Science-based guidance for women for their bodies
Preeclampsia is defined as new-onset hypertension (blood pressure ≥140/90 mmHg) occurring after 20 weeks of gestation, accompanied by proteinuria or other signs of end-organ dysfunction. The condition represents a pregnancy-specific syndrome that reflects widespread maternal endothelial dysfunction triggered by factors released from a dysfunctional placenta.
Hypertensive disorders of pregnancy form a spectrum of conditions that must be carefully differentiated for appropriate management. Chronic hypertension exists before pregnancy or develops before 20 weeks. Gestational hypertension involves elevated blood pressure after 20 weeks without proteinuria or organ dysfunction. Preeclampsia superimposed on chronic hypertension occurs when a woman with pre-existing hypertension develops new proteinuria or other signs of organ dysfunction.
Modern understanding conceptualizes preeclampsia as a two-stage disease. Stage 1 involves abnormal placentation during the first trimester, when trophoblast invasion of the spiral arteries is shallow or incomplete. Stage 2 occurs later in pregnancy when the poorly perfused placenta releases factors into the maternal circulation that cause widespread endothelial dysfunction and the clinical syndrome of preeclampsia.
The origins of preeclampsia begin in the first weeks of pregnancy, long before any clinical symptoms appear. Understanding this early pathology is essential for appreciating why the condition remains so difficult to prevent and treat.
In normal pregnancy, specialized cells called extravillous trophoblasts invade the decidua and myometrium, transforming the spiral arteries from narrow, muscular vessels into wide, low-resistance channels. This remodeling dramatically increases blood flow to the intervillous space, meeting the growing metabolic demands of the fetus. By 18-20 weeks of normal pregnancy, spiral artery transformation is complete, increasing vessel diameter by 5-10 fold.
In preeclampsia, trophoblast invasion is shallow and incomplete, affecting only the decidual portions of the spiral arteries while leaving the myometrial segments unremodeled. These narrow, high-resistance vessels cannot adequately perfuse the placenta, resulting in placental ischemia and hypoxia. The stressed placenta then releases an array of factors that trigger the maternal syndrome.
Chronic placental hypoxia triggers multiple adaptive and maladaptive responses. The placenta upregulates hypoxia-inducible factors, increases production of anti-angiogenic factors like soluble fms-like tyrosine kinase 1 (sFlt-1), and decreases production of pro-angiogenic factors like placental growth factor (PlGF). This imbalance of angiogenic factors is central to the maternal vascular dysfunction that characterizes preeclampsia.
The clinical manifestations of preeclampsia result from widespread maternal endothelial dysfunction caused by placental factors entering the maternal circulation.
Soluble fms-like tyrosine kinase 1 (sFlt-1): This protein binds and neutralizes vascular endothelial growth factor (VEGF) and PlGF, disrupting their normal protective effects on the endothelium. sFlt-1 levels are markedly elevated in preeclampsia and correlate with disease severity.
Soluble endoglin (sEng): This factor interferes with transforming growth factor-β signaling, further impairing endothelial function. When combined with elevated sFlt-1, soluble endoglin dramatically increases the risk of severe preeclampsia and HELLP syndrome.
Endothelial dysfunction leads to the classic features of preeclampsia through several mechanisms:
Vasoconstriction: Loss of endothelial-dependent vasodilation causes hypertension
Increased permeability: Damage to the endothelial barrier allows proteins to leak into tissues and urine
Activation of coagulation: Endothelial injury triggers platelet aggregation and microthrombi formation
End-organ damage: These processes combine to produce injury in the brain, liver, kidneys, and other organs
Preeclampsia involves significant immune dysregulation, reflecting the delicate immunological balance required for successful pregnancy.
Successful pregnancy requires tolerance of the semi-allogenic fetus while maintaining immune competence. In preeclampsia, this balance is disrupted. Decreased regulatory T cells, increased inflammatory cytokines, and altered natural killer cell function all contribute to defective placentation and subsequent disease manifestations.
Normal pregnancy involves a controlled inflammatory state that intensifies as term approaches. In preeclampsia, this inflammation is exaggerated and poorly controlled. Elevated levels of tumor necrosis factor-α, interleukin-6, and other inflammatory mediators contribute to endothelial activation and dysfunction.
Multiple maternal characteristics increase the risk of developing preeclampsia, though many women with these risk factors will have uneventful pregnancies while some women without identifiable risk factors will develop the condition.
Previous preeclampsia: History of preeclampsia increases risk by 7-8 fold
Nulliparity: First pregnancies carry 2-3 times higher risk than subsequent pregnancies
New paternity: Changing partners partially "resets" the protective effect of prior pregnancy
Pregnancy interval: Intervals longer than 10 years increase risk similar to first pregnancies
Previous adverse outcomes: Prior stillbirth, placental abruption, or fetal growth restriction increase risk
Chronic hypertension: 15-25% of women with chronic hypertension develop superimposed preeclampsia
Diabetes mellitus: Pre-existing or gestational diabetes doubles the risk
Chronic kidney disease: Risk increases with degree of renal impairment
Autoimmune diseases: Systemic lupus erythematosus and antiphospholipid syndrome significantly increase risk
Obesity: BMI >30 doubles the risk; BMI >35 triples it
Age: Maternal age over 40 increases risk by 2-fold; teenage pregnancies also have elevated risk
Race/ethnicity: Black women have 1.5-2 times higher risk than white women, with higher rates of severe disease
Socioeconomic status: Lower education and income levels are associated with increased risk
Family history: Mother or sister with preeclampsia doubles the risk
Certain characteristics of the current pregnancy independently increase preeclampsia risk.
Twin pregnancies have 2-3 times higher risk of preeclampsia than singleton pregnancies, with higher-order multiples having even greater risk. The increased placental mass and enhanced placental demands may explain this association. Multiple gestation preeclampsia also tends to occur earlier in pregnancy and with greater severity.
Pregnancies conceived through IVF and other assisted reproductive technologies carry 1.5-2 times higher risk of preeclampsia. Donor oocyte pregnancies have particularly elevated risk (2-4 fold increase), supporting the role of immune factors in preeclampsia pathogenesis—the genetic dissimilarity between mother and fetus may impair normal placentation.
Molar pregnancy: Dramatically increased risk, with preeclampsia occurring before 20 weeks in complete molar pregnancies
Triploidy: Chromosomally abnormal pregnancies with excess placental tissue
Hydrops fetalis: Associated with increased placental mass and preeclampsia risk
Preeclampsia can present with a wide spectrum of findings, from asymptomatic blood pressure elevation detected at routine prenatal visits to fulminant multi-organ failure.
Elevated blood pressure is the hallmark of preeclampsia. Diagnostic criteria require systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg on two occasions at least 4 hours apart after 20 weeks of gestation. Severe hypertension (systolic ≥160 mmHg or diastolic ≥110 mmHg) requires urgent treatment to prevent stroke and other complications.
Protein in the urine reflects glomerular endothelial damage. Significant proteinuria is defined as ≥300 mg in a 24-hour urine collection, protein/creatinine ratio ≥0.3 mg/dL, or persistent 2+ on urine dipstick. However, proteinuria is no longer required for diagnosis if other severe features are present.
While edema is common in normal pregnancy, sudden or severe edema—particularly of the face and hands—may signal preeclampsia. Rapid weight gain (more than 2 pounds per week) can indicate fluid retention. However, edema alone is not diagnostic and many women with preeclampsia have minimal swelling.
The distinction between preeclampsia with and without severe features is crucial for management decisions and prognosis.
Systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg on two occasions at least 4 hours apart (or once if antihypertensive therapy is initiated) indicates severe disease requiring immediate treatment and close monitoring.
Severe headache: Persistent, often described as "worst headache of life"
Visual disturbances: Blurred vision, photopsia (flashing lights), scotomata (blind spots), or cortical blindness
Altered mental status: Confusion, agitation, or decreased consciousness
Hyperreflexia with clonus: Sign of cerebral irritability that may precede seizures
Right upper quadrant or epigastric pain: Indicates liver capsule distension
Elevated liver enzymes: AST or ALT greater than twice normal
Subcapsular hematoma: Rare but life-threatening complication
Hepatic rupture: Catastrophic complication with high mortality
Serum creatinine greater than 1.1 mg/dL or doubling of baseline creatinine indicates severe disease. Oliguria (urine output less than 500 mL in 24 hours) may occur in advanced cases. Acute kidney injury complicates 1-2% of preeclampsia cases and usually resolves after delivery.
Any ONE of the following indicates severe preeclampsia:
• Systolic BP ≥160 mmHg or diastolic BP ≥110 mmHg
• Platelet count <100,000/μL
• Liver enzymes elevated to twice normal with right upper quadrant or epigastric pain
• Serum creatinine >1.1 mg/dL or doubling of baseline
• Pulmonary edema
• New-onset headache unresponsive to medication
• Visual disturbances
Preeclampsia does not always follow the classical pattern, and atypical presentations can lead to delayed diagnosis.
Preeclampsia developing before 34 weeks is considered early-onset and typically reflects more severe placental pathology. Early-onset disease carries higher risks of maternal complications, fetal growth restriction, and adverse neonatal outcomes. It accounts for approximately 10-15% of preeclampsia cases but contributes disproportionately to maternal and perinatal mortality.
Preeclampsia can develop for the first time after delivery, typically within 48 hours but sometimes up to 6 weeks postpartum. Late postpartum preeclampsia (occurring more than 48 hours after delivery) is increasingly recognized and requires high clinical suspicion, as women may have been discharged from hospital care.
Rarely, preeclampsia can present with proteinuria and severe features before significant hypertension develops. This "normotensive" preeclampsia is dangerous because it may not trigger usual warning protocols. Serial blood pressure monitoring and attention to other symptoms are essential.
HELLP syndrome represents one of the most severe manifestations of the preeclampsia spectrum, characterized by Hemolysis, Elevated Liver enzymes, and Low Platelets.
Hemolysis: Abnormal peripheral blood smear with schistocytes, elevated LDH (>600 U/L), elevated total bilirubin (>1.2 mg/dL)
Elevated Liver enzymes: AST or ALT >2 times upper limit of normal
Low Platelets: Platelet count <100,000/μL
Complete HELLP syndrome requires all three criteria; partial HELLP involves one or two features.
HELLP syndrome often presents with non-specific symptoms that can mimic other conditions. Right upper quadrant or epigastric pain occurs in 40-90% of cases. Nausea and vomiting are common. Malaise and fatigue may be attributed to normal pregnancy discomforts. Notably, 15-20% of women with HELLP syndrome do not have hypertension or proteinuria at presentation, making diagnosis challenging.
Disseminated intravascular coagulation (DIC): Occurs in 20-40% of cases
Placental abruption: Complicates 16% of HELLP cases
Acute kidney injury: Occurs in 8-10% of patients
Hepatic hemorrhage or rupture: Rare but potentially fatal
Pulmonary edema and ARDS: Can develop rapidly
Stroke: Risk increased especially with severe hypertension
Eclampsia is defined as new-onset tonic-clonic seizures in a woman with preeclampsia that cannot be attributed to other causes. It represents a neurological emergency with significant maternal and fetal risks.
Eclamptic seizures result from cerebral endothelial dysfunction, disruption of the blood-brain barrier, and cerebral edema. Posterior reversible encephalopathy syndrome (PRES) is commonly seen on brain imaging. The mechanism involves loss of cerebral autoregulation, allowing blood pressure surges to cause vasogenic edema primarily in the posterior brain regions.
Antepartum: Approximately 38-53% of cases occur before delivery
Intrapartum: 18-36% occur during labor and delivery
Postpartum: 11-44% occur after delivery, sometimes several days later
Late postpartum eclampsia (occurring more than 48 hours after delivery) accounts for approximately 16% of cases.
While eclampsia can occur without warning, many women experience prodromal symptoms:
Severe persistent headache: Present in 50-70% of cases before seizure
Visual disturbances: Reported by 20-30% of women
Right upper quadrant pain: Especially with HELLP syndrome
Hyperreflexia and clonus: Signs of cerebral irritability
However, 20-25% of women have no warning signs before their first seizure.
Accurate diagnosis of preeclampsia requires careful clinical assessment combined with appropriate laboratory testing.
Proper technique is essential for accurate diagnosis:
• Patient should be seated and resting for 5 minutes
• Appropriate cuff size (bladder encircling 80% of arm circumference)
• Arm supported at heart level
• Two measurements at least 4 hours apart to confirm diagnosis
• In severe cases, one severely elevated measurement justifies treatment initiation
24-hour urine collection: Gold standard for quantifying proteinuria; ≥300 mg is significant
Protein/creatinine ratio: Acceptable alternative; ≥0.3 mg/dL is significant
Urine dipstick: Screening tool only; 2+ is suspicious but requires confirmation
Urinalysis: May show red blood cells and casts in severe cases
A comprehensive laboratory evaluation helps confirm diagnosis, assess severity, and guide management.
Hemoglobin/hematocrit: May be elevated due to hemoconcentration; falling values may indicate hemolysis
Platelet count: <100,000/μL indicates severe disease; declining trend is concerning
Peripheral smear: Schistocytes and helmet cells indicate microangiopathic hemolytic anemia
AST and ALT: Elevation to twice normal indicates severe disease
LDH: Elevated with hemolysis; often >600 U/L in HELLP syndrome
Bilirubin: Elevated with hemolysis
Albumin: May be decreased, contributing to edema
Serum creatinine: >1.1 mg/dL or doubling indicates severe disease
BUN: May be elevated with renal dysfunction
Uric acid: Often elevated in preeclampsia; values >5.5 mg/dL correlate with severity
Initial evaluation:
• Complete blood count with platelet count
• Comprehensive metabolic panel (creatinine, AST, ALT)
• LDH
• Urine protein quantification
Additional tests in severe cases:
• Peripheral blood smear
• Coagulation studies (PT, PTT, fibrinogen)
• Uric acid
• Typing and screening (anticipating possible transfusion)
Novel biomarkers are increasingly used to aid diagnosis and risk stratification.
The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) has emerged as a valuable diagnostic and prognostic tool. An sFlt-1/PlGF ratio <38 has high negative predictive value for preeclampsia developing within one week. A ratio >85 (>110 if <34 weeks) has high positive predictive value for preeclampsia within 4 weeks.
Preeclampsia affects the fetus through reduced placental perfusion and direct effects of the disease process on fetal well-being.
Intrauterine growth restriction (IUGR) complicates 25-30% of preeclampsia cases, particularly in early-onset disease. Chronic placental insufficiency limits nutrient and oxygen delivery, resulting in asymmetric growth restriction where the fetal brain is preferentially spared. Severe growth restriction increases risks of stillbirth and neonatal complications.
Reduced amniotic fluid volume reflects decreased fetal urine production due to redistribution of blood flow away from the fetal kidneys. Oligohydramnios is associated with poorer outcomes and may indicate need for delivery. Amniotic fluid index below 5 cm or single deepest pocket below 2 cm warrants concern.
The risk of placental abruption (premature separation of the placenta from the uterine wall) is increased 3-fold in preeclampsia. Abruption can cause acute fetal distress, hemorrhage, and maternal DIC. Warning signs include vaginal bleeding, abdominal pain, uterine tenderness, and fetal heart rate abnormalities.
Regular fetal surveillance is essential to assess fetal well-being and determine optimal timing of delivery.
Non-stress tests (NST) assess fetal heart rate reactivity and are typically performed 1-2 times weekly in preeclampsia without severe features, and more frequently in severe disease. A reactive NST (with adequate accelerations) is reassuring, while a non-reactive test requires further evaluation.
The biophysical profile (BPP) combines NST with ultrasound assessment of fetal breathing movements, body movements, tone, and amniotic fluid volume. Scores of 8-10 are reassuring; 6 is equivocal; 4 or below indicates fetal compromise and typically mandates delivery.
Umbilical artery Doppler: Assesses placental resistance; absent or reversed end-diastolic flow is ominous
Middle cerebral artery Doppler: Low resistance indicates fetal brain-sparing response to hypoxia
Ductus venosus Doppler: Abnormalities indicate cardiac compromise and predict stillbirth
The only definitive treatment for preeclampsia is delivery of the baby and placenta. Management decisions balance the risks of prematurity against the risks of continuing pregnancy.
In preeclampsia without severe features remote from term (typically 24-37 weeks), expectant management with close monitoring may allow fetal maturation. This approach requires hospitalization or very close outpatient surveillance with:
• Daily blood pressure monitoring
• Regular laboratory assessment (at least twice weekly)
• Fetal surveillance with NST and AFI 1-2 times weekly
• Patient education about warning symptoms
• Ready access to delivery facilities
Delivery is indicated regardless of gestational age when:
• Gestational age ≥37 weeks (or ≥34 weeks with severe features)
• Severe uncontrolled hypertension despite maximum therapy
• Eclampsia
• HELLP syndrome
• Progressive organ dysfunction (worsening renal function, liver abnormalities, thrombocytopenia)
• Fetal compromise (non-reassuring testing, absent or reversed umbilical artery flow)
Treatment of severe hypertension is essential to prevent maternal cerebrovascular complications while maintaining adequate placental perfusion.
Severe hypertension (systolic ≥160 mmHg or diastolic ≥110 mmHg) requires treatment within 30-60 minutes to prevent stroke and other complications. First-line agents include:
Labetalol: 20 mg IV initially, may repeat with escalating doses (40 mg, then 80 mg) every 10-20 minutes
Hydralazine: 5-10 mg IV every 20-40 minutes
Nifedipine: 10-20 mg oral every 20-30 minutes (immediate release)
Once severe hypertension is controlled, maintenance therapy helps prevent recurrent severe elevations. Common agents include:
Labetalol: 200-800 mg orally 2-3 times daily
Nifedipine extended-release: 30-120 mg daily
Hydralazine: 25-50 mg orally 2-4 times daily
Methyldopa: 250-500 mg orally 2-3 times daily
Magnesium sulfate is the drug of choice for seizure prevention and treatment in preeclampsia and eclampsia.
Magnesium sulfate is recommended for:
• All women with severe preeclampsia
• During labor and for 24-48 hours postpartum in severe cases
• Treatment of eclamptic seizures
The decision to use magnesium in preeclampsia without severe features is more controversial, with some guidelines recommending it for all women and others reserving it for those at higher risk.
Loading dose: 4-6 g IV over 15-30 minutes
Maintenance: 1-2 g/hour by continuous IV infusion
Therapeutic level: 4-7 mEq/L (4.8-8.4 mg/dL)
Duration: Continue for 24-48 hours after delivery or last seizure
Signs of magnesium toxicity occur at progressively higher levels:
Loss of deep tendon reflexes: At levels >7 mEq/L
Respiratory depression: At levels >10 mEq/L
Cardiac arrest: At levels >25 mEq/L
Monitor urine output (should be >30 mL/hour), reflexes, and respiratory rate every 1-4 hours. Calcium gluconate should be available as an antidote.
When preterm delivery is anticipated, corticosteroids should be administered to promote fetal lung maturity and reduce neonatal complications.
Betamethasone: 12 mg IM every 24 hours × 2 doses (preferred)
Dexamethasone: 6 mg IM every 12 hours × 4 doses (alternative)
Timing: Maximum benefit occurs 48 hours to 7 days after administration
Gestational age: Recommended for deliveries anticipated at 24-34 weeks; may consider at 34-36+6 weeks if not previously administered
Preeclampsia itself is not an indication for cesarean delivery, and vaginal delivery is often achievable.
Vaginal delivery is often preferred when:
• Cervix is favorable (Bishop score ≥6)
• Fetal status is reassuring
• No absolute contraindications to vaginal delivery
• Maternal condition is stable
Induction of labor is successful in approximately 70-80% of women with preeclampsia who undergo labor trial.
Cesarean may be necessary when:
• Fetal status requires immediate delivery
• Cervix is very unfavorable and induction unlikely to succeed in reasonable timeframe
• Prior cesarean delivery
• Other obstetric indications (malpresentation, placenta previa)
• Maternal condition is deteriorating rapidly
Regional anesthesia (epidural or spinal) is generally preferred when platelet count is adequate (>70,000/μL in many protocols, though thresholds vary). Epidural analgesia during labor can help control blood pressure by reducing pain and anxiety. General anesthesia carries increased risks but may be necessary in some emergencies.
Preeclampsia does not resolve immediately after delivery and may even worsen in the first few days postpartum.
Close monitoring should continue for at least 48-72 hours after delivery:
• Blood pressure monitoring every 4-6 hours initially
• Daily assessment of symptoms (headache, visual changes, epigastric pain)
• Laboratory studies as indicated (typically at 24-48 hours postpartum)
• Fluid balance assessment (urine output, peripheral edema)
Hypertension often persists or worsens 3-6 days postpartum before improving. Antihypertensive medications may need adjustment:
Safe for breastfeeding: Labetalol, nifedipine, hydralazine, methyldopa, enalapril, captopril
Target blood pressure: <150/100 mmHg initially; normalize over weeks
Duration: Many women can discontinue medications within 6-12 weeks postpartum
Careful planning for discharge and follow-up is essential to identify late complications and provide appropriate ongoing care.
Before discharge, women with preeclampsia should have:
• Blood pressure <150/100 mmHg (ideally trending toward normal)
• No severe symptoms (headache, visual changes, epigastric pain)
• Stable or improving laboratory values
• Adequate urine output
• Clear understanding of warning symptoms and when to seek care
Women with preeclampsia should be seen within 72 hours of discharge, or 7-10 days after delivery at the latest. Blood pressure monitoring at home may be helpful. Follow-up should continue until blood pressure normalizes, which typically occurs within 12 weeks postpartum.
Low-dose aspirin is currently the most effective evidence-based intervention for preeclampsia prevention in high-risk women.
Aspirin inhibits thromboxane production by platelets, shifting the thromboxane/prostacyclin balance toward vasodilation and reduced platelet aggregation. Early initiation (before 16 weeks) may improve trophoblast invasion and spiral artery remodeling, addressing the underlying placental pathology.
Dose: 81-150 mg daily (most guidelines recommend 81 mg in the United States, 150 mg in the UK)
Timing: Begin between 12-16 weeks (before 16 weeks is essential for efficacy)
Duration: Continue until delivery
Timing of dose: Evening administration may be more effective
High-risk factors (one is sufficient):
• Prior preeclampsia
• Chronic hypertension
• Pregestational diabetes
• Chronic kidney disease
• Autoimmune disease (SLE, antiphospholipid syndrome)
• Multiple gestation
Moderate-risk factors (two or more):
• Nulliparity
• Obesity (BMI >30)
• Age ≥35 years
• Family history of preeclampsia
• Personal history of SGA infant or adverse pregnancy outcome
• Pregnancy interval >10 years
• IVF pregnancy
Calcium supplementation may reduce preeclampsia risk in women with low dietary calcium intake.
WHO recommends calcium supplementation (1.5-2 g daily) in populations where dietary calcium intake is low (<600 mg/day). In such settings, calcium supplementation reduces preeclampsia risk by approximately 50%. The benefit is less clear in populations with adequate calcium intake, where routine supplementation is not currently recommended.
Several other interventions have been studied for preeclampsia prevention with varying results.
Antioxidants (Vitamin C and E): Large trials have not shown benefit and may increase some risks
Fish oil supplementation: Not proven to prevent preeclampsia
Salt restriction: Not recommended; no evidence of benefit
Bed rest: Not proven effective and may increase VTE risk
Folic acid supplementation: Inconsistent evidence; trials ongoing
Pravastatin: Promising in observational studies and small trials; larger RCTs underway
Metformin: Some evidence of benefit in obese women; being studied
L-arginine supplementation: Limited and inconsistent evidence
Exercise: Regular physical activity may reduce risk; generally recommended
Preeclampsia is now recognized as an important risk factor for future cardiovascular disease, not simply a pregnancy complication.
Women with a history of preeclampsia have:
2-fold increased risk of chronic hypertension
2-fold increased risk of ischemic heart disease
2-fold increased risk of stroke
3-fold increased risk of heart failure
2-fold increased risk of cardiovascular mortality
The relationship between preeclampsia and future cardiovascular disease likely reflects both shared underlying risk factors and direct effects of the preeclamptic pregnancy on vascular health. Women with preeclampsia often have pre-existing endothelial dysfunction, insulin resistance, and other cardiovascular risk factors that persist after pregnancy. Additionally, the preeclamptic pregnancy itself may cause lasting vascular damage.
Women with history of preeclampsia should:
• Have blood pressure checked annually (and sooner if symptomatic)
• Be screened for metabolic syndrome, diabetes, and kidney disease
• Receive counseling about lifestyle modifications (weight, diet, exercise)
• Discuss cardiovascular risk with their healthcare providers
• Consider preeclampsia history as a cardiovascular risk factor comparable to smoking or family history
Women who have experienced preeclampsia face increased risk in subsequent pregnancies, though many will have uncomplicated pregnancies.
Overall recurrence: 13-18% after one preeclamptic pregnancy
After early-onset preeclampsia: 25-40% recurrence
After HELLP syndrome: 20-25% recurrence
After eclampsia: 2-5% recurrence of eclampsia; 20-25% recurrence of preeclampsia
After two preeclamptic pregnancies: Up to 30% recurrence
Higher recurrence risk is associated with:
• Earlier gestational age of prior preeclampsia
• More severe prior disease
• Underlying medical conditions
• Shorter interval between pregnancies
• Same partner (some data)
Lower recurrence risk is seen with:
• Later onset of prior disease
• Resolution of modifiable risk factors (weight loss, blood pressure control)
• Aspirin prophylaxis
Beyond cardiovascular effects, preeclampsia has implications for metabolic health and kidney function.
Preeclampsia is associated with a 4-5 fold increased risk of end-stage renal disease. Even in the absence of overt kidney disease, women with history of preeclampsia may have subclinical renal dysfunction detectable by more sensitive measures. Annual monitoring of kidney function (creatinine, eGFR, urinalysis) is reasonable.
Preeclampsia is associated with a 2-fold increased risk of developing type 2 diabetes, likely reflecting shared pathways involving insulin resistance, inflammation, and endothelial dysfunction. Regular screening for diabetes (fasting glucose or HbA1c) should be part of long-term follow-up.
Twin and higher-order multiple pregnancies carry significantly elevated preeclampsia risk.
Preeclampsia complicates approximately 13-14% of twin pregnancies compared to 5-8% of singleton pregnancies. The risk in triplet and higher-order pregnancies may exceed 25%. This increased risk is attributed to larger placental mass, increased circulating anti-angiogenic factors, and potentially immune factors related to carrying genetically distinct fetuses.
Women with pre-existing hypertension are at high risk for superimposed preeclampsia.
Superimposed preeclampsia is diagnosed when a woman with chronic hypertension develops:
• New-onset proteinuria (or worsening of pre-existing proteinuria)
• Sudden increase in hypertension
• Signs of end-organ dysfunction (elevated liver enzymes, low platelets, elevated creatinine)
• New neurological symptoms
Systemic lupus erythematosus and antiphospholipid syndrome significantly increase preeclampsia risk.
Women with SLE have 2-4 times higher preeclampsia risk. Additional challenges include distinguishing lupus nephritis flare from preeclampsia (both cause proteinuria) and managing immunosuppressive medications. Active lupus nephritis at conception is a particularly strong risk factor. Complement levels (C3, C4) may help differentiate lupus flare from preeclampsia.
APS carries one of the highest risks of preeclampsia (up to 50% in some series). Management includes low-dose aspirin and prophylactic heparin. Despite treatment, rates of preeclampsia, growth restriction, and pregnancy loss remain elevated. Close surveillance and early delivery planning are often needed.
Preeclampsia can rapidly progress to life-threatening complications requiring emergency intervention.
Stroke is a leading cause of death in preeclampsia/eclampsia. Both hemorrhagic and ischemic strokes can occur. Severe hypertension is the major modifiable risk factor. Aggressive treatment of severe hypertension to levels below 160/110 mmHg within 30-60 minutes is essential to prevent stroke. Signs include severe headache, focal neurological deficits, altered consciousness, and seizures.
Pulmonary edema complicates 2-5% of severe preeclampsia and typically occurs postpartum. Risk factors include aggressive fluid administration, diastolic dysfunction, and increased capillary permeability. Management includes oxygen, upright positioning, diuretics, and positive pressure ventilation if needed.
Subcapsular hematoma: Presents with severe right upper quadrant pain; diagnosis by ultrasound or CT; may require surgery
Hepatic rupture: Rare but catastrophic; high maternal mortality; requires immediate surgical intervention
Hepatic infarction: May cause liver failure in severe cases
Patients should seek immediate medical attention for:
• Severe headache not relieved by acetaminophen
• Visual disturbances (blurred vision, spots, temporary blindness)
• Severe right upper quadrant or epigastric pain
• Difficulty breathing or shortness of breath
• Decreased urine output
• Sudden swelling of face, hands, or feet
• Seizure activity
• Blood pressure >160/110 mmHg at home
Eclamptic seizures require immediate, systematic management to protect mother and fetus.
Protect airway: Position on side, clear secretions, prepare for intubation if needed
Prevent injury: Pad side rails, do not restrain
Magnesium sulfate: 4-6 g IV bolus over 15-20 minutes, then 1-2 g/hour maintenance
Oxygen: Supplemental oxygen via face mask
Blood pressure control: Treat severe hypertension after seizure controlled
Preeclampsia and eclampsia contribute disproportionately to maternal mortality in developing countries.
Hypertensive disorders of pregnancy cause approximately 14% of maternal deaths worldwide—over 70,000 deaths annually. The vast majority occur in low- and middle-income countries where access to prenatal care, emergency obstetric services, and intensive care is limited. Maternal mortality from preeclampsia is 100-200 times higher in some developing regions compared to high-income countries.
Significant disparities exist in preeclampsia incidence and outcomes across racial and ethnic groups.
Black women in the United States have 1.5-2 times higher rates of preeclampsia compared to white women. They also have higher rates of severe preeclampsia, HELLP syndrome, eclampsia, and maternal death. These disparities persist after controlling for age, parity, and socioeconomic factors, suggesting contributions from chronic stress, racism, and systemic healthcare inequities.
Improving early prediction of preeclampsia could enable more targeted prevention and surveillance.
Multiparameter algorithms combining maternal factors, mean arterial pressure, uterine artery Doppler, and serum biomarkers (PlGF, PAPP-A) can identify women at high risk for preterm preeclampsia with detection rates of 75-90% at a 10% false-positive rate. These algorithms are increasingly used in clinical practice to guide aspirin prophylaxis decisions.
Research continues to identify additional biomarkers that may improve prediction:
Cell-free fetal DNA: Elevated levels may precede clinical disease
MicroRNAs: Placenta-specific microRNAs show promise as early markers
Proteomics and metabolomics: Comprehensive molecular profiling may reveal new markers
Extracellular vesicles: Placental exosomes carry information about placental function
New treatment approaches aim to address the underlying pathophysiology of preeclampsia.
Because elevated sFlt-1 is central to preeclampsia pathophysiology, therapies that remove or neutralize this factor are being studied:
Apheresis: Extracorporeal removal of sFlt-1 from maternal blood has shown promise in prolonging pregnancy in early-onset severe disease
siRNA therapy: Silencing sFlt-1 expression in the placenta is in early development
Recombinant VEGF: Could potentially counteract sFlt-1 effects
Pravastatin has pleiotropic effects that may address multiple aspects of preeclampsia pathophysiology, including improving endothelial function, reducing inflammation, and modulating angiogenic balance. Clinical trials are ongoing to determine whether pravastatin can prevent preeclampsia or treat established disease.
Preeclampsia remains one of the most significant challenges in obstetric care, affecting millions of pregnancies worldwide each year. Despite advances in understanding its pathophysiology, predicting who will develop the condition, and managing its complications, much remains to be discovered about this complex syndrome.
The two-stage model of preeclampsia—abnormal placentation followed by maternal syndrome—provides a framework for understanding both preventive and therapeutic approaches. Low-dose aspirin, initiated early in pregnancy, can reduce preeclampsia risk by improving placentation. Once the maternal syndrome develops, management focuses on balancing the risks of prematurity against the risks of disease progression, with delivery remaining the only definitive treatment.
Research continues to advance our understanding and capabilities. Novel biomarkers improve our ability to predict and diagnose preeclampsia. Therapeutic approaches targeting the underlying angiogenic imbalance offer hope for future treatments beyond delivery. Understanding the genetic and immunological factors that predispose to preeclampsia may eventually enable truly personalized prevention and treatment.
For now, the cornerstone of preeclampsia management remains vigilant prenatal care, early recognition of disease, timely intervention to prevent complications, and appropriate counseling about long-term health implications. Every woman deserves access to these fundamental elements of care, and closing the gap between evidence and practice remains a critical public health priority.
As we continue to unravel the mysteries of this ancient disease—recognized since antiquity but only now beginning to be understood at a molecular level—we move closer to a future where preeclampsia can be predicted, prevented, and treated effectively, reducing its burden on mothers and babies worldwide.
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