hypertension in pregnancy

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: 1) chronic hypertension, 2) preeclampsia-eclampsia, 3) preeclampsia superimposed on chronic hypertension, and 4) 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 is first 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, 10% of first pregnancies, and 20-25% of women with a history of chronic hypertension. 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. Secondary causes are briefly discussed in Causes.

Preeclampsia

Although the exact pathophysiologic mechanism is not clearly understood, preeclampsia can be thought of as a disorder of endothelial function with vasospasm. In some cases, light microscopy demonstrates 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 indicates 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 systems. Endothelial damage leads to pathologic capillary leak that can manifest in the mother as rapid weight gain, nondependant edema (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. Usually, 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, an alteration that may be seen even before the hypertension becomes apparent. In addition, 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.

Frequency:

• 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 among the leading causes of maternal mortality, along with thromboembolism, hemorrhage 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 and/or 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: Black 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 black people, 4.6% of white people, and 6.2% of Mexican Americans. Hispanic women generally have blood pressure levels that are the same as or lower than those of non-Hispanic white women.

Age: Preeclampsia is more common at the extremes of maternal age (<18 y or >35 y). The increased prevalence of chronic hypertension in women older than 35 years can explain the increased frequency of preeclampsia among older gravidas.

Clinically:

History: Sometimes, determining whether elevated blood pressure identified during pregnancy is due to chronic hypertension or to preeclampsia is a challenge. Clinical characteristics, such as history, physical examination, 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 and/or molar pregnancy.

• Women diagnosed with severe or early preeclampsia (in the second trimester or early third trimester) have a higher prevalence of thrombophilias. Studies are ongoing to evaluate whether administering anticoagulants in subsequent pregnancies decreases 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

• Black race

• Medical risk factors for preeclampsia

• Chronic hypertension

• Secondary causes of chronic hypertension such as hypercortisolism, hyperaldosteronism, pheochromocytoma, or renal artery stenosis

• Preexisting diabetes (type 1 or type 2), especially with microvascular disease

• Renal 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. However, 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, is typically constant, and 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 edema is no longer included among the criteria for 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
• Blood pressure should be measured 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, unless the cuff is carefully maintained at the level of the heart.
• Women should be allowed to sit quietly for 5-10 minutes before each blood pressure measurement.
• Record Korotkoff sounds I (the first sound) and V (the disappearance of sound) to denote the systolic blood pressure (SBP) and DBP, 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) as the fourth sound will more closely approximate the true DBP.
• Maternal SBP greater than 160 mm Hg or DBP greater than 110 mm Hg denotes severe disease; consider delivery.
• Automated blood pressure cuffs provide reasonable estimates of true blood pressure during normal pregnancy but tend to underestimate blood pressure in preeclamptic women. Manual blood pressure measurement with a mercury sphygmomanometer remains the criterion standard in this setting. Automated machines should only be used if they have been tested and validated by the manufacturer for use in this population.
• Home and ambulatory BP measurements are increasingly being used in the pregnant population. Assuming the BP device is accurate (validated relative to an office measurement) they may provide valuable additional data regarding hypertension severity and control during pregnancy.

• 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. While the condition typically resolves completely, it generally reflects severe preeclampsia and should lead to consideration of delivery.

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

• Brisk, or hyperactive, reflexes are common during pregnancy. Clonus is a sign of neuromuscular irritability that usually reflects severe preeclampsia.

• Among pregnant women, 30% 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, the authors' 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 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 and the 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 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.

Lap:

Lab Studies:

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

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

• Optional tests include: creatinine clearance, microalbuminuria, 24-hour urinary protein, serum calcium, uric acid, glycosylated hemoglobin, and thyroid-stimulating hormone (TSH).

• Serum lipids (ie, 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 count, electrolytes, BUN, creatinine, liver enzymes and bilirubin, and a urine dip for protein.

• CBC count
• In cases in which an incidental platelet count is less than 150,000/mL, 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 100,000/mL suggest preeclampsia or ITP.
• 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.
• Recently, spot urine specimens for albumin/Cr or protein/Cr ratios have been validated as screening tools for abnormal proteinuria during pregnancy. They appear to be more accurate than urinalysis, although an abnormal response should still be confirmed with a 24-hour urine collection.

• Serum creatinine usually 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, the reference range for protein excretion in pregnancy is up to 300 mg/d. 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, laboratory findings 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) and/or international normalized ratio (INR) and/or activated partial prothrombin time (aPTT) results may be abnormal in consumptive coagulopathy and disseminated intravascular coagulopathy 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 disseminated intravascular coagulopathy, along with coagulation testing. Checking LDH, bilirubin, haptoglobin, fibrinogen, and D-dimers is unnecessary unless PT/INR/aPTT results are abnormal, thrombocytopenia is present, or the hemoglobin level is dropping.

Imaging Studies:

• Imaging studies should not be performed in an unstable patient and should not delay rapid facilitated delivery in a woman thought to have severe preeclampsia or eclampsia.

• New seizures in pregnancy suggest preeclampsia-eclampsia, but primary neurological disorders must be excluded. Tests to order when evaluating eclampsia include those suggested to evaluate for preeclampsia.

• Chest radiograph

• Obtain chest radiographs to evaluate for pulmonary edema in the setting of dyspnea or hypoxia occurring in a woman with preeclampsia.

• The fetal ionizing radiation exposure of one maternal chest radiograph with abdominal shielding is only 0.001 rads. While no dose of ionizing radiation is absolutely safe during pregnancy, a commonly held acceptable cumulative dose is 5 rads during pregnancy (approximately 5000 maternal chest radiographs 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 rads. CT scan can also be used to exclude mass lesion.

• 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 produce no symptoms and resolve as the preeclamptic process reverses.

• MRI of the brain

• An MRI may be performed to evaluate for abnormalities of the cerebral cortex (ie, 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.

• 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.

• Limited echocardiography is performed to evaluate for left ventricle hypertrophy (LVH).

Other Tests:

• Perform 12-lead ECG to evaluate chronic hypertension.

• Electroencephalogram

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

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

• Fetal monitoring

• Close fetal monitoring under the direction of an obstetrician is essential in pregnant women with preeclampsia. Preeclampsia is a disease of the placenta. When the placenta is severely affected, subtle hypoperfusion of the fetus can occur, which may initially manifest as a decrease in the amniotic fluid level (oligohydramnios), fetal growth restriction, and intrauterine fetal death as a consequence of placental insufficiency. Fetal concerns may be an indication for delivery in women with otherwise mild preeclampsia. In this setting, order fetal assessments twice each week. Obstetricians generally alternate a biophysical profile with a fetal nonstress test to assess fetal well-being. At this point, the authors advise collaboration with a perinatologist.

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

• In women with chronic hypertension, consider advising the obstetrician to obtain a fetal ultrasound at 18 weeks' gestation to document growth. Serial ultrasounds may be necessary.

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:

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 (ie, SBP 140-160 mm Hg, DBP 90-100 mm Hg) have a similar decrease in blood pressures and may not require any medication during this period. Conversely, DBP 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 SBP is greater than 160 mm Hg or the DBP is greater than 100 mm Hg. The goal of pharmacologic treatment should be a DBP of about 80-90 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 blood pressure. Because blood pressure drops during normal pregnancy and no data support the use of medication in patients with pressures less than 160/100 mm Hg, the authors 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.
• 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 laboratory 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 serve as baseline values to be referred to later in the pregnancy if a concern regarding superimposed preeclampsia arises.
• 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.
• 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, <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).

• An 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.

Diet: Multiple dietary interventions have been investigated for a role in preventing preeclampsia (see Deterrence/Prevention), but none with any effect.

Activity:

• Women with worsening hypertension during pregnancy often are placed on bed rest or restricted activity, although no scientific evidence demonstrates that this is beneficial in prolonging gestation or reducing maternal or fetal morbidity/mortality.

• Women with hypertension and suspected preeclampsia typically are admitted to a hospital for close observation and investigation. Those with established preeclampsia must be observed very closely, either in hospital or in a comprehensive home monitoring program under the care of an obstetrician.

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, although less effective, therapy.
Remember that a healthy fetus depends on a healthy mother, so use medications when clear benefit to the mother exists. The US Food and Drug Administration (FDA) categorization for drug use during pregnancy is overly simplistic. To quote the FDA descriptions, any medication in class A through D may be used "when the potential benefit justifies the potential risk."
Medications to avoid during pregnancy include angiotensin-converting enzyme (ACE) inhibitors, which are associated with fetal renal dysgenesis or death when used in the second and third trimesters. ACE inhibitors reduce angiotensin II levels, decreasing aldosterone secretion. Angiotensin II receptor antagonists/blockers are not used during pregnancy because of similar mechanism of action as ACE inhibitors.
Drug Category: Alpha-adrenergic inhibitors -- Used to treat chronic hypertension during pregnancy. At low doses, an alpha-adrenergic receptor blocker may be used as monotherapy in the treatment of hypertension. At higher doses, it may cause sodium and fluid to accumulate. As a result, concurrent diuretic therapy may be required to maintain the hypotensive effects of the alpha-receptor blockers

Further Inpatient Care:

• 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 dictates the frequency of blood work.

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

• Treating hypertension secondary to preeclampsia with medications may reassure the clinician falsely but does not slow progression of the process; therefore, if treatment with antihypertensives is undertaken, clinicians must remain vigilant for all other symptoms, signs, and laboratory evidence of worsening preeclampsia.

• 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. Blood pressure greater than 170/110 mm Hg should be urgently treated with IV antihypertensives. Oral antihypertensive therapy should be undertaken for sustained pressures 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.

• Consider being more aggressive with blood pressure control with patients who are older than 40 years and with those who have a history of poorly controlled hypertension, other cardiac disorders, known left ventricular hypertrophy, or diabetes. These women are more likely to have diastolic dysfunction and/or pulmonary edema in a very high afterload setting.

Further Outpatient Care:

• 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 laboratory abnormalities related to preeclampsia (eg, proteinuria, thrombocytopenia, liver enzyme elevations) until the abnormalities return to the reference range. This is vital to ensure that no other underlying maternal medical disorder is missed.

In/Out Patient Meds:

• Available data suggest that all studied agents are excreted into human breast milk, but most are excreted to a negligible degree. All antihypertensive medications are believed to be compatible with breastfeeding, but using medications with a well-established record is reasonable.

• 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:

• Transfer women with preeclampsia remote from term (ie, <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:

• Multiple interventions to prevent preeclampsia have been investigated. Pharmacologic treatment and normalization of chronic hypertension does not reduce the risk of developing superimposed preeclampsia. Other therapies that have been tried include low-dose acetylsalicylic acid (ASA), supplemental calcium, salt restriction, supplemental magnesium, and fish oil therapy. While several large trials of ASA in high-risk populations showed minimal benefit in reducing the frequency of preeclampsia, a recent meta-analysis reported an approximate 15% reduction in preeclampsia among pregnant women taking low-dose ASA. This therapy appears very safe and might be considered in high-risk women. None of the other therapies have demonstrated any significant preventive benefit. One recent trial demonstrated some preventive benefit to supplemental antioxidants (vitamins C and E), but these results remain to be confirmed.

Complications:

• 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

• Disseminated intravascular coagulopathy

• 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.

• TTP and HUS: While unrelated to preeclampsia, consider these important disorders in the setting of presumed severe HELLP syndrome.

Prognosis:

• 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 (ie, before 27 weeks' gestation).

• Transient hypertension of pregnancy, ie, 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.

Medical/Legal Pitfalls:

• 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 outweighs potential adverse effects on the fetus.

Special Concerns:

• 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 solidifies the physician's reputation as a caring and competent doctor. Consultation with experienced clinicians helps the physician care for the patient and reassure her that all avenues of treatment are being explored.

Pregnancy-Induced Hypertension (PIH)

What is pregnancy-induced hypertension (PIH)?

Pregnancy-induced hypertension (PIH) is a form of high blood pressure in pregnancy. It occurs in about 5 percent to 8 percent of all pregnancies. Another type of high blood pressure is chronic hypertension - high blood pressure that is present before pregnancy begins.

Pregnancy-induced hypertension is also called toxemia or preeclampsia. It occurs most often in young women with a first pregnancy. It is more common in twin pregnancies, in women with chronic hypertension, preexisting diabetes, and in women who had PIH in a previous pregnancy.

Usually, there are three primary characteristics of this condition, including the following:

• high blood pressure (a blood pressure reading higher than 140/90 mm Hg, or a significant increase in one or both pressures)
• protein in the urine
• edema (swelling)

Eclampsia is a severe form of pregnancy-induced hypertension. Women with eclampsia have seizures resulting from the condition. Eclampsia occurs in about one in 1,600 pregnancies and develops near the end of pregnancy, in most cases.

HELLP syndrome is a complication of severe preeclampsia or eclampsia. HELLP syndrome is a group of physical changes including the breakdown of red blood cells, changes in the liver, and low platelets (cells found in the blood that are needed to help the blood to clot in order to control bleeding).

What causes pregnancy-induced hypertension (PIH)?

The cause of PIH is unknown. Some conditions may increase the risk of developing PIH, including the following:

• pre-existing hypertension (high blood pressure)
• kidney disease
• diabetes
• PIH with a previous pregnancy
• mother's age younger than 20 or older than 40
• multiple fetuses (twins, triplets)

Why is pregnancy-induced hypertension a concern?

With high blood pressure, there is an increase in the resistance of blood vessels. This may hinder blood flow in many different organ systems in the expectant mother including the liver, kidneys, brain, uterus, and placenta.

There are other problems that may develop as a result of PIH. Placental abruption (premature detachment of the placenta from the uterus) may occur in some pregnancies. PIH can also lead to fetal problems including intrauterine growth restriction (poor fetal growth) and stillbirth.

If untreated, severe PIH may cause dangerous seizures and even death in the mother and fetus. Because of these risks, it may be necessary for the baby to be delivered early, before 37 weeks gestation.

What are the symptoms of pregnancy-induced hypertension?

The following are the most common symptoms of high blood pressure in pregnancy. However, each woman may experience symptoms differently. Symptoms may include:

• increased blood pressure
• protein in the urine
• edema (swelling)
• sudden weight gain
• visual changes such as blurred or double vision
• nausea, vomiting
• right-sided upper abdominal pain or pain around the stomach
• urinating small amounts
• changes in liver or kidney function tests

How is pregnancy-induced hypertension diagnosed?

Diagnosis is often based on the increase in blood pressure levels, but other symptoms may help establish PIH as the diagnosis. Tests for pregnancy-induced hypertension may include the following:

• blood pressure measurement
• urine testing
• assessment of edema
• frequent weight measurements
• eye examination to check for retinal changes
• liver and kidney function tests
• blood clotting tests

Treatment for pregnancy-induced hypertension:

Specific treatment for pregnancy-induced hypertension will be determined by your physician based on:

• your pregnancy, overall health, and medical history
• extent of the disease
• your tolerance for specific medications, procedures, or therapies
• expectations for the course of the disease
• your opinion or preference

The goal of treatment is to prevent the condition from becoming worse and to prevent it from causing other complications. Treatment for pregnancy-induced hypertension (PIH) may include:

• bed rest (either at home or in the hospital may be recommended)
• hospitalization (as specialized personnel and equipment may be necessary)
• magnesium sulfate (or other antihypertensive medications for PIH)
• fetal monitoring (to check the health of the fetus when the mother has PIH) may include:
• Fetal movement counting - keeping track of fetal kicks and movements. A change in the number or frequency may mean the fetus is under stress.
• Non stress testing - a test that measures the fetal heart rate in response to the fetus' movements.
• Biophysical profile - a test that combines non stress test with ultrasound to observe the fetus.
• Doppler flow studies - type of ultrasound that uses sound waves to measure the flow of blood through a blood vessel.
• continued laboratory testing of urine and blood (for changes that may signal worsening of PIH)
• medications, called corticosteroids, that may help mature the lungs of the fetus (lung immaturity is a major problem of premature babies)
• delivery of the baby (if treatments do not control PIH or if the fetus or mother is in danger). Cesarean delivery may be recommended, in some cases.

Prevention of pregnancy-induced hypertension:

Early identification of women at risk for pregnancy-induced hypertension may help prevent some complications of the disease. Education about the warning symptoms is also important because early recognition may help women receive treatment and prevent worsening of the disease.