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The diagnosis of chronic hypertension in pregnancy should be confirmed. The American College of Obstetricians and Gynecologists (2013) recommends use of ambulatory monitoring to exclude suspected white-coat hypertension before initiating antihypertensive therapy. Goals for chronic hypertension management include rate reductions of adverse maternal or perinatal outcomes just discussed. Treatment is targeted to prevent moderate or severe hypertension and to delay or dampen the severity of pregnancy-aggravated hypertension. To some extent, these goals can be achieved pharmacologically. Blood pressure self-monitoring is encouraged, but for accuracy, automated devices must be properly calibrated (Brown, 2004; Staessen, 2004). Personal health modification includes dietary counseling and reduction of behaviors such as tobacco, alcohol, cocaine, or other substance use (see Table 50-2). A low-sodium diet is not required (American College of Obstetricians and Gynecologists, 2013).
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Some women—especially those with long-term or untreated hypertension—have complications that increase the risk of adverse pregnancy events. For example, in one study, a fourth of gravidas with chronic hypertension also had concentric ventricular hypertrophy (Ambia, 2017; Kim, 2016a). Thus, if not already accomplished, assessment during pregnancy is done for the cardiovascular and renal systems (Morgan, 2016a,b).
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Antihypertensive Drugs
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As concluded by the American College of Obstetricians and Gynecologists (2013, 2016a), treatment of hypertension during pregnancy has included every drug class, but information is still limited regarding safety and efficacy (Czeizel, 2011; Podymow, 2011). Although many studies indicate greater perinatal adverse effects in gravidas requiring treatment, it is still not known whether this is due to cause or effect (Orbach, 2013). The following summary of antihypertensive drugs is abstracted from several sources, including the 2016 Physicians’ Desk Reference. Many of these drugs are also discussed throughout Chapter 12 (Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blocking Drugs) and have been reviewed by Umans and associates (2015).
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Adrenergic-Receptor Blocking Agents
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Peripherally acting β-adrenergic-receptor blockers cause a generalized decline in sympathetic tone and decreased cardiac output. Examples are propranolol, metoprolol, and atenolol. Labetalol is a popular and commonly used α/β-adrenergic blocker that is considered safe.
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Some adrenergic-blocking drugs act centrally by reducing sympathetic outflow to effect a generalized decreased vascular tone. These include clonidine and α-methyldopa. Drugs in this class most frequently used in pregnancy to treat hypertension are methyldopa or an α- or β-receptor blocking agent such as labetalol.
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Calcium-Channel Blocking Agents
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These drugs are divided into three subclasses based on their modification of calcium entry into cells and interference with binding sites on voltage-dependent calcium channels. Common agents include nifedipine—a dihydropyridine, and verapamil—a phenylalkyl amine derivative. These agents have negative inotropic effects and thus can worsen ventricular dysfunction and congestive heart failure. Theoretically, they may potentiate the vasoactive actions of magnesium sulfate that is given for eclampsia neuroprophylaxis. Although data are limited regarding their use during pregnancy, they appear to be safe therapy for chronic hypertension (Briggs, 2015; Umans, 2015).
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Thiazide diuretics are sulfonamides, and these were the first drug group used to successfully treat chronic hypertension (Beyer, 1982). These agents and loop-acting diuretics such as furosemide are commonly used in nonpregnant hypertensive patients. In the short term, they provide sodium and water diuresis with volume depletion. But with time, there is sodium escape, and volume depletion is partially corrected. Some aspect of lowered peripheral vascular resistance likely contributes to their effectiveness in reducing long-term morbidity (Umans, 2015).
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Thiazide drugs may be mildly diabetogenic, and expected volume expansion may be curtailed in pregnant women. Sibai and colleagues (1984) showed that plasma volume expanded only about 20 percent over time in hypertensive pregnant women who continued diuretic therapy compared with a 50-percent expansion in women who discontinued treatment. Although perinatal outcomes were similar in these women, such concerns have led to practices of withholding diuretics as first-line therapy for chronic hypertension, particularly after 20 weeks’ gestation (Working Group Report, 2000). Even so, in a Cochrane review, Churchill and associates (2007) reported no differences in perinatal outcomes in 1836 nonhypertensive women randomly assigned to a thiazide diuretic or placebo for primary preeclampsia prevention. Overall, thiazide diuretics are considered safe in pregnancy (Briggs, 2015). But for preeclampsia treatment, they are considered to be ineffective (Umans, 2015).
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Hydralazine relaxes arterial smooth muscle and has been used parenterally for decades to safely treat severe peripartum hypertension (Chap. 40, Hydralazine). Oral hydralazine monotherapy for chronic hypertension is not generally used because of its weak antihypertensive effects and resultant tachycardia. It may be an effective adjunct for long-term use with other antihypertensives, especially if there is chronic renal insufficiency. In one study, vasodilator treatment of chronically hypertensive women was associated with a twofold rise in rates of low-birthweight and growth-restricted neonates (Su, 2013).
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Angiotensin-Converting Enzyme Inhibitors
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These drugs inhibit the conversion of angiotensin-I to the potent vasoconstrictor angiotensin-II. They can cause severe fetal malformations when given in the second and third trimesters. These include oligohydramnios, hypocalvaria, and renal dysfunction (Chap. 12, Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blocking Drugs). Some preliminary studies also suggest teratogenic effects, and because of this, they are not recommended at any time during pregnancy (Briggs, 2015; Podymow, 2011).
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Angiotensin-receptor blockers act in a similar manner. But, instead of blocking the production of angiotensin-II, they inhibit binding to its receptor. They are presumed to have the same fetal effects as angiotensin-converting enzyme inhibitors and thus are also contraindicated.
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Antihypertensive Treatment in Pregnancy
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Severe Chronic Hypertension
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The prognosis for pregnancy outcome with chronic hypertension is somewhat dependent on the severity of disease antedating pregnancy. This may be related to findings that many women with severe hypertension have renal disease—as either cause or effect (Cunningham, 1990; Morgan, 2016a). It follows that women whose hypertension is severe enough to require antihypertensive therapy are at inordinately high risk for superimposed preeclampsia.
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Sibai and coworkers (1986) described outcomes from 44 pregnancies in women whose blood pressure at 6 to 11 weeks’ gestation was ≥170/110 mm Hg. All were given oral treatment with α-methyldopa and hydralazine to maintain pressures <160/110 mm Hg. Of the 44 pregnancies, superimposed preeclampsia developed in half, and all adverse perinatal outcomes were in this group. Moreover, all neonates of women in the superimposed group were delivered preterm, nearly 80 percent were also growth restricted, and 48 percent suffered perinatal death. Conversely, those women with severe chronic hypertension who did not develop superimposed preeclampsia had reasonably good outcomes. There were no perinatal deaths, and only 5 percent of fetuses were growth restricted. Webster and colleagues (2017) found labetalol and nifedipine to be equally effective for chronic hypertension in pregnant women.
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Morgan and coworkers (2016a) reported 447 women whose chronic hypertension required treatment beginning prior to 20 weeks. More than half of these women developed superimposed severe preeclampsia. The rate of preeclampsia was 53 percent for those whose 24-hour protein excretion was <300 mg. But for those with antecedent baseline proteinuria >300 mg/day, 79 percent developed severe preeclampsia.
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Mild or Moderate Hypertension
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Continuing prepregnancy antihypertensive treatment during pregnancy is debatable for those with mild or moderate hypertension. Although blood pressure reduction certainly benefits the mother long term, it at least theoretically can reduce uteroplacental perfusion. In older observational reports, most pregnancy outcomes in women with mild to moderate hypertension generally were good without treatment and unless superimposed preeclampsia developed (Chesley, 1978; Umans, 2015).
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Newer data are accruing that address potential salutary effects on pregnancy outcomes by simply lowering blood pressure. Earlier studies were relatively small and had widely varying inclusion and outcome criteria. In a Cochrane review of 49 of these studies that included a total of 4723 women with mild to moderate hypertension, Abalos and coworkers (2014) confirmed that the risk for subsequent severe hypertension was lowered with therapy. Compared with untreated women, the frequencies of superimposed preeclampsia, eclampsia, abruption, preterm birth, fetal-growth restriction, and perinatal or maternal mortality did not differ. This latter Cochrane review raised concerns for fetal-growth restriction with β-blocking drugs, notably atenolol. It is not resolved, however, because diminished placental perfusion secondary to lowered maternal blood pressure is confounded by the fact that worsening blood pressure itself is associated with abnormal fetal growth. Some also posit that the drugs have a direct fetal action (Umans, 2015). In two of the larger randomized trials, however, the incidence of growth restriction was not altered in women randomly assigned to treatment (Gruppo di Studio Ipertensione in Gravidanza, 1998; Sibai, 1990a).
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The observations of Morgan and colleagues (2016a) support the findings of the Cochrane review by Abalos. Specifically, they reported that despite therapy for chronic hypertension, there was frequent superimposed preeclampsia, fetal-growth restriction, preterm delivery, and perinatal mortality. Moreover, and as shown in Table 50-4, women with baseline proteinuria >300 mg/d had even worse obstetrical outcomes.
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During the past decade, the concept of tight control of blood pressure has been espoused as a means of optimizing maternal and perinatal outcomes. Such control is analogous to that of glycemic control for management of the pregnant diabetic patient. The observational study by Ankumah (2014) noted earlier lends credence to tighter control of blood pressure. These investigators showed that the risk of adverse pregnancy outcomes in 759 women with chronic hypertension was lower when blood pressures before 20 weeks were <140 mm Hg compared with higher pressure categories and increasing blood pressures. Unfortunately, this did not hold up when less-tight was compared with tight control. Specifically, Magee and coworkers (2015) randomized 987 women with chronic hypertension or gestational hypertension to either one of these two management schemes. Except for a lower rate of severe hypertension in the tightly controlled group, they found no significant differences between these two groups’ other adverse pregnancy outcomes (Table 50-5). Tight control was also not more costly (Ahmed, 2016). These and similar findings prompted an ongoing randomized controlled trial—Project CHAP (ClinicalTrials.gov, 2016)—to answer this question.
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Recommendations for Therapy
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Until there are data to confirm any salutary effects of treatment of uncomplicated mild to moderate chronic hypertension in pregnancy, it seems reasonable to follow the guidelines of the American College of Obstetricians and Gynecologists (2013) and the Society for Maternal-Fetal Medicine (2015). Pregnant women with severe hypertension must be treated for maternal neuro-, cardio-, and renoprotection. Treatment is also mandatory for women with prior adverse outcomes such as strokes, MIs, and evidence for cardiac or renal dysfunction. With end-organ dysfunction, treatment to diastolic pressure level ≤90 mm Hg is reasonable to mitigate further organ damage.
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For most women with mild to moderate hypertension, the College recommends that treatment be withheld as long as systolic blood pressure is <160 mm Hg and diastolic blood pressure is <105 mm Hg. Some find it reasonable to begin antihypertensive treatment in otherwise healthy pregnant women with persistent systolic pressures >150 mm Hg or diastolic pressures of 95 to 100 mm Hg or greater (August, 2015; Working Group Report, 2000). At Parkland Hospital we initiate treatment with antihypertensive agents for blood pressures of 150/100 mm Hg or higher. Our preferred regimens include monotherapy with a β-blocking drug such as labetalol or a calcium-channel blocking agent such as amlodipine. For women in the first half of pregnancy, therapy with a thiazide diuretic seems reasonable. This is especially true in black women, in whom there is a high prevalence of salt-sensitive chronic hypertension.
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It is controversial whether or not women who present early in pregnancy and who are already taking antihypertensive drugs should continue to take these (Rezk, 2016). According to the American College of Obstetricians and Gynecologists (2013) and the Society for Maternal-Fetal Medicine (2015), for women with mild to moderate hypertension, it is reasonable to discontinue medications during the first trimester and to restart them if blood pressures approach the severe range. Our practice at Parkland Hospital is to continue treatment if the woman is already taking drugs when she presents for prenatal care. Exceptions are discontinuation of angiotensin-converting enzyme inhibitors and receptor blockers.
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Some women will have persistently worrisome hypertension despite usual therapy (Samuel, 2011; Sibai, 1990a). In these women, primary attention is given to the likelihood of pregnancy-aggravated hypertension, with or without superimposed preeclampsia. Other possibilities include inaccurate blood-pressure measurements, suboptimal treatment, and antagonizing substances such as chronic ingestion of nonsteroidal antiinflammatory drugs (NSAIDs) (Moser, 2006; Sowers, 2005).
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Pregnancy-Aggravated Hypertension or Superimposed Preeclampsia
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As discussed, the frequency of superimposed preeclampsia for women with chronic hypertension varies depending on the study population and hypertension severity (Ankumah, 2014). Importantly, in 40 to 50 percent of chronically hypertensive women, superimposed preeclampsia develops before 37 weeks (Chappell, 2008; Harper, 2016). This proportion is even higher in women who required hypertension treatment during pregnancy (Morgan, 2016a).
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The diagnosis may be difficult to make, especially in women with hypertension who have underlying renal disease with chronic proteinuria (Cunningham, 1990; Morgan, 2016b). As discussed in Chapter 40 (Preeclampsia Superimposed on Chronic Hypertension), conditions that support the diagnosis of superimposed preeclampsia include worsening hypertension, new-onset proteinuria, neurological symptoms such as severe headaches and visual disturbances, generalized edema, oliguria, and certainly, convulsions or pulmonary edema. Making the diagnosis based on worsening proteinuria in women with baseline proteinuria is problematic. Supporting laboratory abnormalities are rising serum creatinine or hepatic transaminase levels, thrombocytopenia, or any of the facets of HELLP (hemolysis, elevated liver enzyme levels, low platelet count) syndrome. For women with chronic hypertension and superimposed preeclampsia with severe features, magnesium sulfate for maternal neuroprophylaxis is recommended (American College of Obstetricians and Gynecologists, 2013). Severe hypertension is treated as described in Chapter 40 (Management Considerations).
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Some pregnant women with chronic hypertension have worsening hypertension with no other findings of superimposed preeclampsia. This is most commonly encountered near the end of the second trimester. In the absence of other supporting criteria for superimposed preeclampsia, this likely represents the higher end of the normal blood-pressure curve shown in Figure 50-1. In such women, if preeclampsia can be confidently excluded, it is reasonable to begin or to increase the dose of antihypertensive therapy.
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Women with well-controlled chronic hypertension who have no complicating factors can generally be expected to have a good pregnancy outcome. Because even those with mild hypertension have a greater risk of superimposed preeclampsia and fetal-growth restriction, serial antepartum assessment of fetal well-being is recommended by many. That said, according to the American College of Obstetricians and Gynecologists (2013), with the exception of sonographic fetal-growth monitoring, described in Chapter 44 (Fetal-Growth Restriction Recognition), no conclusive data address either benefit or harm associated with various antepartum surveillance strategies.
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Expectant Management of Early-Onset Preeclampsia
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Given that many women with chronic hypertension develop superimposed preeclampsia before term, considerations for expectant management may be reasonable in some cases. In a study from Magee-Women’s Hospital, 41 carefully selected women with a median gestational age of 31.6 weeks were expectantly managed (Samuel, 2011). Despite liberal criteria to mandate delivery, 17 percent developed either placental abruption or pulmonary edema. The latency period was extended by a mean of 9.7 days. There were no perinatal deaths, however, salutary outcomes were similar. These investigators recommend randomized trials to study expectant management before this becomes usual care.
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For chronically hypertensive women who have complications such as fetal-growth restriction or superimposed preeclampsia, the decision to deliver is made by clinical judgment. The route of delivery is dictated by obstetrical factors. Certainly, most women with superimposed severe preeclampsia are better delivered even when the fetus is markedly preterm. Increased risk for placental abruption, cerebral hemorrhage, and peripartum heart failure attend delivery delays (Cunningham, 1986, 2005; Martin, 2005).
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For women with chronic hypertension without preeclampsia, expectant management at later gestational ages was reported recently by Harper and colleagues (2016). They concluded that expectant management beyond 39 weeks’ gestation was associated with an increasing incidence of severe preeclampsia and that planned delivery before 37 weeks was associated with a rise in rates of adverse neonatal outcomes.
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For women with mild to moderate chronic hypertension who continue to have an uncomplicated pregnancy, the American College of Obstetricians and Gynecologists (2013) recommends delivery not be pursued until 380/7 weeks. The consensus committee findings by Spong and associates (2011) recommend consideration for delivery at 38 to 39 weeks, that is, ≥37 completed weeks. A trial of labor induction is preferable, and many of these women respond favorably and will be delivered vaginally (Alexander, 1999; Atkinson, 1995).
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Intrapartum Considerations
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For women with severe preeclampsia, peripartum management is the same as described in Chapter 40 (Consideration for Delivery). Epidural analgesia for labor and delivery is optimal with the caveat that it is not given to treat hypertension (Lucas, 2001). That said, women with severe superimposed preeclampsia are more sensitive to the acute hypotensive effects of epidural analgesia (Vricella, 2012). Also in this group, magnesium sulfate neuroprophylaxis is initiated for prevention of eclampsia. Severe hypertension—diastolic blood pressure ≥110 mm Hg or systolic pressure ≥160 mm Hg—is treated with either intravenous hydralazine or labetalol. Some prefer to treat women when the diastolic pressure reaches 100 to 105 mm Hg. Vigil-De Gracia and colleagues (2006) randomly assigned 200 women to intravenous hydralazine or labetalol to acutely lower severe high blood pressure in pregnancy. Outcomes were similar except for significantly more maternal palpitations and tachycardia with hydralazine and significantly more neonatal hypotension and bradycardia with labetalol.
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In most respects, postpartum observation, prevention, and management of adverse complications are similar in women with severe chronic hypertension and in those with severe preeclampsia–eclampsia. For persistent severe hypertension, consideration is given for a cause such as pheochromocytoma or Cushing disease (Sibai, 2012). And, in women with chronic end-organ damage, certain complications are more common. These include cerebral or pulmonary edema, heart failure, renal dysfunction, or cerebral hemorrhage, especially within the first 48 hours after delivery (Martin, 2005; Sibai, 1990b, 2012). These frequently are preceded by sudden elevations—“spikes”—of mean arterial blood pressure and of the systolic component (Cunningham, 2000, 2005).
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Following delivery, as maternal peripheral resistance rises, left ventricular workload also grows. This elevation is further aggravated by appreciable and pathological amounts of interstitial fluid that are mobilized to be excreted as endothelial disruption from preeclampsia resolves. In these women, sudden hypertension—either moderate or severe—may exacerbate diastolic dysfunction, cause systolic dysfunction, and lead to pulmonary edema (Cunningham, 1986; Gandhi, 2001). Prompt hypertension control, along with furosemide-evoked diuresis, usually quickly resolves pulmonary edema.
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The antihypertensive regimen given antepartum can be restarted in the puerperium. It is also possible in many women to forestall postpartum hypertension by administering intravenous or oral furosemide to augment the normal postpartum diuresis. In one study, 20-mg oral furosemide given daily for 5 days to postpartum women with severe preeclampsia aided blood pressure control (Ascarelli, 2005). Daily weights are helpful in this regard. On average, a woman should weigh 15 pounds less immediately after delivery. Excessive extracellular fluid can then be estimated. Other studies are in progress to determine aspects of postpartum blood pressure management (Cursino, 2015).
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Some evidence supports that chronic ingestion of NSAIDs in the puerperium elevates blood pressure in women with severe preeclampsia (Vigil-De Gracia, 2017). This may not be problematic if these drugs are given only as needed (Wasden, 2014).
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Women with chronic hypertension have special considerations for contraceptive and sterilization choices. These are discussed in detail throughout Chapters 38 and 39.
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Ultimately, women with chronic hypertension are at high risk for lifetime cardiovascular complications, especially when accompanied by diabetes, obesity, and the metabolic syndrome. Recent evidence also suggests that these women are at greater risk to develop cardiomyopathy remote from pregnancy (Behrens, 2016).