Lana K. Wagner, Larry Leeman, and Sarah Gopman
Summary Preeclampsia is a multi-organ disease that is specific to pregnancy and is charac-terized by the development of proteinuria and hypertension. It complicates 5–7% of pregnan-cies and specific criteria must be met for diagnosis. The exact etiology or pathophysiology of preeclampsia is poorly understood and as such, there are no well-established methods of primary prevention or of reliable and cost-effective screening. Calcium and aspirin may have a role in preventing preeclampsia in certain subpopulations, and research continues regarding these and other possible nutritional interventions. Preeclampsia is associated with increased maternal mortality and morbidity, and childbirth is the only known cure. Women with preeclampsia need to have regular surveillance. The associated hypertension may war-rant treatment under certain conditions and magnesium sulfate is the drug of choice for the prevention and treatment of eclamptic seizures.
Keywords: Preeclampsia, Eclampsia, Hypertensive disorders of pregnancy, Gestational hypertension
11.1 INTRODUCTION
Preeclampsia is a multi-organ disease that occurs after 20 weeks gestation and is characterized by the development of proteinuria and hypertension. It is specific to pregnancy and complicates 5–7% of pregnancies [1]. It falls into the larger category of hypertensive disorders of pregnancy, which is addressed briefly within this chapter. The exact etiology or pathophysiology of this disorder is poorly understood. Additionally, there are no well-established methods of primary prevention or of reliable and cost-effective screening. Yet, preeclampsia is associated with increased maternal mortality and morbidity including placental abruption, acute renal failure, cerebrovascular and cardiovascular complications, and disseminated intravascular coagulation [2].
11.2 HYPERTENSIVE DISORDERS OF PREGNANCY
Complications from hypertension are a leading cause of pregnancy-related deaths, ranking third behind hemorrhage and embolism [2]. Hypertensive disorders that may be found during pregnancy include chronic hypertension, preeclampsia–
From: Nutrition and Health: Handbook of Nutrition and Pregnancy
Edited by: C.J. Lammi-Keefe, S.C. Couch, E.H. Philipson © Humana Press, Totowa, NJ 155
eclampsia, preeclampsia superimposed on chronic hypertension, and gestational hypertension [3].
Chronic hypertension is hypertension that exists outside of the pregnancy. As such, it will predate the pregnancy, be documented prior to 20 weeks, or will still be present 12 weeks after delivery [3]. Treatment of mild-to-moderate chronic hypertension during pregnancy has not been shown to prevent preeclampsia and has shown no proven fetal benefit [4–6].
Preeclampsia–eclampsia is the onset of hypertension with proteinuria that occurs after 20 weeks of pregnancy. Eclampsia, which occurs in less than one percent of women with preeclampsia [1], is the new onset of seizures during preeclampsia.
If a patient has chronic hypertension but develops new or worsened proteinuria, then this is preeclampsia superimposed on chronic hypertension [7]. Also, if there is an acute increase in the hypertension (assuming preexisting proteinuria) or if HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome develops, then this is also considered to be preeclampsia superimposed on chronic hypertension [7].
Gestational hypertension, which used to be known as “pregnancy induced hyper-tension,” [3] is hypertension that develops in the absence of proteinuria. Gestational hypertension develops after 20 weeks of pregnancy and returns to normal within 12 weeks of delivery [7].
11.3 DIAGNOSIS OF PREECLAMPSIA
As mentioned previously, both proteinuria and hypertension after 20 weeks of gestation must be present for a diagnosis of preeclampsia to be made. The diagnostic criteria for preeclampsia are presented in Table 11.1. Blood pressures should be measured with an appropriately sized cuff, with the patient in an upright position [8]. Edema and blood pressure elevations above the patient’s baseline are no longer included in diagnostic criteria [3, 7].
In severe preeclampsia, blood pressures may be higher and proteinuria more pronounced. The diagnostic criteria for severe preeclampsia are also presented in Table 11.1.
Any signs or symptoms indicating end organ damage make the diagnosis of severe preeclampsia.
Although 24-h urine collections are the gold standard for measuring proteinuria, a random urinary protein-to-creatinine ratio can rule out significant proteinuria if the ratio is less than 0.19 [9]. The urine protein-to-creatinine ratio using the 0.19 cutoff has a sensitivity of 90%, specificity of 70%, and a negative predictive value of 87% [9].
11.4 PATHOPHYSIOLOGY AND RISK FACTORS
The etiology of preeclampsia remains poorly understood. Multiple theories have been proposed regarding the pathophysiology, and no single causal factor has been found [10].
Theories of pathophysiology include genetic predisposition [11–14], abnormal placental implantation [15, 16], angiogenic factors [17], exaggerated inflammatory responses [18], inappropriate endothelial activation [18], vasoconstriction [19], and coagulation cascade defects [19]. Although hypertension and proteinuria are the criteria by which preeclampsia is diagnosed, the pathophysiologic changes associated with preeclampsia affect virtually every organ system. Microthrombi from activation of the coagulation
Chapter 11 / Preeclampsia 157
cascade, as well as systemic vasospasm, decrease blood flow to organs [19]. Perfusion is further compromised by vascular hemoconcentration and third spacing of intravascular fluids [18].
Risk factors for preeclampsia are presented above in Table 11.2 [20]. Note that young maternal age is no longer considered a risk factor, as this was not supported by a sys-tematic review [20]. Women with preeclampsia should be counseled about the increased risk of recurrent preeclampsia in future pregnancies. The recurrence rate may be as high as 40% in nulliparous women with preeclampsia before 30 weeks gestation and even higher in multiparous women [3].
Table 11.1
Diagnostic Criteria for Preeclampsia and Severe Preeclampsia [3, 7]
Preeclampsiaa Severe preeclampsiab Blood pressurec 140 mmHg or higher systolic 160 mmHg or higher systolic
Or 90 mmHg or higher diastolic
110 mmHg or higher diastolic Proteinuria 0.3 grams or more in a 24-h urine 5 g or more in a 24-h urine
(this usually corresponds with Or
a 1+ or greater on dipstick) 3+ or more on two random urine samples collected at least 4 h apart Other features Oliguria (less than 500 ml of urine in
24 h)
Cerebral or visual disturbances Pulmonary edema or cyanosis Epigastric or right
upper-quadrant pain
Impaired liver function
Thrombocytopenia
Fetal growth restriction
a Both hypertension and proteinuria components must be present
b One or more must be present in addition to criteria for preeclampsia
c Taken on two occasions at least 6 h apart
Table 11.2
Risk Factors for Preeclampsia [20]
Increased maternal age (>40 years of age) Nulliparity
Multiple gestation
Preeclampsia in a prior pregnancy Elevated body mass index Certain medical conditions:
Chronic hypertension Chronic renal disease Antiphospholipid syndrome Diabetes mellitus
11.5 PREVENTION AND NUTRITION
As was stated earlier, there are no well-established methods of primary prevention for preeclampsia, although numerous supplements have been studied regarding their ability to impact its occurrence. Thus far, randomized controlled trials do not support routine prenatal supplementation with magnesium, omega-3 fatty acids, antioxidants (vitamins E and C), or calcium to prevent preeclampsia [21–24].
However, calcium and aspirin may have a role in preventing preeclampsia in certain subpopulations, though the optimal treatment regimens will require further research.
Calcium supplementation in high-risk women and in women with low dietary calcium intakes reduced the risk of hypertension and preeclampsia [25]. Also, calcium supple-mentation has been shown to decrease the incidence of neonatal mortality and severe maternal morbidity due to hypertensive disorders when given to normotensive nullipa-rous women [26].
Low-dose aspirin was shown to have small to moderate benefits for prevention of preeclampsia within certain groups of women. A Cochrane analysis demonstrated that in women at increased risk for preeclampsia, 69 women would need to be treated with low-dose aspirin to prevent one case of preeclampsia [27]. However, in the subgroup of women at highest risk for preeclampsia (because of histories of previous severe preeclampsia, diabetes, chronic hypertension, renal disease, or autoimmune disease), only 18 would need to be treated with low-dose aspirin to prevent one case of preeclampsia [27].
Research continues regarding possible nutritional interventions for preeclampsia.
While larger studies that are more reliable are needed to confirm results, diets high in fiber and potassium may reduce the risk of preeclampsia [28]. Additionally, diets high in calories, sucrose, and polyunsaturated fatty acids may increase the risk for preeclampsia [29].
11.6 MANAGEMENT OF PREECLAMPSIA
Childbirth is the cure for preeclampsia as the disease process usually resolves within days of delivery. Delivery is always preferable from the perspective of maternal health.
However, decisions on induction of labor or cesarean delivery must include a considera-tion of prematurity-related neonatal risks and the severity of the preeclampsia. Women with mild preeclampsia should be carefully followed until they are close to term and delivered at 37–39 weeks [30]. Women with severe preeclampsia may be expectantly managed until 32–34 weeks, or delivered sooner based on maternal and fetal status [31].
Women with preeclampsia need to have regular surveillance of the fetus with nonstress testing and amniotic fluid volume assessment. Blood work should be checked periodi-cally to detect renal or hepatic involvement, hemolysis, or thrombocytopenia.
The hypertension of preeclampsia only warrants treatment if the systolic blood pres-sure is above 160 mmHg or the diastolic blood prespres-sure is above 110 mmHg [3]. If these pressures occur near term, then the blood pressure may be managed with intravenous hydralazine or labetalol until delivery [32]. Women with severe preeclampsia undergo-ing expectant management may have their blood pressure controlled with oral labetalol, methyldopa, or nifedipine [3]. Magnesium sulfate is the drug of choice for the preven-tion and treatment of eclamptic seizures [33]. All women with severe preeclampsia need intravenous magnesium in labor and for 24 h postpartum [34]. The use of magnesium
Chapter 11 / Preeclampsia 159 sulfate in women with mild preeclampsia remains controversial, as 400 women may need to be treated to prevent one eclamptic seizure [35].
Neonatal morbidity and mortality is due to the risk of prematurity, uteroplacental insufficiency, or placental abruption. An ultrasound for estimated fetal weight should be done at the time of diagnosis to evaluate for possible intrauterine growth restriction secondary to uteroplacental insufficiency [3]. If delivery is required prior to term, then the birth should occur at an institution with a neonatal intensive care unit capable of caring for infants at the anticipated gestational age. Placental abruption is an unpredict-able event, which can lead to fetal death or morbidity.
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