Disorders of pregnancy and parturition: pre-eclampsia tutorial Flashcards
LO:
- Pregnancy physiology: Summarise the key changes in maternal physiology across the course of pregnancy.
- Pregnancy disorders: Summarise the major pathology and pathophysiology of key disorders of pregnancy.
- Fetal development: Summarise the key developmental events occurring in the fetus in the second and third trimesters
We’ve become better in avoiding mortality
Precipitous decline in frequency of maternal death, but there is a slight increase occuring.
In Africa maternal mortality is still a big problem
Pre-eclampsia
- quite high 2-4% and there is suggestion of rising incidence in USA and Europe
- Genetic predisposition to it, there are higher levels seen in Africa and Asia.
- 10% of deaths in Africa are related to gestational hypertensive disorders
- Cause is unknown
- How is pre-eclampsia diagnosed? Are there distinct forms of the condition?
Key diagnostic factors:
- >20 weeks’ gestation (so late pregnancy condition mid 2nd to 3rd trimester)
- BP ≥140 mmHg systolic and/or ≥90 mmHg diastolic and previously normotensive
- headache
- upper abdominal pain
Other diagnostic factors
- reduced fetal movement
- fetal growth restriction
- oedema
- visual disturbances
Subtypes:
Mild and severe
Early and late onset (late-foetus has had 34 weeks of growth already, so is less impacted, less changes to placenta unlike early onset which is caused by failed conversion of spiral arteries)
What maternal risk factors may pre-dispose to developing PE?
- primiparity
- pre-eclampsia in previous pregnancy
- family history of pre-eclampsia
- BMI >30
Maybe getting pregnant under 20, may also predispise to it.
Women who have undergone IVF with prestimulated hormonal treatment are more likely to get it ie in programmed cycle IVF where they have gonadotrophins which are thought to potentially cause preeclampsia.
What are the risks of PE to the fetus and the mother during pregnancy?
Placental abruption can lead to bleeding in the uterus.
As invasion hasn’t occured as it should and placenta is abnormal, gas exchange may not be able to occur and growth can be retarded.
- What structural/developmental changes in the placenta are believed to underpin pre-eclampsia?
Normal: replacement of maternal endothelial cells with foetal endothelium
PE: occlusion of maternal vessels. Normally get invasion of extravillous trophoblasts. Vessels end up retaining spiral structure so are low capacity, high resistance so exchange btween blood and maternal villi is limited.
Angiogenic factors are also essential for maintenance of normal vessel health; they provide important cues for organ development. Increased levels of the antiangiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble Endoglin (sEng) trap circulating vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and transforming growth factor β (TGFβ) respectively, decreasing their free levels, leading to endothelial dysfunction and the clinical manifestations of the disease
PlGF (L is lowercase! not i)
How might sFlt1a (soluble VEGF1R) and PLFG (PlGF) contribute to the maternal symptoms of pre-eclampsia?
My answer:
Extravillous trophoblasts invade into spiral arteries and leads to their remodelling so get high capacity, low resistance vessels important for blood supply to foetus.
In preeclampsia, remodelling of spiral arteries doesn’t happen in depth. as don’t have remodelling of spiral arteries, you get limited placental perfusion, resulting in a lot of clinical signs you see.
During normal placental development, the maternal uterine spiral arteries undergo an extensive remodeling, transforming them into low resistance, high bore blood vessels adequate to provide nutrients to the placenta and fetus (Brosens et al. 1967). In preeclampsia, cytotrophoblasts (CTBs) fail to invade the myometrium and the physiological changes of the spiral arteries are restricted to the decidua (Fig. 2). Invading CTBs up-regulate expression of molecules that are central to uterine invasion and pseudovasculogenesis (the process by which CTB switch their adhesion molecules to mimic that of vascular cells)
VEGF, and possibly PlGF, are required to maintain endothelial health in several tissues including the kidney and perhaps the placenta. In normal pregnancy, the placenta produces modest concentrations of VEGF, PlGF, and sFlt-1. In preeclampsia, excess placental sFlt-1 binds circulating VEGF and PlGF and prevents their interaction with endothelial cell-surface receptors leading to endothelial dysfunction.
actual
Normal placenta releases VEGF etc, to promote health of maternal endothelium. PE distressed placenta, releases more of this soluble rceeptor which mops up VEGF so we end up with dysfunctional endothelium in PE.
Can sFlt1a and PlGF be used to predict pre-eclampsia?
There are currently 4 PlGF-based tests commercially available.
o Triage PlGF test (Quidel)
o Elecsys immunoassay sFlt-1/PlGF ratio (Roche diagnostics)-test that allows you to predict in short term if woman will develop PE so you can monitor women more and have measures in place. Used in women in 20-36 weeks so used in that window to allow early diagnosis.
o DELFIA Xpress PlGF 1-2-3 test (Perkin Elmer)
o BRAHMS sFlt-1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio (Thermo Fisher Scientific)
Soluble sFlt1a is potentially being produced by defective placenta and that can reduce VEGF in circulation causing endothelial dysfunction in mother. So can look at a ratio between markers ie sFlt1a and PiGF as looking at a baseline is hard to guess the effect.
Actual
PLGR alone or sFlt-1/PlGF ratio
Management of PE
Core management strategy is delivering the placenta as essentially disease of placenta.
Possible to administer antihypertensive therapy to women with PE
Give corticosteroids to women with PE early on to ensure foetal lungs and organ structures can develop.
Are there preventative measures that can be taken avoid PE developing?
My answer:
Low-dose aspirin (75-150 mg/day orally starting at 11-14 weeks’ gestation) reduces the incidence and severity of pre-eclampsia.[2][27][28] The effect appears to be uniform across all risk groups, but its use should be targeted at high-risk groups such as those with hypertension, diabetes, renal disease, autoimmune disease, multiple pregnancy, body mass index >30, maternal age >40 years, or interval of ≥10 years since previous pregnancy.
It is important to optimise treatment for hypertension and renal disease prior to pregnancy. Controlled weight loss reduces the incidence of pre-eclampsia.[2] Exercise in pregnancy should be encouraged in the absence of complications, including maternal comorbidities, and risk factors for bleeding or premature delivery. A regular supervised exercise programme may reduce the risk of pre-eclampsia, independently of body mass index.[31][32]
Epidemiological studies have found that low dietary calcium is associated with pre-eclampsia. One Cochrane review found that the addition of high-dose calcium (≥1 g daily) reduced the risk of pre-eclampsia and preterm birth compared with placebo. In populations where dietary calcium intake is low, the World Health Organization recommends that pregnant women should receive 1.5 g to 2.0 g of supplementary calcium daily in order to reduce pre-eclampsia severity.
Are there any ongoing risks to the mother after pregnancy?
Early onset preeclampsia is a much greater risk factor for future issues that late onset.
Early onset is due to failure of evt invasion which causes spiral artery remodelling
My answer:
In “uncomplicated preeclampsia,” the mother’s high blood pressure and other symptoms usually go back to normal within 6 weeks of the infant’s birth. However, studies have shown that women who had preeclampsia are four times more likely to later develop hypertension (high blood pressure) and are twice as likely to later develop ischemic heart disease (reduced blood supply to the heart muscle, which can cause heart attacks), a blood clot in a vein, and stroke as are women who did not have preeclampsia.5
Less commonly, mothers who had preeclampsia can experience permanent damage to their organs, such as their kidneys and liver. They can also experience fluid in the lungs. In the days following birth, women with preeclampsia remain at increased risk for developing eclampsia and seizures.3,6
In some women, preeclampsia develops between 48 hours and 6 weeks after they deliver their baby—a condition called postpartum preeclampsia.7,8 Postpartum preeclampsia can occur in women who had preeclampsia during pregnancy and among those who did not. One study found that slightly more than one-half of women who had postpartum preeclampsia did not have preeclampsia during pregnancy.9 If a woman has seizures within 72 hours of delivery, she may have postpartum eclampsia. It is important to recognize and treat postpartum preeclampsia and eclampsia because the risk of complications may be higher than if the conditions had occurred during pregnancy. Postpartum preeclampsia and eclampsia can progress very quickly if not treated and may lead to stroke or death.
