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Hypertensive Disorders of Pregnancy
Hypertensive disorders of pregnancy consist of a broad spectrum of medical complications, including gestational hypertension, preeclampsia, eclampsia, and pregestational hypertension. The incidence is estimated to be between 3% and 10% of all pregnancies. Worldwide, preeclampsia and related conditions are among the leading causes of maternal mortality. Although maternal death caused by preeclampsia is less common in developed countries, maternal morbidity remains high. Hypertensive disorders of pregnancy are also the leading cause of fetal growth restriction and indicated preterm deliveries, with the associated complications of prematurity such as neonatal deaths and serious long-term morbidity being substantial.
Preeclampsia is a pregnancy-specific syndrome that is clinically recognized by new onset hypertension and proteinuria after 20 weeks’ gestation. Vascular dysfunction is central to the systemic maternal manifestations of preeclampsia, including increased peripheral vascular resistance, heightened sensitivity to vasopressors, endothelial dysfunction, vasospasm, ischemia, inflammation, activation of the coagulation cascade, and platelet aggregation leading to multiorgan damage. The term eclampsia is derived from the Greek, meaning “sudden flashing” or “lightning,” and refers to the seizures that can accompany this syndrome. Although the Egyptians and Indians described this disorder more than 2000 years bce , the only known cure for preeclampsia remains delivery of the fetus and placenta.
Classification of Hypertensive Disorders of Pregnancy
Precise classification of the hypertensive disorders of pregnancy has remained challenging because of the changing nomenclature over time, with terms such as toxemia and pregnancy-induced hypertension now considered outdated. Furthermore, varying diagnostic criteria are used in different regions of the world. The classification system most commonly used in the United States is based on the Working Group Report on High Blood Pressure in Pregnancy published in 2000 and revised in 2013 by the American College of Obstetricians and Gynecologists (ACOG) Task Force for Hypertensive Disorders of Pregnancy. The goals of the Task Force were to evaluate the existing evidence and update the classification system as well as the management of hypertensive disorders of pregnancy. Four major categories are described: gestational hypertension, preeclampsia-eclampsia, chronic hypertension, and preeclampsia superimposed on chronic hypertension ( Table 17.1 ).
TABLE 17.1
Classification of Hypertensive Disorders of Pregnancy
| Preeclampsia |
AND
OR in the absence of proteinuria, new-onset hypertension with the new onset of any of the following:
|
| Severe features of preeclampsia (any of these findings) |
|
| Eclampsia |
|
| Superimposed preeclampsia (likely when any of these are present) |
Severe features:
|
| HELLP syndrome |
|
| Gestational hypertension |
|
*Precise diagnosis is often challenging, and high clinical suspicion is warranted given the increase in maternal and fetal-neonatal risks associated with superimposed preeclampsia.
Gestational Hypertension
Gestational hypertension is defined by elevated blood pressure (≥140 mm Hg systolic or ≥90 mm Hg diastolic) in a previously normotensive woman. High blood pressure should be sustained with documented elevations on at least two occasions 4 hours apart. Blood pressure should be measured in the semi-Fowler or seated position with an appropriately sized cuff. Disappearance of sounds (Korotkoff phase V) is used to determine diastolic pressure. Gestational hypertension is a provisional diagnosis during pregnancy and includes women in three categories: (1) women who will progress to develop preeclampsia, (2) women with “transient hypertension of pregnancy” who do not develop preeclampsia and revert to normal blood pressures by 12 weeks’ postdelivery, and (3) women who may have previously unrecognized chronic hypertension. Definitive diagnosis is possible only after reassessment at 6-12 weeks’ postpartum.
Preeclampsia
Preeclampsia (see Table 17.1 ) is defined as new onset of elevated blood pressure and new onset of proteinuria after 20 weeks of gestation; or in the absence of proteinuria, hypertension with any of the following: thrombocytopenia (platelet count of less than 100,000/µL), impaired liver function blood (elevated blood concentrations of liver transaminases to twice the normal concentration), the new development of renal insufficiency (elevated serum creatinine of greater than 1.1 mg/dL or doubling of serum creatinine in the absence of other renal disease), pulmonary edema, or new onset of cerebral or visual disturbances. The term “mild” preeclampsia has been replaced by “preeclampsia without severe features” to emphasize the need for ongoing vigilance as well as the progressive and systemic nature of this syndrome. Severe features of preeclampsia include:
-
Systolic blood pressure of 160 mm Hg or higher, or diastolic blood pressure of 110 mm Hg or higher on two occasions at least 4 hours apart while a patient is on bed rest (unless antihypertensive therapy is initiated before this time)
-
Thrombocytopenia (platelet count <100,000/µL)
-
Impaired liver function as indicated by abnormally elevated blood concentrations of liver enzymes (to twice the normal concentration), severe persistent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by alternative diagnoses, or both
-
Progressive renal insufficiency (serum creatinine concentration of >1.1 mg/dL or a doubling of the serum creatinine concentration in the absence of other renal disease)
-
Pulmonary edema
-
Persistent cerebral or visual disturbances
Eliminating the dependence on proteinuria from the diagnosis of preeclampsia is a major revision from the previous diagnostic criteria, with the intent to recognize the systemic and progressive nature of preeclampsia. This is more consistent with other diagnostic criteria used internationally. Fetal growth restriction was also removed from the diagnosis but remains an important aspect in the evaluation and management of women with preeclampsia. As in the 2000 Working Group Recommendations, an increase of 30 mm Hg systolic or 15 mm Hg diastolic blood pressure from baseline in early pregnancy measurements is not included in the diagnostic criteria, because women with these changes alone are not at increased risk for adverse outcomes. Although edema may raise clinical suspicion for preeclampsia, it is not a diagnostic criterion for preeclampsia, because nondependent edema occurs in 10%-15% of women who remain normotensive throughout pregnancy and is neither a sensitive nor specific sign of preeclampsia.
Eclampsia
Eclampsia refers to generalized seizures occurring in a woman with preeclampsia that cannot be attributed to other causes.
Chronic Hypertension
Chronic hypertension is defined as hypertension present prior to pregnancy or that is newly diagnosed before 20 weeks of gestation. Persistent blood pressure of greater than 140/90 mm Hg is considered hypertension. High blood pressure that persists 6-12 weeks postpartum is also classified as chronic hypertension.
Superimposed Preeclampsia
Preeclampsia superimposed on chronic hypertension is characterized by a sudden and sustained increase in blood pressure with or without substantial increase in proteinuria. Diagnosis is often challenging because both blood pressure and urinary protein excretion increase toward the end of pregnancy. High clinical suspicion is warranted given the increase in maternal and fetal-neonatal risks. End-organ involvement such as thrombocytopenia, elevated liver transaminase enzymes, or a rapid decline of renal function are also diagnostic of superimposed preeclampsia.
HELLP Syndrome
HELLP syndrome is defined by the presence of h emolysis, e levated l iver transaminases, and l ow p latelets. This may or may not occur in the presence of hypertension or proteinuria. It is generally considered a variant of preeclampsia.
A major criticism of the various classification systems is that none have been independently evaluated for the ability to identify the subgroup of women who are at increased risk of adverse pregnancy outcomes. Furthermore, there is disagreement regarding the degree of hypertension, presence or absence of proteinuria, and criteria for disease severity among the different classification systems used internationally. These inconsistencies have led to challenges in comparing and generalizing epidemiologic and other research findings. Studies have sought to develop clinically relevant definitions guided by the evidence and based on predictors of adverse outcomes. The most recent ACOG Task Force recommendations address many of these issues.
Epidemiology of Preeclampsia
The incidence of preeclampsia is increasing in the United States and is likely related to the higher prevalence of predisposing disorders, such as hypertension, diabetes, and obesity, and to delay in child-bearing, as well as to the use of assisted reproductive technologies with their associated increase in multifetal gestation. The global impact of preeclampsia is profound, with short- and long-term effects on both mother and baby.
Maternal Effects
Short Term
In a systematic review by the World Health Organization, hypertensive disorders of pregnancy account for 16% of all maternal deaths in developed countries and as high as 26% in Latin America and the Caribbean. In areas in which maternal deaths are high, mortality is largely attributable to eclampsia rather than preeclampsia. Based on data from the United States National Hospital Discharge Survey, the rate of preeclampsia increased by 25% between 1987 and 2004; however, there was a trend toward a decrease in eclampsia by 22%. Although maternal mortality owing to hypertensive disorders is less common in high-income countries, rates of severe morbidity—including renal failure, stroke and permanent neurologic impairment, cardiac dysfunction or arrest, respiratory compromise, coagulopathy, and liver failure—are high. In a study of hospitals managed by the Health Care America Corporation, preeclampsia was the second leading cause of pregnancy-related admission to intensive care units after obstetric hemorrhage.
Recurrence in Subsequent Pregnancies
Recurrence of preeclampsia varies between 7% and 20%. This wide variation in the estimates is based on the quality of the diagnostic criteria used. The risk of recurrent preeclampsia is even higher with two prior preeclamptic pregnancies or with earlier gestational age of preeclampsia onset.
Long-Term Cardiovascular Risks
A landmark study published in 1976 demonstrated that women who had eclampsia in any pregnancy after their first had a mortality risk that was two- to fivefold higher over the next 35 years compared with controls. Since that time, several large epidemiologic studies have confirmed that women with preeclampsia in any pregnancy have an increased risk of cardiovascular diseases later in life and related mortality. This risk is higher among women with preeclampsia that was recurrent, that necessitated a preterm delivery, or that was associated with fetal growth restriction. Hypertension, dyslipidemia, insulin resistance, endothelial dysfunction, and vascular impairment have all been observed months to years after the preeclamptic pregnancy, further supporting the link between preeclampsia and cardiovascular disease. In 2011, the American Heart Association added preeclampsia to its list of recognized risk factors for cardiovascular disease. Based on these data, women with a history of preeclampsia should have ongoing, close surveillance to prevent or detect cardiovascular disease. Further investigation is needed to resolve whether common risk factors lead to the development of both preeclampsia and subsequent cardiovascular disease or whether preeclampsia itself contributes to this future risk.
Fetal and Neonatal Effects
Fetal and neonatal outcomes related to hypertensive disorders vary widely around the world and are associated with resource availability, presence of neonatal intensive care facilities, and limits of viability as defined by gestational age and birth weight. In developing countries, one-quarter of stillbirths and neonatal deaths are associated with preeclampsia-eclampsia. Infant mortality is three times higher in low-resource settings compared to high-income countries, largely due to the lack of neonatal intensive care facilities.
It is estimated that 12%-25% of fetal growth restriction and small-for-gestational-age (SGA) infants, as well as 15%-20% of all preterm births, are attributable to preeclampsia. These preterm births are generally indicated, because the only known cure for preeclampsia is delivery of the fetus and placenta. The associated complications of prematurity are substantial, including neonatal deaths and serious long-term morbidity. The risk of complications is inversely associated with gestational age at delivery. Extremely premature infants (<25 weeks) have the highest mortality rate, and if they survive, they are at substantial risk for long-term issues. These include neurodevelopmental impairment such as impaired cognitive skills, motor deficits with fine and/or gross motor delay, cerebral palsy, vision problems, hearing loss, and behavioral and psychological problems, as well as recurrent hospitalization and chronic lung problems and other health problems.
Prematurity also impacts adult health and has been associated with increased insulin resistance, hypertension, and cardiovascular disease. There is growing evidence suggesting that the in utero environment affects later life health and disease (termed the Barker hypothesis ) with particular focus on fetal growth restriction and later life cardiovascular disease (see also Chapter 16 ). A systematic review of 18 studies that included 45,249 individuals demonstrated that cardiovascular risk factors, specifically blood pressure and body mass index (BMI), were increased in children and young adults born to preeclamptic pregnancies. Thus, preeclampsia and related complications may be associated with long-term sequelae in both the mother and infant.
Risk Factors
Risk factors for preeclampsia reflect the heterogeneous nature of the syndrome and can be broadly classified into pregnancy-specific characteristics and maternal pre-existing features ( Box 17.1 ).
Box 17.1
Risk Factors for Preeclampsia
Pregnancy-Specific Factors
-
Nulliparity
-
Partner-related factors: new paternity, limited sperm exposure (e.g., barrier contraception)
-
Multifetal gestation
-
Hydatidiform mole
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