Preeclampsia

Preeclampsia has typically been characterized by new-onset hypertension combined with new-onset proteinuria after 20 weeks’ gestation. It is a disorder that involves multiple systems and increases mortality and morbidity in both mothers and infants.¹ Preeclampsia complications include progression to eclampsia, renal failure, pulmonary edema, HELLP syndrome, disseminated intravascular coagulation, placental abruption, and fetal death. Preeclampsia is a leading cause of maternal death in the United States.²

In November 2013, the American College of Obstetricians and Gynecologists (ACOG) released an updated guideline for preeclampsia that changed the diagnostic criteria for the condition. The new guideline no longer includes proteinuria as essential criterion for diagnosis of preeclampsia. ACOG also removed massive proteinuria (5 g/24 hr) and fetal growth restriction as features of severe preeclampsia. In addition, ACOG no longer considers oliguria a characteristic of advanced disease.³

Incidence and Prevalence
The incidence of preeclampsia is approximately 2% to 6% in nulliparous women with otherwise healthy pregnancies in the United States. Of those cases, 10% occur prior to 34 weeks’ gestation. Preeclampsia occurs in 5% to 14% of all pregnancies worldwide.⁴ Women 35 and older have the greatest risk.^4,5 In low- to middle-income countries, approximately 10% to 15% of maternal deaths are associated with preeclampsia and eclampsia.²

SEE ALSO: Perinatal Nurse Staffing

Pathophysiology
The exact pathophysiology of preeclampsia is not completely understood. However, it is widely accepted that the disorder begins in the placenta. In the early stages of pregnancy, fetal chorionic villi makes contact with the uterine wall and generate columns of cytotrophoblasts that invade the uterine wall. At 10 to 12 weeks’ gestation, the cytotrophoblasts invade the decidual segments of the spiral arteries. At 15 to 16 weeks, the invasion goes deeper into the myometrium. In preeclampsia, this further invasion of cytotrophoblasts into the myometrial arteries is abnormal, and the spiral arteries become narrowed and resistive. This results in hypoperfusion of the placenta, which prompts oversecretion of placental antiangiogenic peptides. These overabundant peptides can cause end-organ preeclampsia manifestations.⁶

History
Risk factors (with odds ratios if available) include age older than 40 (3:1); black race (1.5:1); nulliparity (3:1); twin gestation (4:1); family history of pregnancy-induced hypertension (5:1); chronic hypertension (10:1); chronic renal disease (20:1); diabetes mellitus (2:1); interpregnancy interval less than 2 years or more than 10 years; preeclampsia or gestational hypertension in a prior pregnancy; use of selective serotonin reuptake inhibitors beyond first trimester; maternal infections; mother born small for gestational age; and past medical history of obesity, thrombophilia, systemic lupus erythematosus, migraines and hyperlipidemia.^4,6

Women with preeclampsia may present with complaints of visual disturbances, new severe headache, epigastric pain, and new or progressing edema of the extremities or face.³ They may also complain of retrosternal chest pain, nausea and vomiting, shortness of breath, altered mental status, bleeding from mucosal membranes, and jaundiced skin.⁷ Since these symptoms can be obscure, a complete differentials list should always be considered.

Differential Diagnoses^3,4,7
Closely related differential diagnoses for preeclampsia include the following:

• Chronic/preexisting hypertension: characterized by hypertension preceding pregnancy
• Gestational hypertension: blood pressure elevation after 20 weeks’ gestation without proteinuria or other systemic findings associated with preeclampsia
• Eclampsia: characterized by seizures not attributable to other diagnoses in a woman with preeclampsia

Other differential diagnoses include, but are not limited to:

• Chronic renal failure
• Acute cause of abdominal pain: cholecystitis or appendicitis
• Cholelithiasis
• Headache
• Transient ischemic attack
• Cerebrovascular accident
• Seizure disorder
• Functional proteinuria
• Thrombotic thrombocytopenic purpura
• Metastatic disease.

Physical Findings and Diagnosis
At all office visits by pregnant women, vital signs and weight should be obtained. Blood pressure should be measured with the woman comfortably seated, relaxed, not talking, legs uncrossed, back supported, and arm placed such that the middle of the cuff is at the level of the right atrium.³

In a woman with preeclampsia, generalized or facial edema, or a weight gain of more than 2 pounds per week, may occur.⁸ Examine the skin for jaundice, petechiae or ecchymosis. Palpate the abdomen to assess for a fundal height that is less than expected for gestational age, enlarged liver, and abdominal pain in the right upper quadrant. In severe preeclampsia, hyperreflexia with or without clonus may be observed in the neurological examination.

Any pregnant woman presenting with new-onset hypertension should undergo the following laboratory tests: complete blood cell count, serum alanine aminotransferase, aspartate aminotransferase, serum creatinine, and uric acid. A 24-hour urine protein analysis or a urine dipstick should be obtained.

Diagnosis is made based on patient history, physical findings and lab results. Table 1 shows the essential diagnostic criteria set by ACOG for preeclampsia. In contrast to previously published guidance, ACOG removed proteinuria as an essential criterion.^3,9 However, preeclampsia should not be ruled out for women presenting with hypertension without proteinuria. If proteinuria is absent, end-organ dysfunction such as renal or hepatic compromise, thrombocytopenia, pulmonary edema or cerebral symptoms warrant diagnosis.³

Extreme proteinuria has a poor correlation with outcome, and fetal growth restriction has a consistent management whether or not preeclampsia is diagnosed.³ Therefore, ACOG has removed both proteinuria > 5 grams/24 hours and fetal growth restriction as possible features of severe preeclampsia. Oliguria has also been removed as a feature of advanced disease.^3,9 Table 2 lists the clinical features of severe preeclampsia as defined by ACOG.

Predicting Preeclampsia
According to ACOG, no single test reliably predicts the occurrence of preeclampsia.³ Antiangiogenic factors, such as soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (P1GF) and soluble endoglin early in the second trimester, may act as biomarkers for prediction of early onset preeclampsia.³ Combining the presence of biomarkers with uterine artery Doppler studies provides the best predictive accuracy for identifying early-onset preeclampsia.¹⁰ However, these biomarkers are not available for clinical use since they are not approved by the Food and Drug Administration.³

Implications for Primary Care
Providers in the primary care setting should be alert to the possibility of preeclampsia in all pregnant patients. Women with new-onset hypertension should always be evaluated for preeclampsia, even in the absence of proteinuria. Women in the primary care setting with gestational hypertension should have weekly clinic visits for blood pressure and urine protein monitoring. A second weekly blood pressure reading should be taken at home for closer monitoring. For mild gestational hypertension or preeclampsia (SBP < 160 mm Hg or DBP < 110 mm Hg), antihypertensive medication is not recommended.³

The ACOG task force on hypertension in pregnancy does not recommend screening to predict preeclampsia beyond the medical history. However, if a patient has past medical history of early-onset preeclampsia and preterm delivery at less than 34 weeks’ gestation or a history of preeclampsia in more than one pregnancy, ACOG recommends initiating the administration of daily low-dose aspirin (60 mg to 80 mg) beginning in the first trimester.

The World Health Organization (WHO) also recommends initiation of aspirin prophylaxis (75 mg) prior to 20 weeks’ gestation for women with increased risk factors.¹¹ According to a prospective study of 614 women, the development of preeclampsia while on aspirin prophylaxis is more likely to be associated with elevated blood pressure during the first trimester.¹² Early monitoring of blood pressure in women with increased risk is vital.

WHO recommends calcium supplementation of 1.5 g to 2.0 g elemental calcium daily for prevention of preeclampsia in all women who live where dietary calcium intake is low.¹¹ The ACOG task force and WHO do not recommend administration of vitamin C, D or E, dietary salt restriction, prophylactic diuretic use, or strict bed rest/activity restriction for prevention of preeclampsia.^3,11

Best evidence recommends hospitalization and induction for suspected preeclampsia in any of the following scenarios: 37 weeks or more gestation; suspected abruption placentae; and 34 weeks or more gestation plus progressive labor or rupture of membranes; ultrasonographic estimate of fetal weight less than the 5th percentile; and oligohydramnios and/or persistent biophysical profile 6/10 or less.

WHO recommends induction of labor for severe preeclampsia at any gestational age when the fetus is not viable and unlikely to become viable within 1 to 2 weeks.¹¹ For women who do not deliver, care can be managed inpatient or outpatient with serial maternal and fetal evaluation.^3,11

Primary care providers, including nurse practitioners and physician assistants, can provide education to women at risk for preeclampsia. They can also be the first line of defense for early detection and initiation of management. By understanding the latest evidence and guidelines provided by ACOG and WHO, primary care providers can play a vital role in preventing devastating complications of preeclampsia.

Christan Santos is a recent graduate of the family nurse practitioner program at the University of North Florida.

References
1. Hutcheon JA, et al. Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol. 2011;25(4):391-403.

2. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33(3):130-137.

3. American College of Obstetricians and Gynecologists. Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Members only document. http://www.acog.org/Resources_And_Publications/Task_Force_and_Work_Group_Reports/Hypertension_in_Pregnancy

4. Lim KH, Steinberg G. Preeclampsia. http://emedicine.medscape.com/article/1476919-overview

5. Ananth CV, et al. Pre-eclampsia rates in the United States, 1980-2010: Age-period-cohort analysis. BMJ. 2013;347:f6564.

6. Vest AR, Cho LS. Hypertension in pregnancy. Curr Atheroscler Rep. 2014;16(3):395.

7. Sibai BM, Stella CL. Diagnosis and management of atypical preeclampsia-eclampsia. Am J Obstet Gynecol. 2009;200(5):481:e1-e7.

8. Sibai BM. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol. 2005;105(2):402-410.

9. American College of Obstetricians and Gynecologists. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Int J Gynaecol Obstet. 2002;77(1):67-75.

10. Giguere Y, et al. Combining biochemical and ultrasonographic markers in predicting preeclampsia: A systematic review. Clin chem.2010;56(3):361-375.

11. World Health Organization. WHO recommendations for prevention and treatment of preeclampsia and eclampsia. http://whqlibdoc.who.int/publications/2011/9789241548335_eng.pdf

12. Block-Abraham D, et al. First-trimester risk factors for preeclampsia development in women initiating aspirin by 16 weeks of gestation. Obstet Gynecol. 2014;123(3):611-617.