Review: Pharmacologic treatment of hypertension during pregnancy reduces perinatal deaths and severe maternal hypertension
ACP J Club. 1998 May-June;128:63. doi:10.7326/ACPJC-1998-128-3-063
Rey E, LeLorier J, Burgess E, Lange IR, Leduc L. Report of the Canadian Hypertension Society Consensus Conference: 3. Pharmacologic treatment of hypertensive disorders in pregnancy. CMAJ. 1997 Nov 1; 157:1245-54.
To determine the effectiveness of pharmacologic treatment of hypertensive disorders during pregnancy.
English- and French-language studies were identified by using MEDLINE (1962 to September 1996) with the search terms human pregnancy toxemia, preeclampsia, eclampsia, complications (cardiovascular), and hypertension; and by using the Cochrane Database of Systematic Reviews (Pregnancy and Childbirth Module). Bibliographies of retrieved studies, review articles, and personal files of panel members were also reviewed.
Studies were selected if they included the outcomes of perinatal death, preterm delivery, intrauterine growth retardation (IUGR), severe hypertension, superimposed gestational hypertension, blood pressure (BP), and seizures.
Data were extracted on drug treatments, outcomes, and safety. Evidence from studies was assessed for quality by using a 6-point rating based on study design, methods, and findings.
Randomized controlled trials (RCTs) showed that methyldopa reduced perinatal deaths after 12 weeks of gestation and prevented severe hypertension in women with preexisting hypertension. Atenolol, labetalol, nifedipine, oxprenolol, pindolol, metoprolol plus hydralazine, and clonidine plus hydralazine prevented severe hypertension in women with gestational hypertension. Antihypertensive drugs did not affect IUGR (although data on atenolol conflicted) and did not prevent gestational hypertension with proteinuria in women with preexisting hypertension. No fetal malformations were attributed to methyldopa, β-blockers, or clonidine, although data on first trimester use were limited. Angiotension-converting enzyme inhibitors were associated with miscarriage, fetal death, renal failure, and malformations.
Controlled trials found that hydralazine, labetalol, and nifedipine decreased BP in women with severe hypertension. 2 RCTs that compared magnesium sulfate and phenytoin in women with severe gestational hypertension reported no convulsions or perinatal deaths in the treatment groups. 1 RCT of 3534 women with BP > 140/90 mm Hg found that seizures were less frequent in the magnesium sulfate group than in the phenytoin group but found no difference in perinatal deaths. In a multicenter RCT of 1680 women, those receiving magnesium sulfate had a 52% lower risk for recurrent seizures than those receiving diazepam and a 67% lower risk than those receiving phenytoin. All 3 groups had similar perinatal death rates. No adverse neonatal effects were reported with short-term use of phenytoin.
Pharmacologic treatment of women with hypertension during pregnancy reduces perinatal deaths and severe maternal hypertension but does not affect intrauterine growth retardation or development of gestational hypertension with proteinuria in women who have preexisting hypertension.
Sources of funding: Canadian Hypertension Society and Roberts Pharmaceutical Canada, Inc.
For article reprint: Dr. E. Rey, Department of Obstetrics and Gynecology, Hôpital Sainte-Justine, 3175 Côte Sainte-Catherine, Montreal, Quebec H3T 1C5, Canada. FAX 514-345-4878.
Hypertension in pregnancy is a major cause of maternal and fetal mortality worldwide. The review by Rey and colleagues provides excellent evidence-based guidelines for physicians who treat pregnant women. Methyldopa is still the first-line drug recommended for treatment of nonsevere hypertension in pregnancy, not necessarily because it is the best drug but because it is the best-studied. Methyldopa, atenolol, labetalol, oxprenolol, pindolol, and combinations of the these drugs may prevent severe hypertension, but no drug has clearly been shown to prevent preterm delivery, IUGR, or preeclampsia.
Methyldopa, timolol, and nifedipine are effective for treating hypertension during the postpartum period and are compatible with breast feeding. The highest level of evidence has proven magnesium sulfate to be the first-line drug for treatment of eclampsia convulsions. Prophylactic use of magnesium sulfate is recommended for hypertension-related convulsions but awaits further evidence from a large trial that compares magnesium sulfate with placebo.
For severe hypertension during pregnancy, Rey and colleagues recommended intravenous (IV) hydralazine, 5 to 10 mg every 20 minutes; IV labetalol, 10 to 20 mg every 10 minutes up to 300 mg or 1 to 2 mg IV/min; or oral nifedipine, 10 mg every 2 to 3 hours. Because the diastolic BP nadir occurs about 40 minutes after IV hydralazine and oral nifedipine administration and because lower doses are efficacious, it seems safer to start with IV hydralazine, 5 mg, or oral nifedipine, 5 mg, and, if necessary, to give 10 mg (of either drug) 1 hour later (1).
Although the authors state that delivery is the best approach for gestational hypertension, they do not address the question of when to successfully interrupt gestation, perhaps because fetal survival depends on resource availability at delivery locations.
Álvaro Nagib Atallah, MD, PhD, MCE
Universidade Federal de São PauloSão Paulo, Brazil