Hypertensive Diseases in Pregnancy

Hypertensive Diseases in Pregnancy

Conisha M. Holloman

Baha M. Sibai


Hypertensive disorders of pregnancy affect approximately 10% of pregnancies. Globally, approximately 2% to 8% of pregnancies are complicated by preeclampsia. With its prevalence rising over the past decade, chronic hypertension (CHTN) affects up to 5% of pregnancies. The incidence of hypertensive disorders vary according to the population studied and the criteria used for diagnosis but is still one of the leading causes of maternal and perinatal mortality worldwide. In Latin America and the Caribbean, they are responsible for almost 26% of maternal deaths, which contrasts to the 9% of deaths in Africa and Asia. Despite maternal mortality being higher in lower to middle-income countries when compared to high-income counties, 16% of maternal deaths are attributed to hypertensive disorders in countries like the United States. Between 1987 and 2004, preeclampsia increased by 25% in the United States.1,2,3,4 Due to the increasing prevalence of baseline hypertension, obesity, and diabetes in women of childbearing age, and the increase in advanced maternal age mothers, this published rate may be an underestimate of the true incidence.5

Patients with hypertension in pregnancy have higher incidence of eclampsia, abruptio placentae, preterm delivery, disseminated intravascular coagulation (DIC), hemorrhage, pulmonary edema, renal insufficiency, stroke, and death. Apart from being the most common medical complication of pregnancy, hypertensive disorders are associated with significant maternal, fetal, and neonatal morbidity and mortality.6

Clinical Presentation

Classification of Hypertensive Disorders in Pregnancy

Numerous attempts have been made to classify hypertensive disorders of pregnancy. However, it is often difficult to differentiate between preeclampsia (hypertension with proteinuria diagnosed after 20 weeks of gestation), gestational hypertension (elevated blood pressures without symptoms or proteinuria after 20 weeks of gestation), CHTN (elevated blood pressure prior to conception or prior to 20 weeks of gestation), and CHTN with superimposed preeclampsia. In 2013, the American College of Obstetricians and Gynecologists’ (ACOG’s) Task Force on Hypertension in Pregnancy modified some of the components of the classification of hypertensive disorders and was reaffirmed by the 2019 ACOG Practice Bulletins on hypertension.2,7 The four categories comprising hypertension during pregnancy include the following: (1) preeclampsia-eclampsia, (2) CHTN (of any cause), (3) CHTN with superimposed preeclampsia, and (4) gestational hypertension. In order to recognize the syndromic nature of preeclampsia, the task force eliminated the requirement of proteinuria for the diagnosis of preeclampsia.8,9,10,11


Clinical Assessment

Preeclampsia is a syndrome primarily defined as new-onset hypertension that develops in the second half of pregnancy (after 20 weeks of gestation). Diagnostic criteria require the development of hypertension defined as a persistent systolic blood pressure (BP) of 140 mm Hg or greater or diastolic BP of 90 mm Hg or higher on two occasions at least 4 hours apart after 20 weeks gestation in a woman with previously normal blood pressure. The optimal measurement of BP is with the patient seated comfortably, with legs uncrossed, and arm and back supported so that the middle of the cuff on the upper arm is at the level of the atrium. Ideally, 5 to 10 minutes should pass before taking the blood pressure.12

Proteinuria is defined as the excretion of 300 mg or more of protein in a 24-hour urine collection or protein/creatinine ratio of at least 0.3 mg/dL. A urine dipstick protein of 2+ is also used as a surrogate marker when quantitative methods are unavailable (due to increased false-positive and false-negative results). Prior to 2013, proteinuria was a requirement for the diagnosis of preeclampsia, but it was later recognized that some patients have advanced disease before protein is detected in the urine. This criterion was removed in the 2013 ACOG Task Force and instead features of end-organ dysfunction were highlighted such as thrombocytopenia, liver or renal impairment, pulmonary edema, and neurologic or visual dysfunction.13 Although it is often accompanied with an acute development of proteinuria, preeclampsia can be associated with other signs and symptoms such as persistent headache, visual changes, right upper quadrant pain, epigastric pain, nausea, and vomiting. However, maternal symptoms, such as headache and right upper quadrant pain, may not always correlate with laboratory-confirmed abnormalities or have multiple etiologies.14,15

Preeclampsia is also classified in the presence or absence of severe features (Tables 27.1 and 27.2): blood pressure greater than 160 mm Hg systolic or 110 mm Hg diastolic, acute kidney injury with creatinine greater than 1.1 or an increase greater than twofold above the baseline, doubling of liver function tests, persistent or severe central nervous system symptoms, platelet count less than 100 × 109/L, and the presence of pulmonary edema. Severe proteinuria (≥5 g in a 24-hour urine collection) is no longer used because it does not correlate to outcomes.16,17


Significant strides have been made in the last 15 years to uncover the cause of preeclampsia. To date, the most likely mechanism of preeclampsia is believed to be due to placental ischemia following placental release of antiangiogenic factors into the circulation. In normal pregnancy, invasion of uterine arteries transforms cytotrophoblasts from an epithelial to an endothelial phenotype. This process is called pseudovasculogenesis (Figure 27.1). The remodeling is meant to increase the supply of oxygen and nutrients to the fetus. This is achieved by the cytotrophoblasts’ upregulated expression of molecules that are important to uterine inversion such as those from the vascular endothelial growth factor (VEGF) family (eg, VEGF-A, VEGF-C, and placental growth factor [PlGF]). The end result is cytotrophoblastic invasion of the uterine wall and replacement of the highly resistant uterine spiral arteries and arterioles with a low resistance vascular system. In preeclampsia, this process is thought to be defective (probably secondary to altered immunologic response at the fetal-maternal interface) and leads to ischemia. As a result, there is an excessive production of soluble Flt1 (sFlt-1) that binds in the blood to both the VEGF and PlGF. The state of high sFlt-1 and low VEGF/PlGF contributes to the development of hypertension.18,19,20,21,22

Several factors have been identified as predisposing to the development of preeclampsia and may be present prior to conception (Table 27.3) or may appear during pregnancy (Table 27.4).23 Clear racial differences can be noted in the United States in regard to the incidence and level of severity of preeclampsia.
African American women have a higher incidence of preeclampsia than Caucasian women and a threefold higher rate of maternal fatality. Disparities in access to health care combined with differences in comorbid conditions may be to blame for this stark difference.24


Clinical Presentation

Eclampsia is the occurrence of seizures or coma (not attributable to any other cause) in a woman with preeclampsia. It can occur during the antepartum period, during delivery, or in the postpartum period. More than 90% of cases occur at 28 weeks gestation or later. Up to 44% of cases of eclampsia take place in the postpartum period.25

Eclampsia is associated with multiorgan dysfunction. Factors determining the degree of dysfunction include a delay in the treatment of preeclampsia and the presence of complicating obstetric and medical factors. Prior to seizure development, the most common signs and symptoms are severe features such as elevated blood pressure, headache, visual changes, right upper
quadrant pain, and epigastric pain. However, some cases present without warning signs or symptoms. A small proportion of cases will occur despite normal blood pressure, but such cases will show other features of preeclampsia (proteinuria, elevated liver enzymes, etc). In one study, there were no preceding symptoms in 25% of women with eclampsia. Out of 20,000 patients, 21% experienced postpartum eclampsia.26 The seizures are usually generalized tonic-clonic in nature, lasting 60 to 90 seconds and followed by a postictal phase.10,27 Laboratory findings also vary. Serum uric acid and creatinine are usually elevated, and creatinine clearance is reduced. Hemoconcentration, reflected by an increased hematocrit and reduced plasma volume, is common as liver enzymes are found in 11% to 74% of eclamptic patients. HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome complicates approximately 10% of eclampsia and usually occurs in longstanding disease and in patients with medical complications.24

According to the World Health Organization, there is a reported increase in eclampsia from 0.1% to 0.8% in developed countries. This contrasts from the incidence of eclampsia in Western countries of 4 to 5 per 10,000 pregnancies.28 Other sources report the rate of eclampsia in high-income countries from 1.6 to 10 out of 10,000 deliveries with a case fatality rate of 1% and low-income countries with eclampsia rates from 91 to 157 out of 10,000 deliveries and a case fatality rate from 6.7% to 7.5%.Unfortunately, the factors responsible from improvements in eclampsia rates in high-income countries have not translated into low-income countries.29


The mechanisms responsible for the development of eclamptic seizures is not well understood.

Why some women with symptoms of preeclampsia develop convulsions or coma while others do not is unknown. There is evidence that elevated blood pressure can cause a disruption in the autoregulatory function of the cerebral circulatory system, resulting in either hypoperfusion or
hyperperfusion of the brain, endothelial dysfunction, and edema.30 Several mechanisms have been suggested as predisposing factors to the development of eclampsia:

  • Cerebral vasospasm;

  • Cerebral hemorrhage;

  • Cerebral ischemia;

  • Cerebral edema;

  • Hypertensive encephalopathy; and

  • Metabolic encephalopathy.

Clinical Assessment

Most women with eclamptic seizures have an abnormal electroencephalogram. However, electroencephalographic changes are almost always transient and resolve completely. The neurologic and cerebrovascular changes of eclampsia serve as a model for hypertensive encephalopathy, with the occipital and parietal zones most vulnerable. The similar pathogenetic events of forced vasodilation and altered cerebral autoregulation seen in hypertensive encephalopathy may be operative in eclampsia. However, an additional factor, such as endothelial cell dysfunction, seems to be present in eclampsia. Although routine neuroimaging studies are not advocated for all women with eclampsia, focal neurologic deficits or prolonged coma (atypical eclampsia) require prompt investigation.31

Preeclampsia and eclampsia may be associated with the development of posterior reversible encephalopathy syndrome (PRES). This syndrome is a result of the development of vasogenic cerebral edema and focal neurologic deficits. The signs and symptoms of PRES are reversible with treatment but with the possibility of permanent deficits.32 Imaging changes in PRES mainly involve the occipital lobe of the brain; therefore, visual changes are common. These include scotomata, hallucinations, diplopia, and blurred vision. Using magnetic resonance imaging (MRI), the PRES changes are hyperintense signals on T2 and fluid-attenuated inversion recovery sequences.33

HELLP Syndrome

Clinical Presentation

HELLP syndrome has been recognized as a complication of preeclampsia or eclampsia for many years (Table 27.5). Most experts consider HELLP syndrome to be a manifestation of preeclampsia rather than a distinct hypertensive pathology of pregnancy.8,33 A unique difference between preeclampsia and HELLP syndrome is that nulliparity is not a risk factor HELLP syndrome, and over 50% of patients developing HELLP syndrome are multiparous. Risk factors include a prior history of preeclampsia or HELLP syndrome, obesity, and <17 and >35 years of age. The pathophysiology of HELLP syndrome is similar to preeclampsia with a greater amount of hepatic inflammation and activation of the complement and coagulation cascades.34

The reported complication rate of HELLP syndrome is about 1% of all pregnancies and 10% to 20% of pregnancies with preeclampsia ranges. Typical symptoms include right upper quadrant/epigastric abdominal pain, nausea, and vomiting. In the series reported by Sibai, women with HELLP syndrome may present with a variety of signs and symptoms, none of which is diagnostic and all of which may be found in women with severe preeclampsia or eclampsia without HELLP syndrome.35 Nausea, vomiting, and epigastric pain are the most common symptoms. Right upper quadrant or epigastric pain is thought to result from obstructed blood flow in the hepatic sinusoids, which are blocked by intravascular fibrin deposition and capsular distention.35,36,37

About 15% to 50% of HELLP cases have mild hypertension, about 12% to 18% have no hypertension, and 13% of cases have no proteinuria.38 As a result, patients are often misdiagnosed as having
various medical and surgical disorders, including appendicitis, gastroenteritis, glomerulonephritis, pyelonephritis, viral hepatitis, or even acute fatty liver of pregnancy (AFLP).

Microangiopathic hemolytic anemia develops in response to destructive forces that act on red blood cells in small blood vessels, resulting in the formation of schistocytes. The exact mechanism for the cause of underlying liver hematoma with HELLP syndrome is not known. The speculated mechanism involves ischemic lesions of the liver secondary to the preeclampsia-associated microangiopathy, further progressing to hepatic necrosis and hemorrhage. The process of neovascularization in the affected parenchyma and newly formed vessels are more prone to bleeding with hypertensive episodes. The subcapsular hematoma is formed from intrahepatic hemorrhage that can rupture into the peritoneal cavity with hematoma expansion after hypertension or trauma.39

Clinical Assessment

The criteria for the diagnosis of HELLP syndrome can be found in Table 27.5: (1) hemolysis (abnormal peripheral blood smear, total bilirubin exceeding 1.2 mg/dL, and lactic dehydrogenase [LDH] > 600 U/L), (2) elevated liver enzymes (serum aspartate aminotransferase [AST] > 70 U/L, elevated alanine aminotransferase [ALT] and LDH > 600 U/L), and (3) low platelet count (<100,000/µL).40

Chronic Hypertension

CHTN is diagnosed if there is persistent elevation of blood pressure to at least 140/90 mm Hg on two occasions more than 24 hours apart prior to conception, prior to 20 weeks of gestation, or beyond 12 weeks postpartum.41 Other factors that may suggest the presence of CHTN include

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Jun 19, 2022 | Posted by in OBSTETRICS | Comments Off on Hypertensive Diseases in Pregnancy
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