Pregnancy outcome after first trimester exposure to bisoprolol: an observational cohort study.

ABSTRACT

OBJECTIVES: Beta-blockers are frequently used during pregnancy, with labetalol and metoprolol being considered as drugs of choice. As there are no prospective pregnancy studies for bisoprolol yet, our aim was to analyze pregnancy outcomes after bisoprolol exposure. METHODS: Pregnancies exposed to bisoprolol during the first trimester were retrieved from the German Embryotox pharmacovigilance database. Pregnancy outcomes of prospectively ascertained pregnancies were compared with women neither exposed to beta-blockers nor other antihypertensives. In addition, retrospective reports on adverse drug reactions were screened for patterns of birth defects. RESULTS: Inclusion criteria for the prospective study were met by 339 bisoprolol-treated women and 678 patients in the comparison cohort. Neither the risk for spontaneous abortions [adjusted hazard ratio (HRadj.) 1.06; 95% confidence interval (CI) 0.66-1.70] nor for major congenital malformations [adjusted odds ratio (ORadj.) 0.77; 95% CI 0.34-1.75] was increased after first trimester bisoprolol treatment. However, higher rates of preterm births [ORadj. 1.90; 95% CI 1.17-3.11] and reduced birthweights in singleton pregnancies (adjusted standard deviation score difference -0.48; 95% CI -0.62 to -0.34) were noted. Continued treatment with beta-blockers until birth was found to be associated with a higher risk for growth restriction than first trimester exposure only. A sensitivity analysis did not suggest higher rates of adverse pregnancy outcomes in hypertensive women on bisoprolol compared with nonhypertensive bisoprolol-exposed women. CONCLUSION: Our study supports the hypothesis that first trimester bisoprolol treatment does not increase the risk for spontaneous abortions or major birth defects. However, an influence of prolonged bisoprolol exposure on fetal growth cannot be ruled out.