10.6 - Disorders of Pregnancy & Parturition: Pre-Eclampsia

Question 1

How common is pre-eclampsia in USA and Europe?

Answer 1

2-4%

Question 2

How common is pre-eclampsia in Africa and Asia?

Answer 2

8-16%

Question 3

What is the precise underlying cause of pre-eclampsia?

Answer 3

We don’t know

Question 4

How do we diagnose pre-eclampsia?

Answer 4

• new onset hypertension (in a previously normotensive woman) - BP >140mmHg systolic and/or >90mmHg diastolic (occurring after 20 weeks gestation)
• reduced foetal movement and/or amniotic fluid volume (by ultrasound) in 30% cases
• oedema common but not discriminatory for PE
• headache (in 40% of severe PE patients)
• abdominal pain (in 15% of severe PE patients)
• visual disturbances, seizures and breathlessness associated with severe PE and risk of eclampsia (seizures)

Question 5

What is early onset pre-eclampsia?

Answer 5

• one of the subtypes of PE
• <34 weeks
• associated with foetal and maternal symptoms
• changes in placental structure

Question 6

What is late onset pre-eclampsia?

Answer 6

• one of the subtypes of PE
• > 34 weeks
• more common (90%)
• mostly maternal symptoms
• foetus generally OK
• less overt/no placental changes

Question 7

What maternal risk factors predispose to pre-eclampsia?

Answer 7

• previous pregnancy with PE
• BMI >30 (especially >35)
• family history
• increased maternal age (>40, <20?)
• gestational hypertension or previous hypertension
• pre-existing conditions: diabetes, PCOS, renal disease, subfertility, autoimmune disease
• non-natural cycle IVF

Question 8

What risks do pre-eclampsia pose to the mother?

Answer 8

• damage to kidneys, liver, brain and other organ systems
• possible progression to eclampsia (seizures, loss of consciousness)

Question 9

What risks do pre-eclampsia pose to the foetus?

Answer 9

• reduced foetal growth
• preterm birth
• pregnancy loss/stillbirth

Question 10

What risk does pre-eclampsia pose to the placenta?

Answer 10

Placental abruption (separation of the placenta from the endometrium)

Question 11

What happens normally in placental development?

Answer 11

• EVT cell invasion of maternal spiral arteries leads to endothelial and smooth muscle breakdown
• EVT becomes endothelial EVT
• spiral arteries become high capacity

Question 12

How does placental development change in PE?

Answer 12

• EVT invasion of maternal spiral arteries is limited to decidual layer
• spiral arteries are not extensively remodelled, thus placental perfusion is restricted

Question 13

What is PLGF?

Answer 13

• placental growth factor
• VEGF related
• pro-angiogenic factor released in large amounts by the placenta

Question 14

What is Flt1?

Answer 14

• soluble VEGFR1
• soluble receptor for VEGF-like factors which binds soluble angiogenic factors to limit their bioavailability

Question 15

What happens to Flt1 in pre-eclampsia?

Answer 15

Excess production of Flt-1 by distressed placenta leads to reduction of available pro-angiogenic factors like PLGF and VEGF in maternal circulation, resulting in endothelial dysfunction

Question 16

How are Flt1 and PLGF levels in healthy placenta?

Answer 16

• releases PLGF and VEGF into the maternal circulation
• these growth factors bind receptors on the endothelial surface to promote vasodilation, anti-coagulation and ‘healthy’ maternal endothelial cells

Question 17

How are Flt1 and PLGF levels in pre-eclampsia placenta?

Answer 17

• releases sFlT1, which acts as a sponge
• mops up PLGF and VEGF and stops them binding to the endothelial surface receptors
• in the absence of these signals, the endothelial cells become dysfunctional

Question 18

How are PLGF levels used to predict onset of pre-eclampsia?

Answer 18

• e.g. Triage test
• rules out PE in next 14 days in women 20-36 weeks and 6 days
• PLGF <12pg/ml = positive test, highly abnormal = increased risk for preterm delivery
• PLGF 12<x<100pg/ml = positive test, abnormal = increased risk for preterm delivery
• PLGF >100pg/ml = negative test, normal = unlikely to progress to delivery within 14 days of test

Question 19

How is sFlt1/PLGF ratio used to predict onset of pre-eclampsia?

Answer 19

• 24-36 weeks plus 6 days gestation
• sFlt1/PLGF <38 = rule out pre-eclampsia
• sFlt1/PLGF >38 = increased risk of pre-eclampsia

Question 20

What is the only way pre-eclampsia can be resolved?

Answer 20

• by delivery of the placenta
• if <34 weeks, preferable to try and maintain pregnancy if possible for benefit of the foetus
• if >37 weeks, delivery preferable
• in between - case by case basis

Question 21

How is pre-eclampsia managed?

Answer 21

• anti-hypertensive therapies
• corticosteroids for <34 weeks to promote foetal lung development before delivery

Question 22

What are the three main ways of preventing pre-eclampsia?

Answer 22

• weight loss (especially if BMI>35)
• exercise throughout pregnancy (seems to work independent of BMI)
• low-dose aspirin (from 11-14 weeks) for high-risk groups - but may only prevent early onset

Question 23

What are the long term impacts of pre-eclampsia on maternal health?

Answer 23

• elevated risk of cardiovascular disease, T2DM and renal disease after PE
• roughly 1/8 risk of having PE in next pregnancy - greater if early onset