Reference: BJOG 2016 Jan;123(1):40 (Level 2 [mid-level] evidence)
Hypertensive disorders of pregnancy include pre-eclampsia, eclampsia, gestational hypertension, and chronic hypertension. As a group, these disorders represent the second most common direct cause of maternal mortality in both developed countries (16% of all maternal deaths) and developing countries (9–25% of all maternal deaths) behind hemorrhage (Lancet. 2006;367(9516):1066). Options for first-line treatment of acute severe hypertension in pregnant women include labetalol (either IV bolus or continuous infusion), nifedipine (oral), hydralazine (IV bolus or continuous infusion), or methyldopa (oral) (ACOG Strong Recommendation, Moderate Evidence; Obstet Gynecol. 2013 Nov;122(5):1122). While hydralazine was historically the drug of choice for severe maternal hypertension, it has fallen out of favor due to evidence of increased maternal and fetal complications associated with its use (BMJ 2003;327:955; BMJ 1999;318:1332). Currently, the usage pattern among health care providers suggests a strong preference for labetalol in this setting. A recent Cochrane review of 35 randomized trials comparing different antihypertensive drugs showed that use of calcium channel blockers (nifedipine, isradipine) was associated with decreased persistent high blood pressure compared to hydralazine. However, there was insufficient data regarding the comparative effects of labetalol and nifedipine (Cochrane Database Syst Rev. 2013 Jul 31;(7):CD001449). This raises the question: despite the general tendency towards the use of labetalol for treatment of severe hypertension in pregnancy, is nifedipine a better choice?
A systematic review of 7 randomized trials compared oral nifedipine to IV labetalol in 363 pregnant women with severe hypertension in their second or third trimester of pregnancy. Dosing varied across trials for both medications, but most commonly women received nifedipine 50-90 mg or labetalol 220-300 mg. Primary maternal outcomes were persistent hypertension, maternal hypotension, and serious maternal morbidity. Primary perinatal outcomes included fetal heart rate abnormalities while on treatment, intrauterine fetal death and neonatal death.
Compared to IV labetalol, oral nifedipine was associated with a decreased risk of persistent maternal hypertension in analysis of all trials (risk ratio [RR] 0.42, 95% CI 0.18 – 0.96, NNT 16-313, with persistent maternal hypertension in 8% of the labetalol group). The wide confidence interval that approaches 1 includes the possibility of a clinically insignificant effect. Oral nifedipine was also associated with a decreased risk of neonatal death in analysis of 4 trials with 221 patients (RR 0.27, 95% CI 0.09 – 0.87, NNT 11-77, with neonatal death occurring in 10% of the labetalol group). Risk of maternal side effects was lower with oral nifedipine than with IV labetalol in analysis of 3 trials with 207 patients (RR 0.57, 95% CI 0.35-0.94, NNT 5-53 with maternal side effects in 32% of the labetalol group). There were no significant differences in the risk of other maternal or fetal and perinatal outcomes including maternal death, serious maternal morbidity, hypotension, cesarean section, intrauterine death, fetal heart rate abnormalities, low Apgar score, or neonatal intensive care unit admission.
The authors acknowledge that this study is limited by a low to moderate quality of evidence of the included studies and a small number of studies to date. These concerns limit the strength of the overall findings that oral nifedipine may decrease the risk of neonatal death and maternal side effects when compared to IV labetalol. Nifedipine does have low cost and ease of oral administration, and could be considered by clinicians for urgent control of severe hypertension in pregnancy, particularly in resource-limited settings.
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