Pre-Eclampsia: A Clinical Guide

Definition

Pre-eclampsia is a multi-systemic disorder unique to pregnancy, occurring after 20 weeks of gestation, that is primarily defined by the new onset of hypertension accompanied by evidence of maternal end-organ dysfunction (3, 4, 7). This modern understanding moves beyond the historical triad of hypertension, proteinuria, and oedema, recognising that proteinuria is just one of several potential manifestations of the underlying pathology of widespread endothelial dysfunction (2).

Epidemiology

In Malaysia, hypertensive disorders of pregnancy represent a significant burden. A cross-sectional study in Kuala Lumpur reported a pre-eclampsia prevalence of 1.6% (1). The Malaysian Clinical Practice Guidelines identify key risk factors for the local population, including primigravida status, maternal age over 35, multiple pregnancies, a long interpregnancy interval, high BMI, and a family history of pre-eclampsia (1). Globally, pre-eclampsia complicates an estimated 2% to 8% of all pregnancies and is a leading cause of maternal and perinatal mortality, responsible for approximately 76,000 maternal and 500,000 fetal deaths annually (8, 10). The incidence is alarmingly higher in developing nations, where it can be up to seven times more frequent than in developed countries (8).

Pathophysiology

Pre-eclampsia is best understood through a "two-stage model" (2).

Stage 1: Defective Placentation

The disease process originates in the first trimester with a failure of the physiological transformation of the maternal uterine spiral arteries (2). In a healthy pregnancy, placental cells invade these arteries, converting them from narrow, high-resistance vessels into wide, low-resistance conduits capable of supplying massive blood flow to the fetus (2). In pre-eclampsia, this invasion is shallow and incomplete. The arteries remain narrow, leading to placental underperfusion, hypoxia, and oxidative stress (2, 14). This defective placentation is the primary lesion (2).

Stage 2: Maternal Systemic Syndrome

The underperfused and stressed placenta releases a cascade of inflammatory and anti-angiogenic factors into the maternal circulation (2). Key among these are soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) (2). These factors cause widespread dysfunction of the mother's vascular endothelium—the inner lining of all blood vessels (2). This systemic endothelial dysfunction is the unifying process that leads to the clinical manifestations of pre-eclampsia (2):

• Kidneys: Glomerular damage causes proteinuria (2).

• Liver: Periportal necrosis leads to elevated liver enzymes and right upper quadrant pain (2).

• Brain: Disruption of the blood-brain barrier can cause cerebral oedema, headaches, and seizures (eclampsia) (2).

• Systemic Vasculature: Widespread vasospasm causes hypertension, while increased vascular permeability leads to oedema (2).

Clinical Presentation

The presentation of pre-eclampsia is highly variable, ranging from completely asymptomatic to a life-threatening emergency (3). Many cases are first detected during routine antenatal screening through elevated blood pressure readings or proteinuria (3, 5).

Diagnostic Clues:

The diagnosis is built on a constellation of findings rather than a single pathognomonic sign (3, 15).

Common Symptoms (>50%):

• Hypertension: A sustained blood pressure of ≥140 mmHg systolic or ≥90 mmHg diastolic is the cornerstone of diagnosis (4, 6, 7).

• Proteinuria: While no longer essential for diagnosis if other end-organ damage is present, it remains a key sign (4, 6).

• Headache: Often described as frontal or occipital, throbbing, and persistent (5).

• Edema: Sudden, non-dependent swelling, particularly of the face and hands, is suspicious, though it is no longer a formal diagnostic criterion (3).

Less Common Symptoms (10-50%):

• Nausea and Vomiting: Can be mistaken for heartburn but is more severe and does not respond to antacids (5).

⚠️ Red Flag Signs & Symptoms:

The following indicate severe disease and require immediate, urgent clinical action:

• Severe Headache: A persistent headache that is unresponsive to standard analgesia like paracetamol (5, 6).

• Visual Disturbances: Blurred vision, flashing lights (photopsia), or dark spots (scotomata) suggest cerebral vasospasm and oedema (5, 6).

• Epigastric or Right Upper Quadrant (RUQ) Pain: A cardinal symptom of liver involvement due to stretching of the liver capsule (5).

• Shortness of Breath (Dyspnoea): Highly alarming as it may signal the onset of life-threatening pulmonary oedema (12).

• Reduced Fetal Movements: Can be a sign of acute or chronic fetal compromise resulting from placental insufficiency (3).

• Hyperreflexia and Clonus: Signs of central nervous system irritability that indicate a lowered seizure threshold (15).

Complications

• Maternal (Acute):

  • Neurological: Eclampsia (seizures), cerebral haemorrhage (stroke) (5, 12).

  • Hepatic: HELLP Syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets), liver rupture (11, 12).

  • Renal: Acute kidney injury, oliguria (12).

  • Cardiopulmonary: Pulmonary oedema, cardiac failure (12).

  • Haematological: Thrombocytopenia, Disseminated Intravascular Coagulation (DIC) (7, 15).

• Fetal:

  • Fetal Growth Restriction (FGR) due to chronic placental insufficiency (5).

  • Placental abruption (12).

  • Iatrogenic preterm birth (11).

Prognosis

While most women with pre-eclampsia recover fully after delivery, the condition carries significant risks. It is a leading cause of maternal death globally, with case fatality rates being significantly higher in low-resource settings (8, 10). For the infant, prematurity is the major determinant of outcome (5). Importantly, a history of pre-eclampsia doubles a woman's long-term risk of developing chronic hypertension, ischaemic heart disease, and stroke, unmasking a latent cardiovascular vulnerability (9, 14).

Differential Diagnosis

Gestational Hypertension: This is diagnosed when there is new-onset hypertension (≥140/90 mmHg) after 20 weeks of gestation without proteinuria or other signs of end-organ dysfunction (7). It is a crucial differential because a significant proportion of these women will progress to develop pre-eclampsia, mandating close surveillance (7).

Chronic Hypertension: This refers to hypertension present before pregnancy or diagnosed before 20 weeks of gestation (6). It is a major risk factor for developing superimposed pre-eclampsia. Differentiating a flare of chronic hypertension from superimposed pre-eclampsia can be challenging, but the new onset of proteinuria or other severe features after 20 weeks points towards the latter (7).

Other causes of hypertension with organ dysfunction: Conditions like thrombotic thrombocytopenic purpura (TTP), haemolytic uremic syndrome (HUS), or an acute flare of systemic lupus erythematosus (SLE) can mimic pre-eclampsia. The clinical context, timing of onset, and specific laboratory profiles are key to distinguishing these.

Investigations

Immediate & Bedside Tests

• Accurate Blood Pressure Measurement: This is the foundational diagnostic step, requiring a correctly sized cuff on a rested, seated patient with their arm at heart level to confirm sustained hypertension (6, 7).

• Urine Dipstick: This is a crucial bedside screening tool to detect proteinuria (a result of 1+ or greater is significant) (6), which must then be quantified to confirm the diagnosis and assess severity (6).

Diagnostic Workup

• First-Line Investigations:

  • Urine Protein:Creatinine Ratio (P:Cr): "The initial quantitative test of choice is a spot urine P:Cr. It is highly convenient and reliable for confirming significant proteinuria (a ratio of ≥30 mg/mmol is diagnostic) (the rationale), which helps to formally establish a key diagnostic criterion without the delay of a 24-hour collection (the action)." (6)

• Gold Standard:

  • While historically a 24-hour urine protein collection was the gold standard, it is now reserved for cases with diagnostic uncertainty due to its inconvenience and potential for inaccuracy (4, 6). The definitive diagnosis rests on the combination of hypertension and evidence of end-organ dysfunction (4).

Monitoring & Staging

This panel of blood tests, often called "pre-eclampsia labs," is critical not just for diagnosis but for staging the severity of the disease by assessing multi-organ involvement (3, 7).

• Full Blood Count (FBC): "An urgent FBC is essential to identify thrombocytopenia (platelets <100,000 x 10⁹/L is a severe feature) or evidence of haemolysis (the rationale), which are critical for diagnosing HELLP syndrome and assessing bleeding risk before delivery (the action)." (7, 11)

• Renal Function Panel (Urea, Electrolytes, Creatinine): "This panel is vital to detect acute kidney injury (a creatinine >97 µmol/L or a doubling of baseline is a severe feature) (the rationale), guiding fluid management and the need for potential nephrology input (the action)." (4, 7)

• Liver Function Tests (LFTs): "Ordering LFTs is mandatory to check for hepatocellular injury; transaminases (AST/ALT) rising to twice the upper limit of normal signify severe disease (the rationale), indicating liver involvement which is a key component of the HELLP syndrome and a high-risk feature (the action)." (4, 7)

• Uric Acid: "Although no longer a primary diagnostic criterion, serial uric acid measurement is useful to monitor disease progression (the action), as rising levels are a sensitive marker of worsening placental ischaemia and correlate with adverse fetal outcomes (the rationale)." (4, 7)

• Fetal Surveillance:

  • Cardiotocography (CTG): This is performed regularly to assess acute fetal well-being (the action), as placental dysfunction can lead to fetal hypoxia, reflected in heart rate abnormalities (the rationale) (5).

  • Ultrasound with Umbilical Artery Doppler: "Serial growth scans and Doppler studies are fundamental to monitor for fetal growth restriction and assess placental health (the action), as progressively abnormal Doppler flow (absent or reversed end-diastolic flow) indicates severe placental insufficiency and is a key trigger for recommending delivery (the rationale)." (5, 6)

Management

Management Principles

The management of pre-eclampsia revolves around balancing maternal and fetal risks, with the ultimate goals being the prevention of maternal seizures (eclampsia) and other major complications, and timing the delivery to optimise outcomes for both (5, 12). Delivery of the placenta is the only definitive cure (5).

Acute Stabilisation (The First Hour)

• Airway/Breathing: "Administer high-flow oxygen via a non-rebreather mask to maintain SpO₂ >94% (the action), which is crucial to prevent tissue hypoxia driven by vasospasm and potential pulmonary oedema (the rationale)." (12)

• Circulation: For acute severe hypertension (SBP ≥160 mmHg or DBP ≥110 mmHg), immediate antihypertensive therapy is critical. "Secure intravenous access and administer a stat dose of an appropriate agent like IV Labetalol 20mg (the action) to lower the blood pressure into a safer range (target <160/110 mmHg), which is the most important intervention to prevent a maternal stroke (the rationale)." (7, 15)

• Disability (Seizure Prophylaxis): For women with severe features of pre-eclampsia, seizure prophylaxis is paramount. "Commence a loading dose of IV Magnesium Sulphate (4-6g over 20-30 minutes) (the action), as it is the undisputed drug of choice for preventing eclampsia by stabilising cerebral hyperexcitability (the rationale)." (6, 12)

Definitive Therapy

• First-Line Treatment (Severe Hypertension):

  • IV Labetalol: Preferred agent. Dose: 20mg IV bolus, followed by 40mg, then 80mg every 10-15 minutes (max 300mg) or an infusion (15). Avoid in asthma (15).

  • Oral Nifedipine: An effective oral option if IV access is difficult. Dose: 10-20mg immediate-release capsule, repeated in 20-30 minutes if needed (15).

  • IV Hydralazine: Less commonly used now due to a less predictable response and more side effects (reflex tachycardia, headache) (15).

• Timing of Delivery: This is the most critical decision.

  • Pre-eclampsia without Severe Features: Delivery is recommended at 37+0 weeks (6, 7).

  • Pre-eclampsia with Severe Features: Delivery is recommended at or after 34+0 weeks following maternal stabilisation (7).

  • Preterm Severe Pre-eclampsia (<34 weeks): Expectant management may be considered in a tertiary centre to allow for administration of corticosteroids for fetal lung maturity, but this requires intensive monitoring and must be abandoned if the maternal or fetal condition deteriorates (6, 7).

Supportive & Symptomatic Care

• Fluid Management: A policy of fluid restriction is crucial. "Maintain total fluids (IV and oral) at approximately 80-125 mL/hour (the action) to prevent fluid overload and pulmonary oedema, which is a significant risk due to leaky capillaries (the rationale)." (12)

• Antenatal Corticosteroids: "For women likely to deliver before 34 weeks, administer a course of Betamethasone (e.g., 12mg IM, 2 doses 24 hours apart) (the action) to accelerate fetal lung maturation and reduce the risk of neonatal respiratory distress syndrome (the rationale)." (6)

Key Nursing & Monitoring Instructions

• Strict hourly input/output chart monitoring to detect oliguria (<30 mL/hr) (12).

• 4-hourly blood pressure checks (more frequently if unstable) (6).

• Regularly assess for red flag symptoms (headache, visual changes, epigastric pain) (6).

• Perform hourly clinical checks for magnesium toxicity in patients on MgSO₄ infusion: check patellar reflexes, respiratory rate (>12/min), and urine output (12).

• Inform medical staff immediately if SBP ≥160 mmHg, DBP ≥110 mmHg, or if there are any new neurological signs.

Long-Term Plan & Patient Education

• Postpartum Monitoring: Continue close blood pressure monitoring for at least 72 hours postpartum, as the disease can worsen or even present for the first time after delivery (5).

• Future Pregnancy: Counsel the patient on her increased risk of recurrence in future pregnancies and the importance of early antenatal booking and low-dose aspirin prophylaxis (commenced between 12-16 weeks) (5, 13).

• Long-Term Health: Educate the patient that a history of pre-eclampsia significantly increases her lifetime risk of cardiovascular disease. Advise on lifestyle modifications and the need for regular follow-up with her primary care doctor for cardiovascular risk screening (9, 14).

When to Escalate

Call Your Senior (MO/Specialist) if:

• Blood pressure remains ≥160/110 mmHg despite initial treatment.

• The patient develops any new neurological signs (severe headache, visual disturbances, clonus).

• The patient reports severe epigastric or RUQ pain.

• The patient develops shortness of breath or SpO₂ drops below 95%.

• Urine output is <0.5mL/kg/hr for more than 2 consecutive hours.

• There are signs of magnesium toxicity (loss of reflexes, respiratory depression).

• The CTG becomes non-reassuring.

Referral Criteria:

• Refer to the Anaesthetic team early for labour analgesia planning and potential operative delivery. Neuraxial anaesthesia is preferred but requires assessment of platelet count (15).

• Refer to the Neonatology team when preterm delivery is anticipated to counsel the parents and prepare for the resuscitation and care of a premature infant (5).

• Refer to the Nephrology team if acute kidney injury does not resolve postpartum.

• Consider referral to Intensive Care (ICU) for any patient with eclampsia, uncontrolled severe hypertension, pulmonary oedema, or HELLP syndrome.

References

1. Karim, R., Ibrahim, N. R., Norkhafizah, S., Zaleha, M. I., & Muhammad, H. (2022). Prevalence, maternal characteristics, and birth outcomes of preeclampsia: A cross-sectional study in a single tertiary healthcare center in greater Kuala Lumpur Malaysia. Frontiers in Medicine, 9, 991825. https://pmc.ncbi.nlm.nih.gov/articles/PMC9618654/

2. Myatt, L., & Webster, R. P. (2009). Pre-eclampsia part 1: current understanding of its pathophysiology. BJOG: An International Journal of Obstetrics & Gynaecology, 116(1), 127-130. https://pmc.ncbi.nlm.nih.gov/articles/PMC5893150/

3. BMJ Best Practice. (2023). Pre-eclampsia. BMJ Publishing Group. https://bestpractice.bmj.com/topics/en-gb/326

4. The ObG Project. (2017). Diagnosing Preeclampsia - Key Definitions and ACOG Guidelines. https://www.obgproject.com/2017/01/08/diagnosing-preeclampsia-key-definitions/

5. Royal College of Obstetricians & Gynaecologists. (2022). Pre-eclampsia. https://www.rcog.org.uk/for-the-public/browse-our-patient-information/pre-eclampsia/

6. National Institute for Health and Care Excellence. (2019). Hypertension in pregnancy: diagnosis and management (NG133). https://www.nice.org.uk/guidance/ng133/chapter/recommendations

7. American College of Obstetricians and Gynecologists. (2020). Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstetrics & Gynecology, 135(6), e237-e260. https://www.preeclampsia.org/frontend/assets/img/advocacy_resource/Gestational_Hypertension_and_Preeclampsia_ACOG_Practice_Bulletin._Number_222_1605448006.pdf

8. Fox, R., Kitt, J., Leeson, P., Aye, C. Y., & Lewandowski, A. J. (2019). Preeclampsia: Risk Factors, Diagnosis, Management, and the Cardiovascular Impact on the Offspring. Journal of Clinical Medicine, 8(10), 1625. https://pmc.ncbi.nlm.nih.gov/articles/PMC6832549/

9. American Heart Association. (2021). Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals, and Pharmacotherapy. Professional Heart Daily. https://professional.heart.org/en/science-news/-/media/3B48324198D14BB89ADF08DA631403AE.ashx

10. International Federation of Gynecology and Obstetrics. (n.d.). FIGO guideline: First-trimester screening and prevention of pre-term pre-eclampsia. https://assets-global.website-files.com/65e8860735b421bef93b7330/67ff36b5b47f03aab660f0ff_tugero.pdf

11. Carnegie Imaging. (n.d.). Differences between Preeclampsia and Eclampsia. https://www.carnegieimaging.com/blog/preeclampsia-eclampsia-understanding-difference/

12. MSD Manual Professional Version. (n.d.). Preeclampsia and Eclampsia. https://www.msdmanuals.com/professional/gynecology-and-obstetrics/antenatal-complications/preeclampsia-and-eclampsia

13. Cui, Y., Zhu, B., & Zheng, F. (2018). Low-dose aspirin at ≤16 weeks of gestation for preventing preeclampsia and its maternal and neonatal adverse outcomes: A systematic review and meta-analysis. Experimental and Therapeutic Medicine, 15(5), 4361–4369. https://www.spandidos-publications.com/10.3892/etm.2018.5972

14. Phipps, E. A., Thadhani, R., Benzing, T., & Karumanchi, S. A. (2019). Preeclampsia: Pathogenesis, Diagnosis, and Management. New England Journal of Medicine, 380(8), 757–766.

15. Life in the Fast Lane (LITFL). (2019). Pre-eclampsia. https://litfl.com/pre-eclampsia/