The diagnosis of chronic hypertension in pregnancy should be confirmed. For example, Brown and associates (2005) reported “white-coat” hypertension in a third of 241 women diagnosed in early pregnancy. Within this third, pregnancy outcomes were good, and only 8 percent developed preeclampsia.
Management goals for chronic hypertension include reductions of adverse maternal or perinatal outcomes just discussed. Treatment is targeted to prevent moderate or severe hypertension and to delay or ameliorate 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 abuse (see Table 50-2).
Women with severe hypertension must be treated for maternal neuro-, cardio-, and renoprotection regardless of pregnancy status (American College of Obstetricians and Gynecologists, 2012). This includes women with prior adverse outcomes such as cerebrovascular events, myocardial infarction, and cardiac or renal dysfunction. We agree with the philosophy of beginning 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, 2014; Working Group Report, 2000). With end-organ dysfunction, treatment of diastolic pressures ≥ 90 mm Hg is reasonable to mitigate further organ damage.
There are only sparse data indicating salutary effects on pregnancy outcomes with simply lowering blood pressure. These studies are relatively small and have widely varying inclusion and outcome criteria. In a Cochrane review of 46 of these studies that included a total of 4282 women, Abalos and coworkers (2007) confirmed that the risk for severe hypertension was lowered with therapy. There were, however, no differences in the frequencies of superimposed preeclampsia, eclampsia, abruption, preterm birth, fetal-growth restriction, or perinatal or maternal mortality. These studies do attest to the apparent safety of antihypertensive therapy except for angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (Chap. 12, Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blocking Drugs). As emphasized by the Working Group Report (2000), there is a need for further trials in chronically hypertensive women.
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 compared with that of glycemic control for management of the pregnant diabetic. In one study, El Guindy and Nabhan (2008) randomly assigned 125 pregnant women with mild chronic hypertension or gestational hypertension to rigid versus less strict blood pressure control. More women in the latter group developed severe hypertension, they had more hospital admissions, and they were delivered of infants at a lower mean gestational age than the tight-control group. Other than these preliminary observations, there are limited data concerning this type of treatment.
As concluded by the American College of Obstetricians and Gynecologists (2012), treatment during pregnancy has included every drug class, but there still is limited information regarding safety and efficacy (Czeizel, 2011; Podymow, 2011). Although many studies indicate increased perinatal adverse effects in treated women, 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 2014 Physicians’ Desk Reference. Many of these drugs are also discussed throughout Chapter 12 (Antifungal Medications) and have been recently reviewed by Umans and associates (2014).
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 hypertensives. In the short term, they provide sodium and water diuresis with volume depletion. But with time, there is sodium escape, and volume depletion is corrected. Some aspect of lowered peripheral vascular resistance likely contributes to their effectiveness in reducing long-term morbidity (Umans, 2014; Williams, 2001).
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, particularly after 20 weeks (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, 2011; Umans, 2014).
This was the second class of effective antihypertensives. Peripherally acting β-adrenergic receptor blockers cause a generalized decrease in sympathetic tone. Examples are propranolol, metoprolol, and atenolol. Labetalol is a commonly used α/β-adrenergic blocker. Some adrenergic-blocking drugs act centrally by reducing sympathetic outflow to effect a generalized decreased vascular tone. Some of these are clonidine and α-methyldopa. The drugs most frequently used in pregnancy to treat hypertension are methyldopa or a β- or α/β-receptor blocking agent.
Hydralazine relaxes arterial smooth muscle and has been used parenterally for decades to safely treat severe peripartum hypertension (Chap. 40, Persistent Severe Postpartum Hypertension). 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 the study by Su and coworkers (2013), vasodilator treatment of chronically hypertensive women was associated with a twofold increase in low-birthweight and growth-restricted neonates.
Calcium-Channel Blocking Agents
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 actions of magnesium sulfate that is given for eclampsia neuroprophylaxis. There is minimal published experience with these agents during pregnancy (Abalos, 2007). That said, calcium-channel blockers appear to be safe for therapy for chronic hypertension (Briggs, 2011; Podymow, 2011; Umans, 2014).
The safety of acute peripartum nifedipine treatment has been questioned. The drug is used by some for rapid control of severe peripartum hypertension, and it is also widely used for tocolysis in preterm labor (Chap. 42, Calcium-Channel Blockers). Nifedipine for tocolysis should not be combined with intravenous β-agonists (Oei, 2006). Adverse outcomes reported in women given nifedipine for tocolysis or severe gestational hypertension include myocardial infarction and pulmonary edema (Abbas, 2006; Bal, 2004; Oei, 1999; Verhaert, 2004). Severe maternal hypotension with resultant fetal compromise necessitating cesarean delivery and fetal death have also been reported (Johnson, 2005; Kandysamy, 2005; van Veen, 2005).
Angiotensin-Converting Enzyme Inhibitors
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 hypocalvaria and renal dysfunction (Chap. 12, Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blocking Drugs). Some preliminary studies have also suggested teratogenic effects, and because of this, they are not recommended during pregnancy (Briggs, 2011; Podymow, 2011).
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 ACE inhibitors and thus are also contraindicated.
Antihypertensive Treatment in Pregnancy
As discussed, continuation of prepregnancy antihypertensive treatment when women become pregnant is debated. Although blood-pressure reduction is certainly beneficial to the mother long term, it at least theoretically can decrease uteroplacental perfusion. According to older observational reports, in general, most pregnancy outcomes in women with mild to moderate hypertension were good without treatment and unless superimposed preeclampsia developed (Chesley, 1978; Umans, 2014).
There are no large randomized trials to settle the questions surrounding empirical treatment. Abalos and associates (2007) performed a Cochrane database review of 46 small trials enrolling a total of 4282 women. These studies varied widely in definitions of hypertension severity, use of placebos, gestational age at entry, and the type of drug(s) used. The salient results are shown in Table 50-4. These led the investigators to conclude again that treatment reliably lowered risk for severe hypertension during pregnancy.
TABLE 50-4Comparison of Pregnancy Outcomes in Women with and without Antepartum Treatment for Mild to Moderate Chronic Hypertension ||Download (.pdf) TABLE 50-4 Comparison of Pregnancy Outcomes in Women with and without Antepartum Treatment for Mild to Moderate Chronic Hypertension
|Outcome ||Studies (Subjects) ||RR (95% CI)a |
|Severe hypertension ||19 (2409) ||0.50 [0.41, 0.61] |
|Preeclampsia ||22 (2702) ||0.97 [0.83, 1.13] |
|SGA infants ||9 (904) ||1.38 [0.99, 1.92] |
|Perinatal mortality ||26 (3081) ||0.73 [0.50, 1.08] |
|Delivery < 37 weeks ||14 (1992) ||1.02 [0.89, 1.16] |
This Cochrane review does raise concern for fetal-growth restriction with β-blocking drugs. 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, 2014). 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).
Severe Chronic Hypertension
Most data suggest that the prognosis for pregnancy outcome with chronic hypertension is 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). One report by Sibai and coworkers (1986) described outcomes from 44 pregnancies in women whose blood pressure at 6 to 11 weeks was ≥ 170/110 mm Hg. All were given oral treatment with α-methyldopa and hydralazine to maintain pressures < 160/110 mm Hg. If dangerous hypertension developed, then the woman was hospitalized and treated with parenteral hydralazine. 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 latter group were delivered preterm, nearly 80 percent were also growth restricted, and they had a 48-percent perinatal mortality rate. 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.
Recommendations for Therapy in Pregnancy
The Working Group on High Blood Pressure in Pregnancy (2000) concluded that there were limited data from which to draw conclusions concerning any decision to treat mild chronic hypertension in pregnancy. As discussed on Antihypertensive Drugs, the Group did recommend empirical therapy in women whose blood pressures exceed threshold levels of 150 to 160 mm Hg systolic or 100 to 110 mm Hg diastolic or in women with target-organ damage such as left ventricular hypertrophy or renal insufficiency. They also concluded that early treatment of hypertension would probably reduce subsequent hospitalization rates during pregnancy.
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 (Moser, 2006). Causes reported in nonpregnant cohorts were nonsteroidal antiinflammatory drugs including cyclooxygenase-2 inhibitors and alcohol consumption (Sowers, 2005; Xin, 2001).
Pregnancy-Aggravated Hypertension or Superimposed Preeclampsia
As discussed, the incidence of superimposed preeclampsia for women with chronic hypertension varies depending on the study population and hypertension severity. A reasonable average is 20 to 30 percent. The incidence of superimposed preeclampsia may be underreported if the diagnosis is based solely on urine protein dipstick testing (Gangaram, 2005; Lai, 2006). Importantly, in approximately half of chronically hypertensive women, superimposed preeclampsia develops before 37 weeks (Chappell, 2008).
The diagnosis may be difficult to make, especially in women with hypertension who have underlying renal disease with chronic proteinuria (Cunningham, 1990). As discussed in Chapter 40 (Indicators of Preeclampsia Severity), 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. Supporting laboratory abnormalities are increasing serum creatinine levels, thrombocytopenia, serum hepatic transaminase elevations, or the triad 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).
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, including fetal-growth restriction or decreased amnionic fluid volume, this likely represents the higher end of the normal blood-pressure curve shown in Figure 50-1. In such women, if preeclampsia can be reasonably excluded, then it is reasonable to begin or to increase the dose of antihypertensive therapy.
Women with well-controlled chronic hypertension and who have no complicating factors can generally be expected to have a good pregnancy outcome. Because even those with mild hypertension have an increased 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 (2012), with the exception of sonographic fetal-growth monitoring, there are no conclusive data to address either benefit or harm associated with various antepartum surveillance strategies.
Given that half of these women 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, and there were no perinatal deaths. These investigators recommended randomized trials to study expectant management.
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 there is a markedly preterm pregnancy. These women are at increased risk for placental abruption, cerebral hemorrhage, and peripartum heart failure (Cunningham, 1986, 2005; Martin, 2005).
For women with mild to moderate chronic hypertension who continue to have an uncomplicated pregnancy, there are at least two options for timing of delivery (American College of Obstetricians and Gynecologists, 2012). The first is delivery at term, that is, ≥ 39 completed weeks. Another option is from consensus committee findings by Spong and associates (2011), which 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).
For women with severe preeclampsia, peripartum management is the same as described in Chapter 40 (Management of Severe Hypertension). 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). Magnesium sulfate neuroprophylaxis is initiated for prevention of eclampsia (Alexander, 2006). 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 with a diastolic pressure of 100 to 105 mm Hg. Vigil-De Gracia and colleagues (2006) randomized 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.
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 (Chap. 40, Persistent Severe Postpartum Hypertension). For persistent severe hypertension, consideration is given for a cause such as pheochromocytoma or Cushing disease (Sibai, 2012). And because of 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). These frequently are preceded by sudden increases—“spikes”—of mean arterial blood pressure, especially the systolic component (Cunningham, 2000, 2005).
Following delivery, as maternal peripheral resistance increases, left ventricular workload also increases. This rise is further aggravated by appreciable and pathological amounts of interstitial fluid that are mobilized to be excreted as endothelial damage from preeclampsia resolves. In these women, sudden hypertension—either moderate or severe—exacerbates diastolic dysfunction, causes systolic dysfunction, and leads to pulmonary edema (Cunningham, 1986; Gandhi, 2001). Prompt hypertension control, along with furosemide-evoked diuresis, usually quickly resolves pulmonary edema. It is possible in many women to forestall this by the administration of intravenous furosemide to augment the normal postpartum diuresis. Daily weights are helpful in this regard. On average, a woman should weigh 15 pounds less immediately after delivery. Excessive extracellular fluid can be estimated by subtracting the postpartum weight from the predelivery weight—if not determined on hospital admission, the weight at the last prenatal visit provides a relatively accurate estimate. In one study, 20-mg oral furosemide given daily to postpartum women with severe preeclampsia aided blood-pressure control (Ascarelli, 2005).
Women with chronic hypertension have special considerations for contraceptive and sterilization choices. These are discussed in detail throughout Chapters 38 and 39. These women are also at ultimate high risk for lifetime cardiovascular complications, especially when accompanied by diabetes, obesity, and the metabolic syndrome.