HYPERTENSION IN PREGNANCY

By : Febriani Valentina 030.07.091 FACULTY OF MEDICINE TRISAKTI UNIVERSITY JAKARTA 2010

CHAPTER I INTRODUCTION

Hypertension or High blood pressure, defined as a repeatedly elevated blood pressure exceeding 140 over 90 mmHg -- a systolic pressure above 140 with a diastolic pressure above 90. There are 2 types of chronic hypertension: essential hypertension and secondary hypertension. We do not know the cause of essential hypertension, but because hypertension commonly runs in families, we know that genes are involved. A minority of individuals have secondary hypertension, which means that the hypertension is explained by another condition such as kidney disease, narrowing of the artery to the kidney, and adrenal tumors. In many such cases, the hypertension will resolve after treatment for the underlying problem. If you are undergoing evaluation for a secondary form of hypertension, it is advisable to be treated for the underlying condition before becoming pregnant. A third type of hypertension is called pregnancy-induced hypertension. Some women develop new-onset hypertension in pregnancy, which can present in the second half of pregnancy, usually in the third trimester. Many women have been diagnosed with hypertension (blood pressure >140/90 mm Hg) when they were in their childbearing years. Because the hypertension predates the pregnancy, it is called chronic hypertension. This type of hypertension complicates at least 5% of all pregnancies. When managed appropriately, most women with chronic hypertension can experience healthy pregnancies and give birth to healthy babies. To accomplish this goal, it is important that women with chronic hypertension let their doctors know when they are planning a pregnancy so that they can receive pregnancy counseling and so that adjustments to antihypertensive medications can be made if needed.
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A more worrisome complication of chronic hypertension is the development of superimposed preeclampsia. Preeclampsia is a serious condition that can affect many organ systems and cause liver dysfunction, kidney failure, and an increase in bleeding tendency, and at times it can progress to eclampsia seizures. Superimposed preeclampsia is more likely to occur in women who have poorly controlled hypertension, underlying renal disease, and diabetes mellitus. At present, there is no treatment for preeclampsia except for delivery of the baby; therefore, babies of women who have this condition are frequently born prematurely. Another complication of chronic hypertension that may cause premature birth is placental abruption. An abruption is an early separation of the placenta from the wall of the uterus, usually leading to strong contractions, bleeding, and early delivery. Early delivery is associated with prematurity. If an early delivery is planned, your body may not be ready to deliver the baby vaginally, so there is a greater chance that you might need a cesarean section. Hypertension may also affect the development of the placenta, which is important for the nourishment and growth of the fetus. Thus, some babies may be affected by low amniotic fluid levels and/or intrauterine growth restriction. Preeclampsia occurs in up to 5% of all pregnancies, in 10% of first pregnancies, and in 20-25% of women with a history of chronic hypertension. Hypertensive disorders in pregnancy may cause maternal and fetal morbidity, and they remain a leading source of maternal mortality.

CHAPTER II HYPERTENSION IN PREGNANCY 1. Background Hypertension is the most common medical problem encountered during pregnancy, complicating 2-3% of pregnancies. Hypertensive disorders during pregnancy are classified into 4 categories, as recommended by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy: 1) chronic hypertension, 2) preeclampsia-eclampsia, 3) preeclampsia superimposed on chronic hypertension, and 4) gestational hypertension (transient hypertension of pregnancy or chronic hypertension identified in the latter half of pregnancy).1

This terminology is preferred over the older but widely used term pregnancyinduced hypertension (PIH) because it is more precise.

The Society of Obstetricians and Gynecologists of Canada (SOGC) recently released revised guidelines that simplified the classification of hypertension in pregnancy into 2 categories, preexisting or gestational, with the option to add "with preeclampsia" to either category if additional maternal or fetal symptoms, signs, or test results support this. 2

Chronic hypertension is defined as blood pressure exceeding 140/90 mm Hg before pregnancy or before 20 weeks' gestation. When hypertension is first identified during a woman's pregnancy and she is at less than 20 weeks' gestation, blood pressure elevations usually represent chronic hypertension. In contrast, new onset of elevated blood pressure readings after 20 weeks' gestation mandates the consideration and exclusion of preeclampsia. Preeclampsia occurs in up to 5% of all pregnancies, in 10% of first pregnancies, and in 20-25% of women with a history of chronic hypertension. Hypertensive disorders in pregnancy may cause maternal and fetal morbidity, and they remain a leading source of maternal mortality.

2. Epidemiology In United States, Chronic hypertension occurs in up to 22% of women of childbearing age, with the prevalence varying according to age, race, and body mass index. Population-based data indicate that approximately 1% of pregnancies are complicated by chronic hypertension, 5-6% by gestational hypertension (without proteinuria), and 1-2% by preeclampsia.

Black women have higher rates of preeclampsia complicating their pregnancies compared with other racial groups, mainly because they have a greater prevalence of underlying chronic hypertension. Among women aged 30-39 years, chronic hypertension is present in 22.3% of African Americans, 4.6% of non-Hispanic white persons, and 6.2% of Mexican Americans. Hispanic women generally have blood pressure levels that are the same as or lower than those of non-Hispanic white women.
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Table 1.Study characteristics and incidence of pre-eclampsia/eclampsia in developing and developed countries.( * Placebo group only, NR:not reported)

Country Jamaica Saudi Arabia Zimbabwe

Year 1992-94 1994 1992-95

No of women(n) 3026* 10407 51206

Incidence of Pre-eclampsia (%) 6.3 1.68 7.1

Incidence of Eclampsia (%) NR NR NR

Colombia Norway UK Barbados

1993-95 1967-98 1992 1992-94

20277 1869388 774436 1822*

NR 2.77 NR 2.2

0.81 NR 0.049 NR

3. Pathophysiology 3.1. Chronic Hypertension Chronic hypertension may be either essential (90%) or secondary to some identifiable underlying disorder, such as renal parenchymal disease (eg, polycystic kidneys, glomerular or interstitial disease), renal vascular disease (eg, renal artery stenosis, fibromuscular dysplasia), endocrine disorders (eg, adrenocorticosteroid or mineralocorticoid excess, pheochromocytoma, hyperthyroidism or hypothyroidism, growth hormone excess,

hyperparathyroidism), coarctation of the aorta, or oral contraceptive use.

About 20-25% of women with chronic hypertension develop preeclampsia during pregnancy.

3.2.

Pre-eclampsia Although the exact pathophysiologic mechanism is not clearly understood, preeclampsia is primarily a disorder of placental dysfunction leading to a syndrome of endothelial dysfunction with associated vasospasm. In mo st cases, pathology demonstrates evidence of placental insufficiency with associated abnormalities such as diffuse placental thrombosis, an inflammatory placental decidual vasculopathy, and/or abnormal

trophoblastic invasion of the endometrium. This supports abnormal placental development or placental damage from diffuse microthrombosis as being central to the development of this disorder.

The widespread endothelial dysfunction may manifest as a maternal syndrome, fetal syndrome, or both. Endothelial damage leads to pathologic capillary leak that can present in the mother as rapid weight gain, nondependent edema (face or hands), pulmonary edema,

hemoconcentration, or a combination thereof. The diseased placenta can also affect the fetus via decreased utero-placental blood flow. This decrease in perfusion can manifest clinically as nonreassuring fetal heart rate testing, low scores on a biophysical profile, oligohydramnios, or as fetal growth restriction. The hypertension occurring in preeclampsia is due primarily to vasospasm, with arterial constriction and relatively reduced intravascular volume
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compared to normal pregnancy. The vasculature of normal pregnant women typically demonstrates decreased responsiveness to vasoactive peptides such as angiotensin-II and epinephrine. In contrast, women who develop preeclampsia typically show a hyperresponsiveness to these hormones, an alteration that may be seen even before the hypertension and other manifestations of preeclampsia become apparent. In addition, blood pressures in preeclampsia are labile, and the normal circadian blood pressure rhythms may be blunted or reversed. One study found increased arterial stiffness in women with preeclampsia, as well as in those with gestational hypertension, compared with normotensive controls; treatment with alpha methyldopa significantly improved the vascular stiffness in preeclampsia but did not normalize it.3

3.3.

Gestational Hypertension Gestational hypertension refers to hypertension with onset in the latter part of pregnancy (>20 weeks gestation) without any other features of preeclampsia, and followed by normalization of the blood pressure postpartum. Of women who initially present with apparent gestational hypertension, about one third develop the syndrome of preeclampsia. As such, these patients should be observed carefully for this progression. The pathophysiology of gestational hypertension is unknown, but in the absence of features of preeclampsia, the maternal and fetal outcomes are usually normal. Gestational hypertension may, however, be a harbinger of chronic hypertension later in life.

4. Clinical 4.1. Symptoms of Pre-eclampsia 4.1.1. Visual disturbances 4.1.2. Headache or similar to a migraine headache. 4.1.3. Epigastric pain 4.1.4. Mild lower extremity edema 4.1.5. Rapid weight gain

4.2. Physical 4.2.1. Blood pressure 4.2.1.1. Blood pressure should be measured in the sitting position, with the cuff at the level of the heart. Inferior vena caval compression by the gravid uterus while the patient is supine can alter readings substantially, leading to an underestimation of the blood pressure. Blood pressures measured in the left lateral position similarly may yield falsely low values if the blood pressure is measured in the higher arm, unless the cuff is carefully maintained at the level of the heart. 4.2.1.2. Many automated blood pressure cuffs provide reasonable estimates of true blood pressure during normal pregnancy (especially those validated for pregnancy) but tend to underestimate blood pressure in preeclamptic women. Only a few automated BP cuffs have been validated in preeclampsia. Manual blood pressure

measurement with a mercury sphygmomanometer remains the criterion standard in this setting. 4.2.1.3. Home and ambulatory BP measurements are increasingly being used in the pregnant population. Assuming the BP device is accurate (validated relative to an office measurement) they may provide valuable additional data regarding hypertension severity and control during pregnancy. 4.2.2. Retinal vasospasm is a severe manifestation of maternal disease; consider delivery. 4.2.3. Retinal edema is known as serous retinal detachment. This can manifest as severely impaired vision if the macula is involved. It generally reflects severe preeclampsia and should lead to prompt consideration of delivery. The condition typically resolves upon completion of pregnancy and resolution of the hypertension and fluid retention. 4.2.4. Right upper quadrant (RUQ) abdominal tenderness stems from liver swelling and capsular stretch. Consider delivery. 4.2.5. Brisk, or hyperactive, reflexes are common during pregnancy. Clonus is a sign of neuromuscular irritability that usually reflects severe preeclampsia. 4.2.6. In most normal pregnancies, the woman has some lower extremity edema by the third trimester. In contrast, a sudden worsening in dependent edema, edema in nondependent areas (such as the face and hands), or rapid weight gain suggest a pathologic process and warrant further evaluation for preeclampsia.
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5. Investigation 5.1. Laboratory Studies 5.1.1. Laboratory testing to evaluate chronic hypertension includes testing for target organ damage, potential secondary causes of hypertension, and other risk factors. 5.1.1.1. Studies include: urinalysis; CBC; and serum sodium, potassium, creatinine, and glucose levels 5.1.1.2. Other suggested tests include creatinine clearance,

microalbuminuria, 24-hour urinary protein, serum calcium, uric acid, glycosylated hemoglobin, thyroid-stimulating hormone (TSH), and an ECG. 5.1.1.3. Serum lipids predictably increase during pregnancy, so

measurement should be deferred until the postpartum period. 5.1.1.4. The increase in endogenous corticosteroid levels during normal pregnancy makes it difficult to evaluate for secondary hypertension due to adrenal corticosteroid excess. 5.1.2. Routine tests when evaluating a patient for preeclampsia include: CBC count, electrolytes, BUN, creatinine, liver enzymes and bilirubin, and a urine dip for protein. 5.1.3. Researchers in the United Kingdom have developed a method for firsttrimester screening to identify women at risk for the development of preeclampsia or gestational hypertension. The screening algorithm uses a combination of maternal variables, including mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein
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A, and placental growth factor. The algorithm proved especially effective for predicting early preeclampsia (ie, requiring delivery before 34 weeks).4

5.2. Imaging Studies 5.2.1. Chest radiograph

Obtain chest radiographs to evaluate for pulmonary edema in the setting of dyspnea or hypoxia occurring in a woman with preeclampsia.

5.2.2. CT scan of the brain 5.2.3. MRI of the brain 5.2.4. Ultrasonography or CT scan of the liver 5.2.5. Limited echocardiography may be performed to evaluate for left ventricle hypertrophy (LVH) in chronic hypertension. 5.2.6. Electroencephalogram 5.2.7. Fetal monitoring

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6. Treatment 6.1. Medical Care If a pregnant womans blood pressure is sustained greater than 160 mm Hg systolic and/or 110 mm Hg diastolic at any time, lowering the blood pressure quickly with rapid-acting agents is indicated for maternal

safety. Anticonvulsant therapy may be undertaken in the setting of severe preeclampsia (primary prophylaxis) or in the setting of eclamptic seizures (secondary prophylaxis). The most effective agent is IV magnesium sulfate; phenytoin is an alternative, although less effective, therapy. Evidence-based guidelines from the American Association of Clinical Endocrinologists single out methyldopa, labetalol or nifedipine as preferable antihypertensive medications in pregnancy, with magnesium sulfate for women with preeclampsia who are at high risk for seizures, but they recommend all major antihypertensive agents with the exception of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs).5 ACE inhibitors should be avoided during pregnancy, as they are associated with fetal renal dysgenesis or death when used in the second and third trimesters and with increased risk of cardiovascular and central nervous system malformations when used in the first trimester.6 Angiotensin II receptor antagonists/blockers are not used during pregnancy because they have a mechanism of action similar to that of ACE inhibitors. Diuretics do not cause fetal malformations but are generally avoided in pregnancy, as they prevent the physiologic volume expansion seen in normal pregnancy. They

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may be used in states of volume-dependent hypertension, such as renal or cardiac disease.

6.2. Non-medical 6.2.1. Consultation

Women with chronic hypertension in pregnancy should be monitored by an obstetrician. Women with moderate or severe hypertension may benefit from referral to an experienced internist (obstetric medicine specialist), hypertension subspecialist, and/or a specialist in maternalfetal medicine (perinatologist).

6.2.2. Diet Multiple dietary interventions and supplements have been investigated for a role in preventing preeclampsia, but none has shown any consistent beneficial effect.

6.2.3. Activity

Women with worsening hypertension during pregnancy often are placed on bed rest or restricted activity, although no scientific evidence

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demonstrates that this is beneficial in prolonging gestation or reducing maternal or fetal morbidity/mortality.

7. Complication 7.1. Life-threatening complications in preeclampsia 7.1.1. Seizures 7.1.2. Cerebral hemorrhage 7.1.3. Pulmonary edema Due to pulmonary capillary leak, excess IV fluid administration, or myocardial dysfunction 7.1.4. Acute renal failure Due to renal vasospasm, ATN, or renal cortical necrosis 7.1.5. Disseminated intravascular coagulopathy 7.1.6. HELLP syndrome Microangiopathic hemolysis, elevated liver enzymes, and thrombocytopenia (platelets [PLT] <100) 7.1.7. Hepatic infarction/rupture and subcapsular hematoma May lead to massive internal hemorrhage and shock 7.2. Acute fatty liver of pregnancy: Although a distinct and rare disorder, acute fatty liver has some clinical features similar to, and often overlapping with, severe preeclampsia. 7.3. TTP and HUS: While unrelated to preeclampsia, consider these important disorders in the setting of presumed severe HELLP syndrome.

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8. Prognosis

Women who develop preeclampsia are at increased risk for cardiovascular disease later in life. Whether the preeclampsia increases cardiovascular risk or the 2 conditions share a common underlying cause remains unclear.7

Transient hypertension of pregnancy is the development of isolated hypertension in a woman in late pregnancy without other manifestations of preeclampsia, is associated strongly with later development of chronic hypertension.

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CHAPTER III CONCLUSION

Hypertension is the most common medical problem encountered during pregnancy, complicating 2-3% of pregnancies. Hypertensive disorders during pregnancy are classified into 4 categories, chronic hypertension, preeclampsia-eclampsia, preeclampsia superimposed on chronic hypertension, and gestational hypertension. Preeclampsia is primarily a disorder of placental dysfunction leading to a syndrome of endothelial dysfunction with associated vasospasm. The hypertension occurring in preeclampsia is due primarily to vasospasm, with arterial constriction and relatively reduced intravascular volume compared to normal pregnancy. If a pregnant womans blood pressure is sustained greater than 160 mm Hg systolic and/or 110 mm Hg diastolic at any time, lowering the blood pressure quickly with rapidacting agents is indicated for maternal safety. Evidence-based guidelines from the American Association of Clinical Endocrinologists single out methyldopa, labetalol or nifedipine as preferable antihypertensive medications in pregnancy, with magnesium sulfate for women with preeclampsia who are at high risk for seizures, but they recommend all major antihypertensive agents with the exception of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs).5

When treating chronic hypertension during pregnancy, maintaining a balance between uncontrolled blood pressure and adverse medication effects is paramount. Optimal management for both mother and fetus is best achieved via frequent monitoring, especially in the final month of gestation.

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REFERENCES 1. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. Jul 2000;183(1):S1-S22. 2. Magee LA, Helewa M, Moutquin J-M et al. Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy. Journal of Obstetrics and Gynaecology Canada [serial online]. March 2008;30:S1-S48. Accessed July 10, 2009. Available at http://www.sogc.org/guidelines/documents/gui206CPG0803_001.pdf. 3. Khalil A, Jauniaux E, Harrington K. Antihypertensive therapy and central hemodynamics in women with hypertensive disorders in pregnancy. Obstet Gynecol. Mar 2009;113(3):646-54. 4. Poon LC, Kametas NA, Maiz N, Akolekar R, Nicolaides KH. First-trimester prediction of hypertensive disorders in pregnancy. Hypertension. May 2009;53(5):812-8. 5. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of hypertension. National Guideline Clearinghouse. Available at http://www.guideline.gov/summary/summary.aspx?doc_id=9338&nbr=005007. Acces sed June 1, 2009. 6. Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. Jun 8 2006;354(23):2443-51.
7. Craici I, Wagner S, Garovic VD. Preeclampsia and future cardiovascular risk: formal

risk factor or failed stress test?. Ther Adv Cardiovasc Dis. Aug 2008;2(4):249-59.
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