Preeclampsia is a hypertensive disorder of pregnancy, usually affecting gestation at or around the 20th week. It affects 2%-8% of pregnancies worldwide and is one of the leading causes of maternal and perinatal morbidity and mortality. The pathogenesis of preeclampsia is largely down to abnormal maternal immune and inflammatory regulation, leading to the cornerstone symptoms of hypertension (high blood pressure) and proteinuria (high protein in the urine). The stage of preeclampsia onset is associated with the severity of the disease, with more severe cases of preeclampsia leading to systemic organ dysfunction and impacts on both maternal and foetal health.
Causes and risk factors
Preeclampsia is a condition which is defined by the presence of hypertension and significant proteinuria in pregnant women on or after the 20th week of their pregnancy. Though there is no single causal factor for preeclampsia, most theories suggest the disease is a cascade triggered by an abnormal maternal inflammatory response which induces endothelial cell damage and impaired immunity.
Abnormal maternal inflammatory response- During preeclampsia, placental ischemia (restricted blood flow) occurs due to insufficient trophoblast differentiation and invasion of neighbouring tissues. This dysregulates the immune function, leading to an uncontrolled state of inflammation. This induces the production and secretion of several by-products, such as reactive oxygen species and auto-antibodies, both damaging to normal cell function, culminating in the development of the primary symptom: hypertension.5
Multiple risk factors have been identified with preeclampsia, including:
- Nulliparity- a first pregnancy
- Pre-existing hypertension condition
- AGE- The incidence of pre-eclampsia in pregnant women with a maternal age of above 35 years was 3% higher than in younger women7
- PREGNANCY WITH EGG DONORS- When a donor egg is used, foetal receptor cells are less recognizable to the maternal immune system. This can disturb the blood flow to the placenta and facilitate the onset of preeclampsia8
Symptoms and diagnosis
Early symptoms of preeclampsia may be hard to notice during pregnancy, particularly without the aid of a medical professional. However, further and more noticeable symptoms may develop such as:
- Severe headache
- Vision problems (Blurring or flashing)
- Pain just below the ribs
- Sudden swelling of the face, hands or feet
- Weight gain
Severe complications of preeclampsia can include acute renal failure, cerebral edema, cerebral haemorrhage, seizures and liver injury; therefore, early clinical diagnosis of the condition is essential for both maternal and foetal wellbeing.
The American College of Obstetricians and Gynecologists have provided the following stages of criteria for diagnosis of preeclampsia:
Gestation hypertension- Diagnosed if a pregnant woman has high blood pressure but no protein in urine, and blood pressure levels were normal before pregnancy.
Mild preeclampsia- Diagnosed when a pregnant woman has a systolic blood pressure of 140mmHg, urine with 0.3g or more of protein OR blood tests that show kidney/liver dysfunction, fluid in lungs/difficulty breathing/visual impairments.
Severe preeclampsia- Diagnosed when a pregnant woman has a systolic blood pressure of 160mmHg and urine with 5g or more of protein. Test results indicate kidney/liver damage, severe unexplained stomach pain that does not respond to medication and symptoms of vision disturbances.
Eclampsia- Diagnosed when women with preeclampsia develop seizures. These can happen before or during labour or after the baby is delivered.
Superimposed preeclampsia- Diagnosed when the woman develops preeclampsia on top of high blood pressure that was present before the pregnancy began.
Hellp syndrome- Diagnosed when laboratory tests show hemolysis (red blood cell death), elevated liver enzymes and low platelets. There may or may not be extra protein in the urine4.
Impact on maternal health
The majority of preeclampsia cases are considered to be mild. However, in the cases where the condition progresses, individuals are at increased risk for:
- Damage to the kidneys, liver, brain and other major organ systems
- Placental Abruption- Where the placenta separates from the uterus
- Preterm birth
- Pregnancy loss/stillbirth
- Seizures- disruption of the brain’s normal electrical activity, causing changes in motor function (twitching, shaking), and loss of consciousness
According to the National Institute of Health, preeclampsia and eclampsia cause around 14% of maternal deaths; rapid medical diagnosis, tracking, and intervention is required for a healthy maternal outcome.
Risk to maternal health post-pregnancy
In mild cases, high blood pressure and the other experienced symptoms usually subside 6 weeks post-pregnancy. In some cases, however, the risks posed to maternal health can extend into the long term. For example, women who had preeclampsia are:
- Four times more likely to later develop hypertension and;
- Twice as likely to develop ischemic heart disease, venous thrombosis (blood clots in veins), and suffer from strokes than individuals without preeclampsia3
Impact on foetal and neonatal health
Though the precise pathogenesis of preeclampsia is not fully understood, dysfunctional placental formation does have a significant impact on foetal health9. Placentation is the establishment of physical contact between the foetus and the mother for the appropriate transfer of nutrients and hormones as well as the removal of waste products. Failure of the foetus to remodel the uterine spiral arteries during pregnancy leads to abnormal placentation. This causes:
- Higher resistance to placental blood flow
- Reduced blood flow to the placenta (Hypoperfusion) and developing foetus.
These maladaptive processes can lead to:
- Foetal hypoxia- A state in which oxygen is not available in sufficient amounts
- Placental Abruption
- Preterm birth
- Foetal distress or death in utero
There is evidence to suggest that the severity of foetal complications holds correlations to the stage of onset with earlier onset of preeclampsia associated with significantly higher rates of adverse outcomes for the foetus.9
Risk reduction and management
Preeclampsia is not a condition which can be prevented; however, there are several strategies which have been successfully implemented to help in the management of preeclampsia.
- Prediction- The earlier the diagnosis of preeclampsia, the better. Therefore an important focus of antenatal management of preeclampsia has been developing prediction models that identify women at high risk of disease, enabling more appropriate targeting of prophylaxis and increased surveillance of those of high-risk disease. Early administration of prophylaxis in high-risk women prior to 16 weeks gestation reduces the risk of pre-eclampsia by 17% and 14% reduction in foetal and neonatal death, respectively.1
- Diagnosis- Preeclampsia can be very difficult to diagnose, especially in individuals who already have a history of chronic hypertension. Assessment of proteinuria is also variable in test accuracy. New methods of diagnosis include the use of angiogenic biomarkers. Angiogenesis is the formation of new blood vessels, and angiogenic factors are implicated in the pathophysiology of preeclampsia; allowing earlier identification of women in their disease course.1
- Blood tests & foetal assessments- Measure of full blood count, liver function and renal function. The frequency of these check-ups very depending on the severity of the preeclampsia. Antenatal appointments will carry out foetal heart auscultations (consultations) and ultrasound assessments.
- Blood pressure management- It is recommended to keep systolic blood pressure below 150mmHg and diastolic blood pressure below 80-100mmHg. Labetalol is a medication which is usually the first line of treatment for hypertension in pregnancies. Tight control of blood pressure within the recommended limits reduces rates of severe maternal hypertension, seizures and intracerebral haemorrhage.
- Delivery- In women who are diagnosed with preeclampsia between 34-37 weeks of gestation. Immediate delivery through induction/caesarean may reduce the risk of adverse maternal outcomes. However, immediate delivery can increase the risk of neonatal respiratory distress syndrome.
- Postnatal monitoring- Postnatal care for mothers depends on the severity of their preeclampsia. Those who were on treatment should be monitored in hospital until the 3rd postnatal day and have a follow-up arranged with the GP/clinic within 2 weeks. Blood pressure can take up to 3 months to return to normal; for patients who remain hypertensive, blood pressure and proteinuria assessments should continue to be carried out and appropriate treatment administered.
Though preeclampsia is one of the leading causes of maternal and perinatal morbidity worldwide, standardised diagnostic and management strategies are in place to effectively manage the condition. Early detection is key to prevent disease progression into more severe stages, with the identification of high-risk patients being key step. Research is ongoing to determine further risk factors for disease onset and prevalence, aiming to lead to development of therapeutics for those undergoing pregnancy with preeclampsia.
- Duhig K, Vandermolen B, Shennan A. Recent advances in the diagnosis and management of pre-eclampsia. 2018 Feb 28 [cited 2023 Aug 8];7:242. Available from: https://f1000research.com/articles/7-242/v1
- Preeclampsia: practice essentials, overview, pathophysiology. 2023 Jun 30 [cited 2023 Aug 8]; Available from: https://emedicine.medscape.com/article/1476919-overview?form=fpf
- Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ 2007 Nov 10 [cited 2023 Aug 8];335(7627):974. Available from: https://www.bmj.com/lookup/doi/10.1136/bmj.39335.385301.BE
- Haram K, Svendsen E, Abildgaard U. The hellp syndrome: clinical issues and management. A review. BMC Pregnancy Childbirth. 2009 Dec [cited 2023 Aug 8];9(1):8. Available from: https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/1471-2393-9-8
- Harmon AC, Cornelius DC, Amaral LM, Faulkner JL, Cunningham MW, Wallace K, et al. The role of inflammation in the pathology of preeclampsia. Clinical Science. 2016 Mar 1 [cited 2023 Aug 8];130(6):409–19. Available from: https://portlandpress.com/clinsci/article/130/6/409/71487/The-role-of-inflammation-in-the-pathology-of
- Kenny L, English F, McCarthy F. Risk factors and effective management of preeclampsia. IBPC. 2015 Mar [cited 2023 Aug 8];7. Available from: http://www.dovepress.com/risk-factors-and-effective-management-of-preeclampsia-peer-reviewed-article-IBPC
- Sun M, Luo M, Wang T, Wei J, Zhang S, Shu J, et al. Effect of the interaction between advanced maternal age and pre-pregnancy BMI on pre-eclampsia and GDM in Central China. BMJ Open Diabetes Research and Care. 2023 Apr 1 [cited 2023 Aug 8];11(2):e003324. Available from: https://drc.bmj.com/content/11/2/e003324
- Schwarze JE, Borda P, Vásquez P, Ortega C, Villa S, Crosby JA, et al. Is the risk of preeclampsia higher in donor oocyte pregnancies? A systematic review and meta-analysis. JBRA Assisted Reproduction. 2017 [cited 2023 Aug 8]; Available from: http://www.gnresearch.org/doi/10.5935/1518-0557.20180001
- Fox R, Kitt J, Leeson P, Aye CYL, Lewandowski AJ. Preeclampsia: risk factors, diagnosis, management, and the cardiovascular impact on the offspring. JCM. 2019 Oct 4 [cited 2023 Aug 8];8(10):1625. Available from: https://www.mdpi.com/2077-0383/8/10/1625