The term, pregnancy-induced hypertension (PIH) has been used inconsistently to either broadly describe all new onset hypertension in pregnancy with or without accompanying proteinuria or it has been used interchangeably with the term, preeclampsia. Therefore, the term pregnancy-induced hypertension has been abandoned by classification systems used in the United States. This module incorporates this new classification system.²

The term, transient hypertension previously described a group of women with gestational hypertension that resolves during the postpartum period.⁵ Gestational hypertension is defined as blood pressure elevation with onset after 20 weeks’ gestation without proteinuria that often presents near term. Gestational hypertension may manifest for the first time postpartum, but resolves postpartum. Failure of blood pressure to normalize in the postpartum period (which is no longer specified to the specific postpartum day) constitutes chronic hypertension. The term, transient hypertension has been abandoned as well.²

Mild preeclampsia is no longer used to describe preeclampsia with the absence of severe manifestations because the Task Force on Hypertension in Pregnancy² believed it to misrepresent the dynamic and progressive nature of the disease. Even without severe manifestations, there remains a significant risk for morbidity and mortality. ACOG has further recommended that the term severe preeclampsia be replaced with preeclampsia with severe features for similar reasons.

OR

NOTE: Hypertension with an onset after 20 weeks’ gestation that fails to normalize postpartum changes the diagnosis to chronic hypertension.

NOTE: Although hypertensive disorders are discussed as separate diagnoses, recognition that preeclampsia may be superimposed upon gestational hypertension or chronic hypertension and progress to severe disease rapidly provides the foundation for ongoing assessment of these patients. Because the classification system is not precise and a missed diagnosis may lead to increased risk of adverse maternal and perinatal outcomes, a more prudent approach for clinical management is to overdiagnose preeclampsia.

Preeclampsia with severe features may be diagnosed with any of the following findings:

NOTE: Some clinical findings have been removed from the criteria for preeclampsia with severe features because they do not correlate with outcome or are not managed any differently than if the patient were not diagnosed with preeclampsia. The clinical findings that have been removed from consideration of severe disease include urine proteinuria greater than 5 g in 24 hours, intrauterine fetal growth restriction, and oliguria.

HELLP syndrome is a preeclampsia subtype; the acronym represents Hemolysis, Elevated Liver enzymes, and Low Platelets and is typically characterized by the following laboratory findings¹¹:

Preeclampsia is believed to originate from abnormal implantation of the placenta. Normally, through a complex process early in placental development, placental trophoblast cells invade the uterine spiral arteries, converting them from small, high-resistance vessels to dilated, low-resistance vessels, to increase placental circulation. This process of vascular growth, termed angiogenesis, is essential to sustain the fetus throughout the pregnancy.¹⁴ In pregnancies with preeclampsia, the partial invasion of trophoblasts into the superficial decidua fails to achieve this transformation, resulting in constricted and narrowed uterine arteries, compromising uteroplacental perfusion. Placental ischemia leads to the production of placental factors that enter the maternal circulation giving rise to widespread maternal endothelial dysfunction ensuing in a variety of manifestations of the disease from reduced end-organ perfusion.^2,11,14 Some of the placental factors released into the maternal circulation have received a great deal of attention; among them are inflammatory factors and antiangiogenic factors.² Antiangiogenic
proteins (soluble fms-like tyrosine kinase-1 [sFlt-1] and soluble endoglin) antagonize proangiogenic proteins (vascular endothelial growth factor [VEGF] and placental like growth factor [PLGF]), thereby reducing free levels of these proangiogenic proteins that normally stimulate uteroplacental vascular growth and dilation and maintain endothelial integrity.¹¹ Increased circulating levels of sFLT-1 precede the development of preeclampsia by weeks to months and are accompanied by decreased circulating-free PLGF and VEGF levels.^2,14 Appearance of these biomarkers is being further studied to determine their value in predicting preeclampsia.²

The cause of preeclampsia remains unknown. Yet many mechanisms have been proposed to establish the pathophysiologic progression from abnormal placentation to development of the maternal syndrome. Predominant pathophysiologic mechanisms that have been implicated in the disease process include^2,11 oxidative stress, an exaggerated inflammatory response, and altered coagulation.

Under normal conditions, maternal blood flow to the placenta increases oxygen tension along with an increase in antioxidant enzymes. In preeclampsia, there is a diminished antioxidant response to oxygen stimulation, leading to the generation of oxygen-free radicals that promote tissue damage with resultant neutrophil activation that extends the generation of cytotoxic superoxide ions and ultimately, activation of the vascular endothelium. Reduced antioxidant activity and increased oxidative stress in the placenta and in the maternal circulation¹⁵ have instigated clinical trials that study the role of antioxidants, such as Vitamin C and Vitamin E, in preventing preeclampsia. Further study may conclude a risk reduction for preeclampsia; until definitive data demonstrate a clear benefit, Vitamin C and Vitamin E supplements are not currently recommended.² The lipid profile in preeclamptic women (increased concentrations of serum free fatty acids, triglycerides, and very-low density lipoprotein [VLDL]) may predispose to oxidative stress. The VLDL particles are smaller in preeclamptic women when compared to normotensive women, which may facilitate their oxidative degradation.¹⁵

During normal pregnancy, the maternal immune system adaptations directed at establishing an immune tolerance to fetal antigens manifests as a systemic inflammatory response. Preeclampsia further enhances the immune response, as evidenced by elevated levels of proinflammatory mediators, interleukin-6, interleukin-8, tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein 1 (MCR-1).¹⁶ Neutrophil activation may contribute to vascular injury as a result of leukocyte adhesion to the endothelium, perpetuating the inflammatory response and promoting coagulation through uncontrolled activation of the complement system.¹⁷

Decreased placental perfusion and endothelial damage promote platelet aggregation and coagulation, resulting in an imbalance between vasoactive prostaglandins. Prostacyclin, a potent vasodilator and inhibitor of platelet aggregation, is normally produced by the vascular endothelium and renal cortex. In preeclampsia, a deficiency in prostacyclin is accompanied by an increase in thromboxane A₂ (TXA₂), a potent vasoconstrictor and platelet aggregator, which is produced by platelets and trophoblasts. The imbalance favoring TXA₂ suggests an exacerbation of the pathophysiologic derangements of preeclampsia,¹¹ leading to clinical trials examining the effects of low-dose aspirin in ameliorating the exaggerated inflammatory response by blocking the production of thromboxanes. Because of its protective effect, daily low-dose aspirin (60 to 80 mg) initiated in the late first trimester is recommended for women with significant risk for preeclampsia, primarily women with a medical history of early-onset preeclampsia and preterm birth at less than 34 0/7 weeks’ gestation or women with a history of preeclampsia in more than one prior pregnancy.²

The hypercoagulable state of normal pregnancy is potentiated in preeclampsia. Procoagulant proteins, such as tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), and von Willebrand are elevated while proteins that inhibit the coagulation cascade, including
anti-thrombin III, activated protein C, and protein S, are reduced. The compromise in placental perfusion may trigger fibrin deposition and formation of thrombi in the placental circulation, further worsening placental ischemia and resultant endothelial damage.⁷

Understanding the pathophysiology underlying the diagnostic signs and symptoms in preeclampsia facilitates a greater comprehension of the clinical manifestations and rationale for interventions. The primary pathophysiologic process underlying the multiorgan system involvement in preeclampsia is illustrated in Figure 11.1.

In response to the increased demands of normal pregnancy, significant physiologic adaptations occur in order to maintain maternal and fetal oxygenation. Among these physiologic changes are an increase in circulating blood volume, increase in cardiac output, and relaxation and dilation of systemic blood vessels; all directed at maximizing blood flow to maternal end-organs and the uteroplacental circulation.¹⁸ There is decreased end-organ perfusion in preeclampsia arising from endothelial dysfunction which further propagates oxidative stress and systemic inflammation. The disease process is progressive, often resulting in:

The spectrum of multisystem manifestations of preeclampsia include the following¹¹:

Decreased end-organ perfusion contributes to organ system derangements in preeclampsia, which are observed on a continuum that extends from a presentation without severe features to catastrophic organ system failure. Signs and symptoms that may possibly indicate progression in severity of the disease and that potentially end with adverse outcomes necessitate vigilant assessment.

WATCH FOR SIGNS OF THE FOLLOWING²¹: