Disorders of pregnancy & parturition

Question 1

How does the placenta change throughout pregnancy? Why?

Answer 1

Increased branching of chorionic villi
Increases SA for exchange
Increased foetal nutritional demands
Increased energy consumption

Question 2

Early embryo nutrition is histiotrophic - what does this mean?

Answer 2

Reliant on uterine gland secretions and breakdown of endometrial tissue

Question 3

When does provision of nutrition switch to haemotrophic?

How is haemotrophic nutrition achieved?

Answer 3

Start of 2nd trimester

Haemochorial-type placenta

Question 4

What cells are responsible for the invasion of endometrial tissue for nutrition?

What do they differentiate from?

Answer 4

Syncytiotrophoblasts

Cytotrophoblasts

Question 5

What are the 3 phases of chorionic villi development?

Answer 5

1. primary - outgrowth & branching of cytotrophoblast
2. secondary - growth of foetal mesoderm into primary villi
3. tertiary - growth of umbilical artery & vein into mesoderm

Question 6

How does the structure of a chorionic villus change over the course of the pregnancy?

Answer 6

Early: thicker diameter, thicker trophoblast layer between capillary and materal blood
Late: decreased diameter, decreased trophoblast layer in between foetal and maternal blood

Question 7

Describe the process of maternal spiral artery remodelling

Why is this done?

Answer 7

1. foetal extra-villus trophoblast cells (EVT) surrounding villi invade down to spiral arteries
2. triggers chemokine release and immune cell recruitment by endothelium
3. invaded EVT cells break down ECM and deposit fibrinoid matrix
4. smooth muscle and endothelium of spiral arteries broken down by immune cells
5. EVT lines inside of spiral arteries instead

Converts spiral artery to low pressure, high volume system

Question 8

What are the consequences of failed conversion of spiral artery remodelling?

Answer 8

Intimal hyperplasia & atherosis
Residual contractile capacity from remaining smooth muscle

Leads to:
- turbulent flow
- local hypoxia
- free radical damage
- inefficient deliver into intervillous space

Question 9

What is preeclampsia?

Answer 9

Gestational hypertensive disorder occurring during or after birth

Question 10

How is preeclampsia diagnosed?

Answer 10

New onset hypertension after 20 weeks gestation

Hypertension >140sys and/or 90dias

Question 11

How is preeclampsia diagnosed?

What is difference between early onset and late onset?

Answer 11

New onset hypertension after 20 weeks gestation
Hypertension >140sys and/or >90dias

before/after 34 weeks

Question 12

What symptoms are seen in preeclampsia?

Answer 12

Headache
Proteinuria
Reduced foetal movement/amniotic fluid volume
Oedema
Abdominal pain
Visual disturbances & seizures

Question 13

Which subtype of preeclampsia is more severe? Which is more common?

Answer 13

Severe: early onset
Common: late onset

Question 14

What are the maternal risk factors for PE?

Answer 14

Previous pregnancy with PE
BMI >30
FHx
Increased maternal age >40
Gestational/previous hypertension
Comorbidities: diabetes, PCOS, CKD, subfertility
Autimmune disease (w/ anti PPLP antibodies)
IVF

Question 15

What are the risks to the mother in PE?

Answer 15

Damage to organs (kidneys, liver, brain etc)
Can progress to eclampsia
HELLP syndrome
Placental abruption (separation of placenta from endometrium)

Question 16

What is HELLP syndrome?

Answer 16

Haemolysis
Elevated Liver enzymes
Low Platelets

Question 17

What are the risks to the foetus in PE?

Answer 17

Early delivery
Reduced foetal growth
Death

Question 18

What are the placental defects underpinning early onset PE?

Answer 18

EVT invasion limited to decidual layer, doesn’t extend to myometrium
Spiral arteries not completely remodelled
Decreased placental perfusion

Question 19

What are VEGF and PlGF?

Answer 19

Pro-angiogenic factors released by placenta, needed to promote healthy endothelium
Anticoagulant & vasodilatory

Vascular endothelial growth factor and placental growth factor

Question 20

What is Flt1? What is its significance in PE?

Answer 20

Soluble VEGF receptor released by placenta
Binds to soluble angiogenic factors, limiting bioavailability
Procoagulant & vasoconstrictive
Released in excessive amounts in PE, leading to endothelial dysfunction

Question 21

What is the significance of a high sFlt-1/PlGF ratio?

What time period is it only useful to be used in? Why?

Answer 21

Increased chance of developing PE if >38

20-35wks - PlGF levels naturally decline in last few weeks of gestation

Question 22

How does the PlGF test indicate PE?

What are the reference ranges?

Answer 22

Low PlGF = higher risk of developing PE in next 14 days
0-12 pg/ml highly abnormal
12-100 abnormal
100+ normal

Question 23

How is PE managed?

Answer 23

Can only be resolved by delivery of placenta

Regular monitoring
Anti-hypertensives
Magnesium sulphate to counteract seizures
Corticosteroids if <34 weeks to promote foetal lung development
If early onset, try to maintain pregnancy for foetal benefit
If >37wks, delivery preferable

Question 24

Prevention of PE methods

Answer 24

1. Reduce BMI
2. Exercise throughout pregnancy
3. Low dose aspirin in wk11-14 in high risk groups

Question 25

What is the definition of small for gestational age?

Answer 25

Lowest 10th centile
Severe: 3rd centile or less

Question 26

What are the 3 subclassifications of SGA?

Answer 26

1. small throughout pregnancy but healthy
2. FGR/IUGR - normal early growth but slows later
3. non-placental growth restriction e.g. genetic, metabolic, infection

Foetal growth restriction/intrauterine growth restriction

Question 27

Symmetrical vs asymmetrical IUGR
Period of insult
Etiology
Body size
Cell size and number
Prognosis

Answer 27

Symmetrical:
Due to early gestational insult
Caused by genetics/infection
Whole body proportionally reduced in size
Cell size normal, but cell number reduced
Poor prognosis

Asymmetrical:
Due to later gestational insult
Caused by utero-placental insufficiency
Head size normal, smaller body
Cell size reduced, cell number normal
Good prognosis

Question 28

What are the implications of FGR/IUGR?
Cardiovascular, resp, neuro

Answer 28

Cardio: foetal cardiac hypertrophy and vessel remodelling from chronic vasoconstriction to preserve O2

Resp: poor lung maturation

Neuro: motor defects and cognitive impairments