Pregnancy, Parturition and Late Fetal Development Flashcards
What are the risks of PE to the mother during pregnancy?
- damage to kidneys, liver, brain and other organs
- possible progression to eclampsia (seizures, loss of consciousness)
- placental abruption (separation of the placenta from the endometrium)
- HELLP syndrome
What maternal risk factors may pre-dispose to developing PE?
- history/family history of pre-eclampsia
- BMI >30
- Age > 40, and <20
- pregnancy (multiple)
- sub-fertility
- gestational diabetes
- PCOS
- diabetes
- autoimmune disease
- non-natural cycle IVF
What are the sub-types of pre-eclampsia?
- early onset (<34 weeks)
- late onset (>34 weeks)
How do you characterise HELLP syndrome?
- haemolysis
- elevated liver enzymes
- low platelets
What are the characteristics of pre-eclampsia?
- reduced fetal movement
- reduced amniotic fluid volume
- oedema (not discriminatory)
- new onset hypertension (>140/90)
- > 20 weeks gestation
- headache
- abdominal pain
- visual disturbances
- seizures
- breathlessness
What is early onset pre-eclampsia?
- <34 weeks
- associated with fetal and maternal symptoms
- changes in the placental structure
- reduced placental diffusion
What is late onset pre-eclampsia?
- > 34 weeks
- more common (90%)
- maternal symptoms
- fetus generally OK
- less overt/no placental changes
What form of nutrition is the early embryo dependent on?
histiotrophic
What is histiotrophic nutrition?
- the derivation of nutrients from the breakdown of surrounding (endometrial) tissues and maternal capillaries
- uterine milk from uterine glands
When is the embryo reliant on histiotrophic nutrition?
the first trimester
When does the embryo swap to haemotrophic support?
at the start of the second trimester
What is haemotrophic nutrition?
derive its nutrients from maternal blood through a haemochorial-type placenta where maternal blood directly contacts the fetal membrane
When does the activation of the haemochorial-type placenta happen?
12 weeks gestation
What arises from the chorion?
- chorionic villi
- outgrowth of cytotrophoblast from the chorion that form the basis of the fetal side of the placenta
What is the role of chorionic villi?
provide substantial surface area for exchange
How many stages are there in chorionic villi development?
3
What is the primary stage of chorionic villi development?
outgrowth of the cytotrophoblast and the branching of these extensions
What is the secondary stage of chorionic villi development?
growth of the fetal mesoderm into the primary villi
What is the tertiary stage of chorionic villi development?
growth of the umbilical artery and the umbilical vein into the villus mesoderm, providing vasculature
Describe the microstructure of the terminal chorionic villus?
- convoluted knot of vessels
- vessel dilation
- slows blood flow to enhance exchange between fetal and maternal blood
- whole structure covered in trophoblast
What is the structure of the chorionic villi during early pregnancy?
- diameter: 150-200 micrometers
- trophoblast thickness: 10 micrometer (between capillaries and maternal blood)
What is the structure of the chorionic villi during late pregnancy?
- diameter: thin-40 micrometers
- trophoblast thickness: 1-2 micrometer (between capillaries and maternal blood)
What is the function of spiral arteries?
provide the maternal blood supply to the endometrium
What are extra-villus trophoblasts?
cells coating the villi that invade down into the maternal spiral arteries
What happens when extra-villus trophoblasts grow into the spiral arteries?
they become endovascular EVT cells
What do endovascular EVT cells do?
- breaks down the endothelium and smooth muscle
- coats the vessels to form a new endothelial layer
What term is used to describe the process of endovascular EVT cells replacing the endothelium of the vessels?
conversion
What is the purpose of conversion?
turns the spiral artery into a low pressure, high capacity conduit for maternal blood flow
What do the spiral arteries supply?
the intervillus spaces/maternal blood spaces with blood
How is pre-eclampsia diagnosed?
- persistant hypertension
- proteinuria
- urine analysis
- umbilical artery (Doppler Velocimetry)
How can pre-eclampsia be excluded?
placenta growth factor test
What are the risks of PE to the fetus during pregnancy?
- reduced fetal growth
- preterm birth
- pregnancy loss/stillbirth
What happens in the development of a normal placenta?
- EVT invasion of maternal spiral arteries leads to endothelial and smooth muscle breakdown.
- EVT become endothelial EVT and spiral arteries become high capacity
What happens in the development of a placenta with a risk of pre-eclampsia?
- EVT invasion of maternal spiral arteries is limited to decidual layer.
- Spiral arteries are not extensively remodelled, thus placental perfusion is restricted.
What is Placental Growth Factor (PLGF)?
VEGF related, pro-angiogenic factor released in large amounts by the placenta.
What is Flt1 (soluble VEGFR1)?
Soluble receptor for VEGF-like factors which binds soluble angiogenic factors to limit their bioavailabliltiy.
What is the Flt1and PLGF levels seen in pre-eclampsia?
- excess production of Flt-1 by distressed placenta
- reduction of available pro-angiogenic factors in maternal circulation, resulting in endothelial dysfuction.
What can be used to predict the onset of pre-eclampsia?
- PLGF levels
- Flt-1/PLGF levels
What is the benefit of PLGF?
- triage test
- rules out pre-eclampsia in the next 14 days in women 20-36weeks and 6days
What does a PLGF result of <12 pg/ml mean?
- positive test (highly abnormal)
- increased risk of preterm delivery
What does a PLGF result of >12 pg/ml and <100 pg/ml mean?
- positive test (abnormal)
- increased risk of preterm delivery
What does a PLGF result of >100 pg/ml mean?
- negative test (normal)
- unlikely to progress to delivery within 14 days of test
When is a Flt-1/PlGF ratio test done?
24-36weeks and 6days
What does a Flt-1/PlGF ratio of <38 mean?
rules out pre-eclampsia
What does a Flt-1/PlGF ratio of >38 mean?
increased risk of pre-eclampsia
How can pre-eclampsia be resolved?
only by the delivery of the placenta
What are the long term impacts of pre-eclampsia on maternal health?
elevated risk of:
- CVD
- T2DM
- renal disease
- 1/8 risk of pre-eclampsia in next pregnancy
What happens in failed spiral artery remodelling?
- smooth muscle remains
- immune cells become embedded in vessel walls
- vessels occluded by RBCs
What are the consequences of failed spiral artery remodelling?
- vulnerable to intimal hyperplasia and atherosis
- perturbed flow
- local hypoxia
- free radical damage
- inefficient substrate movement into intervillous space
- residual contractile capacity disturbing blood flow to intravillous space
What is released by a healthy placenta?
- PLGF and VEGF
- bind to receptors on endothelial surface
- promote vasodilation, anticoagulation and healthy maternal endothelial cells
What is released by a PE placenta?
- sFlt-1
- mops up PGLF and VEGF, stopping them from binding to endothelial cells
- endothelial cells become dysfunctional
What are extracellular vesicles?
- tiny lipid-bilayer laminated vesicles released by almost all cell types
- contain mRNA, proteins and microRNA which can influence behaviour of cells locally and at a e
What are the changes in extracellular vesicles seen in pre-eclampsia?
- increased in maternal circulation
- increase in endothelial-derived extracellular vesicles
- decrease in placenta-derived endothelial vesicles
What is the role of extracellular vesicles?
- autocrine, endocrine and paracrine cell signalling
- homeostasis
What is the possible mechanism of EVs causing pre-eclampsia?
- placental ischaemia induces apoptosis of trophopblasts and EV release
- EVs enter maternal circulation
- EVs cause endothelial cell dysfunction, inflammation and hypercoagulation
What can cause later onset PE?
- existing genetic predisposition to cardiovascular disease manifesting during pregnancy
- little evidence of issues with spiral artey remodelling
- normal placental perfusion
What is SGA?
- fetal weight <10th percentile
- severe SGA is <3rd percentile
What are the three classifications of SGA?
- small throughout pregnancy but otherwise healthy
- interuterine growth restriction (IUGR)/ fetal growth srestriction (FGR)
- non-placental growth restriction
What is IUGR/FGR?
- normal early growth but slows later in pregnancy
- clinical features of malnutrition and growth restriction, irrespective of weight percentile
What are the two types of IUGR?
Symmetric and asymmetric
What are the features of symmetric IUGR?
- early gestational insult
- genetic disorder or infection of fetus
- everything reduced in proportion
- reduced cell number, normal size
- less features of malnutrition
- poor prognosis
- less common
What are the features of asymmetric IUGR?
- later gestational injury
- utero-placental deficiency
- head normal, rest of body is smaller
- normal cell number, reduced size
- more features of malnutrition
- good prognosis
- more common
What are the implications of IUGR/FGR?
- fetal cardiac hypertrophy
- remodelling of fetal vessels due to chronic vasoconstriction
- poor maturation of lungs leading to bronchopulmonary dysplasia
- long term motor defects and cognitive impairments
What happens during spiral artery remodelling?
- EVT cell invasion triggers chemokine release from endothelial cells
- leads to recruitment of immune cells
- immune cells invade spiral artery walls which disrupts them
- EVT cells replace broken down vessel walls with fibrinoid matrix
