Hypertension and Pregnancy

INTRODUCTION

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Background: Hypertension is the most common medical problem encountered during pregnancy, complicating 2-3% of pregnancies. Hypertensive disorders during pregnancy are classified into 4 categories, as recommended by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy: chronic hypertension, preeclampsia-eclampsia, preeclampsia superimposed on chronic hypertension, and gestational hypertension (transient hypertension of pregnancy or chronic hypertension identified in the latter half of pregnancy). This terminology is preferred over the older but widely used term PIH (pregnancy-induced hypertension) because it is more precise.

Chronic hypertension is defined as blood pressure exceeding 140/90 mm Hg before pregnancy or before 20 weeks' gestation. When hypertension first is identified during a woman’s pregnancy and she is at less than 20 weeks' gestation, blood pressure elevations usually represent chronic hypertension. In contrast, new onset of elevated blood pressure readings after 20 weeks' gestation mandates the consideration and exclusion of preeclampsia. Preeclampsia occurs in approximately 5% of all pregnancies and 10% of first pregnancies. Hypertensive disorders in pregnancy may cause maternal and fetal morbidity and remain a leading source of maternal mortality.

Pathophysiology:

Chronic hypertension

Chronic hypertension is a primary disorder in 90-95% of cases.

Preeclampsia

Although the exact pathophysiologic mechanism is not understood clearly, preeclampsia can be thought of as a disorder of endothelial function with vasospasm. In some cases, light microscopy will demonstrate evidence of placental insufficiency associated with abnormalities, such as diffuse placental thrombosis, an inflammatory placental decidual vasculopathy, and/or abnormal trophoblastic invasion of the endometrium. This association suggests that abnormal placental development or placental damage from diffuse microthrombosis may be central to the development of this disorder.

Evidence also exists that an altered maternal immune response to fetal/placental tissue may contribute to the development of preeclampsia. The widespread endothelial dysfunction may manifest in a pregnant woman as dysfunction of multiple organ systems, including the central nervous, hepatic, pulmonary, renal, and hematological. Endothelial damage leads to pathologic capillary leak that can manifest in the mother as rapid weight gain, edema of the face or hands, pulmonary edema, and/or hemoconcentration. When the placenta is diseased it can affect the fetus via decreased utero-placental blood flow. This decrease in perfusion can manifest clinically as nonreassuring fetal heart rate testing, low scores on a biophysical profile, oligohydramnios, and as fetal growth restriction in severe cases.

Hypertension occurring in preeclampsia is due to vasospasm, with arterial constriction and relatively reduced intravascular volume compared to normal pregnancy. Normally, the vasculature of pregnant women demonstrates decreased responsiveness to vasoactive peptides such as angiotensin II and epinephrine. Women who develop preeclampsia show a hyperresponsiveness to these hormones; their blood pressures are labile, and their normal circadian blood pressure rhythms may be blunted or reversed.

Transient hypertension

Transient hypertension refers to hypertension occurring in late pregnancy without any other features of preeclampsia and with normalization of blood pressure postpartum. The pathophysiology of transient hypertension is unknown, but it may be a harbinger of chronic hypertension later in life.

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Frequency:
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• In the US: Chronic hypertension occurs in up to 22% of women of childbearing age, with the prevalence varying according to age, race, and body mass index. Chronic hypertension complicates 1-5% of pregnancies.

  Preeclampsia complicates about 5% of all pregnancies, 10% of first pregnancies, and at least 20% of pregnancies in women with a history of chronic hypertension.

Mortality/Morbidity:

• Hypertensive disorders in pregnancy are the third leading cause of maternal mortality, after thromboembolism and nonobstetric injuries.

• While maternal diastolic blood pressure (DBP) greater than 110 mm Hg is associated with an increased risk for placental abruption and fetal growth restriction, superimposed preeclamptic disorders cause most of the morbidity due to chronic hypertension during pregnancy. Severe maternal complications include eclamptic seizures, intracerebral hemorrhage, pulmonary edema due to capillary leak or myocardial dysfunction, acute renal failure due to vasospasm, proteinuria greater than 4-5 g/d, hepatic swelling with or without liver dysfunction, and disseminated intravascular coagulation/consumptive coagulopathy (rare). Consumptive coagulopathy usually is associated with placental abruption and is uncommon as a primary manifestation of preeclampsia.

• Fetal complications include abruptio placentae, intrauterine growth restriction, premature delivery, and intrauterine fetal death.

Race: African American women have higher rates of preeclampsia complicating their pregnancies compared to other racial groups, mainly because they have a greater prevalence of underlying chronic hypertension. Among women aged 30-39 years, chronic hypertension is present in 22.3% of African Americans, 4.6% of whites, and 6.2% of Mexican Americans. Hispanic women generally have blood pressure levels that are the same as or lower than non-Hispanic white women.

CLINICAL

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History: At times it is a challenge to determine if elevated blood pressure identified during pregnancy is due to chronic hypertension or preeclampsia. Clinical characteristics, such as history, physical exam, and certain laboratory examinations, are used to help clarify the diagnosis.

• Gestational age

• Hypertension prior to 20 weeks' gestation almost always is due to chronic hypertension; preeclampsia is rare prior to the third trimester.

• New onset or worsening hypertension after 20 weeks' gestation should lead to a careful evaluation for manifestations of preeclampsia.

• The diagnosis of severe hypertension or preeclampsia in the first or early second trimester necessitates exclusion of gestational trophoblastic disease/molar pregnancy.

• Women diagnosed with severe or early preeclampsia (in the second trimester or early third trimester) have a higher prevalence of thrombophilias, but no studies to date have demonstrated that administering anticoagulants in subsequent pregnancies will decrease the risk of recurrent preeclampsia.

• Maternal risk factors for preeclampsia
• First pregnancy
• New partner/paternity
• Age younger than 18 years or older than 35 years
• History of preeclampsia
• Family history of preeclampsia in a first-degree relative
• African American race

• Medical risk factors for preeclampsia

• Chronic hypertensionSecondary causes of chronic hypertension such as hypercortisolism, hyperaldosteronism, pheochromocytoma, or renal artery stenosis
• Preexisting diabetes (type 1 or type 2), especially with microvascular diseaseRenal disease
• Systemic lupus erythematosus
• Obesity
• Thrombophilia

• Placental/fetal risk factors for preeclampsia
  • Multiple gestations
  • Hydrops fetalis
  • Gestational trophoblastic disease
  • Triploidy
• Symptoms of preeclampsia
  • Visual disturbances typical of preeclampsia are scintillations and scotomata. These disturbances are presumed to be due to cerebral vasospasm.
  • Headache is of new onset and may be described as frontal, throbbing, or similar to a migraine headache. But no classic headache of preeclampsia exists.
  • Epigastric pain is due to hepatic swelling and inflammation, with stretch of the liver capsule. Pain may be of sudden onset, it may be constant, and it may be moderate-to-severe in intensity.
  • While mild lower extremity edema is common in normal pregnancy, rapidly increasing or nondependent edema may be a signal of developing preeclampsia. This signal theory remains controversial, however, and recently has been removed from most criteria for the diagnosis of preeclampsia.
  • Rapid weight gain is a result of edema due to capillary leak as well as renal sodium and fluid retention.

Physical:

• Physical findings in preeclampsia
• Blood pressure
  • Measure blood pressure in the sitting position, with the cuff at the level of the heart. Inferior vena caval compression by the gravid uterus while the patient is supine can alter readings substantially, leading to an underestimation of the blood pressure. Blood pressures measured in the left lateral position similarly may yield falsely low values if the blood pressure is measured in the higher arm and the cuff is not maintained at heart level.

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  • Allow women to sit quietly for 5-10 minutes before measuring the blood pressure.
  • Record Korotkoff sounds I (the first sound) and V (the disappearance of sound) to denote the systolic blood pressure (SPB) and DPB, respectively. In about 5% of women, an exaggerated gap exists between the fourth (muffling) and fifth (disappearance) Korotkoff sounds, with the fifth sound approaching zero. In this setting, record both the fourth and fifth sounds (eg, 120/80/40 with sound I=120, sound IV=80, sound V=40).
  • Maternal SPB greater than 160 mm Hg or DPB greater than 110 mm Hg denotes severe disease; consider delivery.

• Retinal vasospasm is a severe manifestation of maternal disease; consider delivery.

• Retinal edema is known as serous retinal detachment. This can manifest as severely impaired vision if the macula is involved. In the author's experience, the condition typically resolves completely, but consider delivery.

• Right upper quadrant (RUQ) abdominal tenderness stems from liver swelling and capsular stretch. Consider delivery.

• Brisk, or hyperactive, reflexes are common during pregnancy, but clonus is a sign of neuromuscular irritability that raises concern.

• Among pregnant women, 30% will have some lower extremity edema as part of their normal pregnancy. However, a sudden change in dependent edema, edema in nondependent areas such as the face and hands, or rapid weight gain suggests a pathologic process and warrants further evaluation.

• Signs suggesting a secondary medical cause of chronic hypertension

• Centripetal obesity, "buffalo hump," and/or wide purple abdominal striae suggest glucocorticoid excess.

• A systolic bruit heard over the abdomen or in the flanks suggests renal artery stenosis.

• Radiofemoral delay or diminished pulses in lower versus upper extremities suggests coarctation of the aorta.

• Clinical signs may demonstrate hyperthyroidism, hypothyroidism, or growth hormone excess.

• Signs of end-organ damage from chronic hypertension

• S4 on cardiac auscultation is not a normal finding in pregnancy. It suggests left ventricular hypertrophy or diastolic dysfunction due to preeclampsia-induced vasospasm. Despite a well-conducted phonocardiographic study of pregnant women that found an S3 to be common in normal pregnancy, our findings at busy obstetric centers have not supported this. In the presence of preeclampsia, consider any cardiac gallop a pathological finding.

• Diminished distal pulses due to peripheral vascular disease

• Retinal changes of chronic hypertension

• Carotid bruits

Causes:

• Chronic hypertension

• Chronic hypertension may be either essential (90%) or secondary to some identifiable underlying disorder, such as renal parenchymal disease (eg, polycystic kidneys, glomerular or interstitial disease), renal vascular disease (eg, renal artery stenosis, fibromuscular dysplasia), endocrine disorders (eg, adrenocorticosteroid or mineralocorticoid excess, pheochromocytoma, hyperthyroidism or hypothyroidism, growth hormone excess, hyperparathyroidism), coarctation of the aorta, or oral contraceptive use.

• About 20-25% of women with chronic hypertension will develop preeclampsia during pregnancy.

• Preeclampsia

• The exact cause is not known.

• The widespread endothelial dysfunction manifests primarily with maternal effects and has the potential to cause dysfunction of multiple organ systems, including the brain, hepatic, pulmonary, renal, and hematological systems. The endothelial damage leads to pathologic capillary leak that can manifest in the mother as rapid weight gain, edema of the face or hands, pulmonary edema, and/or hemoconcentration resulting in hemoglobin greater than 12.0 g/dL or creatinine greater than 0.8 mg/dL. Renal biopsy may show glomerular endotheliosis that is associated with proteinuria greater than 300 mg in 24 hours.

• Effects on the placenta include in-situ thrombosis and decidual vasculopathy that can affect the fetus via decreased utero-placental blood flow. This decrease in flow can manifest clinically as nonreassuring fetal heart rate testing, low score on a biophysical profile, oligohydramnios, and fetal growth restriction in severe cases.

WORKUP

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Lab Studies:
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• Lab testing to evaluate chronic hypertension includes testing for target organ damage, potential secondary causes of hypertension, and other risk factors.

• Studies include urinalysis; CBC; serum sodium, potassium, creatinine, and glucose (the presence of high levels of progesterone, an aldosterone antagonist, during a normal pregnancy may mask the hypokalemia from hyperaldosteronism);
  and 12-lead ECG.

• Optional tests include creatinine clearance, microalbuminuria, 24-hour urinary protein, serum calcium, uric acid, glycosylated hemoglobin, thyroid-stimulating hormone (TSH), and limited echocardiography (for left ventricle hypertrophy [LVH]).

• Serum lipids (total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides) predictably increase during pregnancy, so defer measurement until the postpartum period.

• The increase in endogenous corticosteroid levels during normal pregnancy makes it difficult to diagnose secondary hypertension due to adrenal hormone excess.

• Routine tests when evaluating a patient for preeclampsia include CBC, electrolytes, BUN, creatinine, liver enzymes and bilirubin, and a urine dip for protein.

• CBC

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  • In cases in which the platelet count is less than 150 K, 75% are secondary to dilutional thrombocytopenia of pregnancy, 24% are due to preeclampsia, and about 1% of cases are due to other platelet disorders not related to pregnancy. Counts less than 100 K suggest preeclampsia.

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  • Hemoglobin levels greater than 13 g/dL suggest the presence of hemoconcentration. Low levels may be due to microangiopathic hemolysis.

• Urinalysis may be used as a screen for proteinuria. Trace levels to +1 proteinuria are acceptable, but levels of +2 or greater are abnormal and should be quantified with a 24-hour urine collection.

• Serum creatinine normally is less than 0.8 mg/dL during pregnancy; higher levels suggest intravascular volume contraction or renal involvement in preeclampsia.

• A serum uric acid level greater than 5 mg/dL is abnormal and is a sensitive, but nonspecific, marker of tubular dysfunction in preeclampsia.

• Elevated levels of hepatic transaminases may reflect hepatic involvement in preeclampsia and may occur in the absence of epigastric/RUQ pain.

• In a 24-hour urine collection, normal protein excretion in pregnancy is up to 300 mg/24 h. Higher levels are abnormal and may reflect renal involvement in preeclampsia. Creatinine clearance increases approximately 50% during pregnancy, and levels less than 100 mL/min suggest renal dysfunction that is either chronic or due to preeclampsia.

• Examine peripheral blood smear for evidence of microangiopathic hemolysis and thrombocytopenia. A clinician easily can detect the presence of red blood cell (RBC) fragments; thus, a trip to the lab will establish the diagnosis quickly. The presence of RBC fragments confirms microangiopathic hemolysis. Also consider the diagnoses of hemolytic-uremic syndrome (HUS); thrombotic thrombocytopenic purpura (TTP); and HELLP syndrome (Hemolysis, Elevated Liver enzymes, and Low Platelet [count]). In these cases, consult a hematologist to evaluate the need for plasmapheresis.

• Prothrombin time (PT)/international normalized ratio (INR) and/or activated partial prothrombin time (aPTT) may be abnormal in consumptive coagulopathy and disseminated intravascular coagulopathy (DIC) complicating severe preeclampsia. Checking the PT/INR/aPTT is not necessary in the absence of abnormal liver transaminases or thrombocytopenia.

• Abnormal values of lactate dehydrogenase (LDH), bilirubin, haptoglobin, fibrinogen, and D-dimers may confirm the presence of hemolysis and DIC, along with coagulation testing. Checking LDH, bilirubin, haptoglobin, fibrinogen, and D-dimers is unnecessary unless PT/INR/aPTT are abnormal, thrombocytopenia is present, or the hemoglobin level is dropping.

• Tests when evaluating eclampsia

• New seizures in pregnancy suggest preeclampsia-eclampsia, but primary neurological disorders must be excluded.

• Tests to order include those suggested to evaluate for preeclampsia. Include a CT scan of the brain to exclude hemorrhage or mass lesion. An electroencephalogram (EEG) also may be appropriate to evaluate altered mental status.

Imaging Studies:
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• Chest x-ray

• Perform chest x-rays (CXRs) to evaluate for pulmonary edema in the setting of dyspnea or hypoxia occurring in a woman with preeclampsia.

• The fetal ionizing radiation exposure of 1 maternal CXR with abdominal shielding is only 0.001 rads. While there is no absolutely safe dose of ionizing radiation during pregnancy, a common held acceptable cumulative dose is 5.0 rads during pregnancy (ie, approximately 5000 maternal CXRs could be performed before reaching this safety threshold).

• CT scan of the brain

• Perform a CT scan to exclude cerebral hemorrhage in the setting of seizures, severe headache, or altered level of consciousness. The fetal radiation exposure with abdominal shielding is well under the permissible 5.0 rads.

• Findings in women with preeclampsia may include bilateral hypodense areas, called venous infarcts, in the occipital and parietal regions. They represent focal and reversible areas of edema that are the result of capillary leak or focal areas of impaired venous flow. Generally, these areas are asymptomatic and will resolve as the preeclamptic process reverses.

• Imaging should not be performed in an unstable patient and should not delay rapid facilitated delivery in a woman with suspected severe preeclampsia or eclampsia.

• MRI of the brain

• An MRI may be performed to evaluate for abnormalities of the cerebral cortex (edema, infarction, hemorrhage) in preeclamptic women with severe visual disturbance, seizures, or altered mental status. An MRI is more sensitive than a CT scan for detecting cerebral cortical abnormalities but less useful in detecting cerebral hemorrhage.

• The classic finding of preeclampsia on T2-weighted images is bilateral occipital bright spots that represent focal edema. This finding is similar to the changes observed when a nonpregnant patient has hypertensive encephalopathy.

• Magnetic resonance venography also may be performed to exclude cerebral venous sinus thrombosis.

• Imaging should not be performed in an unstable patient and should not delay rapid facilitated delivery in a woman with suspected severe preeclampsia or eclampsia.

• Use an ultrasound or CT scan of the liver to evaluate for subcapsular hemorrhage or infarction in the setting of persistent severe RUQ pain or markedly elevated hepatic transaminases.

Other Tests:
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• Electroencephalogram

• An EEG may be indicated to evaluate recurrent seizure activity or persistent altered level of consciousness.

• Following eclampsia, the EEG may reveal epileptiform activity. More commonly, the test shows nonspecific diffuse slowing that may persist for several weeks after delivery.

• Echocardiography

• Fetal monitoring

• Close fetal monitoring under the direction of an obstetrician is essential in pregnant women with preeclampsia. In this setting, the fetus is at risk for oligohydramnios, impaired growth, and intrauterine fetal death as a consequence of placental insufficiency. Fetal concerns may be an indication for delivery in women with otherwise mild preeclampsia.

• Fetal heart rate tracing is a useful tool to assess utero-placental perfusion.

Histologic Findings: Endothelial dysfunction and vasospasm observed in preeclampsia affect multiple regions of the body, including the maternal brain, kidneys, liver, lungs, heart, and placenta. Pathology demonstrates areas of edema, microinfarctions, and microhemorrhage in the affected organs. The placenta typically shows incomplete decidualization of the spiral arterioles, which may be part of the pathogenesis of preeclampsia. The kidneys may reveal glomerular endotheliosis or, more rarely, acute tubular necrosis (ATN) or cortical necrosis.

TREATMENT

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Medical Care: Although the primary risk of chronic hypertension in pregnancy is development of superimposed preeclampsia, no evidence suggests that pharmacological treatment of mild hypertension reduces the incidence of preeclampsia in this population.

• In normal pregnancy, women's mean arterial pressure drops 10-15 mm Hg over the first half of pregnancy. Most women with mild chronic hypertension (SBP 140-160 mm Hg, DBP 90-100 mm Hg) will have a similar decrease in blood pressures and may not require any medication during this period. Conversely, DPB greater than 110 mm Hg has been associated with an increased risk of placental abruption and intrauterine growth restriction. Therefore, place pregnant patients on antihypertensive therapy if the SPB is greater than 160 mm Hg or the DPB is greater than 100 mm Hg.

• Three treatment options are available in cases of mild chronic hypertension in pregnancy.

• Antihypertensive medication may be withheld or discontinued, with subsequent close observation of her blood pressure. Since blood pressure drops during normal pregnancy, and there are no data to support the use of medication in patients with pressures less than 160/100, we recommend this option most often.

• If a woman is on pharmacologic treatment with an agent not recommended for use in pregnancy, she may be switched to an alternative antihypertensive agent preferred for use in pregnancy.

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• If a woman is on pharmacologic treatment with an agent acceptable for use in pregnancy, she may continue her current antihypertensive therapy.

• For a woman with chronic hypertension in her first trimester, obtain the following lab studies—CBC, electrolytes, BUN, creatinine, liver enzymes, urine dip for protein, and a 24-hour urine collection for creatinine clearance and protein excretion. These tests will serve as baseline values to be referred to later in the pregnancy if a concern regarding superimposed preeclampsia arises.

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• Closely observe women with chronic hypertension in pregnancy for the development of worsening hypertension and/or the development of superimposed preeclampsia (risk is approximately 20%). Repeat laboratory investigations for preeclampsia if the patient’s blood pressure increases or if she develops signs or symptoms of preeclampsia.

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• Promptly hospitalize women with suspected or diagnosed preeclampsia for close observation. When diagnosed with preeclampsia, delivering the baby always is in the mother’s best interest. Any delay in delivery should be due to uncertainty about the diagnosis or immaturity of the fetus. When preeclampsia develops remote from term (ie, less than 34-36 weeks' gestation), attempts often are made to prolong the pregnancy to allow for further fetal growth and maturation. Monitor both maternal and fetal status closely if pregnancy is prolonged. Perform fetal testing at least twice weekly, using a combination of biophysical profiles and nonstress testing supervised by an obstetrician. Facilitated delivery should occur if either maternal or fetal deterioration is noted, with the mode of delivery decided by obstetric indications.

Consultations:

• An obstetrician should follow all cases of women with chronic hypertension throughout pregnancy; refer women with moderate or severe hypertension to an experienced internist (Obstetric Medicine specialist), a medical subspecialist, and/or a specialist in maternal-fetal medicine (Perinatologist).

• Internal medicine consultation may be useful in the care of women with chronic hypertension due to a secondary cause, women with target organ damage, and women in whom preeclampsia causes significant organ failure.

• Diagnosis of secondary hypertension during pregnancy can be difficult.

• While not absolutely contraindicated, renal captopril scans involve radioactive isotopes and usually are deferred to the postpartum period.

• Hyperaldosteronism and hypercortisolism are difficult to diagnose during pregnancy due to the high levels of progesterone and the normal increase in endogenous cortisol output.

MEDICATION

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Women with mild chronic hypertension often do not require antihypertensive therapy during most of pregnancy. Pharmacologic treatment of mild hypertension does not reduce the likelihood of developing preeclampsia later in gestation and increases the likelihood of an adverse effect in the mother or the fetus. However, if maternal blood pressure exceeds 160/100 mm Hg, drug treatment is recommended.

If a pregnant woman's blood pressure is sustained greater than 170 mm Hg systolic and/or 110 mm Hg diastolic at any time, lowering her blood pressure quickly with rapid-acting agents is indicated for maternal safety. Initiate anticonvulsant therapy for severe preeclampsia (prophylaxis) or in the setting of eclamptic seizures. The most effective agent is IV magnesium sulfate; phenytoin is an alternative, though less effective, therapy.

FOLLOW-UP

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Further Inpatient Care:
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• When women have mild preeclampsia remote from term or labile blood pressures due to chronic hypertension and/or gestational hypertension, they often are admitted to hospital for bed rest and frequent fetal monitoring.

• The severity of any abnormalities on admission will dictate the frequency of blood work.

• Daily examination should include a funduscopic exam for retinal spasm or edema, lung exam for signs of volume overload, cardiac exam for gallop rhythms, abdominal exam for hepatic tenderness, exam of extremities/sacrum for increasing edema, and neurologic exam for clonus.

• Treating hypertension secondary to preeclampsia with medications may reassure the clinician falsely but will not slow progression of the process, therefore it is NOT recommended.
  
  Other symptoms and signs of worsening preeclampsia must be sought routinely and delivery facilitated if the maternal or fetal condition worsens.

• Hypertension due to preeclampsia may worsen or even present in the postpartum period.

• After delivery, women with preeclampsia require ongoing close blood pressure monitoring. Urgently decrease blood pressure greater than 170/110 mm Hg with IV antihypertensives. Consider oral antihypertensive therapy for sustained pressure above 160/100 mm Hg.

• Blood pressure changes due to preeclampsia usually resolve within days to weeks after delivery but may persist for 3 months. Persistent hypertension beyond this point probably represents chronic hypertension.

Further Outpatient Care:
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• Women with preeclampsia require follow-up with an internal medicine specialist after hospital discharge.

• Women with persistent hypertension due to preeclampsia require ongoing reassessment of their blood pressure. As vasospasm resolves, patients may be weaned off antihypertensive therapy.

• Follow cases involving persistent lab abnormalities related to preeclampsia (eg, proteinuria, thrombocytopenia, liver enzyme elevations) until the abnormalities return to normal. This is vital to ensure that no other underlying maternal medical disorder is missed.

In/Out Patient Meds:
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• Available data suggest that all studied agents are excreted into human breast milk, but most to a negligible degree. All antihypertensive medications are believed to be compatible with breastfeeding, but it is reasonable to use medications with a well established track record.

• Atenolol, as well as the other beta-blocking agents nadolol and metoprolol, appear to be concentrated in breast milk. Labetalol and propranolol do not share this property and are preferred agents if a beta-blocker is indicated.

Transfer:
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• Transfer women with preeclampsia remote from term (<34-36 weeks' gestation) to a facility with adequate resources to care for premature newborn infants. This is essential because worsening preeclampsia disease activity may require urgent delivery at any time.

Deterrence/Prevention:
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Complications:
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• Life-threatening complications in preeclampsia

• Seizures

• Cerebral hemorrhage

• Pulmonary edema - Due to pulmonary capillary leak, excess IV fluid administration, or myocardial dysfunction

• Acute renal failure - Due to renal vasospasm, ATN, or renal cortical necrosis

• DIC

• HELLP syndrome - Microangiopathic hemolysis, elevated liver enzymes, and thrombocytopenia (platelets [PLT] <100)

• Hepatic infarction/rupture and subcapsular hematoma - May lead to massive internal hemorrhage and shock

• Acute fatty liver of pregnancy: Although a distinct and rare disorder, acute fatty liver has some clinical features similar to, and often overlapping with, severe preeclampsia.

• Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (HUS): While unrelated to preeclampsia, consider these important disorders in the setting of presumed severe HELLP syndrome.

Prognosis:
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• Women who develop preeclampsia during pregnancy have an increased risk of recurrent preeclampsia during subsequent pregnancies. The overall risk is about 18%. The risk is higher (50%) in women who develop severe early preeclampsia (before 27 weeks' gestation).

• Transient hypertension of pregnancy—the development of isolated hypertension in a woman in late pregnancy without other manifestations of preeclampsia—is associated strongly with later development of chronic hypertension.

MISCELLANEOUS

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Medical/Legal Pitfalls:
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• Most internists do not have extensive exposure to diagnosing and treating medical disorders during pregnancy and therefore feel some discomfort doing so. Consult with an obstetric internist, maternal-fetal medicine specialist (perinatologist), and/or medical subspecialist. The experience of these experts allows them to assess quickly which treatments offer the best risk-benefit ratio. In most situations, the benefit of maximizing maternal well-being with the usual therapies will outweigh potential adverse effects on the fetus.

Special Concerns:
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• Pregnancy

• Most patients enter pregnancy with the expectation that their pregnancy and delivery will involve nothing but happiness. When severe complications occur, patients often feel scared, angry, and helpless. The best approach is to discuss all issues with patients. Take all possible steps to help the patient and her family understand the complications and treatment. Begin the discussion by providing the diagnosis and reassure the pregnant woman that, in most cases, the complications are not due to her actions or failure to act. Follow with discussion of plans for evaluation and treatment, providing her an opportunity to ask questions. Empower the patient by involving her in the decision-making process.

• Patients ask very important questions. Physicians should feel comfortable being honest and telling patients and families when they do not have all of the answers. Physicians should let patients know that they will work to find the answers. This honesty and thoroughness will solidify the physician's reputation as a caring and competent doctor. Consultation with experienced clinicians will help the physician care for the patient and reassure her that all avenues of treatment are being explored.

• Many reference texts and articles are available regarding the treatment of medical disorders during pregnancy. Becoming educated about these topics will help physicians feel more comfortable treating and counseling patients.