Pre-eclampsia
Definition
A hypertensive syndrome that occurs in pregnant women after 20 weeks' gestation
New-onset, persistent hypertension (defined as a BP of ≥140 mmHg systolic and/or ≥90 mmHg diastolic, based on at least 2 measurements taken at least 4 hours apart)
With proteinuria (defined as urinary excretion of ≥0.3 g protein/24 hours). [1] [2] [3]
The severity of the condition is based on the BP measurement and the presence of systemic involvement. [1] [2] [3]
Risk Factors
Strong
Primiparity
Pre-eclampsia in previous pregnancy
Family history of pre-eclampsia
Body mass index >30
Maternal age >35 years
Multiple (twin) pregnancy
Gestational hypertension
Pre-gestational diabetes
Autoimmune disease
Renal disease
Chronic hypertension
Weak
BP ≥80 mmHg diastolic at booking
Interval of 10 years or more since previous pregnancy
Differential diagnosis
Epidemiology
Pre-eclampsia has been reported to occur in about 5% to 8% of all pregnancies in the US. [3]
When figures include patients who develop pre-eclampsia postpartum, the incidence is between 4% to 6% of all pregnancies throughout the world. [4] [5]
The incidence of severe disease and complications varies.
Severe disease, which is associated with an increased risk of morbidity and mortality, has an incidence of only 0.5% in the developed world, [6]
Rises to 1% in low-income countries. [5]
Similarly, the incidence of complications such as eclampsia is also variable.
In the UK, the incidence has decreased from 4.9 per 10,000 per year in 1992 [7] to 3.89 per 10,000 per year by 2000. [5]
This decrease is observed mostly in the intrapartum and postpartum groups, suggesting a possible beneficial effect of prophylactic magnesium sulphate. [5]
However, in low-income countries the incidence of eclampsia is 10-fold greater, at about 50 per 10,000 per year. [6]
Aetiology
Pre-eclampsia is associated with a failure of normal invasion of trophoblast cells leading to maladaptation of maternal spiral arterioles
Associated with hyperplacentation disorders such as diabetes, hydatidiform mole, and multiple pregnancy. [8]
There are numerous risk factors that increase the probability and severity
However, these risk factors do not account for all cases
Complications such as eclampsia, HELLP syndrome, and fetal growth restriction are not present in all patients.
HELLP is a subtype of severe pre-eclampsia characterised by haemolysis (H), elevated liver enzymes (EL), and low platelets (LP)
Clinical features
Common
>20 weeks' gestation
BP ≥140 mmHg systolic and/or ≥90 mmHg diastolic and previously normotensive
headache
upper abdominal pain
reduced fetal movement
fetal growth restriction
oedema
Uncommon
visual disturbances
seizures
breathlessness
oliguria
hyper-reflexia and/or clonus
Pathophysiology
Pre-eclampsia is associated with a failure of the normal invasion of trophoblast cells leading to maladaptation of maternal spiral arterioles. [8]
The maternal arterioles are the source of blood supply to the fetus.
Maladaptation of these vessels can interfere with normal villous development leading to placental insufficiency and fetal growth restriction.
Abnormalities of spiral artery adaptation are immunologically based, with genetic influences. [4] [8]
Not all women with this potential placental trigger develop the syndrome
Therefore, the maternal response must be the decisive factor in development of systemic disease.
This systemic maternal response is what manifests itself as pre-eclampsia. [4]
Clinically, pre-eclampsia does not manifest until after 20 weeks' gestation.
However, more recent studies suggest that preclinical changes may occur, suggested by the presence of various biomarkers, although none are currently used in routine clinical practice. [4]
Hypertension and proteinuria are due to the vascular inflammatory response that produces vasoconstriction and capillary leak. [4]
Other presentations are complications of the vascular inflammation and capillary leak
eclampsia (due to cerebral vascular dysregulation and oedema)
HELLP syndrome (due to liver vascular dysregulation and oedema causing abdominal pain)
pulmonary oedema (due to capillary leak).
Investigations
urinalysis
1+ protein; urinary excretion of ≥0.3 g protein in 24 hours; or urine protein:creatinine ratio ≥30 mg/mmol
fetal ultrasound
variable depending on severity
fetal cardiotocography
no abnormalities in tracing indicate assured fetal wellbeing
fetal biometry
may reveal fetal growth restriction
umbilical artery Doppler velocimetry
absence of end diastolic flow is a sign that delivery will probably be necessary in the near future
amniotic fluid assessment
deepest vertical pocket ≥2 cm implies normality; <2 cm is associated with increased fetal morbidity and delivery should be considered
FBC
low platelet count is partly diagnostic for HELLP syndrome
LFTs
Increased transaminase levels are partly diagnostic for HELLP syndrome.
Serum creatinine
Elevated serum creatinine implies underlying renal disease.
Renal failure is a rare complication, and when it occurs, it is usually acute tubular necrosis associated with co-existing sepsis or placental abruption
coagulation screen
May be abnormal with advanced disease affecting the liver, or in association with abruption
Management
Before delivery
hospital admission and monitoring
decision regarding delivery
At <32 weeks' gestation: prolonging the pregnancy is beneficial for the fetus, as long as maternal and fetal assessments are satisfactory
At >36 weeks' gestation: delivery is the most sensible approach
corticosteroid
Antenatal corticosteroids are recommended before 34 weeks' gestation to mature fetal lungs
consider for outpatient follow-up when stable
with BP ≥150 mmHg systolic and/or ≥100 mmHg diastolic
with seizures
magnesium sulphate
After delivery
close monitoring of fluid balance
continue antihypertensives and magnesium sulphate
Prognosis
Pre-eclampsia is a self-limiting condition of pregnancy that usually resolves once the placenta has been delivered, although it may persist for a few days post delivery.
There are few long-term sequelae; however, there are some long-term disease associations.
The course of pre-eclampsia is altered by treatment, and the condition can be controlled easily in the majority of cases, usually within a few hours of starting treatment.
Once controlled, the length of the disease depends on when delivery is decided.
After delivery, the condition normally settles within 2 to 4 days; however, some women have hypertensive problems and proteinuria for some weeks after.
The overall risk of recurrence in subsequent pregnancies ranges from about 10% to 50%
Depending on the severity of pre-eclampsia, the gestation it occurred at, and subsequent interventions in the next pregnancy. [2] [2]
Generally, in previous severe or early onset (i.e., <30 weeks) pre-eclampsia, the risk of recurrence is 50%.
In mild to moderate or late-onset pre-eclampsia, the risk of recurrence is reduced to around 10%. [2]
There are good epidemiological data that suggest that women with pre-eclampsia have an increased long-term risk of cardiovascular disease, including hypertension and stroke. [2] [17]