Pre-eclamptic toxaemia; PET; EPH gestosis; metabolic toxaemia of late pregnancy
Pre-eclampsia is a medical condition that occurs in around 5% of all pregnancies. Although the origins of pre-eclampsia are widely thought to lie in events of the first four to eight weeks of pregnancy, symptoms arise during mid to late pregnancy and typically include high blood pressure in the mother and protein in her urine. The more severe the pre-eclampsia, the greater the risks to the mother and baby. Mild pre-eclampsia can cause few symptoms; however, severe pre-eclampsia can lead to serious complications for the mother and baby with a risk of death.
Only 1 in 100 women with pre-eclampsia go on to develop full eclampsia – a type of seizure and a life-threatening complication of pre-eclampsia. In the UK, about six women and several hundred babies die each year as a result of complications arising from severe cases of the condition, but early diagnosis and treatment greatly reduce these risks. In developing countries, where early diagnosis and treatment are not readily available, maternal mortality rates due to pre-eclampsia are much higher.
Other rare problems that can occur as a result of the condition include stroke, placental bleeding (which can lead to small babies and risk of cutting off the blood supply to the baby during labour), lung, liver or kidney complications and problems with blood and liver cell function (known as HELLP syndrome) in the pregnant woman.
The cause of pre-eclampsia is unknown, but studies support a number of possible theories.
1. The mother having an immune response to the placenta in her womb. The mother’s immune system detects the ‘foreign’ placenta which is made up of 50% of the father’s genes and generates an inflammatory response in which a number of hormones and chemicals have been implicated.
2. The blood vessels in the mother’s womb (that take blood to the placenta) may not widen enough to allow essential oxygen and nutrients to reach the developing baby. This may be caused by changes in the normal levels of hormones that are needed to control the relaxation and contraction of blood vessels, such as angiotensin, adrenomedullin, thromboxin, endothelin-1 and prostacyclin, or by the vessels physically failing to widen in response to the pregnancy.
Studies have shown that the levels of growth factors that normally promote healthy blood vessel formation and maintenance, including placental growth factor and vascular endothelial growth factor, are reduced in women who develop pre-eclampsia. There may also be a link with the poor development of blood vessels within the placenta itself, which could prevent optimal nutrient transfer from the mother to the baby. There may also be a link to low protein levels in the mother’s diet leading to changes in angiotensin levels, which may result in reduced nutrient transfer and pre-eclampsia.
3. Another theory is that pre-existing autoimmune conditions may worsen or trigger the changes in the womb that lead to the development of pre-eclampsia. It is known that women with certain conditions (e.g. diabetes, high blood pressure, renal problems, antiphospholipid syndrome) are at an increased risk of developing pre-eclampsia.
It is likely that there are multiple causes of pre-eclampsia, which vary among individuals, but result in the similar set of symptoms that characterise this condition. Research to investigate all these possibilities is ongoing.
Symptoms of pre-eclampsia can start from 20 weeks of pregnancy but most commonly occurs from 32 weeks until 1 week after birth of the baby. In mild pre-eclampsia, there may be little or no symptoms and therefore screening during pregnancy is important to pick up the condition early. Women who think they are experiencing symptoms of pre-eclampsia should seek immediate medical advice for further investigation.
Women with pre-eclampsia have very high blood pressure as well as protein leaking from the kidneys into the urine. Individuals may find they experience severe headaches, blurred vision, stomach pain (normally on the upper right side of the abdomen), vomiting late on in pregnancy, and sudden swelling of the hands and feet (due to fluid retention). Women who have high blood pressure for the first time in pregnancy, without protein in their urine, are said to be suffering from ‘gestational high blood pressure’, rather than pre-eclampsia. Women with gestational high blood pressure should be followed up as some go on to develop pre-eclampsia.
Changes in the levels of various hormones have also been described in pre-eclampsia, including human chorionic gonadotrophin (hCG) and corticotrophin-releasing hormone (CRH), which are produced by the placenta and are seen increased in pre-eclampsia. Thyroid stimulating hormone (TSH) may also be increased, which may be linked to an increased risk of the mother developing hypothyroidism.
Signs of foetal distress can occur as a result of pre-eclampsia such as the baby being small for gestational age, a low volume of amniotic fluid surrounding the baby, and the baby becoming distressed either before or during labour.
Pre-eclampsia affects around 5% of all pregnancies worldwide. Women are considered at greater risk of developing pre-eclampsia if:
• it is their first pregnancy or it has been over 10 years since their last pregnancy,
• they have previously suffered from pre-eclampsia or they have a family history of pre-eclampsia (e.g. their mum or sister had pre-eclampsia), they have a high body mass index (BMI) of 35 or over (normal BMI is in the range 20 to 24.9),
• they have underlying medical conditions such as diabetes, kidney disease, some autoimmune diseases or high blood pressure before pregnancy,
• they are of black ethnic origin,
• they are aged over 40,
• they are expecting twins or triplets
• their baby was conceived by in vitro fertilisation (IVF)
Whilst the condition is not considered to be inherited, women are at higher risk if a close female relative, such as their mother or sister, have also been affected. Studies have not identified a genetic link with the condition but some research has shown that the father may also contribute to the risk of pre-eclampsia. This is because those men born from a pre-eclamptic pregnancy are more likely to father a child in a pregnancy that is also complicated by pre-eclampsia. Some men also seem to carry a higher risk of fathering a pre-eclamptic pregnancy than others.
Blood pressure is measured at routine midwife appointments throughout a pregnancy. Pre-eclampsia is diagnosed if a woman has high blood pressure (140/90 or higher) as well as protein in the urine after the 20th week of pregnancy. To confirm this, blood pressure should be measured on at least two separate occasions at least 4–6 hours apart; protein in the urine is normally tested using a single dipstick test or by collecting urine over a 24-hour period. Some new tests (e.g. placental growth factor, PLGF) are being studied to determine if they can help rule out pre-eclampsia.
The current challenge for the medical community is to improve methods of identifying those at a higher risk of developing pre-eclampsia early on in pregnancy and then potentially provide preventative treatments. Currently, doctors rely on measurements of blood flow in the arteries of the womb using a Doppler ultrasound; this is one method of predicting the condition, as women with poor blood flow are more than six times more likely to develop pre-eclampsia. However, the method used to make this measurement is found to be inaccurate at predicting this disorder, and it is not considered useful for routine screening of all pregnant women, only for those already considered at high risk. An alternative approach is the analysis of certain markers in the blood and urine (such as urocortin, anandamide and angiotensin II) early in pregnancy that could predict which women are most likely to develop the condition later on. Further research is needed in this area before such tests are used routinely to predict pre-eclampsia.
Treatment for pre-eclampsia aims to prevent development of full eclampsia and the other complications listed above. At present, the only complete cure for pre-eclampsia is to deliver the baby and placenta (which is thought to be linked to the cause of the condition). This occurs either by inducing labour, or by caesarean section. After delivery, the mother’s blood pressure usually returns to normal. This method is appropriate when pre-eclampsia arises late in pregnancy, but if the condition occurs earlier on in pregnancy, further problems can arise for the prematurely delivered baby. In such cases, several factors would be considered, including the severity of the condition and how it is affecting the baby, and what impact early delivery would have.
• medication to reduce maternal blood pressure
• steroids to help the baby’s lungs mature, should early delivery be a possibility
• magnesium sulphate could be given, which is thought to reduce the likelihood of the mother developing eclamptic fits.
Approaches to prevent the condition from developing in women that are considered at high risk are currently very limited, and studies have reported very mixed results. Research however has shown that treatment of women at high risk with low-dose aspirin throughout pregnancy can reduce the risk of pre-eclampsia. Other ongoing research continues to determine whether factors such as exercise, weight management and use of antioxidants could help reduce the risk. Monitoring of blood pressure and foetal growth during pregnancy is very important.
Early delivery of the baby further on in pregnancy (from 34 weeks) rarely causes further complications; however, if the baby is less than 32 weeks, his or her lungs may not yet be mature enough, and they can experience longer-term health complications associated with being born prematurely. Premature babies (born before the 37th week of pregnancy) may need to stay in a neonatal intensive care unit, which aims to replicate the conditions inside the mother’s womb while the baby develops fully.
In the majority of cases, pre-eclampsia is treated effectively and both the mother’s and baby’s long-term health is unaffected. Continued monitoring of blood pressure and urine samples at postnatal appointments is very important to ensure they return to normal levels. Pre-eclampsia may be associated with a higher risk of affected women developing cardiovascular problems, such a coronary-artery disease or stroke, later on in life. The risk of developing these conditions may, however, be reduced by various life-style changes, including regular exercise, maintaining a healthy weight, eating a balanced diet and not smoking.
In some cases of pre-eclampsia there is poor blood flow to the placenta, which means the baby does not receive all the nutrients it needs to develop fully. This can lead to the baby not growing as large as it should – a condition known as foetal growth restriction. This can result in various problems after the baby is born and later in adult life, as it makes an individual more likely to develop cardiovascular problems and diabetes.
Last reviewed: Mar 2021
