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
- antihypertensive therapy
- Labetalol is considered the antihypertensive of choice, [2] [3] and is effective as monotherapy in 80% of cases
- Acceptable alternatives include methyldopa, nifedipine (a calcium-channel blocker), and hydralazine
- 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]
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