Disorders of Pregnancy and Parturition Tutorial Flashcards
What is pre-eclampsia (PE)?
Complication of pregnancy - sudden rise in blood pressure and swelling (mostly in face, hands, and feet), also proteinuria
Severe pre-eclampsia can develop into eclampsia (seizures) and increase risk of stroke during pregnancy and delivery
What are the trends of maternal mortality and pre-eclampsia?
Decrease overtime
But increasing again slightly
Esp. central Africa
Africa and Asia
(8-16% of pregnancies)
<10 maternal deaths per 100,000 births from pre-eclampsia
How common is pre-eclampsia?
2-4% of pregnancies in the USA and Europe
Some evidence of this is rising
More common in Africa and Asia = suggestive of genetic component
What is the burden of maternal deaths?
~1/10 maternal deaths in Africa and up to 1/4 in South America are associated with gestational hypertensive disorders (including PE)
Estimated to cause 50,000-60,000 maternal deaths per year
Precise underlying causes remain a mystery
How is pre-eclampsia diagnosed?
Diagnostic factors:
New onset of hypertension in a previously normotensive woman:
(after) >20 weeks festation
>140mmHg diastolic
Usually reduced to fetal movement and/or amniotic fluid volume (by ultrasound) in 30% of cases
Oedema common but not discrimatory for PE
Headache - more likely in late onset pre-eclampsia (in 40% of severe PE patients)
Upper abdominal pain - in 15% of severe PE patients
Visual disturbances, seizures, breathlessness - severe PE, risk of eclampsia
Are there distinct forms of the condition?
Can be categorised into mild or severe - determines management
There is also early and late
Early (<34 weeks of gestation) = presents as maternal and foetal problems, changes in placental structure
Failure of maternal spirals forming deeper than the decidual layer from EVT cell invasion
Late (>34 weeks) = more common (90%), predominantly maternal symptoms probably due to endothelial defects as a consequence of the reduced circulating factors, fetus generally fine, less overt / no placental changes
What maternal risk factors may pre-dispose to developing PE?
Hypertension - gestational or previous
Family history
BMI >30 (obesity) - esp >35
Primiparity (first pregnancy)
Pre-eclampsia from previous pregnancy
Low immunological compatibility between father and mother
Maternal age (>40 or <20)
Pre-existing conditions: diabetes, PCOS, renal disease, subfertility, autoimmune disease
Non-natural cycle - e.g. cycle induced using high dose of gonadotrophins during IVF implantation rather than implantation during natural cycle
What are the risks of PE to the fetus and the mother during pregnancy?
Mother:
High BP - increased risk of CVD events
Cause clotting problems
Impair kidney function
Damage to kidneys, liver, brain and other organ systems
Possible progression to eclampsia (seizures, loss of consciousness)
Placental abruption = placental detachment off the endometrium = severe bleeding within and outside the uterus = impaired foetal growth / preterm or stillbirth
Foetus:
Separation of placenta from uterus = pre-term / still birth
Lack of O2 / nurtrients = impaired growth of foetus
What structural/developmental changes in the placenta are believed to underpin pre-eclampsia?
Normally villi coated in EVT (extravillous trophoblast) cells - these EVT cells invade into the maternal spiral arteries = leads to endothelial and smooth muscle breakdown
So EVT cells become endothelial EVT and spiral arteries become high in capacity
Ensures nutrient and gas exchange is sufficient
BUT in pre-eclampsia = occlusion of the maternal vessels results in failure of EVT cell invasion so maternal spiral arteries are limited to the decidual layer = limited perfusion of blood spaces = lack of exchange between maternal blood and placenta
Spiral arteries are not extensively remodelled, thus placental perfusion is restricted
How might sFlt1a (AKA soluble VEGF1R) and PLFG (PlGF) contribute to the maternal symptoms of pre-eclampsia?
PlGF = placental growth factor
PlGF (pee el gee eff - placental growth factor) = proangiogenetic molecule normally released in large amounts by the placenta, this is abnormally low in PE
SFlt1a (es eff el tee one a) - receptor circulating that can bind things like PlGF (acts like a sponge) - so high levels of this circulating = lowered levels of PlGF as these receptors just mop up the bioavailability of these proangiogenetic molecules that are important for normal blood vessel function
Depletion of normal circulating factors in maternal circulation = leads to endothelial dysfunction in the mother - affects microvasculature e.g. kidneys, disrupted glomerular filtration (proteinuria)
So reduced PlGF = reduced remodelling of spiral arteries in the foetus
In PE, FlT1 is excessively produced by a distressed placenta
Can sFlt1a and PlGF be used to predict pre-eclampsia?
Yes - but they need to be repeated throughout the pregnancy
Measuring PlGF alone = triage test, rules out PE in the next 14 days for women between 20-36 weeks of gestation
placental growth factor levels of normal (>100 pg/mL), low (12–100 pg/mL), and very low (<12 pg/mL)
OR alternatively, use a sFlt-1 / PlGF ratio - i.e. high to low ratio = predictor of pre-eclampsia
Elevated levels of sFlt1a
Lowered levels of PlGF - decreases further with increasing sFlt1a
What management options are available for women who develop PE during pregnancy?
PE can only be resolved by delivery of placenta
If <34 weeks, preferable to try and maintain the pregnancy if possible for benefit of the foetus
If >37 weeks, delivery preferable (may need to be induced)
In between 34-37 weeks - case by case basis
Management of hypertension (anti-hypertensives)
Corticosteroids for <34 weeks to mature the foetus’ organ systems e.g. promoting foetal lug development should early delivery be required
Management of pre-eclampsia (MgSO4 - for seizure potential AND hypertension - continued til after pregnancy)
Plan for the delivery
Are there preventative measures that can be taken avoid PE developing?
Weight loss (esp. 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
Are there any ongoing risks to the mother after pregnancy?
Long-term impacts of PE on maternal health =
Elevated risk of CVD, T2DM and renal disease after PE
Roughly 1/8 risk of having pre-eclampsia in next pregnancy (greater if early onset)
What are the risks for mothers post-pregnancy?
4x more likely to develop hypertension
Blood clot
Stroke
2x more likely to develop IHD
