine how well your liver and kidneys are
functioning and whether your blood has a normal number of platelets — the
cells that help blood clot.
• Prolonged urine collection test. Urine samples taken over at least 12
hours and up to 24 hours can quantify how much protein is being lost in the
urine, an indication of the severity of preeclampsia.
• Fetal ultrasound. Your doctor may also recommend close monitoring of
your baby's growth, typically through ultrasound. This test directs high-
frequency sound waves at the tissues in your abdominal area. These sound
waves bounce off the curves and variations in your body, including your
baby. The sound waves are translated into a pattern of light and dark areas
— creating images of your baby on a monitor that can be recorded
electronically or on film for a look at the inside of your uterus.
• Nonstress test or biophysical profile. These make sure your baby is
getting enough oxygen and nourishment. A nonstress test is a simple
procedure that checks how your baby's heart rate reacts when your baby
moves. Your baby is doing fine if the heart rate increases at least 15 beats a
minute for at least 15 seconds twice in a 20-minute period. A biophysical
profile combines an ultrasound with a nonstress test to provide more
information about your baby's breathing, tone, movement and the volume of
amniotic fluid in your uterus.
Treatments and drugs
By Mayo Clinic staff

The only cure for preeclampsia is delivery. You're at increased risk of seizures, placental
abruption, stroke and possibly severe bleeding until your blood pressure decreases. Of course, if
it's too early in your pregnancy, delivery may not be the best thing for your baby.

If you've had preeclampsia in one or more previous pregnancies, some experts recommend more
frequent prenatal visits than normally recommended for pregnancy. Your doctor may ask you to
come in every two weeks between the 20th and 32nd week of your gestation, and weekly after
that until delivery.

Medications
Your doctor may recommend the following:

• Medications to lower blood pressure. These medications, called

antihypertensives, are used to lower your blood pressure until delivery.
• Corticosteroids. If you have severe preeclampsia or HELLP syndrome,
corticosteroid medications can temporarily improve liver and platelet
functioning to help prolong your pregnancy. Corticosteroids can also help
your baby's lungs become more mature in as little as 48 hours — an
important step in helping a premature baby prepare for life outside the
womb.
• Anticonvulsive medications. If your preeclampsia is severe, your doctor
may prescribe an anticonvulsive medication, such as magnesium sulfate, to
prevent a first seizure.

Bed rest
If you aren't near the end of your pregnancy and you have a mild case of preeclampsia, your
doctor may recommend bed rest to lower your blood pressure and increase blood flow to your
placenta, giving your baby time to mature. You may need to lie in bed, only sitting and standing
when necessary. Or you may be able to sit on the couch or in bed and strictly limit your
activities. Your doctor may want to see you a few times a week to check your blood pressure,
urine protein levels and your baby's well-being.

If you have more severe preeclampsia, you may need bed rest in the hospital. In the hospital, you
may have regular nonstress tests or biophysical profiles to monitor your baby's well-being and
measure the volume of amniotic fluid. A lack of amniotic fluid is a sign of poor blood supply to
the baby.

Delivery
If you're diagnosed with preeclampsia near the end of your pregnancy, your doctor may
recommend inducing labor right away. The readiness of your cervix — whether it's beginning to
open (dilate), thin (efface) and soften (ripen) — also may be a factor in determining whether or
when labor will be induced.
In more severe cases, it may not be possible to consider your baby's gestational age or the
readiness of your cervix. If it's not possible to wait, your doctor may induce labor or schedule a
C-section earlier in your pregnancy. During delivery, you may be given magnesium sulfate
intravenously to increase uterine blood flow and prevent seizures.

After delivery, expect your blood pressure to return to normal within a few weeks.

Prevention
By Mayo Clinic staff

There's no known way to prevent preeclampsia. Eating less salt or changing your activities
during pregnancy doesn't reduce the risk. The best way to take care of yourself — and your baby
— is to seek early and regular prenatal care. If preeclampsia is detected early, you and your
doctor can work together to prevent complications and make the best choices for you and your
baby.

There's some evidence that taking certain vitamins, such as vitamin D, may lower the risk of
preeclampsia. Ask your doctor what he or she recommends. Don't take anything during
pregnancy without your doctor's approval.