creation date: 2025-07-21 19:05
tags: Pathologies
Preeclampsia
Background
Definitions
Preeclampsia is a multisystem progressive disorder that is characterized by new-onset after 20 weeks gestation.
This condition is part of a group of disorders known as hypertensive disorders of pregnancy, which consist of:
- Chronic hypertension with or without superimposed pre-eclampsia/eclampsia
- Gestational hypertension
- Preeclampsia
- Hemolysis, elevated liver enzyme, and low platelet count (HELLP) syndrome
- Eclampsia
These conditions presents a significant risk of morbidity to both mother and fetus, with the primary concern being the progression to preeclampsia/eclampsia and HELLP syndrome.
Etiology and Pathogenesis
The pathogenesis of preeclampsia mirrors that of gestational hypertension:
Placental malfunction has the largest contribution. Abnormal growth resulting in superficial and partial invasion into the maternal arteries result in high-resistance and thin spiral arteries. Typically, pro-angiogenic factors are lacking and with the reduced angiogenesis, results in ischemia and subsequent oxidative stress. This harms placental cells and releases anti-angiogenic substances and inflammatory cytokines into the maternal bloodstream.
Endothelial dysfunction leads to a disruption in vascular homeostasis and health. Reactive oxygen species produced from ischemic damage, in addition to antiangiogenic factors, and inflammatory factors results in widespread maternal vascular inflammation and injury which leads to hypertension, vasospasm, platelet adhesion and aggregation, proteinuria, and other clinical manifestations.
In addition to these factors, other components contribute to worsening conditions:
- Immune maladaptation to semi-allogenic fetus
- Genetic and epigenetic factors
- Pre-existing renal pathologies that reduces blood pressure regulatory ability
Clinical Presentation
Signs & Symptoms
New onset:
- Hypertension
- Proteinuria
Sudden onset facial edema may suggest preeclampsia and warrants evaluation.
Other features may be present:
- Thrombocytopenia
- Impaired renal function
- Impaired liver function
- Pulmonary edema
- Headache
- Visual disturbances
- Abdominal pain
History & Physical Exam
Blood pressure measurements should be documented at each prenatal appointment. While diagnoses are made following 20 weeks gestation, measurements made prior to 20 weeks can be used as a baseline.
However, in cases of severe elevations (SBP ≥160 mmHg and/or DBP ≥110 mmHg), wait is not recommended.
History elucidating seizures would upstage diagnosis to eclampsia.
Risk factors
Risk factors are similar to gestational hypertension. High risk factors include:
- Past history of gestational/chronic hypertension and/or pre-eclampsia
- Pre-existing diabetes
- Chronic kidney disease
- Multifetal pregnancy
- Autoimmune disease with potential vascular complications (eg. antiphospholipid syndrome, systemic lupus erythematosus)
Moderate risk factors include:
- Nulliparity
- Pre-pregnancy overweight or obesity (BMI ≥25 and risk doubles with each 5-7 increase in BMI)
- Family history of preeeclampsia (mother or sister)
- Prior pregnancy complications relating to placental insufficiency
- Advanced maternal age or adolescent pregnancy
- Use of reproductive technology
In patients with high-risk factors, initiate prophylactic treatment. Consider doing so for moderate risk.
Diagnosis
Criteria
Preeclampsia without severe features:
- Hypertension (> 140/90 mmHg)
- Proteinuria, as evidenced by any of the following:
- 24-hour urine collection: ≥300 mg/24 hours
- Urine protein:creatinine ratio ≥0.3
- Urine dipstick: >2+ protein
Preeclampsia with severe features:
- Gestational hypertension, plus ≥1 of the following:
- Severe hypertension (≥160 / ≥110 mmHg)
- Thrombocytopenia (platelets <100,000)
- Impaired renal function (serum creatinine >88 mcmol/L or doubling)
- Impaired liver function (≥2x ULN transminases or severe RUQ/epigastric pain; not explained by other diagnoses)
- Pulmonary edema
- New onset of either:
- Headache unresponsive to medication
- Visual disturbances
Work-up
Following the confirmation of hypertension, patients with suspected preeclampsia should have the following routine testing:
- Complete blood count with platelets
- Serum creatinine
- Liver chemistries (AST, ALT, bilirubin)
- Quantitative urinary protein
Additional lab testing if needed includes:
- Lactate dehydrogenase (if liver chemistries abnormal)
- Coagulation studies (if complications such as placental abruption)
- Glucose, amylase, lipase, ammonia (if upper abdominal pain or liver dysfunction)
- ADAMTS13 activity (if thrombocytopenic purpura suspected)
Assessment of fetal status can be made based on degree of concern such as:
- Nonstress test or biophysical profile
- Ultrasound for amniotic fluid volume and fetal weight
Differential
The primary differentials generally consist of additional signs/symptoms upstaging preeclampsia diagnosis:
- Eclampsia (new-onset seizures)
- HELLP syndrome (hemolysis, elevated liver enzymes, low platelets)
Hypertension may be caused by pre-existing states such as chronic hypertension or chronic kidney disease.
Severe features appearing to be due to preeclampsia may be due to alternative etiologies.
Red Flags / Complications
Patients with preeclampsia are at an increased risk for life-threatening obstetrics and/or medical complications such as:
- Cerebrovascular hemorrhage
- Pulmonary edema
- Acute kidney injury
- Liver rupture
- Eclampsia
Preeclampsia can also lead to growth restriction and oligohydramnios. It can also result in indicated preterm birth. Long-term risks include increased risk of complications in future pregnancies.
Management
Prevention
Prevention of preeclampsia is indicated for high-risk patients and some moderate-risk patients (≥2 moderate risk factors).
- Aspirin 162 mg PO daily until delivery
- Calcium supplementation of >500 mg/d if low dietary intake (<900 mg/d)
- Exercise
Non-pharmacological
Consultation to neurology may be warranted if there are signs of neurologic deficits, abnormal neurologic exam, ocular signs and symptoms, or persistent headache that does not respond to acetaminophen.
The only true resolution to preeclampsia is delivery. As such, prenatal care is based on monitoring of symptoms. This monitoring should continue postpartum as end-organ dysfunction may occur in the few days postpartum and in some cases blood pressure does not return to normal following delivery.
Pharmacological / Interventional
For patients with moderate- and high-risk of developing preeclampsia, low-dose aspirin may reduce the occurrence.
Once diagnosis has been made:
- Antihypertensive therapy for the treatment of gestational hypertension
- Magnesium sulfate to prevent seizures (eclampsia); note that magnesium must be monitored and calcium gluconate used to treat hypermagnesemia.
For patients with preeclampsia with severe features, delivery may be necessary. The indication depends on the gestational age and stability of the mother and fetus:
If gestational age ≥34+0 weeks, delivery is generally indicated.
If gestational age is <34+0 weeks, delivery is generally indicated if:
- Maternal or fetal instability
- Pregnancy has not reached the gestational age for the lower limit of neonatal viability (approximately 22-25 weeks)
If gestational age is <34+0 weeks but above the earliest gestational age which neonatal resuscitation is possible, expectant management may be reasonable for some pregnancies which would allow for antenatal corticosteroids and further fetal growth. This may be feasible if:
- Both mother and fetus are stable
- Both mother and fetus can be closely monitored in hospital with appropriate level of newborn care
- Care from maternal-fetal specialist/neonatologist is available
For patients without severe features, management is based on gestational age.
If gestational age ≥37+0 weeks, delivery is generally indicated.
If gestational age <34+0 weeks, the approach is generally expectant management with close monitoring for progression to severe features.
If gestational age is between 34+0 to 36+6 weeks, the evidence is less clear. While expectant management can be associated with maternal risk, a fully informed decision to use an expectant approach until 37+0 weeks is reasonable as the maternal risk of serious outcome is low for modest neonatal benefits.
Expectant management should include educating patients about:
- Signs and symptoms of severe features
- Restricted activity and rest to reduce blood pressure (unclear evidence)
Laboratory follow-up for platelet count, serum creatinine, and serum aminotransferases should occur twice weekly to assess for disease progression. Fetal assessments (non-stress test and amniotic fluid volume) should also be done twice weekly.
Antenatal corticosteroids (betamethasone or dexamethasone) should be administered if birth within the next 7 days is likely and neonatal resuscitation will be performed.