Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie.
Department of Mathematics, Beuth Hochschule für Technik Berlin (University of Applied Sciences), Berlin, Germany.
J Hypertens. 2018 Oct;36(10):2109-2117. doi: 10.1097/HJH.0000000000001818.
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.
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.
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.
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.
β受体阻滞剂在妊娠期间经常使用，拉贝洛尔和美托洛尔被认为是首选药物。由于目前尚无比索洛尔的前瞻性妊娠研究，我们旨在分析比索洛尔暴露后的妊娠结局。
从德国胚胎毒性药物警戒数据库中检索出在妊娠早期暴露于比索洛尔的妊娠。将前瞻性确定的妊娠结局与既未接触β受体阻滞剂也未接触其他降压药的女性进行比较。此外，还对不良药物反应的回顾性报告进行了筛查，以确定出生缺陷的模式。
前瞻性研究的纳入标准符合 339 名比索洛尔治疗的女性和 678 名对照组患者。与妊娠早期接受比索洛尔治疗后相比，自发性流产的风险（调整后的危险比 [HRadj.] 1.06；95%置信区间 [CI] 0.66-1.70）或主要先天性畸形的风险（调整后的优势比 [ORadj.] 0.77；95% CI 0.34-1.75）均未增加。然而，早产率较高（ORadj. 1.90；95% CI 1.17-3.11）和单胎妊娠的出生体重降低（调整后的标准差评分差异-0.48；95% CI -0.62 至 -0.34）。与仅在妊娠早期接触相比，发现继续使用β受体阻滞剂直至分娩与生长受限的风险增加相关。敏感性分析并未表明在比索洛尔治疗的高血压女性中，不良妊娠结局的发生率高于非高血压的比索洛尔暴露女性。
我们的研究支持了这样的假设，即妊娠早期比索洛尔治疗不会增加自发性流产或主要出生缺陷的风险。然而，不能排除比索洛尔暴露时间延长对胎儿生长的影响。
