Preeclampsia is new-onset or worsening of existing hypertension with proteinuria after 20 weeks gestation. Eclampsia is unexplained generalized seizures in patients with preeclampsia. Diagnosis is by measuring blood pressure and urine protein and by tests to evaluate for end-organ damage (eg, pulmonary edema, impaired liver or kidney function). Treatment is usually with IV magnesium sulfate and delivery at term or earlier for maternal or fetal complications.
Preeclampsia affects 3 to 7% of pregnant women. Preeclampsia and eclampsia develop after 20 weeks gestation; up to 25% of cases develop postpartum, most often within the first 4 days but sometimes up to 6 weeks postpartum.
Untreated preeclampsia is present for a variable time, then can suddenly progress to eclampsia, which occurs in 1/200 patients with preeclampsia. Untreated eclampsia is usually fatal.
Etiology of Preeclampsia and Eclampsia
Etiology of preeclampsia is unknown.
However, high-risk and moderate-risk factors have been identified (1).
High-risk factors include
Previous pregnancy with preeclampsia
Multifetal gestation
Kidney disorders
Autoimmune disorders
Type 1 or type 2 diabetes mellitus
Chronic hypertension
Moderate-risk factors include
First pregnancy
Maternal age ≥ 35
Body mass index > 30
Family history of preeclampsia
Sociodemographic characteristics (African American race, low socioeconomic status)
Personal history factors (eg, previous infants with low birth weight or small for gestational age, previous adverse pregnancy outcome, > 10-year pregnancy interval [2])
Довідкові матеріали щодо етіології
1. Henderson JT, Whitlock EP, O'Conner E, et al: Table 8: Preeclampsia Risk Factors Based on Patient Medical History in Low-dose aspirin for the prevention of morbidity and mortality from preeclampsia: A systematic evidence review for the U.S. Preventive Services Task Force. Rockville (MD): Agency for Healthcare Research and Quality (US), 2014
2. American College of Obstetricians and Gynecologists (ACOG): Gestational hypertension and preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol 135 (6):e237–e260, 2020.
Pathophysiology of Preeclampsia and Eclampsia
Pathophysiology of preeclampsia and eclampsia is poorly understood. Factors may include poorly developed uterine placental spiral arterioles (which decrease uteroplacental blood flow during late pregnancy), a genetic abnormality, immunologic abnormalities, and placental ischemia or infarction. Lipid peroxidation of cell membranes induced by free radicals may contribute to preeclampsia.
Ускладнення
Fetal growth restriction or fetal death may result. Diffuse or multifocal vasospasm can result in maternal ischemia, eventually damaging multiple organs, particularly the brain, kidneys, and liver. Factors that may contribute to vasospasm include decreased prostacyclin (an endothelium-derived vasodilator), increased endothelin (an endothelium-derived vasoconstrictor), and increased soluble Flt-1 (a circulating receptor for vascular endothelial growth factor). Women who have preeclampsia are at risk of placental abruption in the current pregnancy, possibly because both disorders are related to uteroplacental insufficiency.
The coagulation system is activated, possibly secondary to endothelial cell dysfunction, leading to platelet activation.
The HELLP syndrome (hemolysis, elevated liver function tests, and low platelet count) develops in 10 to 20% of women with severe preeclampsia or eclampsia; this incidence is about 100 times that for all pregnancies (1 to 2/1000). Most pregnant women with HELLP syndrome have hypertension and proteinuria, but some have neither.
Symptoms and Signs of Preeclampsia and Eclampsia
Preeclampsia may be asymptomatic or may cause edema or sudden excessive weight gain (> 5 lb/week). Nondependent edema, such as facial or hand swelling (the patient’s ring may no longer fit her finger), is more specific than dependent edema.
Petechiae may develop, as may other signs of coagulopathy.
Eclampsia manifests as generalized (tonic-clonic) seizures.
Цінні поради та підводні камені
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Preeclampsia with severe features may cause organ damage; these features may include
Severe headache
Visual disturbances
Confusion
Hyperreflexia
Epigastric or right upper quadrant abdominal pain (reflecting hepatic ischemia or capsular distention)
Nausea and/or vomiting
Dyspnea (reflecting pulmonary edema, acute respiratory distress syndrome [ARDS], or cardiac dysfunction secondary to increased afterload)
Oliguria (reflecting decreased plasma volume or ischemic acute tubular necrosis)
Stroke (rarely)
Diagnosis of Preeclampsia and Eclampsia
Preeclampsia: New onset after 20 weeks gestation of hypertension (blood pressure [BP] ≥ 140/90 mm Hg) plus new unexplained proteinuria (> 300 mg/24 hours or a urine protein/creatinine ratio of ≥ 0.3) and/or signs of end-organ damage (1)
BP criteria for preeclampsia are one of the following:
Systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg (at least 2 measurements taken at least 4 hours apart)
Systolic BP ≥ 160 mm Hg and/or diastolic BP ≥ 110 mm Hg (at least 1 measurement)
Proteinuria is defined as > 300 mg/24 hours. Alternatively, proteinuria is diagnosed based on a protein/creatinine ratio ≥ 0.3 or a dipstick reading of 2+; the dipstick test is used only if other quantitative methods are not available. Absence of proteinuria on less accurate tests (eg, urine dipstick testing, routine urinalysis) does not rule out preeclampsia.
In the absence of proteinuria, preeclampsia is also diagnosed if pregnant women meet diagnostic criteria for new-onset hypertension and have new onset of any of the following signs of end-organ damage:
Thrombocytopenia (platelets < 100,000/mcL)
Renal insufficiency (serum creatinine > 1.1 mg/dL or doubling of serum creatinine in women without renal disease)
Impaired liver function (aminotransferases > 2 times normal)
Pulmonary edema
New-onset headache (unresponsive to medication and not accounted for by alternative diagnoses)
Visual symptoms
The following points help differentiate among other hypertensive disorders in pregnant women:
Chronic hypertension is identified if hypertension precedes pregnancy, is present at < 20 weeks gestation, or persists for > 6 weeks (usually > 12 weeks) postpartum (even if hypertension is first documented at > 20 weeks gestation). Chronic hypertension may be masked during early pregnancy by the physiologic decrease in BP.
Gestational hypertension is new-onset hypertension at > 20 weeks gestation without proteinuria or other findings of preeclampsia; it resolves by 12 weeks (usually by 6 weeks) postpartum.
Preeclampsia superimposed on chronic hypertension is diagnosed when new unexplained proteinuria develops or proteinuria worsens after 20 weeks in a woman known to have hypertension with BP elevations above baseline or when preeclampsia with severe features develops after 20 weeks in a woman known to have hypertension and proteinuria. Women with chronic hypertension are at high risk of preeclampsia and should be monitored closely.
Подальша оцінка
If preeclampsia is diagnosed, tests include complete blood count (CBC), platelet count, uric acid, liver tests, blood urea nitrogen (BUN), creatinine, and, if creatinine is abnormal, creatinine clearance. The fetus is assessed using a nonstress test or biophysical profile (including assessment of amniotic fluid volume) and tests that estimate fetal weight.
Прееклампсія з тяжкими проявами
Preeclampsia with severe features is differentiated from mild forms by new onset of one or more of the following:
Systolic BP > 160 mm Hg or diastolic BP > 110 mm Hg on 2 occasions ≥ 4 hours apart
Thrombocytopenia, platelet count < 100,000/mcL
Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times normal
Symptoms of liver capsule distention (eg, right upper quadrant or epigastric pain)
Progressive renal insufficiency (serum creatinine > 1.1 mg/dL or doubling of serum creatinine in women without renal disease)
Pulmonary edema
Central nervous system (CNS) dysfunction (eg, blurred vision, scotomata, altered mental status, severe headache unrelieved by acetaminophen)
HELLP syndrome is suggested by microangiopathic findings (eg, schistocytes, helmet cells) on peripheral blood smears, elevated liver enzymes, and a low platelet count.
Довідковий матеріал щодо діагностики
1. American College of Obstetricians and Gynecologists (ACOG): Gestational hypertension and preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol 135 (6):e237–e260, 2020.
Treatment of Preeclampsia and Eclampsia
Usually hospitalization and sometimes antihypertensive treatment
Delivery, depending on factors such as gestational age, fetal status, and severity of preeclampsia
Sometimes magnesium sulfate to prevent or treat new seizures or to prevent seizures from recurring
Загальний підхід
Definitive treatment for preeclampsia is delivery. However, risk of preterm delivery is balanced against gestational age, fetal growth restriction, fetal distress, severity of preeclampsia, and response to other treatments.
Usually, immediate delivery after maternal stabilization (eg, controlling seizures, beginning to control blood pressure [BP]) is indicated for the following:
Pregnancy of ≥ 37 weeks
Preeclampsia with severe features if pregnancy is ≥ 34 weeks
Deteriorating renal, pulmonary, cardiac, or hepatic function (eg, HELLP syndrome)
Nonreassuring results of fetal monitoring or testing
Eclampsia
Other treatments aim to optimize maternal health, which usually optimizes fetal health. If delivery can be safely delayed in pregnancies of < 34 weeks, corticosteroids are given for 48 hours to accelerate fetal lung maturity. Some stable patients can be given corticosteroids after 34 weeks and before 36 weeks (late preterm period) if they have not been given corticosteroids earlier in the pregnancy.
Most patients are hospitalized. Patients with eclampsia or preeclampsia with severe features are often admitted to a maternal special care unit or an intensive care unit (ICU).
Прееклампсія без виражених ознак
Most patients who have preeclampsia without severe features before 37 weeks gestation are hospitalized for evaluation, at least initially.
If maternal and fetal status are reassuring, outpatient treatment is possible; it includes modified activity (modified rest), BP measurements, laboratory monitoring, fetal nonstress testing, and physician visits at least once a week.
As long as no criteria for preeclampsia with severe features develop, delivery can occur (eg, by induction) at 37 weeks.
Моніторинг
All hospitalized patients with preeclampsia are evaluated frequently for evidence of seizures, preeclampsia with severe features, and vaginal bleeding; BP, reflexes, and fetal heart status (with nonstress testing or a biophysical profile) are also checked. Platelet count, serum creatinine, and serum liver enzymes are measured frequently until stable, then at least once a week.
Outpatients are usually followed by an obstetrician or a maternal-fetal medicine specialist and evaluated at least once a week with the same testing as inpatients. Evaluation is more frequent if preeclampsia with severe features is diagnosed or if gestational age is < 34 weeks.
Сульфат магнію
As soon as eclampsia is diagnosed, magnesium sulfate must be given to prevent seizures from recurring. If patients have preeclampsia with severe features, magnesium sulfate may be given to prevent seizures. Magnesium sulfate is given for 12 to 24 hours postpartum. Whether patients who have preeclampsia without severe features always require magnesium sulfate before delivery is controversial.
Magnesium sulfate 4 g IV over 20 minutes is given, followed by a constant IV infusion of 2 g/hour. Dose is adjusted based on the patient’s symptoms or on whether renal insufficiency is present. Patients with abnormally high magnesium levels (eg, with magnesium levels > 10 mEq/L or a sudden decrease in reflex reactivity), cardiac dysfunction (eg, with dyspnea or chest pain), or hypoventilation after treatment with magnesium sulfate can be treated with calcium gluconate 1 g IV.
IV magnesium sulfate may cause lethargy, hypotonia, and transient respiratory depression in neonates. However, serious neonatal complications are uncommon.
Підтримуючі методи лікування
If oral intake is prohibited, hospitalized patients are given IV Ringer lactate or 0.9% normal saline solution, beginning at about 125 mL/hour (to maintain hemodynamic status). Persistent oliguria is treated with a carefully monitored fluid challenge. Diuretics are usually not used. Monitoring with a pulmonary artery catheter is rarely necessary and, if needed, is done in consultation with a critical care specialist and in an intensive care unit (ICU). Anuric patients with normovolemia may require renal vasodilators or dialysis.
If seizures occur despite magnesium therapy, diazepam or lorazepam can be given IV to stop seizures, and IV hydralazine or labetalol is given in a dose titrated to lower systolic BP to 140 to 155 mm Hg and diastolic BP to 90 to 105 mm Hg.
Метод доставки
The most efficient method of delivery should be used. If the cervix is favorable and rapid vaginal delivery seems feasible, a dilute IV infusion of oxytocin is given to accelerate labor; if labor is active, the membranes are ruptured. If the cervix is unfavorable and prompt vaginal delivery is unlikely, cesarean delivery can be considered. Preeclampsia and eclampsia, if not resolved before delivery, usually resolve rapidly afterward, within 6 to 12 hours.
Подальшій контрольний візит
Patients should be evaluated at least every 1 to 2 weeks postpartum with periodic BP measurement. If BP remains high after 6 weeks postpartum, patients may have chronic hypertension and should be referred to their primary care physician for management.
Довідковий матеріал щодо лікування
1. American College of Obstetricians and Gynecologists (ACOG): Gestational hypertension and preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol 135 (6):e237–e260, 2020.
Профілактика
Meta-analyses of randomized trials have shown that low-dose aspirin therapy in women with certain risk factors reduces the rate of severe preeclampsia and fetal growth restriction (1, 2).
Low-dose aspirin (81 mg/day) is recommended for patients with high-risk factors for preeclampsia (previous pregnancy with preeclampsia, multifetal gestation, renal disorders, autoimmune disorders, type 1 or type 2 diabetes mellitus, chronic hypertension). It is also recommended for those with > 1 moderate-risk factors (first pregnancy, maternal age ≥ 35, body mass index > 30, family history of preeclampsia, sociodemographic characteristics such as African American race or low socioeconomic status, personal history factors such as low-birth-weight or small-for-gestational-age infants, previous adverse pregnancy outcome, or a> 10-year pregnancy interval [3]).
Aspirin prophylaxis should be started at 12 to 28 weeks of gestation (ideally before 16 weeks) and continued until delivery.
Довідкові матеріали щодо профілактики
1. Roberge S, Nicolaides K, Demers S et al: The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: Systematic review and meta-analysis. Am J Obstet Gynecol 216 (2):110–120.e6, 2017. doi: 10.1016/j.ajog.2016.09.076
2. Meher S, Duley L, Hunter K, Askie L: Antiplatelet therapy before or after 16 weeks’ gestation for preventing preeclampsia: An individual participant data meta-analysis. Am J Obstet Gynecol 216 (2):121–128.e2, 2017. doi: 10.1016/j.ajog.2016.10.016
3. American College of Obstetricians and Gynecologists (ACOG): Gestational hypertension and preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol 135 (6):e237–e260, 2020.
Ключові моменти
Preeclampsia is new-onset hypertension with proteinuria after 20 weeks gestation, and eclampsia is unexplained generalized seizures in patients with preeclampsia; preeclampsia develops postpartum in 25% of cases.
Preeclampsia is differentiated from chronic hypertension and gestational hypertension by the presence of new-onset proteinuria and/or end-organ damage.
Preeclampsia is severe if it causes significant organ dysfunction (eg, renal insufficiency, impaired liver function, pulmonary edema, visual symptoms), even in the absence of proteinuria.
HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) is a related disorder that occurs in 10 to 20% of women who have preeclampsia with severe features or eclampsia.
Evaluate and closely monitor the mother and fetus, usually in a hospital maternal special care unit, but sometimes outpatient monitoring is possible.
Delivery is usually indicated when the pregnancy is ≥ 37 weeks, but if preeclampsia with severe features is diagnosed, deliver by 34 weeks; if HELLP syndrome or eclampsia is diagnosed, deliver immediately.
Treat eclampsia immediately with magnesium sulfate to prevent seizures from recurring; consider magnesium sulfate for seizure prophylaxis in women who have preeclampsia with severe features, but usually not in those with mild preeclampsia.
If magnesium sulfate is given for seizure prophylaxis, continue for 12 to 24 hours after delivery.
Give women with certain risk factors low-dose aspirin starting at 12 to 28 weeks to reduce risk of preeclampsia, ideally before 16 weeks.