Gestational proteinuric hypertension

Definition

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.

Alternative names

Pre-eclampsia

Cause

The exact cause of pre-eclampsia is not known but the problems seem to originate from the placenta (afterbirth). Amongst other things, the disease affects the blood vessels of a 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, until the vessels are so narrow that they cannot be seen with the naked eye. 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 of the arteries is lined by a thin layer called the endothelium. The walls of capillaries are made up solely of endothelium. The body has a large number of endothelial cells. If they could all be put together as one tissue organ, this organ would be the size of the liver. In pre-eclampsia, the endothelial cells become sick (endotheliosis). Within the walls of the arteries is a layer of muscle which controls the diameter of the arteries. Chemicals released by damaged endothelial cells cause this muscle layer to contract, causing the arteries to become narrower. This narrowing of the arteries, called vasoconstriction, causes high blood pressure or hypertension.

Protein leakage

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 in the bloodstream are kept back and are not normally passed into the urine. If the kidney function is affected by pre-eclampsia, proteins will leak through the kidney tissue and appear in the urine.

Fluid leakage

Due to damage, the endothelial cells become permeable, meaning 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, because fluid is lost. 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 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. The factors that reduce blood flow are: the narrowed arteries (vasoconstriction), the decrease in blood volume, increased blood viscosity and blood clots within the vessels.

Oedema

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 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 that pre-eclampsia has developed.

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?

Pre-eclampsia is more likely to occur 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 (
• Have diabetes, vascular disease (a disease of the blood vessels), chronic kidney disease or a history of high blood pressure.
• Are daughters or sisters of women who have had pre-eclampsia.
• Have a multiple pregnancy - that is, twins, triplets and so on.

Symptoms and signs

Most women will be asymptomatic to begin with. However, headaches and blurred vision may develop. A rise in blood pressure is usually the first sign of pre-eclampsia to be found at the antenatal clinic. A urine test will detect proteins. This is referred to as proteinuria. Swelling (oedema) of the feet, legs, hands, arms or face may also be present but not always. Sometimes, oedema can cause rapid weight gain.

Depending on the severity, pre-eclampsia may have effects on the different body organs which are described below.

The kidneys

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.

The liver

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).

The lungs

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 brain

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

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.

Diagnosis

The measurement of blood pressure plays a central role in the diagnosis of pre-eclampsia. 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. Blood pressure is greatest at the moment of contraction of the heart, when blood is forced out of the heart into the arteries. After contracting, the muscular walls of the heart relax, allowing blood to refill the heart. Blood pressure falls to a lower (diastolic) level while the heart refills, then rises to the upper (systolic) level again upon contraction of the refilled heart.

Blood pressure is measured in units known as millimetres of mercury, abbreviated as mm Hg. 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 170/110 mm Hg.

High blood pressure alone is not sufficient for the diagnosis of pre-eclampsia to be made. Pre-eclampsia is diagnosed when a pregnant woman is found to have high blood pressure (greater than 140/90 mm Hg) as well as protein in her urine (more than 0.3 grams/24 hours).

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.

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:

• Measuring bloodflow through the umbilical cord to the placenta with a Doppler flow velocimetry ultrasound machine. This will measure the function of the placenta.
• Determining the size and condition of the foetus with ultrasound.
• Monitoring the foetal heart beat. This is done with a cardiotocograph machine in order to detect signs of foetal distress.

Prevention

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, fish oil, calcium or vitamin 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.

Treatment

Mild pre-eclampsia usually does not require treatment, only strict surveillance.

Under certain conditions 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.

Outcome

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 the mother. Wise management with correct timing of the delivery, will however decrease these risks significantly.

Therefore, when good medical care is available, however, the most likely outcome of pre-eclampsia is the survival of the baby and the complete recovery of the mother.

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 if you should 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.

Reviewed by Prof D.Hall, Tygerberg Hospital and Stellenbosch University