Beta-Blockers for Mild to Moderate Hypertension in Pregnancy

A Cochrane review [Abstract] 1 included 27 studies with a total of 2400 subjects. Oral beta-blockers decrease the risk of severe hypertension (relative risk 0.37, 95% CI 0.26 to 0.53) and the need for additional antihypertensive drugs (RR 0.44, 95% CI 0.31 to 0.62). There are insufficient data for any conclusions about the effect on perinatal mortality or preterm delivery. Beta-blockers seem to be associated with an increase in small for gestational age infants (RR 1.34, 95% CI 1.01 to 1.79).

A population-based retrospective cohort study 3 (911685 births between 1995 and 2008), using the Danish Fertility Database assessed the association between exposure to beta-blockers during pregnancy and the risk of adverse pregnancy outcomes . Beta-blocker exposure during pregnancy (n=2459) was found to be associated with increased risk of small for gestational age (SGA) (adjusted OR 1.97, 95% CI 1.75 to 2.23), preterm birth (aOR 2.26, 95% CI 2.03 to 2.52) and perinatal mortality (aOR 1.89, 95% CI 1.25 to 2.84). Analyses were adjusted for socioeconomic and maternal variables. The authors found similar risk profiles for labetalol and otherβ-blockers.

A retrospective cohort study 4 in Canada compared infant outcomes between mothers with hypertension treated by beta-blockers alone (n=416) and by methyldopa alone (n=1000) during pregnancy (all eligible women, women with chronic hypertension and women with gestational hypertension or pre-eclampsia/eclampsia, separately). Multiple logistic regression analyses were performed to adjust for potential confounding. Adjusted ORs for infants born to mothers with chronic hypertension with beta-blockers only, as compared with methyldopa only, during pregnancy were: SGA < 10th percentile 1.95, 95% CI 1.21 to 3.15).

A systematic review 2 including 34 studies with a total of 2324 subjects was abstracted in DARE. Overall, mean fall in mean arterial pressure was 6.3 mm lower among labetolol treated patients than among the comparison group. When oral beta-blockers were compared to placebo for severe hypertension (6 RCTs): beta-blockers significantly decreased the incidence of severe hypertension: pooled OR 0.27 (95% CI 0.16 to 0.45). In perinatal outcomes beta-blockers significantly decreased the incidence of RDS. Pooled OR = 0.33 (95% CI 0.13 to 0.85). When oral beta-blockers were compared to other drugs (15 RCTs, 959 women), no significant effect was found for beta-blockers on maternal or perinatal outcomes compared to other drugs. Labetolol was associated with significantly less maternal hypotension (4 RCTs) than other drugs: pooled OR 0.13 (95% CI 0.03 to 0.71). The authors conclude it is not clear that the benefits outweigh the risks when beta-blockers are used to treat mild to moderate chronic or pregnancy induced hypertension, given the unknown overall effect on perinatal outcomes.

Comment: The quality of evidence is downgraded by study limitations; inadequate allocation concealment.

References

• Magee LA, Duley L. Oral beta-blockers for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev 2003;(3):CD002863. [PubMed]
• Magee LA, Elran E, Bull SB, Logan A, Koren G. Risks and benefits of beta-receptor blockers for pregnancy hypertension: overview of the randomized trials. Eur J Obstet Gynecol Reprod Biol 2000 Jan;88(1):15-26. [PubMed]
• Meidahl Petersen K, Jimenez-Solem E, Andersen JT et al. ß-Blocker treatment during pregnancy and adverse pregnancy outcomes: a nationwide population-based cohort study. BMJ Open 2012;2(4). [PubMed]
• Xie RH, Guo Y, Krewski D et al. Beta-blockers increase the risk of being born small for gestational age or of being institutionalised during infancy. BJOG 2014;121(9):1090-6. [PubMed]