INTRODUCTION — There are four major hypertensive disorders that occur in pregnant women [1,2]:
- Preeclampsia-eclampsia
- Preexisting hypertension
- Preeclampsia superimposed upon preexisting hypertension
- Gestational hypertension
The diagnosis of a hypertensive disorder in a pregnant woman depends, in part, upon the gestational age at presentation. Preeclampsia refers to the syndrome of new onset of hypertension and proteinuria after 20 weeks of gestation in a previously normotensive woman (table 1), or worsening hypertension with new onset proteinuria in a woman with preexisting hypertension (superimposed preeclampsia). Preexisting hypertension is defined as systolic pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg that antedates pregnancy, is present before the 20th week of pregnancy, or persists longer than 12 weeks postpartum [3]. Gestational hypertension refers to elevated blood pressure first detected after 20 weeks of gestation in the absence of proteinuria (table 2). Over time, some patients with gestational hypertension will develop proteinuria and be considered preeclamptic, while others will be diagnosed with preexisting hypertension because of persistent blood pressure elevation postpartum.
The treatment of hypertension in pregnant women will be reviewed here. The pathogenesis, clinical features, diagnosis, obstetrical management, and prevention of preeclampsia are discussed separately. (See "Pathogenesis of preeclampsia" and "Clinical features, diagnosis, and long-term prognosis of preeclampsia" and "Management of preeclampsia" and "Prevention of preeclampsia".)
BEDREST — Although widely recommended, there are no large randomized trials evaluating the benefits and risks of bedrest in the management of pregnant women with hypertension of any etiology. A Cochrane review analyzed four small trials including 449 women [4]. Two trials (145 women) compared strict bed rest with some rest in hospital for women with proteinuric hypertension and did not find any differences in outcome between the groups. Two other trials (304 women) compared some bedrest in hospital with routine activity at home for nonproteinuric hypertension and reported some rest was associated with a reduced risk of severe hypertension (1 trial, 218 women; RR 0.58, 95% CI 0.38-0.89) and a borderline reduction in risk of preterm birth (1 trial, 218 women; RR 0.53, 95% CI 0.29-0.99).
Given that restricted activity is disruptive for most women and could be associated with an increased risk of thromboembolic problems, bedrest is not advised for all pregnant women with hypertension. However, a biologically plausible argument can be made that bedrest in the lateral decubitus position augments uteroplacental blood flow, which can be of value if there is uteroplacental insufficiency. In addition, it may reduce the hypoxic stimulus for soluble fms-like tyrosine kinase 1 (sFlt) production. Thus, some rest in the lateral decubitus position remains part of the routine management of women with suspected uteroplacental insufficiency, such as those with fetal growth restriction or preeclampsia. (See "Pathogenesis of preeclampsia".)
PREECLAMPSIA — The definitive treatment of preeclampsia is delivery, which is always beneficial for the mother. As long as the gravida remains undelivered, she is at increased risk of complications such as seizures, abruption, thrombocytopenia, cerebral hemorrhage, pulmonary edema, liver hemorrhage, and renal failure. The risk of these complications subsides with delivery since preeclampsia is a completely reversible disease process.
However, delivery may not be beneficial for the fetus if it is born preterm. Although the fetus is at increased risk of intrauterine growth restriction and stillbirth in the preeclamptic environment, conservative management may be pursued in selected cases to gain fetal maturity. General principles of management of preeclampsia are reviewed separately. (See "Management of preeclampsia".)
Indications for antihypertensive therapy — The indications for antihypertensive therapy in preeclampsia are based on practice patterns established over the years, rather than clinical trials with clearly defined outcomes. Conclusions derived from systematic reviews are limited by several factors, including variation in blood pressure measurement techniques, differences in diagnostic criteria and etiology of hypertension, and differences in target blood pressure.
The major indication for antihypertensive therapy in preeclampsia is prevention of stroke. Lowering blood pressure does not affect the course of preeclampsia because the primary pathogenetic process is an abnormality of the placental vasculature that results in placental underperfusion, which, in turn, leads to release of factors that cause widespread maternal endothelial dysfunction with multiorgan dysfunction.
Many physicians withhold treatment in asymptomatic women with preeclampsia unless the diastolic pressure is ≥105 to 110 mmHg or the systolic pressure is ≥160 mmHg, a level at which the risk of cerebral hemorrhage becomes appreciable [1,3,5-7]. However, we feel that these thresholds may be too high, particularly in younger women whose baseline diastolic pressures are below 75 mmHg.
The clinical characteristics of patients with stroke in association with severe preeclampsia/eclampsia/HELLP were illustrated in a review of 28 such patients (ages 14 to 42, mean 29.6 years) who were otherwise free of risk factors for stroke [7]. Seven of these patients were ascertained from hospital medical records, the other 21 patients were derived from forensic sources. Major findings from this retrospective series were:
- The cause of stroke was arterial hemorrhage in 25 of the 27 patients (93 percent) who underwent intracranial imaging.
- Systolic blood pressure was 159 to 198 mmHg (mean 175 mmHg) immediately prestroke in 24 of 24 patients for whom this information was available.
- Diastolic blood pressure was 81 to 133 mmHg (mean 98 mmHg) immediately prestroke in all 24 patients for whom this information was available. Only three women had diastolic pressures ≥110 mmHg and only five had had diastolic pressure >105 mmHg.
- Maternal death occurred in 15 of the 28 patients (54 percent) and long-term residual deficits were present in 10 of the 13 survivors.
It is important to emphasize that the majority of the cases reported were derived from forensic sources; thus these findings may not represent the risks to the overall population of pregnant women with severe preeclampsia/eclampsia/HELLP.
These and other data suggest that systolic blood pressure may be a better predictor of stroke risk than diastolic pressure. Therefore, we are concerned about withholding antihypertensive treatment until blood pressure is greater than 160 mm Hg systolic; and suggest initiating antihypertensive therapy in preeclamptic/eclamptic women when the systolic blood pressure is ≥150 mm Hg and the diastolic blood pressure is ≥100 mmHg. High quality clinical trials need to be done to clarify the parameters for antihypertensive use in women with preeclampsia. Moreover, greater understanding of the cerebrovascular pathophysiology of preeclampsia/eclampsia, in particular, the role of elevated blood pressure in this disorder, might help clarify the role of antihypertensive therapy in preventing neurologic sequelae.
Effect on fetus — Whereas maternal health may not be harmed by lowering blood pressure, there is some concern that lowering blood pressure may compromise fetal well-being as a result of reduced placental perfusion [8,9]. This conclusion is supported by two meta-analyses that looked at maternal and fetal outcomes in randomized trials of treatment versus no treatment of pregnant women with mild to moderate hypertension (defined as blood pressure of 140 to 169/90 to 109 mm Hg) [10,11]. A limitation of these analyses is that they did not distinguish between women with and without proteinuria. Important conclusions from these reports were:
- There was no demonstrable benefit or risk associated with restricted activity in patients with mild hypertension [10].
- Antihypertensive therapy of mild hypertension significantly decreased the incidence of severe hypertension by one-half to two-thirds and the need for additional antihypertensive drugs by almost two-thirds [10,11].
- Antihypertensive therapy of mild hypertension did not affect perinatal mortality rate or the frequency of prematurity, preeclampsia, delivery of a small for gestational age infant, or abruptio placentae [10,11]. One analysis noted a significant decrease in respiratory distress syndrome [10].
A subsequent meta-analysis by one of these groups showed that fetal growth was significantly impaired by the reduction in mean arterial pressure induced by antihypertensive therapy: a 10 mmHg fall in mean arterial pressure was associated with a 176 g decrease in birth weight [9]. This effect was unrelated to the type of hypertension or choice of medication.
Discussion — Based on the evidence presented above, we do not prescribe antihypertensive therapy for mild hypertension, which we define as blood pressures consistently less than 150/100 mm Hg, associated with preeclampsia. The only demonstrable benefit of antihypertensive therapy in women with mild hypertension is a reduction in risk of developing severe hypertension, which we consider insufficient to warrant exposing the fetus to the potential adverse effects on its growth.
Most experts agree that severe hypertension should be treated to prevent maternal vascular complications [3]. However, there is no consensus as to the optimal blood pressure threshold for initiating therapy. We initiate antihypertensive therapy in adult women at systolic pressures between 150 and 160 mm Hg and diastolic blood pressures between 100 and 105 mm Hg. Treatment may be initiated earlier in women with symptoms that may be attributable to elevated blood pressure (eg, headache, visual disturbances, chest discomfort) and in younger women whose baseline blood pressure was low (less than 90/75 mmHg). Our target blood pressures are 130 to 150 mm Hg systolic and 80 to 100 mm Hg diastolic.
Choice of drug and dose — There are two settings in which antihypertensive therapy is considered:
(1) Acute management of severe hypertension, which may require parenteral therapy, and
(2) Longer-term blood pressure control during expectant management of severe preeclampsia [3,12]. (See "Expectant management of severe preeclampsia".)
Acute therapy
- Labetalol — We recommend intravenous labetalol. Randomized trials comparing labetalol to nicardipine or methyldopa have shown that labetalol is effective and generally safe in pregnancy, although data are limited [12].
Dose: Begin with 20 mg intravenously followed at 10 minute intervals by doses of 20 to 80 mg up to a maximum total cumulative dose of 300 mg. As an example, give 20 mg, then 40 mg, then 80 mg, then 80 mg, then 80 mg. A constant infusion of 1 to 2 mg/min can be used instead of intermittent therapy. The fall in blood pressure begins within 5 to 10 minutes and lasts from three to six hours.
- Hydralazine — Intravenous hydralazine has been used extensively in the setting of preeclampsia. However, a meta-analysis of 11 trials in 570 women found that parenteral hydralazine was associated with significantly more maternal hypotension than other antihypertensive drugs [10]. A subsequent meta-analysis by the same group also did not support the use of hydralazine as a first-line drug for treatment of severe hypertension in pregnant women, although the evidence was not sufficient for making a definitive conclusion [13]. Hydralazine is widely used and is considered by some experts as an acceptable antihypertensive drug in this setting given the limitations in available data [3,14].
Dose: begin with 5 mg intravenously over one to two minutes; if the blood pressure goal is not achieved within 20 minutes, give a 5 to 10 mg bolus depending upon the initial response. The maximum bolus dose is 20 mg. If a total dose of 30 mg does not achieve optimal blood pressure control, another agent should be used. The fall in blood pressure begins within 10 to 30 minutes and lasts from two to four hours.
We discourage the use of immediate release nifedipine (10 mg). Sublingual administration of this drug is not approved by the US Food and Drug Administration (FDA) for treatment of hypertensive emergencies because its use has been associated with an excessive reduction in blood pressure leading to serious cardiovascular morbidity [18-20]. We do not use immediate release nifedipine, either orally or sublingually, for treatment of hypertension in pregnant women.
- Diazoxide — When adequate blood pressure control cannot be achieved with labetalol or hydralazine, diazoxide can be used, but this is rarely necessary [1]. The potential value of small doses of diazoxide was illustrated in a randomized controlled trial performed in Australia that compared "miniboluses" of diazoxide (15 mg every three minutes to a maximum of 300 mg) with hydralazine (5 mg every 20 minutes) in 124 pregnant women with severe hypertension [21]. Mini bolus diazoxide was safe (did not precipitate maternal hypotension) and effective and afforded faster blood pressure control compared with hydralazine.
Drugs contraindicated in pregnancy — Nitroprusside is contraindicated in the later stages of pregnancy due to possible fetal cyanide poisoning if used for more than four hours. However, nitroprusside (0.5 to 10 mcg/kg/min) can be considered an agent of last resort for urgent control of refractory severe hypertension.
Angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), are contraindicated at all stages of pregnancy as they are teratogenic. (See "Angiotensin converting enzyme inhibitors and receptor blockers in pregnancy".)
Long-term oral therapy — Occasionally, preeclamptic women with severe hypertension are stabilized and not delivered immediately. Oral antihypertensive therapy is often indicated for these patients. (See "Expectant management of severe preeclampsia".)
Options for oral antihypertensive therapy are the same as for women with preexisting hypertension (see 'Choice of drug' below.
Target blood pressure — Blood pressure targets that we consider reasonable are 130 to 150 mm Hg systolic and 80 to 100 mm Hg diastolic. We acknowledge the lack of clinical trial data to support these recommendations, and the need to individualize therapy based upon maternal and fetal factors.
GESTATIONAL HYPERTENSION — The indications for and choice of antihypertensive therapy in women with gestational hypertension are the same as for women with preeclampsia. Other aspects of management of these patients are discussed separately. (See "Gestational hypertension".)
POSTPARTUM HYPERTENSION — There are limited data describing blood pressure patterns in the puerperium. One series of 136 previously normotensive women reported that a small rise in blood pressure was common, with an average increase in systolic and diastolic pressure of 6 and 4 mmHg, respectively, in the first four postpartum days [22].
Preeclampsia-related hypertension usually resolves spontaneously within a few weeks (average 16 ± 9.5 days) and is almost always gone by 12 weeks postpartum [23,24]. However, some cases may take as long as six months to resolve [24]. Hypertension that persists beyond this period should be evaluated and treated as in any nonpregnant woman. (See "Hypertension: Who should be treated?".)
Occasionally, blood pressure may be significantly higher in the immediate postpartum period than antepartum or intrapartum. This may be due to a combination of factors, including administration of saline solution in women who have had a cesarean delivery, loss of the pregnancy associated vasodilation after delivery, mobilization of extracellular fluid after delivery, and administration of non-steroidal antiinflammatory agents for postdelivery analgesia [25]. Primary aldosteronism is a rare cause of postpartum hypertension. Women with this disorder may have lower blood pressure during pregnancy due to the natriuretic effects of progesterone, and may present with significant postpartum hypertension with or without hypokalemia [26]. (See "Clinical features of primary aldosteronism".)
Antihypertensive agents may be required temporarily postpartum if hypertension is severe. Oral medications similar to those used in the nonpregnant population may be used or those administered during pregnancy may be continued. Angiotensin converting enzyme (ACE) inhibitors, beta-adrenergic blockers, calcium channel blockers and diuretics are suitable choices for non-breastfeeding mothers. Brief furosemide therapy (20 mg orally once per day for five days) begun at the time of diuresis may facilitate return to normotension in women with severe, but not mild, preeclampsia [27]. This therapy is more likely to benefit the subset of patients with hypervolemic, high cardiac output preeclampsia who also have edema. (See "Choice of therapy in essential hypertension: Recommendations".)
The blood pressure should be monitored closely, ideally with evaluation in the patient's home, to avoid hypotension as the woman's blood pressure returns to her normal baseline level. If prepregnancy blood pressure was normal, it is reasonable to stop the antihypertensive agent after three weeks and monitor blood pressure to assess whether further treatment is indicated.
Breastfeeding mothers — Beta-adrenergic blockers and calcium channel blockers enter breast milk; however, most appear to be safe during lactation [28] and are considered "compatible" with breastfeeding by the American Academy of Pediatrics (see individual drugs in the drug database). Labetalol and propranolol are preferred for initial antihypertensive therapy because these drugs are not concentrated in breast milk, unlike other beta-adrenergic blockers [3]. If there is a contraindication to beta blockade, sustained release nifedipine or verapamil are reasonable alternatives [29]. (See "Principles of medication use during lactation", section on Antihypertensive therapy.) ACE inhibitors and angiotensin receptor antagonists should generally be avoided during lactation in the neonatal period, but may be considered after that time. Theoretically, diuretics may reduce milk volume, but this does not appear to occur at doses of 50 mg or less daily [30]; the American Academy of Pediatrics considers their use compatible with breastfeeding.
PREEXISTENT HYPERTENSION
Pregnancy risks — Women with preexistent hypertension are at increased risk of adverse pregnancy outcome [31]. Superimposed preeclampsia is the most common complication, the incidence is two- to four-fold higher than in the general obstetric population [32,33]. In addition, reviews evaluating the magnitude of maternal and fetal risk during pregnancy in hypertensive women have found a three-fold increase in perinatal mortality (OR 3.4, 95% CI 3.0-3.7), a two-fold increase in abruptio placentae (OR 2.1, 95% CI 1.1-3.9), a five-fold increase in low birth weight (RR 5.5, 95% CI 2.6-11.9), and an increased frequency of impaired fetal growth compared to normotensive women, even in the absence of superimposed preeclampsia [34,35].
The absolute ranges of risk for adverse pregnancy outcome reported in observational studies of women with mild preexisting hypertension were [32]:
- Superimposed preeclampsia — 10 to 25 percent
- Abruptio placentae — 0.7 to 1.5 percent
- Preterm birth <37 weeks — 12 to 34 percent
- Fetal growth restriction — 8 to 16 percent
These risks were even higher in women with severe preexisting hypertension in the first trimester (preeclampsia: 50 percent, abruption: 5 to 10 percent, preterm birth: 62 to 70 percent, growth restriction: 31 to 40 percent), and were highest for those with severe hypertension and superimposed preeclampsia.
Other potential problems stem from the known risks of hypertensive disease (eg, heart failure, hypertensive encephalopathy, retinopathy, cerebral hemorrhage, acute renal failure) [31]. (See "Overview of hypertension in adults", section on 'Complications'.)
Despite these risks, the treatment of preexisting hypertension during pregnancy is controversial. Beneficial effects of treatment appear to be limited to prevention of maternal morbidity and depend upon the severity of the disease (see 'Indications for treatment' below.
Maternal evaluation — The initial evaluation of the hypertensive patient is described separately. (See "Initial evaluation of the hypertensive adult".) Although rare, white, nonobese women under age 30 years with a confirmed negative family history of hypertension may have secondary hypertension (table 3), and this etiology should be considered. (See "Who should be screened for renovascular or secondary hypertension?".)
Baseline laboratory tests that have been recommended in pregnancy include urinalysis, urine culture, and serum creatinine, blood urea nitrogen, glucose, and electrolytes [6,32]. These tests will effectively rule out renal disease, and will also identify important comorbidities, such as diabetes mellitus. If qualitative testing for urine protein is negative, quantitative testing is not necessary. Women who develop evidence of proteinuria on a urine dipstick should have a quantitative test for urine protein. An electrocardiogram should be obtained in women with long-standing hypertension.
The effects of pregnancy on maternal renal disease and of renal disease on the outcome of pregnancy are discussed in detail separately. (See "Renal and urinary tract physiology in pregnant women" and "Pregnancy in women with underlying renal disease".)
Indications for treatment — The goal of treatment of hypertension is to minimize the risk of maternal cardiovascular or cerebrovascular events. Untreated mild hypertension over the course of a pregnancy is unlikely to affect this risk, but untreated severe hypertension could result in a stroke.
Women with uncomplicated preexisting hypertension who are normotensive or mildly hypertensive on medication may continue their therapy or have their antihypertensive agents tapered and/or stopped during pregnancy, with close monitoring of the maternal blood pressure response [3,32,36]. Acceptable blood pressures (systolic less than 140 to 159 or diastolic less than 90 to 99 mmHg) in the absence of their usual antihypertensive therapy is not uncommon in the second trimester due to the normal decrease in blood pressure at this time. There is no consensus on the best approach.
Mild essential hypertension — The indications for instituting antihypertensive drugs in uncomplicated patients with mild essential hypertension (systolic 140 to 159 or diastolic 90 to 99 mmHg) who have not previously been treated or who have discontinued therapy are not clear. Neither the patient nor the fetus appears to be at risk from mild hypertension during pregnancy. Furthermore, controlled studies have not demonstrated that lowering the blood pressure with antihypertensive medications reduces the risk of preeclampsia or abruption, or improves fetal or maternal outcome [5,10,11,35,37,38]. However, two systematic reviews concluded that therapy does decrease the incidence of severe hypertension [11,39]. Eight to 13 women would need to be treated with an antihypertensive drug to prevent one episode of severe hypertension [11].
Despite a large number of trials on treatment of hypertension in pregnancy, these trials lack sufficient power, even with meta-analysis, to detect modest (20 to 30 percent) treatment effects and usually do not differentiate among degrees of severity of mild hypertension.
Based on the available data, we suggest avoiding treatment of pregnant women with uncomplicated mild essential hypertension, especially in the first trimester, since blood pressure may decrease as pregnancy progresses. In women already on antihypertensive therapy who have early pregnancy blood pressures less than 120/80 mmHg, we would strongly consider tapering/discontinuing antihypertensive drugs and closely monitoring the blood pressure response.
Our indications for initiating or reinstituting antihypertensive therapy are persistent diastolic pressures of 95 to 99 mmHg, systolic pressures ≥150 mmHg, or signs of hypertensive end-organ damage. These thresholds, although not in the severe range, allow nonemergent intervention with oral drugs while hypertension is only moderately elevated.
Complicated and secondary hypertension — Subgroups of women with mild hypertension appear to be at greater risk of maternal or fetal complications and may benefit from antihypertensive therapy. Therapy has been suggested for women with [32]:
- Secondary, rather than essential, hypertension (eg, renal disease, collagen vascular disease, coarctation of the aorta)
- End-organ damage (eg, ventricular dysfunction, retinopathy)
- Dyslipidemia
- Maternal age over 40 years old
- Microvascular disease
- History of stroke
- Previous perinatal loss
- Diabetes (see "Treatment of hypertension in diabetes mellitus")
We suggest treatment of these women to attain blood pressures of 120 to 140/80 to 90 mmHg.
Severe hypertension — Severe hypertension (blood pressure ≥160/100 mmHg), particularly if associated with signs of early hypertensive encephalopathy, should be treated to protect the mother from serious complications, such as stroke, heart failure, or renal failure. (See "Hypertensive emergencies: Malignant hypertension and hypertensive encephalopathy".)
Choice of drug — All antihypertensive drugs cross the placenta. There are no data from large well-designed randomized trials on which to base a recommendation for use of one drug over another. Data regarding both comparative efficacy in improving pregnancy outcome and fetal safety are inadequate for almost all antihypertensive drugs.
There is general agreement that ACE inhibitors and angiotensin receptor antagonists should NOT be administered in pregnancy; therefore, it is best to discontinue these agents in women planning pregnancy and switch to another agent [40]. (See "Angiotensin converting enzyme inhibitors and receptor blockers in pregnancy".)
Our preference is to start treatment with either methyldopa or labetalol. A long acting calcium channel blocker (eg, nifedipine) can be added as either second or third line treatment (table 4). These drugs have been used extensively during pregnancy and appear to be reasonably safe and effective [1].
Methyldopa has been one of the most widely used drugs in pregnant women and its long-term safety for the fetus has been demonstrated [41]; it is only a mild antihypertensive agent and a slow onset of action (3 to 6 hours) [1,37,42]. Many women will not achieve blood pressure goals on this agent or are bothered by its sedative effect.
Labetalol is the most widely used beta-adrenergic blocker in pregnancy. The safety of other beta-adrenergic blockers, particularly propranolol, is somewhat controversial due to individual reports of premature labor and neonatal apnea, fetal growth restriction, bradycardia, and hypoglycemia. Beta-adrenergic blockers are not associated with an increased risk of congenital anomalies. Beta-adrenergic blockers that lack intrinsic sympathomimetic activity may decrease uterine perfusion, increase fetal vascular resistance, and lower placental and neonatal weight at delivery [43]. Furthermore, myometrial relaxation in pregnancy is a beta2-receptor-mediated process, and nonselective beta-adrenergic blockers (such as propranolol) may counteract the effect of beta2 stimulation. Beta-adrenergic blockers that lack alpha-blocking properties (eg, atenolol) have been associated with lower placental and fetal weight at delivery when used early in pregnancy [43-45].
Labetalol has both alpha- and beta-adrenergic blocking activity, and may preserve uteroplacental blood flow to a greater extent than other drugs in this class. It has a more rapid onset of action than methydopa (within 2 hours versus 3-6 hours). Although less well studied in pregnant women, pindolol and the long-acting form of metoprolol are acceptable alternative agents [33].
Meta-analyses of beta-adrenergic blockers for treatment of mild hypertension during pregnancy found that these drugs increased the risk of having a small for gestational age infant compared to no therapy/placebo (RR 1.36 to 1.38) [11,45], but this risk was not significantly higher than with other antihypertensive drugs [11]. Beta-blockers were also better tolerated than methyldopa (RR 0.07; 95% CI 0.02 to 0.37) and seemed to be more effective than methyldopa in avoiding an episode of severe hypertension. A limitation of this analysis is that it did not distinguish among different beta-adrenergic blockers (eg, labetalol versus atenolol), and the data were not of high quality.
Experience with calcium channel blockers is accumulating and these agents appear to be safe for use in pregnancy [39]. Long-acting nifedipine (30 to 90 mg once daily as sustained release tablet, increase at 7 to 14 day intervals, maximum dose 120 mg/day) has been used without major problems [8,46,47]. Although amlodipine is widely used in non-pregnant individuals with hypertension, there are sparse data of its use in pregnancy [48]. Nondihydropyridine calcium antagonists such as verapamil and diltiazem have been used as well, although most reports in the literature are of small numbers of women.
The role of thiazide diuretics has been a source of controversy, although guidelines suggest that these agents can be continued as long as volume depletion is avoided [1,3,42,49]. The latter problem is unlikely with long-term therapy, since all of the fluid loss occurs within the first two weeks of use, assuming that drug dose and dietary sodium intake are relatively constant. In a small study of 20 patients taking diuretics in the first trimester, the mean increase in plasma volume was 18 percent in patients continued on diuretics and 52 percent when they were discontinued; however, there was no difference in perinatal outcome between the two groups [50]. (See "Time course of diuretic-induced electrolyte complications".)
Blood pressure goal — A reasonable goal of therapy in women without end-organ damage is systolic pressure between 140 and 150 mmHg and diastolic pressure between 90 and 100 mmHg [32]. As discussed above, overly aggressive blood pressure reduction could be harmful. One analysis reported that a 10 mmHg fall in mean arterial pressure was associated with a 176 g decrease in birth weight [9]. This effect was unrelated to the type of hypertension or choice of medication.
However, in women with end-organ damage, it is desirable to keep the blood pressure below 140/90 mmHg [32]; it may go as low as 120/80 mmHg. Currently unresolved is whether lowering blood pressure to the "normal" range (ie, 120/80 mm Hg) would confer either maternal or fetal benefits.
Other management issues — Antepartum assessment is directed toward early diagnosis of preeclampsia and fetal growth delay. This is best accomplished by frequent prenatal visits for monitoring maternal blood pressure, proteinuria, and fundal growth and by periodic sonographic estimation of fetal size [3,32]. More than 85 percent of hypertensive women will have uncomplicated pregnancies [1].
Fetal evaluation — There is no consensus on the role of antepartum fetal assessment in management of pregnancies complicated by mild maternal hypertension. A baseline ultrasound examination at 16 to 20 weeks of gestation is recommended to confirm gestational age. This avoids uncertainty about a diagnosis of fetal growth delay versus incorrect estimation of the time of conception if a late pregnancy sonogram shows a small fetus [32]. In the absence of preeclampsia or fetal growth restriction, the need for and frequency of antepartum fetal assessment is controversial. Many clinicians perform a nonstress test with amniotic fluid index or biophysical profile weekly or twice per week in the later third trimester. (See "The fetal biophysical profile" and "Antepartum fetal heart rate assessment".)
Close fetal surveillance is warranted when there is a high potential for uteroplacental vasculopathy, as with preeclampsia or intrauterine growth restriction [6]. In these cases, serial sonographic assessment of fetal growth is indicated (eg, at 28 to 32 weeks, then monthly until delivery), with twice weekly nonstress testing or biophysical profile examination [3,6]. (See "Diagnosis of fetal growth restriction" and "Fetal growth restriction: Evaluation and management".)
Delivery — Women with mild, uncomplicated preexisting hypertension can be allowed to go into spontaneous labor and deliver at term [6]. Earlier delivery can be considered for women with severe hypertension, superimposed preeclampsia, or pregnancy complications (eg, fetal growth restriction, previous stillbirth). (See "Management of preeclampsia", section on Delivery.)
INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. (See "Patient information: Preeclampsia".) We encourage you to print or e-mail this topic review, or to refer patients to our public web site, www.uptodate.com/patients, which includes this and other topics.
SUMMARY AND RECOMMENDATIONS — When hypertension is diagnosed in a pregnant women, the major issues are establishing a diagnosis, deciding the blood pressure at which treatment should be initiated and the target blood pressure, and avoiding drugs that may adversely affect the fetus.
In contrast to nonpregnant individuals in whom blood pressure is staged as normal, prehypertension, or stage 1, 2, or 3, blood pressure in pregnant women is either normal, mild hypertension (140 to 159/90 to 109 mmHg), or severe hypertension (≥160/110 mmHg).
Preeclampsia
- We suggest avoiding antihypertensive therapy for mild hypertension associated with preeclampsia (Grade 2B). There are no proven benefits to mother or fetus, other than reduction in risk of severe hypertension, and we are concerned about potential adverse fetal effects. (See 'Indications for antihypertensive therapy' above.)
- We recommend treatment of severe hypertension (Grade 1B). The goal of treatment is to prevent maternal cerebrovascular complications. We initiate antihypertensive therapy in adult women at systolic pressures ≥150 mm Hg and diastolic blood pressures ≥100 mmHg. We initiate treatment at a lower threshold in younger women whose baseline blood pressure was low, and in those with symptoms that may be attributable to elevated blood pressure (eg, headache, visual disturbances, chest discomfort). (See 'Indications for antihypertensive therapy' above.)
- Our target blood pressure goal is systolic pressure of 140 to 150 mmHg and diastolic pressure of 90 to 100 mmHg. (See 'Target blood pressure' above.)
Preexistent hypertension
- We suggest avoiding treatment of uncomplicated mild essential hypertension (Grade 2B). There are no proven benefits to mother or fetus, other than reduction in risk of severe hypertension, and we are concerned about potential adverse effects on fetal growth. (See 'Mild essential hypertension' above.)
- In women with uncomplicated mild essential hypertension already on antihypertensive therapy who have early pregnancy blood pressures less than 120/80 mmHg, we suggest tapering/discontinuing antihypertensive drugs and closely monitoring the blood pressure response (Grade 2C). Our indications for initiating or reinstituting antihypertensive therapy are persistent diastolic pressures of 95 to 99 mmHg, systolic pressures ≥150 mmHg, or signs of hypertensive end-organ damage. These thresholds, although not in the severe range, allow nonemergent intervention with oral drugs while hypertension is only moderately elevated. (See 'Mild essential hypertension' above.)
- Subgroups of women with mild hypertension appear to be at greater risk of maternal or fetal complications and may benefit from antihypertensive therapy. (See 'Complicated and secondary hypertension' above.)
- Severe hypertension is treated to protect the mother from serious complications, such as stroke, heart failure, or renal failure. (See 'Severe hypertension' above.)
- The blood pressure goal in women without end-organ damage is systolic pressure 140 to 150 mmHg and diastolic pressure 90 to 100 mmHg. In women with end-organ damage, the goal is <140/90 mmHg and as low as 120/80 mmHg. (See 'Mild essential hypertension' above.)
- Nonsteroidal antiinflammatory medications may contribute to blood pressure elevation postpartum. (See 'Postpartum hypertension' above.)
