孕早期服用β受体阻滞剂是否会造成胎儿先天性畸形的系统评价与Meta分析

Risk of Congenital Malformations Associated with Exposure to Beta-blockers Early in Pregnancy:A Systematic Review and Meta-analysis

目的分析在怀孕早期服用β受体阻滞剂是否与胎儿出生缺陷存在相关性。方法系统检索Pub Med、EMbase、Cochrane临床试验、clinicaltrials.gov、CBM、万方和CNKI数据库,纳入所有β受体阻滞剂和胎儿出生缺陷相关的队列研究和病例对照研究。检索时间均从建库至2014年12月。评价纳入文献质量,并采用Rev Man5.3进行统计分析。结果共纳入15个研究。纳入文献质量评分5~7分。Meta分析结果显示服用β受体阻滞剂与胎儿总体畸形率无相关性,而与器官畸形率[OR=2.21,95%CI(1.63,3.01)]、唇腭裂[OR=3.11,95%CI(1.79,5.43)]以及神经管畸形率(OR=3.56,95%CI(1.19,10.67)]存在相关性。结论由于纳入的研究存在较大的异质性、且样本量较小,因此很难判断在怀孕早期服用β受体阻滞剂是否会造成胎儿出生缺陷。需要更多高质量大样本研究进一步论证。

Objective To determine teratogenicity of beta-blockers in early pregnancy.Methods We searched Pub Med,EMbase,Cochrane Clinical Trials,clinicaltrials.gov,CBM,Wanfang database,and CNKI from establishment of each database to December 2014.We evaluated the quality of included literature.Statistical analysis was conducted in Rev Man5.3 software.Results Fifteen population-based case-control or cohort studies were identified.The score of included studies changed from 5-7 points.Based on meta-analysis,first trimester oral beta-blocker use showed no increased odds of all or major congenital anomalies.While in analysis examining organ-specific malformations,statistically increased odds of cardiovascular(CV) defects with OR 2.21 and 95% CI 1.63 to 3.01,cleft lip/palate(CL/P) with OR 3.11 and 95% CI 1.78 to 9.89,and neural tube(NT) defects with OR 3.56 and 95% CI1.19 to 10.67 were observed.Conclusion Causality is difficult to interpret given small number of heterogeneous studies and possibility of biases.Given the frequency of this exposure in pregnancy,further research is needed.