Pre-eclampsia is a pregnancy-specific disease defined as new development of hypertension (raised blood pressure), accompanied by substantial proteinuria (proteins in the urine) in the second half of pregnancy (at, or after 20 weeks’ gestation).
Pre-eclampsia forms part of hypertensive disorders in pregnancy and complicates about 2-8% of pregnancies.
It is more common in first pregnancies or first pregnancies from a new partner after a short (< six month) period of unprotected (without a condom) intercourse.
The first sign of the disease is usually high blood pressure. If the disease advances, it can lead to multi-organ dysfunction in the mother, and can slow down the growth of her baby. In such cases, the woman is hospitalised for observation and treatment.
In severe cases, pre-eclampsia may be complicated by eclampsia, a condition in which the woman suffers from convulsions.
In the absence of treatment, there is a high likelihood that the disease will lead to severe complications. Hypertensive (high blood pressure) diseases in pregnancy (including pre-eclampsia) are the most important direct (pregnancy-related) causes of death amongst mothers in South Africa. Treatment significantly reduces the incidence of severe illness and fatalities.
It is important to note that in most cases the mother’s health recovers after the birth of her baby. For this reason earlier delivery is often indicated. The interests of both the mother (dangers of organ dysfunction) and the baby (dangers of premature delivery) must however be balanced.
In the past, pre-eclampsia was called pre-eclamptic toxaemia (PET) and gestational proteinuric hypertension.
What are pre-eclampsia and eclampsia?
Pre-eclampsia is a disease that occurs as a complication of pregnancy. It may appear at any stage after the twentieth week of pregnancy. The first sign of the disorder is usually high blood pressure. If the condition progresses, it can cause damage to many of the pregnant woman’s organs, and can restrict the growth of the unborn baby. In severe pre-eclampsia detachment of the afterbirth (placenta) may also occur with severe consequences for both mother and baby.
If not managed correctly, severe pre-eclampsia can progress to brain swelling, leading to a convulsion (fit or seizure). This complication of pre-eclampsia is called eclampsia. Other organs may also be affected in complicated cases, such as kidney failure or heart failure.
What causes pre-eclampsia and eclampsia?
Although the exact cause of pre-eclampsia remains mainly unknown, the leading theory relies on the disturbed placental (afterbirth) function in early pregnancy. This ‘first stage’ of the disease of placental dysfunction is usually followed by a ‘second stage’ of systemic (the whole body) disease in the mother, where the body reacts to this disease with an excessive inflammatory reaction. This response precedes the onset of the classical symptomatic clinical disease.
Amongst other things, the disease affects the blood vessels of the pregnant woman. Arteries carry oxygen-rich blood away from the heart to all the tissues and organs of the body. Large arteries branch into smaller and smaller arteries. These tiny tubules are called capillaries. The changes in the arteries and capillaries that occur in pre-eclampsia, and the effects these changes have, are explained below.
Narrowing of the arteries
The internal surface (walls) of the arteries is lined by a thin layer called the endothelium. The body has a large number of endothelial cells, put together as one tissue-organ, this organ would be the size of the liver. In pre-eclampsia, the endothelial cells become sick (endotheliosis) and leak. Within the walls of the arteries there is a layer of muscle, which controls the diameter (size) of the arteries. Chemicals released by damaged endothelial cells cause this muscle layer to contract, causing the arteries to become narrower (vasoconstriction) causing high blood pressure (hypertension).
The function of the kidneys is to act as a filter during the production of urine while the blood passes through both kidneys. Proteins, which are present in the bloodstream, are kept back and are not normally passed into the urine. In pre-eclampsia the systematic inflammation also affects the kidneys, i.e. the filter (glomerulus) of the kidney starts to loose its function and causes proteins to appear in the urine.
Due to damage, the endothelial cells become permeable, which means that substances can diffuse through the cells. As a result, fluid leaks out of the blood vessels into the surrounding tissue. This lowers the volume of blood circulating within the blood vessels and leads to the blood becoming thicker, due to loss of fluid. The loss of fluid from the blood also causes swelling of the tissues into which it leaks. This type of swelling is referred to as oedema. Oedema may occur in all the soft tissues of the body, including organs such as the liver, lungs and brain.
Clotting within blood vessels
The damaged cells of the endothelium can release chemicals that cause blood to clot (coagulation). As a result, blood clots form on the walls of damaged vessels. To prevent clot occlusion of blood vessels in the rest of the circulation, the clotting process is counteracted by the activation of a process called fibrinolysis in which clots are dissolved as they form. In severe cases of pre-eclampsia, clotting (coagulation) and fibrinolysis may lead to a condition called disseminated intravascular coagulopathy (DIC), which can exhaust the clotting ability throughout the body, leading to uncontrollable bleeding (haemorrhage).
Clots are built up from proteins and cells in the blood, called platelets. If clotting and fibrinolysis deplete the available platelets before new ones are made, the level of platelets circulating freely in the blood will fall. This condition is known as thrombocytopenia.
Combined effects of these changes
Reduced blood flow
High blood pressure normally increases the rate at which blood flows through the circulatory system. However, a number of other factors work together to decrease the flow of blood [the narrowed arteries (vasoconstriction), the decrease in blood volume, increased blood viscosity and blood clots within the vessels.] The effect of these combined factors outweighs the effect of increased blood pressure. Consequently, blood flow to the tissues and organs of the body is diminished. .
Oedema, caused by damaged endothelium, is made worse by the high blood pressure. However, oedema is not always present in patients with pre-eclampsia, and the absence of oedema does not rule out the possibility that the disease may become severe. It should be remembered that oedema is very common in uncomplicated pregnancies. Thus the mere presence of oedema does not automatically imply the presence of pre-eclampsia.
Destruction of red blood cells
In severe pre-eclampsia, a combination of factors may lead to another complication, namely, the destruction of red blood cells. This process, referred to as haemolysis, reduces the number of red blood cells, which, in turn, reduces the amount of oxygen that can be carried in the blood.
The effect on the mother’s organs
Hypertension with reduced blood flow and decreased oxygen levels in the blood can cause a number of the pregnant woman’s organs, and the placenta, to malfunction. The placenta is a temporary organ of foetal origin that develops inside the uterus (womb) after a woman becomes pregnant. It supplies the foetus (the developing baby) with oxygen and nutrients, and removes waste products produced by the foetus.
Who is at risk?
It is hard to predict who will develop pre-eclampsia but pre-eclampsia is more likely in women who:
Have had pre-eclampsia in a previous pregnancy
Live in a developing country
Are pregnant for the first time; or have been pregnant before, but have become pregnant with a new partner after a short (< six months) period of unprotected (without a condom) intercourse.
Have medical problems such as diabetes, vascular disease (blood vessel disease), kidney disease or a history of high blood pressure
Are daughters or sisters of women who have had pre-eclampsia
Are expecting more than one baby - that is, twins, triplets etc.
Have a body mass index (BMI) of 35 or more
Are aged 40 or over.
What are the symptoms of pre-eclampsia and eclampsia?
Most women will not ‘feel’ sick and will be asymptomatic to begin with, thus checking the blood pressure and urinary protein is of vital importance. Some women may feel tired, have headaches or oedema (swelling) of the legs, arms and even face. Varying visual symptoms (spots, flashes even blurred or double vision) may also occur.
A rise in blood pressure is usually the first sign of pre-eclampsia to be found at the antenatal clinic. Blood pressure measurements are recorded as two separate numbers. The reason for this is that the pressure within the arteries constantly fluctuates between a higher and a lower value. Firstly blood pressure is greatest at the moment of contraction of the heart (systolic level), when blood is forced out of the heart into the arteries. Then after contracting, the muscular walls of the heart relax, allowing blood to refill the heart. Thus blood pressure falls to a lower (diastolic) level while the heart refills. Blood pressure is measured in units known as millimetres of mercury, abbreviated as mmHg.
Normal blood pressure is about 120/80 mmHg. In mild pre-eclampsia, blood pressure rises to levels above 140/90 mm Hg, while in severe cases blood pressure exceeds 160/110 mm Hg. Depending on the severity, pre-eclampsia may have effects on the different body organs, which are described below.
The kidneys contain specialised capillaries that filter out water and waste products from the blood, leading to the production of urine. Normally, the kidneys prevent the passage of proteins into the urine. Due to the damage that occurs to the kidney tissue, however, proteins pass into the urine, which can be detected with a simple urine test. In severe cases, the amount of protein leakage is increased and kidney function is reduced.
Liver cells produce enzymes, which control the chemical reactions that take place within the cells. In severe pre-eclampsia, dysfunction of the liver can occur and liver cells may become damaged, which allows the enzymes they contain to leak into the bloodstream.
Swelling of the liver causes abdominal pain on the right side of the body, just below the ribs, while impairment of liver function may cause nausea, vomiting, fatigue, and malaise (a feeling of being generally unwell).
Oedema of the lungs decreases their capacity to expand and contract, and so reduces the efficiency with which the lungs function. In addition, fluid leaks out of the capillaries and into the internal surfaces of the lungs. This accumulated fluid within the lungs further decreases their function.
Oedema of the lungs causes shortness of breath. The heart rate may also increase in response to the reduced level of oxygen in the blood.
The combination of reduced blood flow and oedema within the brain can cause a number of symptoms, including headache, dizziness, confusion and blurred vision. In severe cases, convulsions (eclampsia) can occur.
Eclamptic convulsions can result in coma if not treated adequately.
One of the risks associated with very high blood pressure is that of bleeding into the brain. This has serious, sometimes fatal, consequences.
The placenta is attached to the wall of the uterus. The foetus is connected to the placenta by the umbilical cord. In patients with pre-eclampsia, the placenta may function poorly causing reduced blood flow inside the placenta. This decreases the supply of oxygen and nutrients to the foetus, and also reduces the rate at which waste products produced by the foetus are removed. The condition is called placental insufficiency. It inhibits the growth of the foetus, referred to as intra-uterine growth restriction (IUGR). IUGR can place the foetus under stress and, if not delivered in time, may lead to the intra-uterine death of the baby.
The changes in the placental tissue and its attachment to the womb can also cause the placenta to become separated from the wall of the uterus. This condition is known as abruptio placentae. Detachment of the placenta can cause vaginal bleeding, and poses a life-threatening risk to the foetus as well as a significant risk to the mother.
How is pre-eclampsia diagnosed?
The diagnosis of pre-eclampsia is largely based upon the characteristic hypertension (blood pressure greater than 140/90 mm Hg) as well as protein in the urine (more than 0.3 grams/24 hours) in a woman who was previously had normal blood pressures.
Additional factors must sometimes be considered due to the fact that high blood pressure alone is not sufficient for the diagnosis of pre-eclampsia to be made.
Additional factors in diagnosis
In normal pregnancy, 80% of women experience swelling of the feet, and sometimes of the hands. Oedema can play a role in the suspected diagnosis of pre-eclampsia, but only if swelling is severe and occurs additionally over the sacrum (back), arms and/or face.
In mild pre-eclampsia, there is usually little evidence of organ dysfunction. In severe cases, however, significant organ malfunction can occur, causing symptoms such as headache, abdominal pain, blurred vision, nausea and vomiting. Recognition of these symptoms plays an important role in the diagnosis of severe pre-eclampsia.
Blood and urine tests are used to assess the extent and severity of the disease and to reveal the degree of impaired kidney function. Blood tests provide important diagnostic information, including the following:
Low red blood cell levels indicate the occurrence of haemolysis (destruction of red blood cells).
Low platelet levels reveal consumption due to clotting.
Raised levels of liver enzymes in the blood are a sign of liver impairment.
If blood tests reveal low levels of red blood cells and platelets, as well as high levels of liver enzymes, then a pregnant woman is said to have HELLP syndrome (Haemolysis, Elevated Liver Enzymes, Low Platelets). HELLP syndrome is a complication of severe pre-eclampsia. HELLP syndrome complicates 10 - 20% of cases of severe pre-eclampsia and is associated with significant complications in the mother and the foetus.
Assessment of the health of the foetus
Tests that give an indication of the growth and health of the foetus play an important role in assessing the severity of pre-eclampsia. A number of investigations may be performed, such as:
Determining the size (growth) and condition of the foetus with ultrasound.
Measuring bloodflow through the umbilical cord to the placenta with a Doppler flow velocimetry ultrasound machine. This will measure the function of the placenta.
Monitoring the foetal heart patterns. This is done with a cardiotocograph machine in order to detect early signs of foetal concern.
Can pre-eclampsia be prevented?
A good understanding has been achieved of the changes that occur in a pregnant woman’s blood vessels that lead to the development of pre-eclampsia. However, the underlying cause of these changes is not fully understood. As a result, it has not been possible to develop medications that can prevent pre-eclampsia.
Nevertheless, some options are available. These include taking low doses of aspirin and calcium supplements in selected patients. Currently, only a woman who has had pre-eclampsia in a previous pregnancy should consider such preventative measures after discussion with her doctor.
When planning a pregnancy, the value of unprotected intercourse for less than six months before the first pregnancy, or the first pregnancy with a new partner has been noted. Of course the HIV status of the partners has to be taken into account under these circumstances. Partners should always know their HIV status and act appropriately.
How are pre-eclampsia and eclampsia treated?
Mild pre-eclampsia usually does not require treatment, only strict surveillance.
Under certain conditions (early gestation of less than 34 weeks) or if severe pre-eclampsia develops, admission to hospital will be required, so that the woman's condition and that of her foetus can be carefully evaluated and closely monitored.
If the blood pressure rises above 160/110 mm Hg, medication to lower blood pressure should be given. Such medications are referred to as antihypertensives. Antihypertensives are generally not given if blood pressure is only moderately high, because lowering blood pressure may decrease bloodflow to the placenta. Very high blood pressure, though, poses a serious risk to the mother and her foetus, and requires treatment. In selected cases, treatment with antihypertensives allows valuable time to be gained for the foetus to mature further. This reduces the risks associated with prematurity due to an early delivery.
Should symptoms such as headache, confusion and blurred vision appear, anticonvulsant medication (magnesium sulphate) will be given in order to prevent the occurrence of eclampsia. Women with severe pre-eclampsia should be placed in a high care unit, where medical intervention can be rapidly provided if necessary. Without such surveillance, foetal distress and maternal complications can lead to a poor outcome and even death of the baby and even the mother.
As a result of the risks posed by pre-eclampsia, preterm delivery of the baby (that is, delivery before the 38th week of pregnancy) is often necessary. Babies born under these circumstances are vulnerable, and require special care.
In order for a decision to be taken on the timing of delivery, ongoing assessments must be made of the condition of both the mother and the baby. The baby should be delivered if the mother’s condition threatens to progress to complications, or when it is judged that the chances of the baby surviving satisfactorily outside the womb are sufficient. If complications such as convulsions occur, the baby must be delivered as soon as the mother’s condition has been stabilised.
Babies delivered before 32 weeks of pregnancy are more frequently delivered by caesarean section but the method of delivery will depend on the condition of the mother and baby.
There is a risk that convulsions may occur even after the delivery. For this reason, careful assessment and monitoring of the mother’s condition must continue during this period.
What is the outcome of pre-eclampsia and eclampsia?
Pre-eclampsia is a complex disease that can lead to many serious complications of pregnancy. Even when properly managed, there is the risk of a poor outcome for the baby and even for the mother. Wise management with correct timing of the delivery will however decrease these risks significantly.
Therefore, when good medical care is available, the most likely outcome of pre-eclampsia is the survival of the baby and the complete recovery of the mother.
Even after a successful delivery with a good outcome it is important to realise that there is a significant risk of recurrence (depending of the severity and time of onset of their pre-eclampsia) in subsequent pregnancies, as well as long-term maternal health risks. These women should always plan their subsequent pregnancies carefully and go for preconceptional counselling at their local health centres.
When to call the doctor?
If you are pregnant, you should go for regular check-up visits, during which your blood pressure will be measured and your urine tested. This will ensure that, should you develop pre-eclampsia, it will be detected early and managed correctly.
If, however, you suddenly develop any of the symptoms discussed in this article, you should visit your doctor or gynaecologist immediately.
Previously reviewed by Prof D.Hall, Dept of Obstetrics & Gynaecology, Tygerberg Hospital and Faculty of Health Sciences, Stellenbosch University
Reviewed by Dr JL van der Merwe, Dept of Obstetrics & Gynaecology, Tygerberg Hospital and Faculty of Health Sciences, Stellenbosch University, (November 2010)