Preeclampsia and EclampsiaWHEC Practice Bulletin and Clinical Management Guidelines for healthcare providers. Hypertensive disease occurs in approximately 12-22% of pregnancies, and it is directly responsible for 17.6% of maternal deaths in the United States. However, there is confusion about the terminology and classification of these disorders. We hope to provide guidelines for the diagnosis and management of hypertensive disorders unique to pregnancy (preeclampsia and eclampsia), as well as the various associated complications. The purpose this document is to provide guidelines for the diagnosis and management of hypertensive disorders unique to pregnancy -- preeclampsia and eclampsia. Various associated complications are also discussed. Expectant management should be considered for women remote from term who have mild preeclampsia. For the prevention and treatment of seizures in women with severe preeclampsia or eclampsia magnesium sulfate is the drug of choice. Practitioners should be aware that various laboratory tests may be useful in the management of women with preeclampsia. The differential diagnosis is also discussed. It is important that clinician make the accurate diagnosis when possible because the management and complications from these syndromes may be different. Introduction: The National High Blood Pressure Education Program Working Group has recommended that the term "gestational hypertension" replace the term "pregnancy-induced hypertension" to describe cases in which elevated blood pressure without proteinuria develops in a woman after 20 weeks of gestation and blood pressure levels return to normal in postpartum period(1). Hypertension during pregnancy is defined as a systolic blood pressure level of 140 mm Hg or higher or a diastolic blood pressure level of 90 mm Hg or higher that occurs after 40 weeks of gestation in a woman with previously normal blood pressure. As many as one quarter of women with gestational hypertension will develop proteinuria, ie, preeclampsia. Women who demonstrate an elevation of more than 30 mm Hg systolic or more than 15 mm Hg diastolic above baseline warrant close observation. Preeclampsia: is a pregnancy-specific syndrome that usually occurs after 20 weeks of gestation. Criteria for diagnosis of preeclampsia are: Severe Preeclampsia: preeclampsia is considered severe if one or more of the following criteria is present: Eclampsia: is defined as the presence of new-onset grand mal seizures in a woman with preeclampsia. Other causes of seizures in addition to eclampsia include a bleeding arteriovenous malformation, ruptured aneurysm, or idiopathic seizure disorder. Superimposed Preeclampsia: the diagnostic criteria include in a woman with hypertension before 20 weeks of gestation, a sudden increase in proteinuria if already present in early gestation, a sudden increase in hypertension, or the development of HELLP syndrome. Women with chronic hypertension who develop headache, scotomata, or epigastric pain also may have superimposed preeclampsia. Risk Factors: The exact incidence of preeclampsia is unknown but it has been reported to be approximately 5-8%. Preeclampsia is primarily a disorder of first pregnancies. Other risk factors include multifetal gestations, preeclampsia in previous pregnancy, chronic hypertension, pregestational diabetes, vascular and connective tissue disease, nephropathy, antiphospholipid antibody syndrome, obesity, age 35 years or older, and African -American race. Women with thrombophilias may have a genetic predisposition to preeclampsia. Pathophysiology: The etiology of preeclampsia is unknown, although much of the literature has focused on the degree of trophoblastic invasion by the placenta. In cases of preeclampsia, invasion by the trophoblast appears to be incomplete. Moreover, the severity of hypertension may be related to the degree of trophoblastic invasion. Preeclampsia also may be associated with significant alterations in the immune response. Differential Diagnosis of Severe Preeclampsia: There are several obstetric, medical, and surgical disorders that share many of the clinical and laboratory findings of patients with severe preeclampsia-hemolysis, elevated liver enzymes, and low platelet syndrome. These conditions are associated with high maternal mortality, and survivors may face long-term sequelae. Differential diagnosis may be difficult due to the overlap of several clinical and laboratory findings of these syndromes. Laboratory Findings Among Imitators of Preeclampsia - Eclampsia (8): Laboratory Findings HEELP Syndrome AFLP TTP HUS Exacerbation of SLE Thrombocytopenia (less than 100,000/mm3) More than 20,000 More than 50,000 20,000 or less More than 20,000 More than 20,000 Hemolysis (%) 50-100 15-20 100 100 14-23 with APA Anemia (%) Less than 50 Absent 100 100 14-23 with APA DIC (%) Less than 20 50-100 Rare Rare Rare Hypoglycemia (%) Absent 50-100 Absent Absent Absent Von Willebrand factor multimers (%) Absent Absent 80-90 80 Less than 10 ADAMTS13 less than 5% (%) Absent Absent 33-100 Rare Rare Impaired renal function (%) 50 90-100 30 100 40-80 LDH (IU/L) 600 or more Variable More than More than 1,000 With APA Elevated ammonia (%) Rare 50 Absent Absent Absent Elevated bilirubin (% 50-60 100 100 Not available Less than 10 Elevated transaminases (%) 100 100 Usually less than 100 IU/L Usually less than 100IU/L With APA Making the right diagnosis is extremely important regarding decisions about need for delivery as well as treatment and complications. Finally, a rapid diagnosis and close consultation with an interdisciplinary team of physicians such as a maternal-fetal medicine specialist, nephrologist, hematologist, and critical care specialist, may result in optimal outcome for the mother and fetus. Antenatal Surveillance for Preeclampsia: No single screening test for preeclampsia has been found to be reliable and cost-effective. Uric acid is one of the most commonly used tests but it has a positive predictive value of only 33% and has not proved useful in predicting preeclampsia. Fetal and maternal evaluation is essential. The Working Group recommends weekly non-stress tests, biophysical profiles, or both, which should be repeated as indicated according to maternal condition. Testing is recommended twice weekly for suspected fetal growth restriction or oligohydramnios. Daily fetal movement assessment also may prove useful. Doppler velocimetry of the uterine arteries was reported not to be a useful test for screening pregnant women at low risk for eclampsia. It is useful in the cases where there is fetal growth restriction or oligohydramnios. (1) Maternal Evaluation: consists of primarily of frequent evaluation for worsening preeclampsia. Initial laboratory tests consist of evaluation of platelet count, liver enzymes, and renal function and a 12 hour to 24 hour urine collection for protein. With mild disease and no progression, these tests can be repeated weekly. The tests should be repeated sooner if disease progression is questionable. The decision to deliver a patient with preeclampsia must balance both the maternal and fetal risk. Severe Preeclampsia: the management of a woman with severe preeclampsia remote from term is best managed in tertiary care setting or in consultation with maternal-fetal medicine sub-specialist. Laboratory evaluation and fetal surveillance may be indicated on a daily basis depending on the severity and progression of the disorder. Considering the serious nature of HELLP syndrome, women with this complication should be delivered regardless of their gestational age. Management: The two main goals of management of women with preeclampsia during labor and delivery are prevention of seizures or eclampsia and control of hypertension. Although there is no unanimity of opinion regarding the prophylactic use of magnesium sulfate for the prevention of seizures in women with mild preeclampsia or gestational hypertension, a significant body of evidence attests to the efficacy of magnesium sulfate in women with severe preeclampsia and eclampsia. Hospitalization is often initially recommended for women with new-onset preeclampsia. After maternal and fetal conditions are serially assessed, subsequent management may be continued in the hospital, at a day-care unit, or at home on the basis of the initial assessment. If day care or home management is selected, it should include frequent maternal and fetal evaluation and access to health care providers. If worsening of preeclampsia is diagnosed, as determined by laboratory findings, symptoms, and clinical signs, hospitalization is indicated. Optimal mode of delivery for women with preeclampsia: Management of Eclampsia: women with eclampsia require prompt intervention. When an eclamptic seizure occurs, the woman should be medically stabilized. First, it is important to control convulsions and prevent their recurrence with intravenous or intramuscular magnesium sulfate. One protocol is a 4 g to 6 g loading dose diluted in 100 ml fluid administered intravenously for 15-20 minutes, followed by 2 g per hour as a continuous intravenous infusion. Antihypertensive medications should be used for women with diastolic blood pressure levels of 105-110 mm Hg or higher. In most situations, clinical assessment of respiration, deep tendon reflexes, and urine output is adequate to monitor for maternal magnesium toxicity without the need to determine the actual maternal serum magnesium levels. If toxic serum levels or side effects are encountered, magnesium sulfate infusion must be discontinued, and calcium gluconate may be administered to reverse the side effects. (2) Anesthesia during labor and delivery in women with preeclampsia: with improved techniques over the past two decades, regional anesthesia has become the preferred technique for women with severe preeclampsia and eclampsia-both for labor and delivery. Many studies have shown that epidural anesthesia is not associated with an increased rate of cesarean delivery, pulmonary edema, or renal failure. The regional anesthesia is generally contraindicated in the presence of a coagulopathy because of the potential for hemorrhagic complications. Moreover general anesthesia carries more risk to pregnant women than does regional anesthesia. (3) Can preeclampsia be prevented? Much of the obstetric research in the past several decades has been directed at finding ways to prevent preeclampsia and eclampsia. Recent studies have focused on low-dose aspirin, calcium supplementation, and antioxidant therapy. Most evidence suggests that low-dose aspirin therapy is of little, if any, benefit in preventing preeclampsia in low-risk women. There is controversy regarding the use of calcium supplementation to prevent preeclampsia. Many studies have shown no benefit. Critical directions for the future: Classic complications of pregnancy include preeclampsia and eclampsia which affect 2.8% of pregnancies in developing countries and 0.4% in developed countries, leading to many life-threatening cases and over 63,000 maternal deaths worldwide every year. Antenatal care started out in the first half of the 20th century as a means to educate "ignorant" women with an emphasis on the welfare of the infant and child. Antenatal care has come a long way, but can go much further. Four directions are critical: to rationalize the rituals of care, to roll out antenatal care as a platform for a number of other key health programs, to establish communication with women more effectively, and to avoid the over-medication that can do more harm than good. Most importantly, the unfinished agenda of reaching all women who are pregnant should be tackled (9). The mainstays of the management of severe preeclampsia include, full assessment of the mother and the baby; and delivery on the best day in the best way. It has been observed that standardizing care is associated with reduced adverse health outcomes. Failure to standardize care has been associated with poorer outcomes. The standardized surveillance guidelines are developed by the PIERS (Preeclampsia Integrated Estimate of RiSk) Study Group (10). It has been shown to reduce maternal and perinatal mortality and morbidity. In addition to routine measurement of maternal blood pressure, the investigations are included: 1) Hematology - full blood screen, international normalized ratio (INR), activated partial thromboplastin time (APTT), and fibrinogen; 2) Renal - urea, creatinine, electrolytes, uric acid, and dipstick. While other testing occur twice weekly, urine was also assessed by 24-hour urine for protein and creatinine clearance (on admission and once weekly thereafter); 3) Hepatic - aspartate transaminases (AST), alanine transaminases (ALT), lactate dehydrogenase (LDH), bilirubin, albumin (plasma), and random glucose; 4) Respiratory - pulse oximetry; 5) Fetal surveillance (antenatally only) - cardiotocography (CTG; daily), ultrasound for assessment of fetal weight (every 14 days), and amniotic fluid volume and umbilical artery Doppler (twice weekly). Summary: Women should be considered as having severe preeclampsia if they have blood pressure levels of 160 mm Hg systolic or higher or 110 mm Hg diastolic or higher on two occasions at least 6 hours apart while the patient is on bed rest, proteinuria of 5 g or higher in a 24 hour urine samples or 3+ or greater on two random urine samples collected at least 4 hours apart, oliguria of less than 500 ml in 24 hours, cerebral or visual disturbances, pulmonary edema or cyanosis, epigastric or right upper-quadrant pain, elevated liver enzymes, thrombocytopenia, or fetal growth restriction. Magnesium sulfate should be used for the prevention and treatment of seizures on women with severe preeclampsia or eclampsia. If analgesia/anesthesia is required, regional or neuraxial analgesia/anesthesia should be used because it is efficacious and safe for Intrapartum management of women with severe preeclampsia in the absence of coagulopathy. Practitioners should be aware that although various laboratory tests may be useful in the management of women with preeclampsia, to date there is no reliable predictive test for preeclampsia. Suggested Reading: References: |