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Many agents are available for the control of hypertension. It is important to be familiar with the maternal and fetal side effects, as well as mode of action, in order to choose the most effective agent for your patient. Antihypertensive agents exert their activity through the following five methods: they decrease cardiac output, decrease peripheral vascular resistance, decrease blood pressure centrally, diurese, and inhibit angiotensin production. Commonly used drugs in pregnancy are listed in Table 16.21 and we will discuss them in this section. For the postpartum patient who is breast-feeding, little information is known for most drugs regarding excretion in breast milk and neonatal effects. In general, ACE inhibitors are discouraged secondary to potential renal effects on the neonate.

TABLE 16.21. Antihypertensive drugs commonly used in pregnancy

Centrally Acting Drugs

Methyldopa Methyldopa is the most commonly used antihypertensive in pregnancy. Its mode of action is by central inhibition of the sympathetic drive. The safety and efficacy of methyldopa is well established. Studies have documented no known congenital malformations or adverse long-term follow-up of children exposed in utero.

Maternal side effects include tiredness, dry mouth, and somnolence. In addition, about 5% to 10% may have elevated liver enzyme values. Methyldopa is the agent of choice for long-term, nonemergent oral therapy.

Clonidine Clonidine is not commonly used and there is limited data regarding safety and efficacy of its use. Limited studies regarding congenital defects associated with the use of clonidine reveal no increased risk.

Beta Blockers

The main mode of action of ß-adrenergic blockade is through the reduction in cardiac output. The drugs in this group are a heterogeneous mixture exerting their effects dependent upon receptor selectivity, lipid solubility, and intrinsic sympathomimetic activity. Fetal effects of ß blockers may include growth restriction and neonatal hypoglycemia. Atenolol in the first trimester in particular has been linked to intrauterine growth restriction. Labetalol is a nonselective ß blocker and a postsynaptic ß-1 blocker. It has lower ß blocking effect than other ß blockers, which does not reduce cardiac output. It is probably, thus, less responsible for fetal growth restriction. The side effects are tremors, headache, and scalp tingling. The use of labetalol should be avoided in patients with asthma and congestive heart failure.

Calcium Channel Blockers

Calcium channel blockers act by inhibiting extracellular calcium influx into cells through slow calcium channels. This, then, reduces peripheral vascular resistance.

Studies have found no increase in congenital malformations associated with the long-term use of calcium channel blockers. However, adverse maternal and fetal outcomes have been associated with sublingual use of nifedipine, including maternal myocardial infarction and profound hypotension. Maternal side effects are flushing, headache, and palpitations.

Vasodilators

Hydralazine Hydralazine works through direct and potent vasodilatation. It may be used orally but is most effective as an intravenous agent to control hypertensive crisis. No congenital defects have been associated with hydralazine. It may cause hypotension in hypovolemic patients, so giving intravenous fluids may be warranted.

Side effects include fluid retention, tachycardia, palpitations, headache, lupuslike syndrome, and neonatal thrombocytopenia.

Diuretics

Diuretics, in general, are not contraindicated in pregnancy. There is no increased risk of congenital defects with their use, but their efficacy is uncertain. It is

recommended that women receiving diuretics prior to pregnancy be continued on them throughout pregnancy. However, diuretics should be discontinued in patients with preeclampsia or oligohydramnios or if there is evidence of reduction in uteroplacental flow.

Thiazide The thiazide diuretics have minimal effect on lowering blood pressure in pregnancy and are rarely used. Limited studies show no increased congenital anomalies with the use of thiazide. The side effect profile includes maternal and fetal hyponatremia and acute pancreatitis, rise in blood uric acid levels, and neonatal thrombocytopenia. It can also precipitate hyperglycemia and glycosuria in the diabetic patient.

Furosemide Furosemide is rarely used as a sole pharmacologic agent but is useful in conjunction with other antihypertensives. Studies showed no increase in

congenital anomalies with use in the second and third trimesters, but first trimester use may be associated with hypospadias. Furosemide use in pregnancy should be limited to postpartum management of fluid overload and pulmonary edema in the preeclamptic patient.

Angiotensin-converting Enzyme Inhibitors

ACE inhibitors act by inhibiting the production of angiotensin II and by reducing peripheral vascular resistance. The use of ACE inhibitors has been associated with an increased risk of intrauterine demise, renal dysgenesis, oligohydramnios, pulmonary hypoplasia, fetal growth restriction, and neonatal renal dysfunction. The

mechanism of action is thought to be due to continuous inhibition of the renin-angiotensin system, leading to the development of tubular dysfunction. Therefore, ACE inhibitors are contraindicated in pregnancy, mainly during the second and third trimesters. However, ACE inhibitors may be an excellent choice for hypertensive control in the postpartum period.

Contraception

Women with hypertensive diseases in pregnancy, whether preeclampsia or chronic hypertension, will seek advice regarding contraceptive methods postpartum. It is important to be familiar with options available to patients and be able to discuss potential risk factors.

No contraindications exist with the use of barrier methods with regard to hypertension. The user failure rate, however, may be significant if failure results in a pregnancy with increased morbidity due to hypertensive disease. There are no contraindications for hypertensive patients desiring to use an intrauterine device. It is important to be aware of any associated underlying medical problems or therapies that the patient may have that would prohibit the use of an intrauterine device. Natural family planning continues to be an acceptable form of contraception when used appropriately.

The greatest concern in finding appropriate contraception for the hypertensive patient is with regard to hormonal contraception. Oral contraceptive pills are the most widely used reversible form of birth control in the United States. Combination oral contraceptives are known to elevate blood pressure minimally, increase clotting factors, and increase total cholesterol levels. Once again, it is extremely important to be familiar with any coexisting disease in a hypertensive patient. Hypertension may have associated underlying antiphospholipid syndrome, for example, which would be a contraindication to combination oral contraceptives given the increased risk for thromboembolic phenomena. Progestin-only contraceptive methods may be a suitable alternative for women with underlying hypercoagulability, because they do not interfere with coagulation. Overall, the contraceptive choices afforded hypertensive patients are basically the same as in normotensive patients. The risks and benefits of contraception must be weighed and patients counseled accordingly. Avoiding the morbidity associated with pregnancy in some patients may be a benefit that outweighs the risk of contraceptive use.

SUMMARY POINTS

Making an appropriate diagnosis is essential in caring for women with hypertensive disease in pregnancy.

There is no known etiology, prevention, or screening method for preeclampsia.

The use of MgSO ₄ is warranted in patients with preeclampsia and eclampsia to prevent seizures.

Fetal outcome in patients with preeclampsia is based largely upon gestational age at delivery; as such, prolonging pregnancies in patients with preeclampsia should be done with close maternal and fetal observation.

Blood pressure =170 mm Hg systolic and =110 mmHg diastolic requires intervention.

Any patient with symptoms of HELLP syndrome should have laboratory evaluation performed, regardless of blood pressure measurements.

Evaluation of a patient with chronic hypertension should include monitoring for target organ damage. Management of these patients is dependent upon the degree of hypertension.

Any patient with chronic hypertension is at increased risk of developing superimposed preeclampsia.

RECOMMENDED READINGS

Abramovici D, Friedman SA, Mercer BM, et al. Neonatal outcome in severe preeclampsia at 24 to 36 weeks' gestation: Does the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome matter? Am J Obstet Gynecol 1999;180:221–225.

American College of Obstetricians and Gynecologists (ACOG). Chronic hypertension in pregnancy. ACOG Practice Bulletin No. 29. Obstet Gynecol 2001;98:177–185.

American College of Obstetricians and Gynecologists. Diagnosis and management of preeclampsia and eclampsia. ACOG Practice Bulletin No. 33. Obstet Gynecol 2002;99:159–167.

Audibert F, Friedman SA, Frangieh AY, et al. Clinical utility of strict diagnostic criteria for the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol 1996;175:460–464.

Barton JR, Bergauer NK, Jacques DL, et al. Does advanced maternal age effect pregnancy outcome in women with mild hypertension remote from term? Am J Obstet Gynecol 1997;176:1236–1243.

Barton JR, O'Brien JM, Bergauer NK, et al. Mild gestational hypertension remote from term: progression and outcome. Am J Obstet Gynecol 2001;184:979–983.

Briggs R, Chari RS, Mercer B, et al. Postoperative incision complications after cesarean section in patients with antepartum syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP): does delayed primary closure make a difference? Am J Obstet Gynecol 1996;175:893–896.

Caritis, S, Sibai B, Hauth J, et al., and the National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Predictors of pre-eclampsia in women at high-risk. Am J Obstet Gynecol 1998;179:946–951.

Chappell LC, Seed PT, Briley AL, et al. Effect of antioxidants on the occurrence of preeclampsia in women at increased risk: a randomised trial. Lancet 1999;354:810–816.

Dekker GA, Sibai BM. Etiology and pathogenesis of preeclampsia: current concepts. Am J Obstet Gynecol 1998;179:1359–1375.

Levine RJ, Ewell MG, Hauth JC, et al. Should the definition of preeclampsia include a rise in diastolic blood pressure =15 mm Hg to a level <90 mm Hg in association with proteinuria? Am J Obstet Gynecol 2000;183:787–792.

Martin JN, Perry KG, Blake PG, et al. Better maternal outcomes are achieved with dexamethasone therapy for postpartum HELLP (hemolysis, elevated liver enzymes, and thrombocytopenia) syndrome. Am J Obstet Gynecol 1997;177:1011–1017.

Mattar F, Sibai BM. Eclampsia VIII. Risk factors for maternal morbidity. Am J Obstet Gynecol 2000;182:307–312.

Nisell H, Lintu H, Lunell NO, et al. Blood pressure and renal function seven years after pregnancy complicated by hypertension. Br J Obstet Gynaecol 1995;102:876–881.

O'Brien JM, Milligan DA, Barton JR. Impact of high-dose corticosteroid therapy for patients with HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Am J Obstet Gynecol 2000;183:921–924.

O'Brien JM, Shumate SA, Satchwell SL, et al. Maternal benefit of corticosteroid therapy in patients with HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome: impact on the rate of regional anesthesia. Am J Obstet Gynecol 2002;186:475–479.

Repke JT. Contraception for the woman with hypertension. In: Sibai BM, ed. Hypertensive disorders in women. Philadelphia: WB Saunders, 2001.

Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000;183:S1–S22.

Samadi AR, Mayberry RM, Zaidi AA, et al. Maternal hypertension and associated pregnancy complications among African-American and other women in the United States. Obstet Gynecol

1996;87:557–563.

Sibai BM, Ramadan MK, Chari RS, et al. Pregnancies complicated by HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): subsequent pregnancy outcome and long-term prognosis. Am J Obstet Gynecol 1995;172:125–129.

Sibai BM. Treatment of hypertension in pregnant women. N Engl J Med 1996;335:257–265.

Sibai BM. Prevention of preeclampsia: a big disappointment. Am J Obstet Gynecol 1998;179:1275–1278.

Sibai BM, Lindheimer M, Hauth J, et al. Risk factors for preeclampsia, abruptio placentae, and adverse neonatal outcomes among women with chronic hypertension. N Engl J Med 1998;339:667–671.

Witlin AG, Sibai BM. Magnesium sulfate therapy in preeclampsia and eclampsia. Obstet Gynecol 1998;92:883–889.

Visser W, Wallenburg HCS. Temporising management of severe preeclampsia with and without the HELLP syndrome. Br J Obstet Gynaecol 1995;102:111–117.

Chapter 17 Medical and Surgical Complications of Pregnancy

Anemia is defined as a hemoglobin (Hb) concentration of less than 12 g/dL in nonpregnant women. Anemia can be acquired or inherited. During pregnancy, plasma volume expands proportionately more than Hb or red blood cell volume, resulting in Hb dilution, such that anemia is defined as a Hb concentration of less than 10 g/dL.

In addition to blood loss, anemia can result from decreased production or increased destruction of red blood cells. The initial workup consists of a history and physical examination, as well as an examination of the red blood cell indices and a peripheral smear, with additional tests as indicated ( Fig. 17.1).