Hypertension is one of the most common conditions affecting pregnancy, with an incidence of 5% to 10%. It accounts for a significant portion of maternal morbidity and mortality. It is also a major contributor to adverse fetal and neonatal outcomes. The disease spectrum ranges from mild to severe and is classified as a major health issue for the United States and the world. In the United States, studies report a maternal death rate from preeclampsia of 12.3%,¹ and there is evidence that half of these cases are preventable.² Due to its tremendous impact on obstetrics, hypertension in pregnancy has been given a great deal of attention, including the formation of a task force by the American College of Obstetricians and Gynecologists (ACOG) to provide recommendations for clinical practice.³ Of course, the best form of therapy is prevention, which is discussed in this chapter, as well as classification, physiology, and management.

Hypertension in pregnancy refers to a wide spectrum of hypertension, ranging from mild blood pressure elevation to severe blood pressure elevation with end-organ damage. There have been classifications for hypertension in pregnancy since the 1970s; however, the need for uniformity of classification has become more evident in recent years, for the purpose of better communication among providers and in research. The initial classification was in 1972 by ACOG, and it was modified in 1990 and 2000. More recently, in 2013,³ the ACOG task force made additional modifications; however, the four-category classification was maintained: namely, preeclampsia-eclampsia, chronic hypertension, chronic hypertension with superimposed preeclampsia, and gestational hypertension. Hypertension is diagnosed when a correctly taken blood pressure exceeds a systolic pressure of 140 mmHg or a diastolic of 90 mmHg.

PREECLAMPSIA/ECLAMPSIA

Preeclampsia has been on the rise in the United States over the last 20 years. It is a pregnancy-specific, multisystem, progressive syndrome. The risk factors for preeclampsia are listed in Table 31-1. A simplistic definition that has been used is gestational hypertension with proteinuria. While a blood pressure > 140/90 mmHg after 20 weeks gestation in a previously normotensive woman with proteinuria meets the criteria for preeclampsia, it has been recognized that proteinuria may not be present in some cases of preeclampsia.³ If there is no proteinuria, along with the blood pressure requirements, there must be new-onset thrombocytopenia, renal insufficiency, liver involvement, cerebral symptoms, or pulmonary edema. These same indicators are used to distinguish whether severe features are present (see Table 31-2). When present, proteinuria is defined as ≥300 mg/dL protein in a 24-hour urine collection or a protein/creatinine ratio of ≥0.3 mg/dL.

HELLP syndrome, as denoted by the acronym, is characterized as hemolysis, elevated liver enzymes, and low platelets. Hypertension may or may not be present. Laboratory criteria include an abnormal peripheral smear, elevated lactate dehydrogenase (>600 U/L), elevated total bilirubin, elevated liver function test, and platelets <100,000/μL. There is evidence that women with preeclampsia complicated by HELLP have worse outcomes.⁴ Complications associated with HELLP syndrome are eclampsia, placenta abruption, acute kidney injury, pulmonary edema, stroke, coagulopathy, acute respiratory distress syndrome, sepsis, subcapsular liver hematoma, and maternal/fetal death. Subcapsular liver hematoma is often discussed in association with HELLP and has an incidence of 1.6%.⁵ Investigators believe that HELLP syndrome has a distinctly different pathophysiology than preeclampsia without HELLP.

CHRONIC HYPERTENSION

Chronic hypertension is defined as hypertension diagnosed before pregnancy, during the first 20 weeks of pregnancy, or 3 months after pregnancy (if elevated blood pressure persists). The incidence of chronic hypertension is about 1% to 5%; however, it depends on characteristics of the patient population, such as age, body mass index (BMI), and ethnicity.⁶ Most cases of chronic hypertension are due to essential hypertension. There are secondary causes that should be considered as well, such as renal disease, autoimmune disorders, thyroid dysfunction, renal artery stenosis, pheochromocytoma, and coarctation of the aorta. About 25% of women with chronic hypertension will develop preeclampsia.

CHRONIC HYPERTENSION WITH SUPERIMPOSED PREECLAMPSIA

A woman diagnosed with chronic hypertension is at increased risk for developing superimposed preeclampsia. With an established diagnosis of chronic hypertension, the clinician faces the difficult task of determining whether the blood pressure elevation is due to worsening chronic hypertension or superimposed preeclampsia. Early-pregnancy 24-hour urine for total protein and creatinine clearance may be helpful in this assessment and give information about renal function.

GESTATIONAL HYPERTENSION

Gestational hypertension is defined as blood pressure elevation occurring after 20 weeks gestation and in the absence of proteinuria. Because the updated preeclampsia diagnostic criteria include women without proteinuria, the distinguishing factor is that this diagnosis is made in the absence of protein and systemic findings (e.g. thrombocytopenia, renal insufficiency, liver involvement, cerebral symptoms, or pulmonary edema).

The etiology of preeclampsia remains elusive; however, after years of research, there have been several important discoveries. Exposure to chorionic villi is a requirement, and those exposed for the first time (e.g. primagravid) or to large amounts (e.g. twins, hydatidiform moles) are more likely to develop preeclampsia. There is a hereditary predisposition for preeclampsia, characterized as multifactorial and polygenic, which has been demonstrated with mother-and-daughter relationships, sisters, and monozygotic female twins at 60% concordance.⁷ In addition, abnormal trophoblastic invasion, endothelial cell activation, and nutritional factors have all been isolated as mechanisms to explain components that cause preeclampsia.^8,9

Many physiologic changes happen with pregnancy. Preeclampsia further complicates the understanding of these changes because it causes several changes itself. The clinical manifestations of preeclampsia occur in the second half of pregnancy; however, the foundation that evolves to become clinically evident begins at an early gestation.¹⁰ This complex process will progress, affecting all organ systems and threatening the life of the mother and fetus unless delivery occurs.

CARDIOVASCULAR CHANGES

The cardiovascular system undergoes several changes when preeclampsia is present, including a decrease in cardiac output. The hypertension connected with preeclampsia is due to vasoconstriction, causing an increase in cardiac afterload. There is diastolic dysfunction that is tolerated by most women; however, women who already have some diastolic dysfunction may have worsened clinical manifestations.

HEMATOLOGIC CHANGES

The most notable hematologic change with preeclampsia is thrombocytopenia. If the platelet count is <100,000/μL, it indicates severe disease. As the platelet count decreases, the risk for adverse maternal and fetal outcome increases.¹¹ Hemolysis may occur, with its presence confirmed by elevations in lactate dehydrogenase (LDH) and bilirubin. In addition, a peripheral smear would show schistocytes, spherocytes, and reticulocytes. Also, the hematocrit may increase due to hemoconcentration or decrease due to hemolysis.

RENAL CHANGES

During pregnancy, renal perfusion and glomerular filtration increase; however, with preeclampsia, they decrease. This is partly due to a reduction in plasma volume. This leads to an elevation in the serum creatinine. A creatinine level >1.1 mg/dL, or doubling of creatinine in the absence of other renal diseases, defines renal insufficiency (a severe feature). As the creatinine increases, so does the severity of the disease. Medication adjustments may be required; specifically, magnesium sulfate may need to be decreased to prevent toxicity. The urine output must be monitored closely, as these women are at risk for oliguria (urine output <500 mL in 24 hours).

Uric acid is elevated with preeclampsia due to a decrease in uric acid clearance, increased tubular absorption, and decreased secretion. Proteinuria when present is defined as ≥300 mg/dL in a 24-hour urine collection, or a protein/creatinine ratio of ≥0.3 mg/dL. Urine dipstick testing for protein is discouraged for making a diagnosis due to the variability of the results; however, its use for screening has long been used (proteinuria suspected if the urine dip result is 1+ or greater). With extreme renal insufficiency, there is a risk for acute tubular necrosis. This is more likely to occur with hypovolemia and hypotension associated with hemorrhage, placental abruption, and HELLP.^5,12

HEPATIC CHANGES

There may be liver symptoms associated with preeclampsia, ranging from mild liver function elevations to liver hematomas and rupture. Elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) correlate with the severity of disease (a feature is severe if the level is double the upper limit of normal). The patient may be experiencing right upper quadrant (RUQ) or epigastric pain. In the absence of symptoms, there may still be a significant amount of liver infarction. This is seen more often with HELLP and eclampsia. It is extension of the hemorrhagic infarction that subsequently forms a subcapsular hematoma that may rupture.

CENTRAL NERVOUS SYSTEM CHANGES

Frequently, clinicians must decipher whether headaches and visual changes are related to preeclampsia. These symptoms are due to cerebral hyperperfusion and may indicate severe neurologic involvement. In addition, they may be the preceding symptoms of eclampsia. Eclamptic seizure is a major cause of maternal mortality. Blindness and cerebral edema are other rare neurologic manifestations of preeclampsia.

Most women with preeclampsia start with no symptoms. As the disease progresses, symptoms are more likely to be present. As preeclampsia affects many organs, the symptoms can span several organ systems. Women should be monitored for persistent nausea and vomiting, severe headache unrelieved with analgesics, RUQ or epigastric pain, visual changes, decreased fetal movement, vaginal bleeding, or symptoms of labor. Swelling is a very common complaint, but that gives no insight into the disease or its severity.

There have been several hypothesized therapies in the prevention of preeclampsia, but they have not been proved when tested under research protocols. Studies spanning decades up to the present time have looked at the use of low-dose aspirin for preeclampsia prevention, as it inhibits platelet thromboxane A2 biosynthesis. In 2014, the US Preventive Services Task Force (USPSTF) evaluated through a meta-analysis¹³ whether the prophylactic use of low-dose aspirin by pregnant women prevented preeclampsia. The review demonstrated several benefits of low-dose aspirin, with no significant harm. These benefits were not seen in low-risk women. In a follow-up report,¹⁴ the USPSTF provided recommendations for the use of low-dose aspirin (81 mg daily) based on various risk factors (see Table 31-3). In July 2016, an ACOG Practice Advisory states that aspirin should be considered in women with any of the USPSTF high-risk factors.¹⁵