Hypertension in pregnancy: Tailoring treatment to risk
Not all hypertensive gravidas should receive drug therapy. In fact, antihypertensive medications should be halted in some patients. Here, 2 experts present a comprehensive plan for high- and low-risk women.
- Labetalol. We consider labetalol a first-line agent for controlling hypertension in pregnancy. This beta-blocking drug provides the added benefit of alpha-adrenergic blockade, which offers the theoretical advantage of vasodilation—not seen with traditional beta-blockers. Overall, labetalol has an excellent record of safety in pregnancy.
In a randomized, controlled trial involving 86 mildly hypertensive patients who initiated labetalol therapy between 6 and 13 weeks’ gestation, no major congenital malformations were identified.6 Although there have been reports of an increased risk for SGA infants in patients treated with labetalol for mild pregnancy-induced hypertension during the second and third trimesters, this association has not been documented in women with chronic hypertension.6
- Thiazide diuretics. If labetalol fails to control blood pressure, we typically add either the calcium-channel blocker nifedipine or a thiazide diuretic. Use of the latter has been well documented in pregnancy. Indeed, thiazide diuretics can be given in the first trimester and throughout gestation without associated risks of major fetal malformations or adverse fetal-neonatal complications.
- Calcium-channel blockers. Calcium-channel–blocking agents also have an excellent safety profile in pregnancy. They have been studied both as antihypertensive medications (primarily in the second and third trimesters) and as tocolytic agents. In a prospective, multicenter, cohort study in which 78 women were exposed to calcium-channel blockers (mainly nifedipine and verapamil) during the first trimester, there was no increase in the rate of birth defects.22
A separate prospective, randomized trial evaluated the benefit of nifedipine in pregnancy. A total of 283 women—47% of whom had chronic hypertension—were enrolled between 12 and 34 weeks’ gestation (mean: 24 weeks). Researchers found patients on nifedipine therapy experienced no improvement in maternal or neonatal outcomes compared to subjects assigned to no treatment.23 Follow-up at 18 months of 94 of the infants exposed to nifedipine in utero showed no adverse effects on development.24
- Methyldopa. For many obstetricians, methyldopa remains a first-line agent for the treatment of chronic hypertension in pregnancy.1 It has a well-documented safety record in both short-term25 and long-term follow-up of children exposed in utero.26 Indeed, many studies have evaluated use of this medication to manage mild to moderate hypertension, with no evidence of adverse maternal or fetal outcome. However, it is now rarely used in the nonpregnant population, and the safety of other medications, such as labetalol and nifedipine, has prompted us to stop giving it.
- Other considerations. Finally, when choosing an antihypertensive drug, the physician must consider the benefits and response of specific agents in particular risk groups (TABLE 5).
In women with diabetes, calcium-channel blockers have a reno-protective effect and are our first-line agent in pregnancy, since ACE inhibitors, which also offer this benefit, must be avoided beyond 16 weeks’ gestation because of the potential adverse fetal effects.
In women with diabetes, calcium-channel blockers have a reno-protective effect and are our first-line agent in pregnancy.
Young African-American women frequently have low-renin, salt-sensitive hypertension, and therefore thiazide diuretics or nifedipine may be better first-line agents in this population.
TABLE 4
Agents for treating chronic hypertension in pregnancy
| DRUG | STARTING DOSE | MAXIMUM DAILY DOSE | COMMON SIDE EFFECTS |
|---|---|---|---|
| Labetalol | 100 mg every 8 h | 1,200–2,400 mg | Headache Tremulousness |
| Thiazide diuretic | 12.5 mg twice daily | 50 mg | Hypokalemia |
| Nifedipine | Hypotension | ||
| Short acting | 10 mg every 8 h | 120 mg | Headache |
| Long acting | 30 mg/d | 240 mg | Tachycardia |
| Alpha methyldopa | 250 mg twice daily | 4 g | Thirst Drowsiness Elevation of liver enzymes |
TABLE 5
Medical factors guiding selection of antihypertensive medication
| If the patient has… | It’s generally best to start with… |
|---|---|
| Diabetes | Calcium-channel blocker |
| Vascular disease | |
| Salt-wasting hypertension* | Thiazide diuretic |
| Left ventricular systolic dysfunction | |
| Mitral stenosis | |
| *Mostly African-American women | |
Severe gestational hypertension and preeclampsia
Women who develop severe gestational hypertension (systolic BP of 160 mm Hg or more or diastolic BP of 110 mm Hg or more) and/or preeclampsia require antihypertensive treatment during management remote from term. In this case, the aim of antihypertensive drug treatment is to keep systolic BP between 150 and 159 mm Hg and diastolic BP between 100 and 109 mm Hg in order to not compromise uteroplacental blood flow.
Because nitroprusside is both a vasodilator and a venodilator, it is an ideal agent for gravidas with hypertensive encephalopathy.
The drugs to use are oral labetalol and/or oral nifedipine. If maternal BP is not adequately controlled with maximum doses of labetalol plus nifedipine, the patient should be delivered.
Severe hypertension and encephalopathy
Hypertensive encephalopathy is a medical emergency. This rare complication of hypertension in pregnancy27 is marked by severely elevated BP, with the diastolic level frequently exceeding 130 mm Hg. Associated findings include headache, visual disturbances, nausea, vomiting, seizures, confusion, stupor, and coma. Also possible are retinal hemorrhage, exudates, papilledema, and evidence of renal or cardiac disease. Transient focal neurologic findings may be present as well, but more often suggest vascular disease, hemorrhage, embolism, or thrombosis.
