Learning Objectives:After participating in this continuing professional development activity, the provider should be better able to:
1. Identify patients at risk for eclampsia and specify the appropriate treatment.
2. Summarize the proposed causes of eclampsia.
3. Describe the short- and long-term effects of eclampsia on the patient and neonate.
Eclampsia is a feared complication of pregnancy, which can result in significant maternal and fetal morbidity and mortality. Therefore, the prompt diagnosis and treatment of eclampsia is imperative in preventing the most severe consequences. Eclampsia is defined as new-onset, generalized seizures in a pregnant person, which are unrelated to other medical conditions.1 The incidence of eclampsia is estimated to be 1.6 to 10 per 10,000 births and has decreased over the last decade.1,2 Despite this decreasing incidence, eclampsia-along with the other hypertensive disorders of pregnancy (HDP)-is still among the top 6 causes of maternal mortality in the United States and is responsible for 14% of maternal deaths worldwide.1,3,4 The rate of eclampsia among all HDP (including gestational hypertension) is approximately 0.8%.1,3 However, the risk for eclampsia increases with increasing severity of HDP. For example, the rate of eclampsia among patients with preeclampsia without severe features is approximately 1%,1 whereas it can reach as high as 2% in patients with preeclampsia with severe features if untreated.1,3
Proposed Causes and Risk Factors
The true pathogenesis of eclampsia remains to be elucidated. Most theories center on cerebral edema leading to seizures.1,5 Multiple models have proposed etiologies for this cerebral edema, which is related to changes in the cerebral vasculature, particularly endothelial cell dysfunction.1 The dysfunction of endothelial cells leads to breakdown of the blood-brain barrier and alters the neural environment.1 Multiple factors indicated in the development of HDP including vascular endothelial growth factor and placental growth factor have been hypothesized to be the cause of the breakdown in the blood-brain barrier.1,2 Additionally, cerebral vasospasm, which occurs in response to acute hypertension, can cause ischemia and necrosis, which in turn leads to breakdown of the blood-brain barrier and cerebral edema.1,5
Posterior reversible encephalopathy syndrome (PRES) is the radiologic finding, which is pathognomonic for patients with eclampsia. PRES patients show parietal and occipital vasogenic edema on imaging.6 This finding is present in up to 90% of patients with eclampsia, but is also seen in other hypertensive crises, autoimmune disorders, and patients with renal disease.6 The treatment for PRES is supportive care and, when associated with eclampsia, magnesium sulfate.5 Most patients experience full recovery once the swelling resolves.5
Pregnant people with HDP are at the greatest risk for developing eclampsia. In addition to those with HDP, patients who are primiparous, and those who are younger than 20 years or older than 40 years at delivery are at increased risk.1,3 Additionally, preexisting medical conditions that increase the risk for HDP also increase the risk for eclampsia. These conditions include prior HDP, prior eclampsia, chronic hypertension, obesity, renal disease, pregestational diabetes, autoimmune conditions, use of assisted reproductive technology, and multifetal gestations.1,4 Although there are some data that chronic seizure disorders may slightly increase the risk for gestational hypertension, they have not been shown to increase the risk of eclampsia.7
Diagnosis
Before addressing the diagnosis of eclampsia, it is imperative to understand how to diagnose the antecedent HDP. Chronic hypertension is defined as either a systolic blood pressure (SBP) of 140 mm Hg or higher, a diastolic blood pressure (DBP) of 90 mm Hg or higher, or both, on 2 or more occasions, diagnosed before 20 weeks' gestation.2 Gestational hypertension is defined as new-onset hypertension characterized by an SBP of 140 mm Hg or higher or a DBP of 90 mm Hg or higher after 20 weeks' gestation.2,4 Preeclampsia is defined as new-onset hypertension after 20 weeks of gestation with proteinuria and/or presence of end-organ damage (central nervous system symptoms, pulmonary edema, thrombocytopenia, renal insufficiency, or liver dysfunction).2,4 Preeclampsia can be with or without severe features depending on the severity of end-organ damage, as shown in Table 1.
The diagnosis of eclampsia, then, is made in patients who have HDP with the addition of convulsions. Although it is standard to have hypertension, generalized edema, proteinuria, and seizures, there is significant variability in how these signs and symptoms present.3 In 20% to 54% of cases of eclampsia, blood pressure can present as a severe range; in 30% to 60% of cases, blood pressures are only in the mild range. According to a 2005 study, 38% to 53% of eclamptic seizures are seen in the antepartum setting whereas 18% to 36% and 11% to 44% are seen intrapartum and postpartum, respectively.3
Proper treatment for eclampsia should be initiated while the patient is being evaluated. The initial, standard evaluation for patients with new-onset seizures should include complete blood count (CBC), comprehensive metabolic panel, urine protein/creatinine ratio, point-of-care blood glucose testing, and consideration for a urine drug screen.1 Depending on the clinical presentation and onset of convulsions, brain imaging with CT scan or MRI may be indicated.1 Patients who have recurrent seizures, those who had either unwitnessed events or witnessed falls with head trauma, should be evaluated with imaging after stabilization. Additionally, those with focal neurologic deficits after resolution of the generalized tonic-clonic seizure should undergo head imaging.
Management and Delivery
When a patient has an eclamptic seizure, it is of the utmost importance to make sure the patient has a secure airway to both ensure oxygenation and avoid aspiration.1 The patient should be placed in the lateral decubitus position with bed rails elevated and padded; IV access should be ensured.1 Magnesium sulfate should be used as the first-line anticonvulsant if there are no contraindications. Contraindications for magnesium sulfate are rare but include a diagnosis of myasthenia gravis, current heart block, and prior hypersensitivity reaction to magnesium sulfate.1 Magnesium should be administered in a loading dose of 6 g over 15 to 20 minutes, and then continued at a dose of 2 g per hour for a continuous infusion for 24 hours.1,4 If the patient has a second convulsion, magnesium sulfate can be administered in a 2-g bolus over 3 to 5 minutes. If recurrent convulsions are noted while the patient is receiving therapeutic magnesium sulfate, lorazepam 4 mg IV should be administered over 3 to 5 minutes. If IV access is unavailable, magnesium sulfate can be administered in intramuscular (IM) injections of 10 mg as a loading dose of 5 mg in each buttock followed by 5 g every 4 hours.1,4
It is important to monitor for magnesium toxicity in patients with eclampsia. Magnesium sulfate toxicity starts with the loss of deep tendon reflexes and, if not recognized promptly, can lead to respiratory depression, and cardiac arrest.1 It is generally accepted that the therapeutic range of magnesium sulfate is 4.8 to 9.6 mg/dL.4 Deep tendon reflexes are generally lost at a magnesium level of 9 mg/dL, respiratory depression occurs at a magnesium level of 12 mg/dL, and cardiac arrest occurs at a magnesium level of 30 mg/dL.1 If magnesium toxicity is suspected, treatment with calcium gluconate (1000 mg) is indicated.4
Prompt treatment of hypertension is equally important in preventing severe morbidity. Patients will often require the use of IV antihypertensives to bring the blood pressure below 160 systolic and 110 diastolic. First-line antihypertensives include labetalol and hydralazine. Care should be maintained not to drop the blood pressure too quickly or too low to prevent uterine hypotension and fetal injury.
Patients who have eclampsia should not be managed expectantly. Therefore, delivery planning should be initiated once maternal stability is established.2 Although eclampsia is an indication for delivery, it is not necessarily an indication for cesarean and the decision for cesarean should be based on gestational age, fetal status, presence of labor, and bishop score.1,3
Fetal and Neonatal Complications
Eclampsia and the other HDP are major contributors to adverse fetal and neonatal outcomes. HDP are associated with placental insufficiency, placing these pregnancies at higher risk for fetal growth restriction.8 Any hypertension in pregnancy should prompt serial evaluation of fetal growth.4
The immediate consequences of an eclamptic seizure on fetal well-being can be visualized on external fetal monitoring (EFM). During maternal eclamptic seizures, there are usually prolonged heart rate decelerations and/or recurrent late decelerations noted on EFM caused by the combination of maternal hypoxia and increased uterine tone.4,9 Additionally, maternal abdominal trauma may occur during the initial eclamptic episode, which can lead to placental abruption.1 Although it can be difficult for providers to watch abnormal fetal heart tracings during these events, it is imperative to stabilize the maternal condition before delivery.
HDP are all risk factors for intrauterine fetal demise (IUFD), which range from 2 to 7 times the rates seen in normotensive pregnancies.10 The higher rates of IUFD are related to multiple factors including placental insufficiency, abruption, trauma, and acute hypoxemic events.10 The total perinatal death rate (including IUFD and neonatal demise) ranges from 5.6% to 11.8%.1 A large proportion of these deaths are due to consequences of prematurity, which accounts for the majority of neonatal and infant deaths in the United States.11
The most common fetal and neonatal complication of eclampsia is premature birth.4,8,10,12 Neonates born preterm are at higher risk for death in the first year of life, and those that survive have elevated risks of serious immediate and long-term health issues.12 Intraventricular hemorrhage leading to cerebral palsy and other severe neurodevelopmental disabilities occurs at much higher rates in premature neonates.13 Additionally, these neonates often require oxygen supplementations, which can cause irreversible lung damage and lead to chronic lung diseases including bronchopulmonary dysplasia and persistent pulmonary hypertension of the newborn.13 The preterm neonate is also at higher risk of infection and life-threatening sepsis.10,13 These conditions come at extreme cost for the child, family, and health care system.14
Once out of infancy, emerging long-term follow-up data show increased rates of hypertension, diabetes, and cognitive disorders among children whose mothers had HDP.10,12 These findings highlight the need for close communication with our pediatric colleagues to ensure proper screening and care for these children.
Care in Future Pregnancies
First and foremost, we must realize that, for patients who have experienced eclampsia, pregnancy and delivery represent a traumatic series of events. All patients should be screened for postpartum depression using a validated tool such as the Edinburgh Postnatal Depression Scale.15 Patients with complications such as eclampsia should be offered resources for support including access to psychotherapy and psychiatric services.
It is important to discuss the risk of recurrence with patients who are considering another pregnancy. In patients without underlying health conditions, the risk of recurrence of HDP is approximately 20%.4 However, this estimate does not take into account the severity of future illness, and also likely underestimates the risk in patients with underlying medical complications. If patients become pregnant again, they should be followed closely as they are at high risk for anxiety disorders, depression, and posttraumatic stress disorder in future pregnancies.
For patients with a history of eclampsia and baseline hypertension, close monitoring of blood pressure and medication titration is important even before pregnancy. It is essential that they have close follow-up and adequate blood pressure control throughout. Low-dose aspirin (81 mg) should be started in the second trimester, before 16 weeks' gestation to reduce the risk of preeclampsia.16 Additionally, baseline laboratory studies, including liver and renal function tests and protein-creatinine ratio, should be obtained at the initial obstetric visit. As the pregnancy progresses, close monitoring of blood pressures, particularly in the third trimester, is essential. There is no current evidence that patients with a history of eclampsia need serial growth ultrasounds, unless another indication is present. As data continue to emerge that hypertensive disorders are more prevalent after 39 weeks, it is reasonable to consider delivery at 39 weeks in subsequent pregnancies. Patients who underwent cesarean delivery for eclampsia should be offered and counseled on a trial of labor as appropriate.
Long-Term Health Consequences
Over the last 2 decades, it has become clearer that pregnancy and the postpartum period are windows to future health. A large population study performed by Garovic et al17 in 2020 evaluated patients with a history of HDP with a median follow-up rate of 36.2 years and demonstrated increased relative risks of a large number of chronic health conditions. The increased relative risk (RR) of coronary artery disease was 1.59 [95% confidence interval (CI), 1.19-2.12], congestive heart failure RR 2.11 (95% CI, 1.19-3.76), stroke RR 1.76 (95% CI, 1.24-2.49), and diabetes RR 1.62 (95% CI, 1.36-1.94).17 Ahmed et al18 reported that cardiovascular disease in the 90 days after pregnancy was twice as common in patients with preeclampsia compared with controls.
The American Heart Association has published recommendations for cardiovascular screening in patients with a history of HDP; the importance of sharing this information with the patient's primary care physician is highlighted. Annual assessment of blood pressure and body mass index (BMI) and regular and consistent cholesterol/lipids and diabetic screening with a primary care provider is essential in maintaining excellent health.19 In addition, lifestyle modifications, which have been shown to decrease cardiovascular disease risk in the general population, including regular exercise and a healthy diet, have also been shown in multiple models to decrease cardiovascular disease risks in patients with a history of HDP.19
Conclusion
Eclampsia is the most severe and life-threatening diagnosis among the group of diagnoses categorized as HDP. It is essential that all obstetrical care providers are able to quickly recognize and treat this condition to allow for maternal and fetal stabilization. The long-term health consequences for the patient and her fetus are broad, and communication and close follow-up are essential for lifelong health.
Practice Pearls
* Eclampsia is a disease on the spectrum of HDP and is characterized by new-onset convulsions in pregnancy.
* Eclampsia is thought to be caused by cerebral edema and injury, although the exact mechanism remains unknown.
* Initial treatment of eclampsia includes magnesium sulfate (IV or IM) and treatment of severe hypertension.
* Delivery is indicated after maternal stabilization, and mode of delivery can be dictated by gestational age, bishop score, and fetal well-being.
* Prematurity is the most significant fetal/neonatal consequence of eclampsia; long-term cardiovascular and metabolic changes also have been linked to maternal disease.
* Patients with eclampsia are at increased risk of HDP in following pregnancies and should be prescribed low-dose aspirin for prevention.
* Patients with eclampsia are at risk for cardiovascular, metabolic, and neurologic diseases later in life and should receive close screening yearly with their primary care provider.
References