Baha M. Sibai, MD
Sara E. Arian, MD
• Hypertension in Pregnancy Task Force Report
DEFINITIONS AND CLASSIFICATIONS
• Hemolysis Elevated Liver Enzymes and Low Platelets Syndrome
• Chronic Hypertension With Superimposed Preeclampsia
MANAGEMENT CONSIDERATIONS FOR HYPERTENSIVE DISORDERS IN PREGNANCY
• Hypertensive Disorders in Pregnancy Without Severe Features
4. Intrapartum Management and Timing of Delivery
5. Postpartum Management and Follow-Up
• Management of Chronic Hypertension in Pregnancy
• Fetal Surveillance for Pregnant Women with Chronic Hypertension
• Prevention of Superimposed Preeclampsia
• Hypertensive Disorders in Pregnancy with Severe Features
• Antihypertensive Agent Selection
• Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blockers
• Drugs for Long-Term Management: Oral Antihypertensive Agents
MANAGEMENT OF WOMEN WITH PRIOR PREECLAMPSIA
PREVENTION AND PREDICTION OF PREECLAMPSIA
CONTROVERSIES AND FUTURES CONSIDERATIONS
FETAL PROGRAMMING AND FETAL ORIGINS OF ADULT DISEASE
INTRODUCTION
Prevalence and Relevance
Hypertension is the most frequent reason for office visits in the general population,1 as well as the most common medical condition complicating up to 10% of pregnancies.2–5 The incidence of hypertension has increased significantly over the last 10 years, with an estimate of 40% to 50% rise, 5,6 and therefore, the above figures may be understated. This goes hand in hand with an increase in obesity rates in the United States, which may subsequently lead to higher incidence of diabetes mellitus.6,7 Other possible reasons for the increase in hypertension in pregnancy include the increased rate of multiple gestation secondary to assisted reproductive technology and increase in the age of pregnant women because of delay in having children.
Hypertension is the second most common cause of maternal death in the United States8 and African American women have a fourfold increase in mortality rate.9 The mortality rate is also increased in women over the age of 35 years.10
Table 12-1 summarizes the potential adverse effects and maternal and fetal complications of hypertension.
Adverse Outcomes in Severe Hypertensive Disorders of Pregnancy |
Hypertension in Pregnancy Task Force Report
The Task Force on hypertension in pregnancy comprised 17 clinician-scientists from the fields of obstetrics, maternal-fetal medicine, hypertension, internal medicine, nephrology, anesthesiology, physiology, and patient advocacy. These experts in the management of hypertension in pregnancy reviewed available data and provided evidence-based recommendations for clinical practice.
Its main contribution was in making evidence-based recommendations to modernize the definition and management of preeclampsia. Proteinuria was eliminated as a required criterion for diagnosis. In addition, preeclampsia is no longer classified as mild versus severe, but rather by having evidence of hypertensive pathology, and its severe form as defined by having severe features.
Management algorithms were provided accordingly for hypertensive disorders in pregnancy with and without severe features. Many of their management recommendations, particularly those for disease with severe features, provide much-needed clarity.
DEFINITIONS AND CLASSIFICATIONS
Hypertension is defined as a systolic blood pressure (BP) ≥140 mmHg or a diastolic BP ≥90 mmHg. These measurements must be made on at least two occasions, no less than 4 hours and no more than a week apart, unless severe BP ranges are encountered. In that case, it is appropriate to make the diagnosis within a time interval of minutes.1
It is important to note that choosing the appropriate cuff size will help eliminate inaccurate BP measurements. Abnormal proteinuria in pregnancy is defined as the excretion of ≥300 mg of protein in 24 hours or a protein/creatinine ratio of ≥0.30. A 24-hour urine collection is the gold standard tool for assessing total urinary protein excretion. Quantitative urine dipstick, however, may be used in some occasions especially when it is the only available measure to determine proteinuria.
Different classifications are available for hypertensive disorders in pregnancy. Although the American College of Obstetrics and Gynecology Task Force on Hypertension in pregnancy has made some modifications to the components of the classification of hypertension, it chose to continue using the basic classification first introduced by the college in 1972. This classification considers hypertension during pregnancy in four categories: (1) gestational hypertension, (2) preeclampsia-eclampsia, (3) chronic hypertension, and (4) chronic hypertension with superimposed preeclampsia.12
The National Institute for Health and Care Excellence (NICE) differs in separating preeclampsia, severe preeclampsia, and Hemolysis Elevated Liver enzymes and Low Platelets (HELLP). In addition, chronic hypertension itself is classified itself as mild, moderate, and severe. Mild hypertension is defined as diastolic BP of 90 to 99 mmHg and systolic BP 140 to 149 mmHg. Moderate hypertension is defined as diastolic BP of 100 to 109 mmHg and systolic BP of 150 to 159 mmHg. Severe hypertension includes diastolic BP of 110 mmHg or greater and systolic BP 160 mmHg or greater.
The International Society for the Study of Hypertension in Pregnancy’s classification of hypertensive disease in pregnancy includes preeclampsia, gestational hypertension, chronic hypertension (including essential or secondary), and preeclampsia superimposed on chronic hypertension.
Table 12-2 lists the classification of hypertension during pregnancy as per American College of Obstetricians and Gynecologists (ACOG).
Classification of Hypertension |
I. Gestational hypertension (onset after 20 weeks)
• Systolic >140 millimeters Hg or
• Diastolic >90 millimeters Hg
No proteinuria, no laboratory abnormalities, and no symptoms
II. Preeclampsia (hypertension ≥20 wk+ proteinuria)
Proteinuria definition:
≥300 mg/24 h
Or
Protein/creatinine ratio ≥0.30
Or
≥1 + on dipstick
III. Preeclampsia with severe features: new-onset hypertension with any of the following
• Severe hypertension
• Systolic ≥160 millimeters Hg or
Diastolic ≥110 millimeters Hg
Persistently severe cerebral symptoms
Thrombocytopenia <100,000/mm3
Elevated liver enzymes >2× upper limit normal
Pulmonary edema
Serum creatinine >1.1 mg/dL or doubling of baseline
IV. Chronic hypertension
Hypertension before pregnancy
Hypertension before 20 weeks of gestation
V. Superimposed preeclampsia
Exacerbation of hypertension
And/or
New-onset proteinuria
And/or
Sudden increase in proteinuria (Changes have to be substantial and sustained)
VI. Superimposed preeclampsia with severe features: CHTN with any of criteria from III
Gestational Hypertension
Gestational hypertension is characterized by new onset of elevated BP during the second half of pregnancy (after 20 weeks of gestation) or in the first 24 hours postpartum, without accompanying proteinuria, without abnormal blood tests (elevated liver enzymes, low platelets, or elevated serum creatinine), and in the absence of symptoms. Normalization of BP occurs in the postpartum period, usually within 10 days. The failure of BP to normalize during the postpartum period requires changing the diagnosis to chronic hypertension. Treatment is generally not warranted in this condition, as most patients will have mild hypertension. Gestational hypertension has little effect on maternal or perinatal morbidity or mortality when it develops at or beyond 37 weeks of gestation. However, approximately 40% of patients diagnosed with preterm gestational hypertension will subsequently develop preeclampsia, or severe features. In addition, these pregnancies may result in fetal growth restriction and placental abruption.
Patients with severe features in the setting of gestational hypertension are at risk for developing adverse maternal and perinatal outcomes. Management of these patients should be similar to patients with preeclampsia with severe features. Use of antihypertensive therapy thus should not be part of outpatient management of patients with severe disease.
Although transient in nature, gestational hypertension can be a sign of future remote chronic hypertension. Therefore, even in the benign cases, it is an important marker for follow-up and prevention of development of chronic hypertension.13
Preeclampsia-Eclampsia
Preeclampsia
The classic definition of preeclampsia with hypertension and proteinuria has been challenged and modified per the Task Force. Currently, the syndrome of preeclampsia requires meeting two criteria; the development of hypertension after 20 weeks of gestation in a woman with previously normal BP.12,14 in addition to the presence of proteinuria or new onset of symptoms. Certain laboratory abnormalities are consistent with severe disease and are used interchangeably or in addition to symptoms.
Symptoms of preeclampsia include cerebral/visual symptoms, severe persistent right upper quadrant/epigastric pain unresponsive to treatment and pulmonary edema. Laboratory abnormalities include thrombocytopenia with a platelet count <100,000, serum creatinine level >1.1 mg/dL, and elevated liver enzymes (>2× normal).
Preeclampsia syndrome can be subdivided into preeclampsia and preeclampsia with severe features. The distinction between the two is based on the severity of hypertension as well as the involvement of other organ systems (Table 12-2). Close surveillance of patients with preeclampsia is warranted, as either type may progress to fulminant disease.
Some maternal symptoms, even in the absence of a confirmed diagnosis of preeclampsia, should be considered as prediagnostic findings warranting increased surveillance and should prompt the health-care provider to closely monitor maternal status for development of preeclampsia.15,16 Women who demonstrate elevations in BP during pregnancy that exceed 15 mmHg diastolic or 30 mmHg systolic “warrant close observation,” as suggested by the National High Blood Pressure Education Program Working Group.12
Diabetes, obesity, nulliparity, extremes of age, renal insufficiency, pre-existing hypertension, personal history of preeclampsia, family history of preeclampsia, molar pregnancy, multifetal gestation, and fetal hydrops are among risk factors for the development of preeclampsia.
Eclampsia
Eclampsia is defined as preeclampsia accompanied by development of new-onset grand mal seizures or coma during pregnancy or the postpartum period, not attributable to other causes. Eclampsia can occur before, during, or after labor. Other causes of seizure during pregnancy can include a bleeding arteriovenous malformation, idiopathic seizure disorder, or ruptured aneurysm.18
Studies on magnesium sulfate for the management and prevention of eclampsia have shown its superiority to other anticonvulsants such as phenytoin and diazepam.78 Patients being treated for eclamptic seizures should receive an intravenous loading dose of 4 to 6 g of magnesium sulfate followed by a maintenance dose of 1 to 2 g/h for at least 24 hours. It is recommended that women with eclampsia undergo delivery after initial stabilization. The Task Force recommends intraoperative administration of parenteral magnesium sulfate.
Hemolysis Elevated Liver Enzymes and Low Platelets Syndrome
A particularly severe form of preeclampsia is HELLP syndrome. HELLP syndrome is the acronym for Hemolysis (H), Elevated Liver enzymes (EL), and Low Platelet count (LP). The diagnosis of HELLP can be elusive, as BP values may only be slightly elevated. Table 12-3 describes the laboratory criteria for the diagnosis of HELLP syndrome. Once a patient is diagnosed with HELLP, she will automatically be considered to have severe features.
Laboratory Criteria for the Diagnosis of HELLP Syndrome |
The development of HELLP syndrome may occur antepartum or postpartum.79 Delivery is indicated if this syndrome develops beyond 34 weeks of gestation or earlier with evidence of DIC, liver infarction or hemorrhage, renal failure, pulmonary edema, abruptio placentae, or non-reassuring fetal testing.79 In women from the gestational age of fetal viability to 33 6/7 weeks of gestation, it is suggested by the Task Force to delay the delivery for 24 to 48 hours if maternal and fetal conditions remain stable, so that the corticosteroid course can be completed.
Chronic Hypertension
Hypertension in pregnancy is defined as chronic if the patient was diagnosed with hypertension before pregnancy, if hypertension is noted before 20 weeks of gestation, or if it persists beyond 6 months postpartum. The incidence of chronic hypertension (CHTN) in pregnancy varies from 1% to 5%.19,20 Essential or primary hypertension is the most common type of chronic hypertension contributing to 90% of CHTN cases, whereas secondary hypertension accounts for only 10% of the cases.
Chronic renal disease (glomerulonephritis, polycystic kidney disease, and renal artery stenosis) is the most common cause of secondary hypertension. Other secondary causes of hypertension include polyarteritis nodosa, lupus erythematosus, endocrine disorders (primary hyperaldosteronism, Cushing disease, pheochromocytoma, diabetes mellitus especially with renovascular involvement), and coarctation of the aorta.12,21 Some etiologies of secondary hypertension, such as renovascular hypertension and pheochromocytoma, may be associated with poor pregnancy prognosis and fetal outcomes. Clinical features that may warrant additional work-up for secondary hypertension include hypertension resistant to medical management, lack of family history of hypertension, extremes of age, electrolyte abnormalities (such as hypokalemia, hypernatremia) and elevated serum creatinine levels suggestive of chronic renal failure. Per Task Force Recommendations, clinical suspicion for secondary hypertension warrants referral to a hypertension specialist for further work-up.18
Women with chronic hypertension are at risk of developing superimposed preeclampsia. Women with chronic hypertension who develop superimposed preeclampsia have higher rates of adverse maternal-fetal outcomes. Chronic hypertension is also associated with a greater risk of cesarean delivery and development of postpartum hemorrhage.24 Other adverse maternal outcomes of chronic hypertension include end-organ damage, increased risk of development of gestational diabetes24–26, and increased risk of abruptio placentae (threefolds).22,27,28 Women with chronic hypertension are also more likely to be hospitalized for hypertension.26
In regard with fetal outcomes, perinatal mortality and perinatal death are higher in pregnancies complicated by chronic hypertension.22,26,28 Fetal growth restriction is more common with chronic hypertension and is usually associated with superimposed preeclampsia.23
Chronic Hypertension With Superimposed Preeclampsia
The Task Force divides superimposed preeclampsia into two categories: (1) superimposed preeclampsia and (2) superimposed preeclampsia with severe features.
Superimposed preeclampsia is defined as an exacerbation of hypertension that was previously well-controlled requiring escalation of BP medications and/or new onset of proteinuria or sudden increase in pre-existing proteinuria that has to be substantial and/or sustained. Superimposed preeclampsia develops in 13% to 40% of women with chronic hypertension, depending on diagnostic criteria, etiology of chronic hypertension, and its severity.59,60
Superimposed preeclampsia with severe features is defined by the presence of severe hypertension despite treatment, symptoms including cerebral/visual symptoms, persistent right upper quadrant (RUQ)/epigastric pain unresponsive to treatment, or pulmonary edema. Lab abnormalities meeting criteria for severe features include low platelets <100,000 elevated liver enzymes (>2× upper normal) and new elevation of serum creatinine to >1.1 mg (Table 12-4).
Criteria for the Diagnosis of Suspected Superimposed Preeclampsia, or Superimposed Preeclampsia with Severe Features |
