Einarson Thomas R, Kennedy Deborah, Einarson Adrienne
The Motherisk Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
J Popul Ther Clin Pharmacol. 2012;19(2):e334-48. Epub 2012 Aug 29.
Many studies examining the teratogenic potential of antidepressants have been published. A variety of observational designs have been used with apparent conflicting results, although odds ratios were rarely >2.
To examine whether these apparent differences were associated with research methods such as model, comparison groups, data source, data collection procedures, definition of malformations, outcome ascertainment or management of confounders.
Medline and Embase were searched using terms: pregnancy, antidepressants, serotonin uptake inhibitors OR SSRI, AND embryonic structures OR congenital malformations OR fetal development for observational studies with original data. Data were analyzed using a structured approach and narrative review. Designs that were compared, included prospective cohort, retrospective cohort, and case-control studies. Rates of major malformations and cardiac malformations were combined by study type using random effects meta-analytic models.
We identified 150 papers; 127 were rejected, 23 were analyzed: 9 prospective cohort, 8 retrospective cohort, and 6 case-control studies. Sample sizes were large (1,818 exposed in case-control and 16,824 in cohort studies), providing relatively robust findings. Overall Odds Ratios for major malformations ranged from 1.03-1.24 and 0.81-1.32 for cardiac malformations. No discrepancies among research designs were identified.
Diverse observational models with differing strengths and weaknesses produced remarkably similar non-significant results. Perceived conflicting results may be due to subsequent dissemination of results with attention given to small statistically differences with negligible clinical importance. Improved methods of knowledge transfer and translation are required to provide sound evidence-based information to assist in decision-making surrounding the use of antidepressants in pregnancy.
许多关于抗抑郁药致畸潜力的研究已经发表。尽管优势比很少大于2，但使用了各种观察性设计，结果明显相互矛盾。
研究这些明显的差异是否与研究方法有关，如模型、对照组、数据来源、数据收集程序、畸形定义、结果确定或混杂因素的处理。
使用以下检索词在Medline和Embase数据库中进行检索：妊娠、抗抑郁药、血清素摄取抑制剂或SSRI，以及胚胎结构或先天性畸形或胎儿发育，以查找有原始数据的观察性研究。采用结构化方法和叙述性综述对数据进行分析。所比较的设计包括前瞻性队列研究、回顾性队列研究和病例对照研究。使用随机效应荟萃分析模型按研究类型合并主要畸形和心脏畸形的发生率。
我们共识别出150篇论文；其中127篇被排除，23篇进行了分析：9篇前瞻性队列研究、8篇回顾性队列研究和6篇病例对照研究。样本量较大（病例对照研究中有1818例暴露者，队列研究中有16824例），得出的结果相对可靠。主要畸形的总体优势比范围为1.03 - 1.24，心脏畸形的总体优势比范围为0.81 - 1.32。未发现研究设计之间存在差异。
具有不同优缺点的多种观察性模型产生了非常相似的无显著差异的结果。所感知到的相互矛盾的结果可能是由于随后对结果的传播，只关注了临床重要性可忽略不计的微小统计学差异。需要改进知识转移和转化方法，以提供可靠的循证信息，协助围绕孕期使用抗抑郁药的决策。
