Pre-eclampsia

Question 1

Pathogenesis

Answer 1

1. Abnormal placentation
   a. Spiral arteries in the placental bed do not undergo normal vascular remodelling as trophoblast invasion is abnormal
   b. Invading placenta unable to optimize blood supply from maternal uterine vessels
   c. Spiral arteries fail to become high capacitance, low resistance vessels
   d. Results in uteroplacental ischaemia
   Can also be due to a large placenta e.g. diabetes, multiple pregnancy, hydropic fetus –> underperfusion of a large placenta leads to uteroplacental ischaemia
2. Maternal response
   a. Systemic inflammatory response of normal pregnancy is exacerbated in pre-eclampsia
   b. Metabolic disturbance - high triglycerides and pro-inflammatory cytokines associated with endothelial dysfunction
   c. Endothelial cell activation leads to increased capillary permeability, increased endothelial expression of cell adhesion molecules, pro-thrombotic factors, platelet activation and increased vascular tone. Decrease in prostacyclin synthesis, increase in thromboxane A2 (TXA2). This reversal in prostanoid balance contributes to platelet activation and vasoconstriction
   d. Leads to widespread microvascular damage and dysfunction –> hypertension, proteinuria and hepatic disturbance
   e. If already underlying metabolic derangement (e.g. obesity, dyslipidemia, insulin resistance) causing chronic systemic inflammation, more susceptible to pre-eclampsia
3. Genetic predisposition - FHx increases risk x 3

Question 2

PHx pre-eclampsia - future risks

Answer 2

• Hypertensive disorder in future pregnancies
• Hypertension - 4 x risk
• Cardiovascular disease - 2 x risk
  ○ Major adverse cardiovascular event - 1.5-3 x risk
• Cerebrovascular disease - 2 x risk
• T2DM - 2-4 x risk
• Chronic kidney disease - 4-8 x risk
  ○ Women with no HTN or proteinuria at postpartum review (6-8 weeks) - the relative risk of end-stage kidney disease is increased, but absolute risk is low and no further follow-up is necessary.