Pre-eclampsia refers to new high blood pressure (hypertension) in pregnancy with end-organ dysfunction, notably with proteinuria (protein in the urine). It occurs after 20 weeks gestation, when the spiral arteries of the placenta form abnormally, leading to a high vascular resistance in these vessels.
Pre-eclampsia is a significant cause of maternal and fetal morbidity and mortality. Without treatment, it can lead to maternal organ damage, fetal growth restriction, seizures, early labour and in a small proportion, death.
Pre-eclampsia features a triad of:
Chronic hypertension is high blood pressure that exists before 20 weeks gestation and is longstanding. This is not caused by dysfunction in the placenta and is not classed as pre-eclampsia.
Pregnancy-induced hypertension or gestational hypertension is hypertension occurring after 20 weeks gestation, without proteinuria.
Pre-eclampsia is pregnancy-induced hypertension associated with organ damage, notably proteinuria.
Eclampsia is when seizures occur as a result of pre-eclampsia.
The pathophysiology of pre-eclampsia is poorly understood. The following is a simplified explanation.
When the blastocyst implants on the endometrium, the outermost layer, called the syncytiotrophoblast, grows into the endometrium. It forms finger-like projections called chorionic villi. The chorionic villi contain fetal blood vessels.
Trophoblast invasion of the endometrium sends signals to the spiral arteries in that area of the endometrium, reducing their vascular resistance and making them more fragile. The blood flow to these arteries increases, and eventually they break down, leaving pools of blood called lacunae (lakes). Maternal blood flows from the uterine arteries, into these lacunae, and back out through the uterine veins. Lacunae form at around 20 weeks gestation.
When the process of forming lacunae is inadequate, the woman can develop pre-eclampsia. Pre-eclampsia is caused by high vascular resistance in the spiral arteries and poor perfusion of the placenta. This causes oxidative stress in the placenta, and the release of inflammatory chemicals into the systemic circulation, leading to systemic inflammation and impaired endothelial function in the blood vessels.
The NICE guidelines categorise the risk factors into high-risk and moderate-risk factors.
High-risk factors are:
- Pre-existing hypertension
- Previous hypertension in pregnancy
- Existing autoimmune conditions (e.g. systemic lupus erythematosus)
- Chronic kidney disease
Moderate-risk factors are:
- Older than 40
- BMI > 35
- More than 10 years since previous pregnancy
- Multiple pregnancy
- First pregnancy
- Family history of pre-eclampsia
These risk factors are used to determine which women are offered aspirin as prophylaxis against pre-eclampsia. Women are offered aspirin from 12 weeks gestation until birth if they have one high-risk factor or more than one moderate-risk factors.
Pre-eclampsia has symptoms of the complications:
- Visual disturbance or blurriness
- Nausea and vomiting
- Upper abdominal or epigastric pain (this is due to liver swelling)
- Reduced urine output
- Brisk reflexes
The NICE guidelines (2019) advise a diagnosis can be made with a:
- Systolic blood pressure above 140 mmHg
- Diastolic blood pressure above 90 mmHg
PLUS any of:
- Proteinuria (1+ or more on urine dipstick)
- Organ dysfunction (e.g. raised creatinine, elevated liver enzymes, seizures, thrombocytopenia or haemolytic anaemia)
- Placental dysfunction (e.g. fetal growth restriction or abnormal Doppler studies)
Proteinuria can be quantified using:
- Urine protein:creatinine ratio (above 30mg/mmol is significant)
- Urine albumin:creatinine ratio (above 8mg/mmol is significant)
The NICE guidelines (2019) recommend the use of placental growth factor (PlGF) testing on one occasion during pregnancy in women suspected of having pre-eclampsia. Placental growth factor is a protein released by the placenta that functions to stimulate the development of new blood vessels. In pre-eclampsia, the levels of PlGF are low. NICE recommends using PlGF between 20 and 35 weeks gestation to rule-out pre-eclampsia.
Aspirin is used for prophylaxis against the development of pre-eclampsia. It is given from 12 weeks gestation until birth to women with:
- A single high-risk factor
- Two or more moderate-risk factors
All pregnant women are routinely monitored at every antenatal appointment for evidence of pre-eclampsia, with:
- Blood pressure
- Urine dipstick for proteinuria
When gestational hypertension (without proteinuria) is identified, the general management involves:
- Treating to aim for a blood pressure below 135/85 mmHg
- Admission for women with a blood pressure above 160/110 mmHg
- Urine dipstick testing at least weekly
- Monitoring of blood tests weekly (full blood count, liver enzymes and renal profile)
- Monitoring fetal growth by serial growth scans
- PlGF testing on one occasion
When pre-eclampsia is diagnosed, the general management is similar to gestational hypertension, except:
- Scoring systems are used to determine whether to admit the woman (fullPIERS or PREP‑S)
- Blood pressure is monitored closely (at least every 48 hours)
- Urine dipstick testing is not routinely necessary (the diagnosis is already made)
- Ultrasound monitoring of the fetus, amniotic fluid and dopplers is performed two weekly
Medical management of pre-eclampsia is with:
- Labetolol is first-line as an antihypertensive
- Nifedipine (modified-release) is commonly used second-line
- Methyldopa is used third-line (needs to be stopped within two days of birth)
- Intravenous hydralazine may be used as an antihypertensive in critical care in severe pre-eclampsia or eclampsia
- IV magnesium sulphate is given during labour and in the 24 hours afterwards to prevent seizures
- Fluid restriction is used during labour in severe pre-eclampsia or eclampsia, to avoid fluid overload
Planned early birth may be necessary if the blood pressure cannot be controlled or complications occur. Corticosteroids should be given to women having a premature birth to help mature the fetal lungs.
Blood pressure is monitored closely after delivery. Blood pressure will return to normal over time once the placenta is removed.
For medical treatment, NICE recommend after delivery switching to one or a combination of:
- Enalapril (first-line)
- Nifedipine or amlodipine (first-line in black African or Caribbean patients)
- Labetolol or atenolol (third-line)
Eclampsia refers to the seizures associated with pre-eclampsia. IV magnesium sulphate is used to manage seizures associated with pre-eclampsia.
HELLP syndrome is a combination of features that occurs as a complication of pre-eclampsia and eclampsia. It is an acronym for the key characteristics:
- Elevated Liver enzymes
- Low Platelets
Last updated September 2020