Hypertension and Pregnancy

Introduction

BackgroundHypertension 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).[1 ]This terminology is preferred over the older but widely used term pregnancy-induced hypertension (PIH) because it is more precise.

The Society of Obstetricians and Gynecologists of Canada (SOGC) recently released revised guidelines that simplified the classification of hypertension in pregnancy into 2 categories, preexisting or gestational, with the option to add "with preeclampsia" to either category if additional maternal or fetal symptoms, signs, or test results support this.[2 ]

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 up to 5% of all pregnancies, in 10% of first pregnancies, and in 20-25% of women with a history of chronic hypertension. Hypertensive disorders in pregnancy may cause maternal and fetal morbidity, and they remain a leading source of maternal mortality.

Noncardiogenic pulmonary edema in a patient with preeclampsia. This is due to capillary leak that can be a primary component of preeclampsia. The radiograph demonstrates a diffuse increase in lung markings without cephalization or vascular redistribution seen in patients with pulmonary edema from systolic dysfunction. This patient had rapid clinical improvement after only 10 mg of intravenous furosemide.

PathophysiologyChronic 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 is primarily a disorder of placental dysfunction leading to a syndrome of endothelial dysfunction with associated vasospasm. In most cases, pathology demonstrates evidence of placental insufficiency with associated abnormalities such as diffuse placental thrombosis, an inflammatory placental decidual vasculopathy, and/or abnormal trophoblastic invasion of the

endometrium. This supports abnormal placental development or placental damage from diffuse microthrombosis as being 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 as a maternal syndrome, fetal syndrome, or both. The pregnant woman may manifest dysfunction of multiple organ systems, including the central nervous, hepatic, pulmonary, renal, and hematological systems. Endothelial damage leads to pathologic capillary leak that can present in the mother as rapid weight gain, nondependent edema (face or hands), pulmonary edema, hemoconcentration, or a combination thereof. The diseased placenta can also 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, or as fetal growth restriction.

The hypertension occurring in preeclampsia is due primarily to vasospasm, with arterial constriction and relatively reduced intravascular volume compared to normal pregnancy. The vasculature of normal pregnant women typically demonstrates decreased responsiveness to vasoactive peptides such as angiotensin-II and epinephrine. In contrast, women who develop preeclampsia typically show a hyperresponsiveness to these hormones, an alteration that may be seen even before the hypertension and other manifestations of preeclampsia become apparent. In addition, blood pressures in preeclampsia are labile, and the normal circadian blood pressure rhythms may be blunted or reversed. One study found increased arterial stiffness in women with preeclampsia, as well as in those with gestational hypertension, compared with normotensive controls; treatment with alpha methyldopa significantly improved the vascular stiffness in preeclampsia but did not normalize it.[3 ]

Gestational hypertension

Gestational hypertension refers to hypertension with onset in the latter part of pregnancy (>20 weeks' gestation) without any other features of preeclampsia, and followed by normalization of the blood pressure postpartum. Of women who initially present with apparent gestational hypertension, about one third develop the syndrome of preeclampsia. As such, these patients should be observed carefully for this progression. The pathophysiology of gestational hypertension is unknown, but in the absence of features of preeclampsia, the maternal and fetal outcomes are usually normal. Gestational hypertension may, however, be a harbinger of chronic hypertension later in life.

FrequencyUnited States

Chronic hypertension occurs in up to 22% of women of childbearing age, with the prevalence varying according to age, race, and body mass index. Population-based data indicate that approximately 1% of pregnancies are complicated by chronic hypertension, 5-6% by gestational hypertension (without proteinuria), and 1-2% by preeclampsia.

Mortality/Morbidity

Hypertensive disorders in pregnancy are among the leading causes of maternal mortality, along with thromboembolism, hemorrhage and nonobstetric injuries. Between 1991 and 1999, pregnancy-induced hypertension caused 15.7% of maternal deaths in the United States.[4 ]

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.

Hypertension before pregnancy or during early pregnancy is associated with a twofold increased risk of gestational diabetes mellitus.[5 ]

RaceBlack women have higher rates of preeclampsia complicating their pregnancies compared with 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 non-Hispanic white persons, 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.

AgePreeclampsia is more common at the extremes of maternal age (<18 y or >35 y). The increased prevalence of chronic hypertension and other comorbid medical illnesses in women older than 35 years may explain the increased frequency of preeclampsia among older gravidas.

Clinical

HistoryDetermining whether elevated blood pressure identified during pregnancy is due to chronic hypertension or to preeclampsia is sometimes a challenge, especially if no recorded blood pressures from the first half of the gestation are available. Clinical characteristics obtained via history, physical examination, and certain laboratory investigations may be used to help clarify the diagnosis.

Gestational ageo Hypertension prior to 20 weeks' gestation is almost always due to chronic

hypertension; preeclampsia is rare prior to the third trimester.o New-onset or worsening hypertension after 20 weeks' gestation should lead to a

careful evaluation for manifestations of preeclampsia.

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

o 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 personal risk factors for preeclampsiao First pregnancyo New partner/paternityo Age younger than 18 years or older than 35 yearso History of preeclampsiao Family history of preeclampsia in a first-degree relativeo Black raceo Obesity (BMI ≥ 30)o Interpregnancy interval less than 2 years or more than 10 years

Maternal medical risk factors for preeclampsiao Chronic hypertension, especially when secondary to such disorders as

hypercortisolism, hyperaldosteronism, pheochromocytoma, or renal artery stenosis

o Preexisting diabetes (type 1 or type 2), especially with microvascular diseaseo Renal diseaseo Systemic lupus erythematosuso Obesityo Thrombophiliao History of migraine[6 ]

o Use of selective serotonin uptake inhibitor antidepressants beyond the first trimester[7 ]

Placental/fetal risk factors for preeclampsiao Multiple gestationso Hydrops fetaliso Gestational trophoblastic diseaseo Triploidy

Symptoms of preeclampsiao Visual disturbances typical of preeclampsia are scintillations and scotomata.

These disturbances are presumed to be due to cerebral vasospasm.o Headache is of new onset and may be described as frontal, throbbing, or similar

to a migraine headache.o 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.

o While mild lower extremity edema is common in normal pregnancy, rapidly increasing or nondependent edema may be a signal of developing preeclampsia. Edema is no longer included among the criteria for diagnosis of preeclampsia.

o Rapid weight gain is a result of edema due to capillary leak as well as renal sodium and fluid retention.

Physical

Physical findings in preeclampsiao 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.

Korotkoff sounds I (the first sound) and V (the disappearance of sound) should be used 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, both the fourth and fifth sounds should be recorded (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; depending on the gestational age and maternal status, delivery should be considered for sustained BPs in this range.

Many automated blood pressure cuffs provide reasonable estimates of true blood pressure during normal pregnancy (especially those validated for pregnancy) but tend to underestimate blood pressure in preeclamptic women. Only a few automated BP cuffs have been validated in preeclampsia. Manual blood pressure measurement with a mercury sphygmomanometer remains the criterion standard in this setting.

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.

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

o Retinal edema is known as serous retinal detachment. This can manifest as severely impaired vision if the macula is involved. It generally reflects severe preeclampsia and should lead to prompt consideration of delivery. The condition typically resolves upon completion of pregnancy and resolution of the hypertension and fluid retention.

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

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

o In most normal pregnancies, the woman has some lower extremity edema by the third trimester. In contrast, a sudden worsening in dependent edema, edema in

nondependent areas (such as the face and hands), or rapid weight gain suggest a pathologic process and warrant further evaluation for preeclampsia.

Signs suggesting a secondary medical cause of chronic hypertensiono Centripetal obesity, "buffalo hump," and/or wide purple abdominal striae suggest

glucocorticoid excess.o A systolic bruit heard over the abdomen or in the flanks suggests renal artery

stenosis.o Radiofemoral delay or diminished pulses in lower versus upper extremities

suggests coarctation of the aorta.o Clinical signs may demonstrate hyperthyroidism, hypothyroidism, or growth

hormone excess. Signs of end-organ damage from chronic hypertension

o S4 on cardiac auscultation is not a normal finding in pregnancy. It suggests left ventricular hypertrophy or diastolic dysfunction due to preeclampsia-induced vasospasm.

o In pregnancy, and particularly in the presence of preeclampsia, any sustained cardiac gallop may be a pathological finding and warrants further evaluation with echocardiography. However, a well-conducted phonocardiographic study of pregnant women found a soft, intermittent S3 to be common in normal pregnancy.

o Retinal changes of chronic hypertension may be noted.o Carotid bruits may reflect atherosclerotic disease due to longstanding

hypertension.

Causes

Chronic hypertensiono 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.

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

Preeclampsiao The exact cause is not known, but placental dysfunction seems to be integral to

the development of the syndrome in most women.o The widespread endothelial dysfunction often manifests with primarily 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.

o Histologically, the placenta often demonstrates in situ thrombosis and decidual vasculopathy. This can affect the fetus via decreased utero-placental blood flow. The decrease in flow can manifest clinically as nonreassuring fetal heart rate testing, low score on a biophysical profile, oligohydramnios, and fetal growth restriction.

Differential Diagnoses

Antiphospholipid Antibody Syndrome and Pregnancy Hemolytic-Uremic SyndromeAntithrombin Deficiency Hydatidiform MoleAortic Coarctation Hyperaldosteronism, PrimaryAutoimmune Thyroid Disease and Pregnancy HyperparathyroidismCardiomyopathy, Peripartum HypertensionCommon Pregnancy Complaints and Questions Hypertension, MalignantCushing Syndrome HyperthyroidismDiabetes Mellitus and Pregnancy HypothyroidismDisseminated Intravascular Coagulation Nephrotic SyndromeEclampsia Normal Labor and DeliveryEncephalopathy, Hypertensive PreeclampsiaEvaluation of Fetal Death Protein C DeficiencyEvaluation of Gestation Protein S DeficiencyFetal Growth Restriction Pulmonary Disease and PregnancyGastrointestinal Disease and Pregnancy Systemic Lupus ErythematosusGlomerulonephritis, Acute Systemic Lupus Erythematosus and PregnancyGlomerulonephritis, Chronic Teratology and Drug Use During PregnancyGraves Disease Thrombotic Thrombocytopenic PurpuraHashimoto ThyroiditisHematologic Disease and Pregnancy

Other Problems to Be ConsideredAssessment of fetal well-being

Workup

Laboratory Studies

Laboratory testing to evaluate chronic hypertension (if not done previously or recently) includes testing for target organ damage, potential secondary causes of hypertension, and other risk factors.

o Studies include: urinalysis; CBC; 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).

o Other suggested tests include creatinine clearance, microalbuminuria, 24-hour urinary protein, serum calcium, uric acid, glycosylated hemoglobin, thyroid-stimulating hormone (TSH), and an ECG.

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

o The increase in endogenous corticosteroid levels during normal pregnancy makes it difficult to evaluate for secondary hypertension due to adrenal corticosteroid 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.

o CBC In cases in which an incidental platelet count is less than 150,000/µL,

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/µL suggest preeclampsia or ITP.

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

o 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 or spot urine protein:creatinine ratio.

o Recently, spot urine specimens for protein:creatinine ratios have been validated as screening tools for abnormal proteinuria during pregnancy. They appear to be more accurate than urinalysis, although an abnormal result should still be confirmed with a 24-hour urine collection.

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

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

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

o 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.

o Examination of the peripheral blood smear for evidence of microangiopathic hemolysis and thrombocytopenia may reveal the presence of red blood cell (RBC) fragments. In this setting, the diagnoses of hemolytic-uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet [count]) should also be considered.

o 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.

o 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.

Researchers in the United Kingdom have developed a method for first-trimester screening to identify women at risk for the development of preeclampsia or gestational hypertension. The screening algorithm uses a combination of maternal variables, including mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein–A, and placental growth factor. The algorithm proved especially effective for predicting early preeclampsia (ie, requiring delivery before 34 weeks).[8 ]

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. Blood tests to order when evaluating eclampsia include those suggested to evaluate for preeclampsia.

Chest radiographo Obtain chest radiographs to evaluate for pulmonary edema in the setting of

dyspnea or hypoxia occurring in a woman with preeclampsia.

Noncardiogenic pulmonary edema in a patient with preeclampsia. This is due to capillary leak that can be a primary component of preeclampsia. The radiograph demonstrates a diffuse increase in lung markings without cephalization or vascular redistribution seen in patients with pulmonary edema from systolic dysfunction. This patient had rapid clinical improvement after only 10 mg of intravenous furosemide.

o 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 braino Perform a CT scan to exclude cerebral hemorrhage in the setting of seizures,

severe headache, or altered level of consciousness, as depicted in the image below. The fetal radiation exposure with abdominal shielding is well under the permissible 5 rads. CT scan can also be used to exclude mass lesion.

Nonenhanced CT scan of a woman's brain following an eclamptic seizure, showing hypodense areas involving white matter of occipital lobes and high frontal/parietal lobes. Courtesy of Aashit K Shah, MD.

o Findings in women with preeclampsia may include bilateral hypodense areas, called venous infarcts or posterior reversible leukoencephalopathy, 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 resolve as the preeclamptic process reverses.

MRI of the braino 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, as depicted in the image below. An MRI is more sensitive than a CT scan for detecting cerebral cortical abnormalities but less useful in detecting cerebral hemorrhage.

Axial T2-weighted MRIs of the brain of a woman with eclampsia, showing abnormal areas (hyperintense lesions) affecting pons, cerebral peduncles, and internal capsules. Courtesy of Aashit K Shah, MD.

o The classic finding of preeclampsia on T2-weighted images is bilateral occipital bright spots that represent focal edema. This is also known as posterior reversible leukoencephalopathy syndrome. This finding is similar to the changes observed when a nonpregnant patient has hypertensive encephalopathy.

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

Ultrasonography or CT scan of the liver may be used to evaluate for subcapsular hemorrhage or infarction in the setting of persistent severe RUQ pain or markedly elevated hepatic transaminases.

Limited echocardiography may be performed to evaluate for left ventricle hypertrophy (LVH) in chronic hypertension and to exclude cardiomyopathy or occult valvular disease in pregnant women with pulmonary edema.

Other Tests

Perform 12-lead ECG to evaluate for LVH in women with chronic hypertension. Electroencephalogram

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

o 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 monitoringo 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.

o Fetal heart rate tracing is a useful tool to assess utero-placental perfusion.o 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 to document fetal growth velocity and/or to monitor amniotic fluid volume.

Histologic FindingsEndothelial 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 CareAlthough 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.[9 ]

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, and SBP greater than 160 mm Hg increases the risk of maternal intracerebral

hemorrhage. Therefore, pregnant patients should be started on antihypertensive therapy if the SBP is greater than 160 mm Hg or the DBP is greater than 100-105 mmHg. The goal of pharmacologic treatment should be a DBP of less than 100-105 mm Hg and an SBP less than 160 mm Hg. Women with preexisting end- organ damage from chronic hypertension should have a lower threshold for starting antihypertensive medication (ie, >139/89) and a lower target BP (<140/90).[2 ]

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

o 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.

o 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.

o 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 (to serve as baseline values, to be referred to later in the pregnancy if a concern regarding superimposed preeclampsia arises):

o CBC, electrolytes, BUN, creatinineo Liver enzymeso Urine dip for protein and a 24-hour urine collection for creatinine clearance and

protein excretion Women with chronic hypertension in pregnancy should be monitored for the

development of worsening hypertension and/or the development of superimposed preeclampsia (risk is approximately 25%). Lab investigations for preeclampsia should be repeated if the patient's blood pressure increases or if she develops signs or symptoms of preeclampsia.

Women with suspected or diagnosed preeclampsia should be hospitalized for close observation.

o 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.

o 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. In this setting, both maternal and fetal status must be very closely monitored in a high-risk obstetric centre. Fetal testing should be performed 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

Women with chronic hypertension in pregnancy should be monitored by an obstetrician. Women with moderate or severe hypertension may benefit from referral to an experienced internist (obstetric medicine specialist), hypertension 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 due to chronic hypertension, and women in whom preeclampsia causes significant organ failure.

o Diagnosis of secondary hypertension during pregnancy can be difficult.o While not absolutely contraindicated, renal captopril scans involve radioactive

isotopes and usually are deferred to the postpartum period.o Hyperaldosteronism and hypercortisolism are difficult to diagnose during

pregnancy due to the high levels of progesterone and the normal increase in endogenous cortisol output.

DietMultiple dietary interventions and supplements have been investigated for a role in preventing preeclampsia (see Deterrence/Prevention), but none has shown any consistent beneficial 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.

Medication

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 intrauterine growth restriction. If maternal blood pressure exceeds 160/100 mm Hg, however, drug treatment is recommended.

If a pregnant woman's blood pressure is sustained greater than 160 mm Hg systolic and/or 110 mm Hg diastolic at any time, lowering the blood pressure quickly with rapid-acting agents is indicated for maternal safety. Anticonvulsant therapy may be undertaken in the setting of severe preeclampsia (primary prophylaxis) or in the setting of eclamptic seizures (secondary prophylaxis). The most effective agent is IV magnesium sulfate; phenytoin is an alternative, although less effective, therapy.

A healthy fetus depends on a healthy mother, so medications should be used when clear benefit to the mother exists. The US Food and Drug Administration (FDA) categorization for drug use during pregnancy is simplistic and sometimes misleading. To quote the FDA descriptions, any

medication in class A through D may be used "when the potential benefit justifies the potential risk."

Evidence-based guidelines from the American Association of Clinical Endocrinologists single out methyldopa or nifedipine as preferable antihypertensive medications in pregnancy, with magnesium sulfate for women with preeclampsia who are at high risk for seizures, but they recommend all major antihypertensive agents with the exception of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs).[10 ]

ACE inhibitors should be avoided during pregnancy, as they are associated with fetal renal dysgenesis or death when used in the second and third trimesters and with increased risk of cardiovascular and central nervous system malformations when used in the first trimester.[11 ]Angiotensin II receptor antagonists/blockers are not used during pregnancy because they have a mechanism of action similar to that of ACE inhibitors. Diuretics do not cause fetal malformations but are generally avoided in pregnancy, as they prevent the physiologic volume expansion seen in normal pregnancy. They may be used in states of volume-dependent hypertension, such as renal or cardiac disease.

The use of antihypertensive drugs in pregnancy has recently been reviewed.

Alpha-adrenergic inhibitorsUsed 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.

Methyldopa (Aldomet)

Centrally acting antihypertensive agent widely considered the first-line agent for treatment of hypertension during pregnancy.Studies have revealed no adverse effects on cognitive development up to the age of 7.5 y among children with in utero exposure to methyldopa.

Dosing

Adult

250 mg PO bid/tid; increase q2d prn; not to exceed 3 g/d

Pediatric

10 mg/kg/d PO divided bid/qid; increase q2d prn to maximum 65 mg/kg/d; not to exceed 3 g/d

Interactions

Effects may decrease with concurrent administration of barbiturates and TCAs; increase in blood pressure may occur with coadministration of iron supplements, MAOIs, sympathomimetics, phenothiazines, and beta-blockers

Contraindications

Documented hypersensitivity; acute liver disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adverse effects include somnolence and dry mouth; 15% of women do not tolerate doses necessary to control blood pressure; caution in liver disease; hemolytic anemia and liver disease may occur; reduce dose in renal disease

Beta-adrenergic receptor blockersCompete with beta-adrenergic agonists for available beta-receptor sites.

Labetalol (Normodyne, Trandate)

Reasonable first-line medication.Combined alpha- and beta-adrenergic blocking agent widely used in treating hypertension during pregnancy. Not associated with mild fetal growth restriction (unlike some other beta-blockers).Intravenous and oral forms are used as an alternative to hydralazine in severe preeclampsia/eclampsia.

Dosing

Adult

100 mg IV bid; not to exceed 2400 mg/dBP >170/110 mm Hg: 20 mg IV bolus; subsequent doses of 40 mg followed by 80 mg IV may be administered at 10- to 20-min intervals to achieve BP control; may also be administered as continuous infusion 1 mg/kg/h

Pediatric

Not established

Interactions

Decreases effect of diuretics; increases toxicity of methotrexate, lithium, and salicylates; may diminish reflex tachycardia resulting from nitroglycerin use without interfering with hypotensive effects; cimetidine may increase labetalol blood levels; glutethimide may decrease labetalol effects by inducing microsomal enzymes

Contraindications

Documented hypersensitivity; cardiogenic shock, pulmonary edema, bradycardia, atrioventricular block, uncompensated congestive heart failure; reactive airway disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in impaired hepatic function; discontinue therapy at signs of liver dysfunction; in elderly patients, a lower response rate and higher incidence of toxicity may be observed

Pindolol (Visken)

Nonselective beta-blocker with intrinsic sympathomimetic activity (ISA).

Dosing

Adult

5-15 mg PO bid

Pediatric

Not established

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effects; toxicity may increase with coadministration of sparfloxacin, phenothiazines, astemizole [recalled from US market], calcium channel blockers, quinidine, flecainide, and contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine

Contraindications

Documented hypersensitivity; uncompensated congestive heart failure, bradycardia, cardiogenic shock, AV conduction abnormalities; asthma

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Concern exists that beta-blockers prescribed during pregnancy, particularly atenolol, may be associated with intrauterine growth restriction (pindolol and oxprenolol are preferred agents

because their intrinsic ISA may mitigate this risk); none have been associated with any consistent adverse effects, although long-term follow-up studies are lacking

Oxprenolol (Apsolox, Trasicor, Captol)

Not commercially available in the United States. Nonselective beta-blocker with ISA.

Dosing

Adult

20-80 mg PO bid/tid

Pediatric

Not established

Interactions

Indomethacin reduces antihypertensive effect of oxprenolol; oxprenolol may increase the effects of ergotamine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Concern exists that beta-blockers prescribed during pregnancy, particularly atenolol, may be associated with intrauterine growth restriction (pindolol and oxprenolol are preferred agents because their intrinsic ISA may mitigate this risk); none have been associated with any consistent adverse effects, although long-term follow-up studies are lacking

Metoprolol (Lopressor, Toprol XL)

Second-line agent because of its similarity to atenolol (see below).Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions.

Dosing

Adult

50-400 mg PO qd

Pediatric

Not established

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels of metoprolol, possibly resulting in decreased pharmacologic effects; toxicity of metoprolol may increase with coadministration of sparfloxacin, phenothiazines, astemizole [recalled from US market], calcium channel blockers, quinidine, flecainide, and contraceptives; metoprolol may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine

Contraindications

Documented hypersensitivity; uncompensated congestive heart failure, bradycardia, cardiogenic shock, AV conduction abnormalities; asthma

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw the drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG

Atenolol (Tenormin)

Was associated with mild intrauterine growth restriction when used in randomized trials focusing on the treatment of chronic hypertension during pregnancy.Selectively blocks beta1 receptors with little or no effect on beta2 types.

Dosing

Adult

50-100 mg PO qd

Pediatric

Not established

Interactions

Coadministration with aluminum salts, barbiturates, calcium salts, cholestyramine, NSAIDs, penicillins, and rifampin may decrease effects; haloperidol, hydralazine, loop diuretics, and MAOIs may increase toxicity of atenolol

Contraindications

Documented hypersensitivity; congestive heart failure, cardiogenic shock, AV conduction abnormalities, heart block (without a pacemaker); pulmonary edema

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Concern exists that beta-blockers prescribed during pregnancy, particularly atenolol, may be associated with intrauterine growth restriction; beta-adrenergic blockade may reduce symptoms of acute hypoglycemia and mask signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism and cause thyroid storm; monitor patient closely and withdraw drug slowly

Calcium channel blockersInhibit calcium ions from entering slow channels, select voltage-sensitive areas, or vascular smooth muscle.

Nifedipine (Adalat, Procardia)

Appears safe in pregnancy. Because it relaxes smooth muscle, it is occasionally used by obstetricians to treat preterm contractions.Dihydropyridine calcium channel blocker. Exerts its antihypertensive effect through relaxation of smooth muscle, which produces vasodilation.

Dosing

Adult

IR cap: 10-30 mg PO tid; not to exceed 120-180 mg/dSR tab: 30-60 mg PO qd; not to exceed 90-120 mg/dBP >170/110 mm Hg: 10 mg PO initial; repeat dose may be administered in 30 min prn

Pediatric

0.25-0.5 mg/kg/dose PO tid/qid prn

Interactions

Caution with coadministration of any agent that can lower BP, including beta-blockers and opioids; H2 blockers (eg, cimetidine) may increase toxicity; avoid concurrent use with magnesium because of risk of profound hypotension (antidote is IV calcium gluconate)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause lower extremity edema; allergic hepatitis (rare)

Centrally acting alpha-adrenergic agonistsDecrease sympathetic outflow, which causes a decrease in vasomotor tone and heart rate.

Clonidine (Catapres)

Usually a third-line agent if other medications cannot be tolerated. Stimulates alpha2-adrenoreceptors in brain stem, activating an inhibitory neuron, which in turn results in reduced sympathetic outflow. These effects result in a decrease in vasomotor tone and heart rate.

Dosing

Adult

Initial: 0.1 mg PO bidMaintenance: 0.2-1.2 mg/d bid/qid PO; not to exceed 2.4 mg/d

Pediatric

Not established

Interactions

TCAs inhibit hypotensive effects of clonidine; coadministration with beta-blockers may potentiate bradycardia; tricyclic antidepressants may enhance hypertensive response associated with abrupt clonidine withdrawal; narcotic analgesics enhance hypotensive effects of clonidine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cerebrovascular disease, coronary insufficiency, sinus node dysfunction, and renal impairment; abrupt discontinuation may lead to rebound hypertension

Diuretics

May have a transient effect on intravascular volume by causing an initial drop in cardiac output produced by diuresis.

Hydrochlorothiazide (Esidrix, HydroDIURIL)

Not commonly used to treat hypertension during pregnancy. May have a transient effect on intravascular volume. Inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water, as well as potassium and hydrogen ions.

Dosing

Adult

25-100 mg PO qd; not to exceed 200 mg/kg/d

Pediatric

<6 months: 2-3 mg/kg/d PO divided bid>6 months: 2 mg/kg/d PO divided bid

Interactions

Thiazides may decrease effects of anticoagulants, antigout agents, and sulfonylureas; thiazides may increase toxicity of allopurinol, anesthetics, antineoplastics, calcium salts, loop diuretics, lithium, diazoxide, digitalis, amphotericin B, and nondepolarizing muscle relaxants

Contraindications

Documented hypersensitivity; anuria, renal decompensation

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prevents normal physiologic volume expansion that occurs in pregnancy and may reduce uterine blood flow; restrict use to women with volume-overload states (eg, renal or cardiac disease)

Furosemide (Lasix)

Not commonly used to treat hypertension during pregnancy. Is often used to treat pulmonary edema associated with preeclampsia. Increases excretion of water by interfering with chloride-binding cotransport system, which in turn inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule.

Dosing

Adult

10 mg IV initial dose20-80 mg/d PO/IV/IM; titrate up to 600 mg/d for severe edematous states

Pediatric

1-2 mg/kg/dose PO; not to exceed 6 mg/kg/dose; not to administer >q6h1 mg/kg IV/IM slowly under close supervision; not to exceed 6 mg/kg

Interactions

Metformin decreases furosemide concentrations; furosemide interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides and furosemide (hearing loss of varying degrees may occur); anticoagulant activity of warfarin may be enhanced when taken concurrently; increased plasma lithium levels and toxicity are possible when taken concurrently

Contraindications

Documented hypersensitivity; hepatic coma; anuria; state of severe electrolyte depletion

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prevents normal physiologic volume expansion that occurs in pregnancy and may reduce uterine blood flow; restrict use to women with volume-overload states (eg, renal or cardiac disease)

VasodilatorsDecrease peripheral resistance by inducing vasodilation.

Nitroprusside (Nitropress)

Reduces peripheral resistance by acting directly on arteriolar and venous smooth muscle. Rapid-acting parenteral antihypertensive of short duration.Used occasionally for the treatment of eclampsia. Restricted to use in cases of severe hypertension not responsive to other drugs listed.Follow maternal cyanide and thiocyanate levels to prevent fetal toxicity.

Dosing

Adult

BP >170/110 mm Hg: 0.25 mcg/kg/min continuous infusion IV, titrate to BP with maximum dose of 5 mcg/kg/min; infusion rates >10 mcg/kg/min IV may lead to cyanide toxicity

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; subaortic stenosis, idiopathic hypertrophic and atrial fibrillation or flutter

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

With prolonged (>4 h) use, concern exists regarding potential fetal cyanide toxicity; caution in increased intracranial pressure, hepatic failure, severe renal impairment, and hypothyroidism; in renal or hepatic insufficiency, nitroprusside levels may increase and can cause cyanide toxicity; sodium nitroprusside has the ability to lower blood pressure; use in patients with mean arterial pressures >70 mm Hg

Hydralazine (Apresoline)

Intravenous form is useful when treating severe hypertension due to preeclampsia/eclampsia.Long record of safe use during pregnancy, but troublesome adverse effects occur. Decreases systemic resistance through direct vasodilation of arterioles.

Dosing

Adult

10-20 mg/dose IV q4-6h prn initial; increase to 40 mg per dose prnBP >170/110 mm Hg: 0.1-0.2 mg/kg/dose IV q4-6h prn; not to exceed 20 mg or 1.7-3.5 mg/kg/d IV divided q4-6h

Pediatric

Not established

Interactions

MAOIs and beta-blockers may increase hydralazine toxicity; indomethacin may decrease pharmacologic effects of hydralazine

Contraindications

Documented hypersensitivity; mitral valve rheumatic heart disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Hydralazine has been implicated in myocardial infarction; caution in suspected coronary artery disease

AnticonvulsantsAdministered to prevent seizures in severe preeclampsia or eclampsia.

Phenytoin (Dilantin)

Less effective than magnesium at preventing eclamptic seizures but may be used if renal failure is present, magnesium fails, or serious magnesium-related toxicity occurs. May act in motor cortex where may inhibit spread of seizure activity. Activity of brain stem centers responsible for tonic phase of grand mal seizures also may be inhibited.

Dosing

Adult

1000 mg IV over 1 h, followed by 500 mg PO 10 h later; not to exceed 1500 mg/24 h; rate of infusion not to exceed 50 mg/min to avoid hypotension and arrhythmias

Pediatric

Not established

Interactions

Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimide, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase phenytoin toxicity; phenytoin effects may decrease when taken concurrently with barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate; phenytoin may decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, and valproic acid

Contraindications

Documented hypersensitivity; heart block, myocardial damage, sinus bradycardia, Adams-Stokes syndrome; severe hepatitis; Addison disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Perform blood counts and urinalyses when phenytoin therapy is begun and at monthly intervals for several mo to monitor for blood dyscrasias; discontinue use if a skin rash appears and do not resume use if rash is exfoliative, bullous, or purpuric; rapid phenytoin infusion may result in death from cardiac arrest, marked by QRS widening; caution in acute intermittent porphyria and diabetes (may elevate blood sugars); discontinue use if hepatic dysfunction occurs

Magnesium sulfate

Women with eclampsia or severe preeclampsia should receive anticonvulsant therapy. Magnesium has been demonstrated to be superior to phenytoin for preventing and treating eclamptic seizures.

Dosing

Adult

4-6 g IV load, followed by 2-3 g/h to maintain levels 4-8 mg/dL

Pediatric

20-100 mg/kg/dose IV q4-6h prn; in severe cases, may use doses as high as 200 mg/kg/dose IV

Interactions

Concurrent use of magnesium sulfate with nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade observed with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants, betamethasone, and cardiotoxicity of ritodrine

Contraindications

Documented hypersensitivity; heart block, myocardial damage; Addison disease; severe hepatitis

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Levels of 8-12 mg/dL may cause loss of reflexes, diplopia, flushing, or slurring of speech; levels >12 mg/dL may cause muscular paralysis, ventilatory failure, and circulatory collapse; patients should have frequent neurological evaluations; loss of deep tendon reflex indicates that the

magnesium level may be toxic; some clinicians follow serum magnesium levels q6h along with neurological examination; magnesium may alter cardiac conduction, leading to heart block in digitalized patients; in overdose, calcium gluconate 10-20 mL IV of 10% solution can be administered as antidote for clinically significant hypermagnesemia

Follow-up

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.

o The severity of any abnormalities on admission dictates the frequency of blood work.

o 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.

o 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.

o 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.

o After delivery, women with preeclampsia require ongoing close blood pressure monitoring. Blood pressure sustained greater than 160/110 mm Hg should be urgently treated with IV antihypertensives. Oral antihypertensive therapy should be undertaken for sustained pressures above 155/105 mm Hg.

o 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 CareWomen with preeclampsia require follow-up after hospital discharge to ensure normalization of blood pressure and any lab abnormalities noted. This follow-up may be undertaken via an internal medicine specialist (obstetric internist) and obstetrician or a family physician.

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

Laboratory abnormalities related to preeclampsia (eg, proteinuria, thrombocytopenia, liver enzyme elevations) should be followed until the abnormalities return to the reference range. This is vital to ensure that no other underlying maternal medical disorder with potential long-term consequences is missed.

Inpatient & Outpatient Medications

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.

TransferWomen with preeclampsia remote from term (ie, <34-36 weeks' gestation) should be promptly transferred 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/PreventionMultiple 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),[12 ]supplemental calcium,[13 ]salt restriction,[14 ]supplemental magnesium,[15 ]and fish oil therapy.[16 ]While several large trials of ASA in high-risk populations showed minimal benefit in reducing the frequency of preeclampsia, a meta-analysis reported an approximate 15% reduction in preeclampsia among pregnant women taking low-dose ASA.[17 ]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 trial demonstrated some preventive benefit to supplemental antioxidants (vitamins C and E), but a 2008 review found that the evidence did not support routine use of antioxidants for this purpose.[18 ]In 2010, Roberts et al conducted a multicenter, randomized, double-blind trial of nulliparous women at low risk for preeclampsia. Outcome data were available for nearly 1000 women. No significant differences between the vitamin and placebo groups were observed in reducing the rate of adverse maternal or perinatal outcomes related to pregnancy-associated hypertension.[19 ]

Complications

Life-threatening complications in preeclampsiao Seizureso Cerebral hemorrhageo Pulmonary edema - Due to pulmonary capillary leak, excess IV fluid

administration, or myocardial dysfunctiono Acute renal failure - Due to renal vasospasm, ATN, or renal cortical necrosiso Disseminated intravascular coagulopathyo HELLP syndrome - Microangiopathic hemolysis, elevated liver enzymes, and

thrombocytopenia (platelets [PLT] <100)

o 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).

Women who develop preeclampsia are at increased risk for cardiovascular disease later in life. Whether the preeclampsia increases cardiovascular risk or the 2 conditions share a common underlying cause remains unclear.[20 ]

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.

Patient EducationFor excellent patient education resources, visit eMedicine's Circulatory Problems Center and Pregnancy and Reproduction Center. Also, see eMedicine's patient education articles High Blood Pressure and Pregnancy.

Miscellaneous

Medicolegal PitfallsMost 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

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.

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

Multimedia

Media file 1: Nonenhanced CT scan of a woman's brain following an eclamptic seizure, showing hypodense areas involving white matter of occipital lobes and high frontal/parietal lobes. Courtesy of Aashit K Shah, MD.

Media file 2: Axial T2-weighted MRIs of the brain of a woman with eclampsia, showing abnormal areas (hyperintense lesions) affecting pons, cerebral peduncles, and internal capsules. Courtesy of Aashit K Shah, MD.

Media file 3: Noncardiogenic pulmonary edema in a patient with preeclampsia. This is due to capillary leak that can be a primary component of preeclampsia. The radiograph demonstrates a diffuse increase in lung markings without cephalization or vascular redistribution seen in patients with pulmonary edema from systolic dysfunction. This patient had rapid clinical improvement after only 10 mg of intravenous furosemide.

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Keywords

hypertension and pregnancy, pregnancy-induced hypertension, PIH, preeclampsia, hyperpiesis, hyperpiesia, high blood pressure, gestational hypertension, chronic hypertension, preeclampsia-

eclampsia, preeclampsia superimposed on chronic hypertension, gestational hypertension, transient hypertension of pregnancy, chronic hypertension in the latter half of pregnancy

Contributor Information and Disclosures

Author

Paul Gibson, MD,, Associate Professor, Departments of Medicine and Obstetrics and Gynecology, Divisions of General Internal Medicine and Maternal-Fetal Medicine, University of CalgaryPaul Gibson, MD, is a member of the following medical societies: Alberta Medical Association, Canadian Society of Internal Medicine, Royal College of Physicians and Surgeons of Canada, and Society of Obstetric MedicineDisclosure: Nothing to disclose.

Coauthor(s)

Michael P Carson, MD, Clinical Associate Professor, Department of Medicine, Clinical Assistant Professor, Department of Obstetrics/Gynecology and Reproductive Sciences, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School; Director of Research/Outcomes, Department of Medicine, Jersey Shore University Medical CenterMichael P Carson, MD is a member of the following medical societies: American College of Physicians, Society of General Internal Medicine, and Society of Obstetric MedicineDisclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicineDisclosure: eMedicine Salary Employment

CME Editor

Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Hancock Medical CenterFrederick B Gaupp, MD is a member of the following medical societies: American Academy of Family Physicians Disclosure: Nothing to disclose.

Chief Editor

Carl V Smith, MD, The Distinguished Chris J and Marie A Olson Chair of Obstetrics and Gynecology, Professor, Department of Obstetrics and Gynecology, University of Nebraska Medical CenterCarl V Smith, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, American Medical Association, Arkansas Medical Society, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Council of University Chairs of Obstetrics and Gynecology, Nebraska Medical Association, and Society for Maternal-Fetal Medicine Disclosure: Nothing to disclose.

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