Wurst Keele E, Poole Charles, Ephross Sara A, Olshan Andrew F
Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA.
Birth Defects Res A Clin Mol Teratol. 2010 Mar;88(3):159-70. doi: 10.1002/bdra.20627.
Several studies have evaluated maternal first trimester paroxetine use and the prevalence of congenital defects, particularly cardiac defects. To synthesize current epidemiologic information, a meta-analysis was conducted.
A systematic literature search was conducted for original research published from January 1, 1992, through September 30, 2008. Results were extracted using predefined criteria, and authors were contacted for additional information when necessary. Compiled results were evaluated for funnel plot asymmetry, heterogeneity, and study characteristic associations. Where appropriate, fixed-effect summary estimates were calculated and sensitivity analyses performed.
Twenty reports (11 including results for aggregated congenital and combined cardiac defects, six for aggregated congenital defects only, and three for combined cardiac defects only) met prespecified inclusion criteria. There was little evidence of funnel plot asymmetry or overall heterogeneity. Summary estimates were produced for combined cardiac defects (prevalence odds ratio [POR], 1.46; 95% confidence interval [CI], 1.17-1.82) and aggregated congenital defects (POR, 1.24; 95% CI, 1.08-1.43) and first trimester paroxetine use. Some study characteristics may be associated with differential POR estimates for paroxetine and either combined cardiac or aggregated congenital defects.
This meta-analysis found little evidence of publication bias or overall statistical heterogeneity and only weak evidence of associations with some study characteristics. Although subject to limitations, the summary estimate indicates an increased prevalence of combined cardiac defects with first trimester paroxetine use. The summary estimate also indicates an increased prevalence of aggregated congenital defects with paroxetine; however, this association may be explained, in part, by the increased prevalence of combined cardiac defects.
多项研究评估了孕早期母亲使用帕罗西汀与先天性缺陷尤其是心脏缺陷患病率之间的关系。为了综合当前的流行病学信息，进行了一项荟萃分析。
对1992年1月1日至2008年9月30日发表的原始研究进行系统的文献检索。使用预定义标准提取结果，必要时与作者联系以获取更多信息。对汇总结果进行漏斗图不对称性、异质性和研究特征关联评估。在适当情况下，计算固定效应汇总估计值并进行敏感性分析。
20篇报告（11篇包括先天性缺陷合并心脏缺陷的结果，6篇仅包括先天性缺陷汇总结果，3篇仅包括心脏缺陷合并结果）符合预先设定的纳入标准。几乎没有证据表明存在漏斗图不对称性或总体异质性。得出了孕早期使用帕罗西汀与心脏缺陷合并症（患病率比值比[POR]，1.46；95%置信区间[CI]，1.17 - 1.82）以及先天性缺陷汇总症（POR，1.24；95%CI，1.08 - 1.43）的汇总估计值。一些研究特征可能与帕罗西汀以及心脏缺陷合并症或先天性缺陷汇总症的不同POR估计值相关。
这项荟萃分析几乎没有发现发表偏倚或总体统计异质性的证据，仅发现与某些研究特征存在关联的微弱证据。尽管存在局限性，但汇总估计值表明孕早期使用帕罗西汀会使心脏缺陷合并症的患病率增加。汇总估计值还表明帕罗西汀会使先天性缺陷汇总症的患病率增加；然而，这种关联可能部分是由心脏缺陷合并症患病率的增加所解释的。
