Pre-Eclampsia

Question 1

What is pre-eclampsia?

Answer 1

vascular disorder

pregnancy specific disorder

hypertensive disorder of pregnancy

Question 2

Hypertensive disorders of pregnancy are the leading cause of maternal and fetal morbidity and mortality. What are the 4 different types

Answer 2

chronic hypertension
- women who enter pregnancy already having high blood pressure

Gestational hypertension
- women who develop high blood pressure throughout their pregnancy

Pre-eclampsia
- high blood pressure with organ failure

chronic hypertension + superimposed pre-eclampsia
- women who enter pregnancy already having high blood pressure that then go on to develop pre-eclampsia

Question 3

What is the clinical classification of pre-eclampsia?

Answer 3

1. development of high blood pressure in the second half of pregnancy

COMBINED WITH ONE OF THE FOLLOWING:

1. proteinuria
   - increased protein in the urine (a sign of kidney dysfunction)
2. other maternal organ dysfunction
3. fetal growth restriction
   - indicated dysfunction of the placenta

Question 4

What are the symptoms of pre-eclampsia and why can these symptoms make it hard to determine if it is pre-eclampsia without getting checked ?

Answer 4

• generalised edema
  (accumulation of body fluids)
• severe head aches
• abdominal pain

These symptoms are all relatively common in pregnancy so it is hard to determine pre-eclampsia with just symptoms alone

Question 5

When do symptoms of pre-eclampsia usually begin to arise and why is this an issue?

Answer 5

late in the course of disease (usually 3rd trimester)

symptoms occur to late in disease progression to help prevent and treat

Question 6

pre-eclampsia can progress to eclampsia. What is eclampsia?

Answer 6

results in seizures and coma

• seen more often in developing countries

Question 7

What are the two subtypes of pre-eclampsia?

Answer 7

early diagnosis/onset (before 34 weeks)

late diagnosis/onset ( after 34 weeks)

Question 8

What are the risk factors involved in pre-eclampsia?

Answer 8

1. family history
   - relatives/mother-in law has had pre-eclampsia
2. maternal/paternal factors
   - advaced maternal age
   - african american descent
   - previous pre-eclamptic pregnancy
   - obesity
   - poor nutrition (selenium deficient diets = increased risk)
   - nulliparous (first pregnancy)
   - multiple gestation
3. existing disease
   - chronic hypertension
   - chronic renal disease
   - vascular disease
   - diabetes

Question 9

COVID 19 is a new determined risk factor for pre-eclampsia

Answer 9

women who develop covid 19 in pregnancy are 2x more likely to develop pre-eclampsia

Question 10

How do vaccinations help with pre-eclampsia prevalence?

Answer 10

women who have been vaccinated for COVID 19 are not at risk for developing pre-eclampsia or many other complications in pregnancy

maternal and fetal outcome for those who get vaccinated have been positive

Question 11

What are the current options for treatment for pre-eclampsia?

Answer 11

note there is no specific treatment or drug for pre-eclampsia but there are drugs that can help manage the symptoms

High blood pressure can be managed by anti-hypertensives (labetalol, nifedipine, methyldopa)
- to minimise vascular damge by high blood pressure
- usually need two or three of these depending on mothers actual blood pressure and their response to the drugs

However, usually there is just monitoring of fetus and mother

Question 12

What are the complications with treating the high blood pressure in pregnancy?

Answer 12

lowering the blood pressure may reduce the blood flow to the maternal organs and also the fetus

last think that we want to happen is to reduce blood flow to a baby that may already be growth restricted from the pre-eclampsia

Question 13

What medication could be taken to help prevent pre-eclampsia progression?

Answer 13

aspirin (low dose)
- needs to start early (16 weeks) until late pregnancy

at the moment there is now evidence that suggests aspirin has any negative consequences for fetus

only recommended for women with moderate (at least 2 risk factors) to high risk (based on risk factors)

Question 14

What is the ‘cure’ for pre-eclampsia

Answer 14

remove the placenta (give birth)
- could be okay for those elate onset
- has many risks for women with early onset

pre-eclampsia resolves in 48 hours of birth

Question 15

What is thought to be the cause of pre-eclampsia?

Answer 15

lack of spiral artery remodelling into the myometrium and not as effective remodelling occurs in the endometrium

Therefore there is low caliber/high resistance vessels

Question 16

What occurs in normal pregnancy with vasculature remodelling?

Answer 16

trophoblasts invade the endometrium and first third of the myometrium to remove the smooth muscle cells and endothelial cells

This remodelling allows for the spiral arteries in the uterus to open up creating a high calibre/low resistance vessels capable of delivering and increased amount of blood to the placenta and in turn fetus

Question 17

What are the differences seen between pre-eclamptic and normal spiral arteries in pregnancy?

Answer 17

• diameter is increased so more blood can flow easily through the vessel
• a lot less smooth muscle cells so ability of the vessel to constrict is significantly reduced
• there are receptors on endothelial cells which enable to vessel to respond to things that cause restriction
  (with lowered amounts there are less receptors to respond creating a weaker response)

Question 18

How does the limited remodelling of the spiral arteries impact the placenta?

Answer 18

1. placenta develops in a low oxygen environment due to lack of blood flow (this is normal for the first trimester as babies grow in a hypoxic environment)
2. The blood is stop start and not a continuous flow (there is enough then there isnt)
   - this causes disruption of placental development

These two together cause ischeamia re-profusion injury which causes abnormal placental development leading to reduced placental perfusion ( less blood is coming into that placenta and then going to the baby)

The placenta responds to this by producing negative factors which enter the maternal blood stream

This is then why growth restricted babys are seen

Question 19

How does the impacted placenta lead to the clinical symptoms seen pre-eclampsia?

Answer 19

dysfunctional placenta produces proteins which enter the maternal circulation and also has oxidative stress because of the ischemia re-profusion injury
- this leads to blood vessel dysfunction systematically in mother
- leading to vasoconstriction of blood vessels

This damage to vessels causes the high blood pressure, damage to maternal organs and comprise fetal growth

Question 20

endothelial cells respond to what is going on in the blood how?

Answer 20

can be by:
- the shear tension and stress by blood movement
- factors flowing in blood (can influence and cause vasculature to create and release vasoactive substances which can diffuse into smooth muscle cells to influence blood vessel activity)

Question 21

In a healthy pregnancy how do the vessels allow for decreased peripheral resistance and arterial pressure to allow increased blood flow for fetus?

Answer 21

endothelial cells produce an increased amount of nitric oxide (NO) and prostacyclin (PGI2) which diffuse into smooth muscle cells of vessel causing vasodilation

Question 22

Why is there a drop in arterial blood pressure in the first trimester?

Answer 22

due to mass vasodilation occurring

the body is preparing for an increase in blood volume for the fetus

Question 23

What changes occur in pre-eclampsia to change the overall vasculature activity?

Answer 23

Placental factors get produced in high amounts causing:
- reduction in the bioavailability of NO and PGI2
- increase kidney production of angiotension 2 (causes an increase in blood pressure)
- increases vasoconstrictors (angiotensin 2 and endothelin-1)
- increases the sensitivity of the smooth muscle to the vasoconstrictors

Question 24

The production of placental factors in pre-eclampsia causes what overall shift to the maternal vasculature?

Answer 24

shifts from vasodilation to vasoconstriction state

therefore there is an increase to peripheral resistance and arterial pressure

Question 25

Placental factors that are released into maternal circulation are anti-angiogenic factors. What does this mean?

Answer 25

they are not good for blood vessel formation and development and homeostasis

Question 26

What are the ligands for specific endothelial bound membrane receptors which promote endothelial health and vasodilation?

Answer 26

TGF-beta 1 (transforming growth factor beta 1)
VEGF (vascular endothelial growth factor)
PIGF (placental growth factor)

Question 27

What occurs in pre-eclampsia to these good guy ligands?

Answer 27

1. placenta realises there is not enough blood flowing to it and ischemia profusion injury
2. it releases its placental factors to increase the amount of membrane bund receptors for the good guys but it cannot do this so instead produces soluble versions of this
3. soluble version bind to the good guys in the blood which prevents them from binding to the endothelial membrane bound receptors for the good guys
4. this causes impaired vasodilation and endothelial dysfunction

Question 28

How does oxidative stress cause vascular dysfunction in pre-eclampsia?

Answer 28

1. placental ischemia causes an increase in amount of superoxide, hydrogen peroxide and peroxynitriate (ROS)
2. due to too much ROS there is damage to cellular level (e.g. DNA damage and damage to proteins that are needed for maintaining endothelial health )
3. this then further contributes to vascular dysfunction

in pre-eclampsia there is a decrease in the bioavailability of internal antioxidants
(cannot mop up all of the ROS)

Question 29

What are the tools clinicians use at the moment to help pre-eclampsia

Answer 29

monitor mother
monitor development of baby
try to maintain clinical symptoms (e.g. aspirin and anti-hypertensive drugs)
if it gets to severe then baby and placenta is delivered