Chronic Hypertension in Pregnancy

Chronic Hypertension in Pregnancy

1. What every clinician should know

Clinical features and incidence

Chronic hypertension is defined as elevated blood pressure (BP) that is present and documented before pregnancy. In women whose pre-pregnancy BP is unknown, the diagnosis is based on the presence of sustained hypertension before 20 weeks’ gestation, defined as either systolic BP of at least 140 mm Hg or diastolic BP of at least 90 mm Hg on at least two occasions measured at least 4 hours apart.

The prevalence of chronic hypertension in pregnancy ranges from 1-3%. The rate depends on maternal race and ethnicity, age, and body mass index (BMI). Risk factors for chronic hypertension include advanced maternal age (> 40 years), obesity (BMI ≥30 kg/m²), type 2 diabetese mellitus, renal disease, and gestational diabetes mellitus in the index pregnancy.

Chronic hypertension can be primary (essential) or secondary to other etiology. Primary hypertension is the most common cause of chronic hypertension in young pregnant women (90%). Secondary hypertension can be due to one or more of the underlying disorders listed in Table I.

Table 1.n

Chronic hypertension is sub-classified as either mild or severe, depending on the systolic and diastolic BP readings. Severe hypertension is defined as a systolic BP of at least 160 mm Hg or a diastolic BP of at least 110 mm Hg. These elevations should be on at least two occasions.

For counseling and management purposes, chronic hypertension in pregnancy is also categorized as either low-risk or high-risk. The patient is considered to be at low risk when she has mild essential hypertension without organ involvement, requiring only one antihypertensive drug to control BP prior to pregnancy, and without history of adverse outcomes in previous pregnancies.

Blood pressure criteria to establish severity of the hypertension are based on blood pressure measurements prior to pregnancy or at the initial visit irrespective of whether patients are on antihypertensive medications. A patient is considered high-risk if she has any of the criteria listed in Table II. It is important to keep in mind that some patients initially classified as low-risk early in pregnancy may become high-risk later in pregnancy if they have poor compliance or if they develop severe hypertension despite maximum doses of antihypertensive medications.

Table 2.n

2. Diagnosis and differential diagnosis

Primary essential hypertension

Essential hypertension is characterized by the finding of established chronic hypertension prior to pregnancy (patient history, evidence in medical records, patient receiving antihypertensive medications), or the finding of hypertension prior to 20 weeks’ gestation during regular prenatal visits.

What you should be alert for in the history

An in-depth history should delineate in particular the duration of hypertension, the use of antihypertensive drugs, their type, and the response to these medications. Women with essential hypertension usually are < 30 years old with short duration of hypertension (< 5 years), and will have no evidence of target organ damage (kidney, heart, or brain)

Attention should be given to history of cardiac or renal disease, diabetes, thyroid disease, and a history of cerebrovascular accident or congestive heart failure. This is important in order to identify the presence of target organ damage and/or possible secondary hypertension.

For women with previous pregnancies, a detailed obstetric history should include maternal as well as perinatal outcome of previous pregnancies, with emphasis on history of development of superimposed preeclampsia, preterm delivery, fetal growth restriction (FGR), abruptio placentae, and perinatal death.

Characteristic findings on physical examination

The blood pressure is usually elevated (mild or severe levels), but it can be normal in women receiving antihypertensive medications, and the heart rate is normal. Examination of the eyes, neck, lungs and heart reveal normal findings. There is no evidence of skin edema, and pulses are felt adequately in upper and lower extremities.

Expected results of diagnostic tests

Generally, the diagnosis of essential hypertension is established on the basis of history and clinical examination. Laboratory evaluation is obtained to assess the function of different organ systems that are likely to be affected by chronic hypertension, and as a baseline for future assessment. These include urine analysis, urine culture and sensitivity, 24-hour urine evaluation for protein, electrolytes, complete blood count, and glucose tolerance test. These tests are usually normal; however, some patients can have asymptomatic proteinuria or gestational diabetes.

Women with long-standing hypertension, particularly those with history of poor compliance or poor blood pressure control, should be evaluated for left ventricular hypertrophy or retinopathy. These women should receive ECG and echocardiography, as well as ophthalmologic evaluation in consultation with a cardiologist and/or ophthalmologist.

Diagnosis confirmation and differential diagnosis

The diagnosis is established when there is a history of hypertension prior to pregnancy or prior to 20 weeks’ gestation with normal blood tests and absence of other causes of hypertension. The diagnosis can be missed in women with previously undiagnosed chronic hypertension who begin prenatal care after 20 weeks’ gestation. In such cases, the differential diagnosis will overlap with gestational hypertension.

Secondary hypertension

Secondary hypertension is characterized by the finding of preexisting medical disorders that are associated with hypertension. The nature of the disorder is usually known prior to pregnancy; however, the signs and symptoms may develop for the first time during pregnancy or postpartum.

What you should be alert for in the history

A detailed medical history with attention to certain signs and symptoms will point towards the etiology of the hypertension. Hyperthyroidism should be considered in the presence of palpitations, sweating, tachycardia, dry skin, or heart failure. Renal artery stenosis is considered when there is hypertension that is refractory to treatment. Pheochromocytoma should be suspected if there is paroxysmal severe hypertension, anxiety, headaches, palpitation, or chest pain. A history of skin malar rash, joint pain, and fever is suspicious for connective tissue disease.

Characteristic findings on physical examination

In women with hypertension secondary to hyperthyroidism, the patient usually has exophthalmos, and neck examination can reveal thyroid gland enlargement. The pulse is rapid, and there is wide pulse pressure, and tremor in the hands. In women with renal artery stenosis, auscultation of the abdomen will reveal the presence of a systolic-diastolic renal unit. The presence of centripetal obesity, deep pigmented abdominal striae and moon facies is suggestive of Cushing’s disease.

Women with lupus will have a malar rash and tenderness over the joints. Presence of delayed or absent femoral pulse is suggestive of coarctation of the aorta. Women with vascular diabetes mellitus can have proliferative retinopathy on ophthalmologic examination.

Expected results of diagnostic tests

In women with renal disease, urine analysis will reveal the presence of proteinuria, hematuria, and renal casts. Serum creatinine can be elevated (≥ 1.0 mg/dl), and creatinine clearance may be reduced (< 100 ml/min). Women with IgA nephropathy and those with diabetic nephropathy will have significant proteinuria.

Women with hyperthyroidism will have elevated thyroid-stimulating immunoglobulins and thyroid receptor antibodies, reduced TSH levels (< 0.3 mEq/L), and elevated free thyroxine (T4) levels. The presence of hypokalemia (serum K⁺ < 3.0 mEq/L) and metabolic alkalosis suggests possible primary hyperaldosteronism. If this is present, computerized tomography (CT) imaging of the abdomen will reveal the presence of an adrenal tumor. Women with suspected pheochromocytoma should have measurements of 24-hour urine excretion of epinephrine, norephinephrine and their metabolites (metanephrine and normetanephrine). If these are elevated, CT scan or MRI of the abdomen will reveal the presence of adrenal tumor.

In women with suspected renal artery stenosis, the diagnosis can be confirmed by CT scan angiography of the kidneys. Women with lupus will have positive antinuclear antibodies, reduced complement levels, and positive antimitochondrial antibodies. In addition, 30-40% will have positive anticardiolipin antibodies (IgG ≥ 40 GPL or IgM ≥ 40 MPL) or positive lupus anticoagulant. Some patients will also have thrombocytopenia.

Diagnosis confirmation and differential diagnosis

The diagnosis of any of these conditions will depend on their clinical history, medications being used, as well as the selective laboratory and diagnostic test results. To confirm the diagnosis, it is advisable to seek consultation with certain specialists such as a nephrologist, endocrinologist, or rheumatologist.

3. Management

Management of patients with chronic hypertension will depend on the etiology (essential or secondary), severity of the hypertension (mild or severe), and the presence or absence of target organ damage. In addition, management depends on previous obstetric history as well as maternal compliance. The primary objective is to reduce the maternal risks and achieve optimal perinatal outcome.

This objective is achieved by formulating a rational approach that includes preconceptional evaluation and counseling, early antenatal care, frequent antepartum visits to monitor maternal and fetal well-being (early detection of severe hypertension, fetal growth restriction, preeclampsia), timely delivery with intensive intrapartum monitoring, and proper postpartum management.

Low-risk hypertension

In general, women with mild essential hypertension who do not develop severe hypertension or superimposed preeclampsia later in pregnancy usually have a favorable obstetric outcome with proper management. Women seen in the preconception period who are receiving potentially teratogenic agents such as angiotension converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ACR) should be instructed to stop these medications. If needed, they can be treated with either oral labetalol or nifedipine.

At time of initial and subsequent visits, patient should be educated about nutritional requirements, signs and symptoms to report, and monitoring for potential maternal and fetal complications (Table III). The frequency of prenatal visits is similar to normotensive pregnancies, but adjusted based on clinical progress, need for antihypertensive medications to control BP, and development of complications.

Table 3.n

Antihypertensive medications are initiated if systolic BP is persistently ≥ 155 mm Hg or if diastolic BP is ≥ 105 mm Hg. Patients receiving thiazide diuretics prior to pregnancy can continue with these medications. If new drugs are needed, my policy is to start with oral labetalol 200 mg every 12 hours for a maximum of 2400 mg/d. Patients requiring increase in their medications should be seen weekly until desired BP is reached. If the target maternal BP is not achieved with the maximum dose of labetalol, my policy is to add oral long-acting nifedipine starting at 30-60 mg/d and then increased to a maximum dose of 120 mg/d. The goal of therapy is to keep systolic BP between 140-150 mm Hg and diastolic between 90-100 mm Hg.

The development of persistent severe hypertension, superimposed preeclampsia (new onset proteinuria or symptoms), or evidence of abnormal fetal growth or oligohydramnios by ultrasound requires fetal testing with NST or biophysical profile. Women who are not receiving antihypertensive medications who develop severe hypertension, preeclampsia, or fetal growth restriction (FGR) at ≥ 37 weeks’ gestation are hospitalized and delivered. Women who are receiving antihypertensive medications who develop severe hypertension, preeclampsia, or severe FGR (estimated fetal weight < 5^th percentile) or develop oligohydramnios (largest vertical pocket ≤ 2 cm) require immediate hospitalization and consideration for delivery by 34 weeks’ gestation. In the absence of these complications, delivery is performed at 39 weeks’ gestation.

High-Risk Hypertension

Women with target organ damage and/or those with seconary hypertension are at increased risk for serious adverse maternal and perinatal complications. The frequency of these complications will depend on the etiology of the hypertension as well as the degree of target organ damage. At time of first prenatal visit, the women are advised that pregnancy may exacerbate their condition with the potential for congestive heart failure, renal failure, stroke, or even death. All such women should be managed by or in consultation with a subspecialist in maternal-fetal medicine, as well as in association with other medical specialists as needed. In addition, they must be observed and then delivered at a tertiary care center with appropriate maternal-neonatal care facilities.

My policy is to hospitalize these women at time of the first visit for evaluation of cardiovascular, renal status, and their medical disorders and for regulation of antihypertensive medications, and other prescribed medications (insulin, cardiac drugs, thyroid drugs, or immunosuppressive agents) if needed. Women receiving ACE inhibitors or angiotensin receptor blockers, or atenololwill have these medications discontinued under close observation. During hospitalization, the patient and her family meet with all future medical providers to discuss a multidisciplinary management plan that emphasizes the need for frequent prenatal visits, the importance of compliance with visits, the need for frequent and prolonged hospitalization for expected complications, and the potential for adverse pregnancy outcomes.

Women with essential hypertension plus target organ damage

Women with target organ damage are at increased risk for adverse maternal outcome from mild hypertension as a result of further injury to affected organs. These women require more frequent antenatal visits. In such women, antihypertensive medications are initiated when maternal BP is ≥ 140 mm Hg systolic or if diastolic BP is ≥ 90 mm Hg. The target BP during treatment is kept between 130-140 mm Hg systolic and 80-90 mm Hg diastolic. For women with diabetes and vascular involvement, my target BP during treatment is < 130/80 mm Hg. My drug of choice for such women is oral nifedipine or diltiazem plus labetalol if needed. (Table IV).

Table 4.n

Women with left ventricular hypertrophy and/or left ventricular dysfunction by echocardiography are at increased risk for congestive heart failure because of sodium and water retention during pregnancy. These women require chronic use of an oral thiazide diuretic (12.5-25 mg/d) with potassium supplementation through gestation. Women with history of peripartum cardiomyopathy require chronic use of a vasodilator such as oral hydralazine (10-25 mg every 6 hours) for a maximum of 200 mg/d and a diuretic such as oral furosemide (20-40 mg/d). It is important that these women be managed in collaboration with a cardiologist.

Fetal evaluation in such women is similar to that for women with low-risk hypertension, but it is modified for women with insulin-dependent diabetes.

Women with Secondary Hypertension

Early and frequent prenatal visits are important for successful pregnancy outcome in such women. These women need close observation throughout pregnancy and serial laboratory evaluation at least once every trimester depending on the etiology. In addition, they require liberal antenatal hospitalization for adjustment of prescribed medications and for management of associated medical disorders.

In some women, blood pressure may be difficult to control initially, demanding the use of intravenous therapy with either hydralazine, labetalol, or oral short-acting nifedipine. For maintenance therapy, the choice of antihypertensive drug will depend on the etiology. Some women may require at least 2 or 3 different drugs to keep the BP in the desired goal (e.g., women with renal disease, diabetic nephropathy, pheochromocytoma, or severe hypertension prior or early in pregnancy). In other women, treatment may require antihypertensive drugs and surgical removal of the cause (Table IV.

Fetal monitoring in high-risk hypertension

Pregnant women with high-risk hypertension are at increased risk for poor perinatal outcome. In addition to screening for fetal aneuploidy and anomalies, my policy is to start serial ultrasound evaluation for fetal growth at 28 weeks and subsequently every 3 weeks until delivery. Also, non-stress testing (NST) and biophysical profile testing is started at 28 weeks and then repeated weekly.

The development of uncontrolled severe hypertension, preeclampsia, significant deterioration in renal function, congestive heart failure, or evidence of fetal growth restriction requires hospitalization for more frequent monitoring of maternal and fetal conditions. The onset of these complications at or beyond 34 weeks’ gestation is considered an indication for delivery. For all other women, delivery is performed at 36-37 weeks’ gestation.

Diagnosis of preeclampsia in chronic hypertension

Superimposed preeclampsia is the most common obstetric complication in women with chronic hypertension. The diagnosis can be challenging in these women because one or more of the factors used to diagnose preeclampsia are already present in these women.

In women with low-risk hypertension, preeclampsia is defined as new-onset proteinuria (≥ 300 mg/24-hour collection) after 20 weeks’ gestation. The diagnosis becomes more certain if there is also exacerbation in BP requiring therapy or if the patient develops headaches, blurred vision, or epigastric pain.

In women with chronic hypertension and preexisting proteinuria before 20 weeks’ gestation, the diagnosis is suspected if there is an exacerbated increase in blood pressure despite adequate antihypertensive therapy, and is confirmed if it is associated with symptoms, elevated liver enzymes (unrelated to prescribed medications), or if the platelet count is less than 100,000/mm³, or if there is evidence of congestive heart failure.

Intrapartum management

Intrapartum management will depend on the severity of the hypertension, whether the patient is considered high-risk, and presence or absence of associated medical disorders. In general, the goal of monitoring and management during labor and delivery is early detection of fetal heart rate abnormalities, progression to severe hypertension, and prevention of maternal complications.

• Attention is given to changes in BP and the need for antihypertensive therapy to achieve the desired goal. My policy is to use intravenous medications during the active phase of labor; otherwise, oral drugs may be continued.

• Attention to fluid intake-output, respiratory symptoms, and pulse oximetry in women with target organ injury.

• Monitoring of serum glucose levels in women with diabetes and for signs and symptoms of thyrotoxicosis in women with hyperthyroidism.

• Prophylactic intravenous magnesium sulfate is used in case of superimposed preeclampsia in the following:

• Women with cerebral symptoms or HELLP syndrome (Hemolysis, Elevated Liver enzymes, and Low Platelet count)

• Women with persistent severe hypertension

• Women developing preeclampsia while on antihypertensive drugs

• Women with pulmonary edema.

Mode of delivery will depend on fetal condition, gestational age,fetal presentation and lie, and maternal condition.

Postpartum Management

Women with complicated low-risk hypertension (superimposed preeclampsia, exacerbation of severe hypertension) and those with high-risk chronic hypertension are at increased risk for postpartum complications such as pulmonary edema, eclampsia, renal failure, and stroke. In these women, blood pressure must be closely monitored and controlled for at least 48 hours after delivery.

Intravenous labetalol or hydralazine or oral rapid-acting nifedipine can be used as needed to keep systolic and diastolic BPs in the target range.

Intravenous magnesium sulfate should be continued in women receiving it before delivery for at least 24 hours after delivery.

In addition, oral or intravenous furosemide (20-40 mg) is used to treat women with circulatory congestion or pulmonary edema.

In women with high-risk hypertension and/or superimposed preeclampsia, systolic and diastolic blood pressures usually increase again at 3-6 days postpartum. In these women, oral antihypertensive drugs may be needed to control BP to the desired goal. My policy is to continue with the drug that was used during pregnancy or to initiate the drug that was used prior to pregnancy. In some women, it is necessary to switch to an ACE inhibitor or to an angiotensin receptor blocker, particularly in those with diabetes, renal disease, or cardiomyopathy. In general, most antihypertensive medications are compatible with breast feeding.

4. Complications

Maternal complications in women with chronic hypertension will depend on etiology and severity of the hypertension. In women with low-risk hypertension, the most common complications are superimposed preeclampsia (15-25%), and abruptio placentae (1-2%). There are no current strategies to reduce the rates of these compications; however, adverse effects from these complications can be reduced by close monitoring and timely delivery.

In women with severe hypertension, potential complications include superimposed preeclampsia (40-50%), abruptio placentae (2-5%), pulmonary edema (3%-5%), and stroke (~ 1%). There are no strategies to reduce the rates of preeclampsia, but the other complications can be reduced by proper management of maternal hypertension, close observation, and timely hospitalization and delivery.

In women with significant renal dysfunction (serum creatinine > 1.4 mg/dl), there is the potential for deterioration in renal function, and need for preterm delivery. These complications may be reduced by aggressive control of maternal hypertension, prolonged antenatal hospitalization, and timely delivery. Women with severe renal dysfunction (serum creatinine > 2.5 mg/dl) should be advised against pregnancy and should consider termination if they are seen early in pregnancy.

5. Prognosis and outcome

For women with low-risk hypertension, pregnancy outcome is usually good. The risk for preterm delivery is < 15%, the likelihood for the infant requiring admission to the neonatal intensive care unit is < 5%, and the perinatal survival is almost 100%. In women with severe chronic hypertension in the first trimester, the rate of preterm delivery is approximately 60%, the rate of FGR is 30%, and perinatal mortality is 3-5%. There are also increased risks to the mother secondary to preeclampsia and abruptio placentae.

Women with high-risk chronic hypertension are at an increased risk for life-threatening maternal complications such as pulmonary edema, retinopathy, renal dysfunction or failure, hypertensive encephalopathy and cerebral hemorrhage. These risks are particularly increased in women with poor compliance and/or uncontrolled severe hypertension, in those with significant renal dysfunction early in pregnancy, and in those with left ventricular dysfunction before conception or very early in pregnancy. Fetal and neonatal complications such as perinatal death, preterm delivery, FGR, and admission to the neonatal intensive care unit are also increased in such women.

6. What is the evidence for specific management and treatment recommendations

Powrie, RO. “A 30-year-old woman with chronic hypertension trying to conceive”. JAMA. vol. 298. 2007. pp. 1548-59. (This case presentation and review of the literature provides excellent information regarding preconception, counseling and evaluation of patients with chronic hypertension. The author provides detailed information on how the patient should be evaluated, classified, and then managed throughout pregnancy and postpartum. The author also provides information on medications to use, including doses and costs.)

Sibai, BM. “Chronic hypertension in pregnancy”. Obstet Gynecol. vol. 100. 2002. pp. 369-77. (This report by an expert in the field describes the author’s recommendations for evaluation and management of women with chronic hypertension in pregnancy. The author describes the importance of classifying these women based on etiology and severity of the hypertension as well as presence or absence of target organ damage, and then targeting the management according to this classification. This review also provides information on target blood pressure to treat, drugs to use, as well as antepartum, intrapartum, and postpartum management of such women.)

Podymow, T, August, P. “Antihypertensive drugs in pregnancy”. Seminars in Nephrology. vol. 31. 2011. pp. 70-85. (This is a comprehensive review of antihypertensive treatment of specific hypertensive disorders in pregnancy. The authors describe the indications, doses, and contraindications for various antihypertensive medications used during pregnancy and postpartum, including safety of drugs in lactating women. There is also a review of recommendations by various international working groups regarding the threshold blood pressure for initiating therapy, as well as the target blood pressure achieved during therapy.)

Abalos, E, Duley, L, Steyn, D, Henderson-Smart, D. “Antihypertensive drug therapy for mild to moderate hypertension during pregnancy”. Cochrane Database Syst Review. vol. 1. 2007. pp. CD002252(In this Cochrane meta-analysis, the authors review data from all randomized trials evaluating the benefits and risks of antihypertensive therapy for mild to moderate hypertension (defined as blood pressure 140-160 mm Hg systolic or diastolic blood pressure 90-109 mm Hg) in pregnancy. The authors of this review noted that antihypertensive treatment was associated with a 50% reduction in the development of severe hypertension (number needed to treat of 10), but such reduction was not associated with reductions in rates of preeclampsia, small for gestational age infants, or other adverse neonatal outcomes.)

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