Andrade Chittaranjan
Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, India.
J Clin Psychiatry. 2017 Sep/Oct;78(8):e1052-e1056. doi: 10.4088/JCP.17f11916.
During the past year, at least 5 new studies, all observational in design, examined the risk of autism spectrum disorder (ASD) in children exposed to antidepressant medication in utero. These studies had not found inclusion in the many systematic reviews and meta-analyses that had also been published in the past year.
Noteworthy methods and findings of the new studies are summarized. One of these studies is examined in detail to help the reader understand methodological and conceptual issues that are critical in the field. Some general caveats in the interpretation of the literature are also discussed.
In order to reduce the limitations associated with their observational design, the new studies used many innovations, including maternal controls with mental illness, propensity score-matched controls, preconception antidepressant exposure controls, sibling controls, paternal antidepressant user controls, and modeling for the presence of an unknown confound. Two studies found an association between maternal antidepressant use during pregnancy and the risk of ASD in the offspring; these associations remained statistically significant even after covariate adjustments. The other 3 studies found that the significant association between antidepressant exposure and ASD risk was lost after statistical adjustment; that preconception antidepressant exposure was also associated with increased risk of ASD; that siblings discordant for antidepressant exposure had similar ASD risk; and that paternal antidepressant use was also associated with increased risk.
The new studies do not change the conclusions of the available meta-analyses. In fact, at least some of the new data strengthen the conclusion that antidepressant use during pregnancy is likely to be a marker of more severe illness and that inadequately measured, unmeasured, or unknown genetic, behavioral, and environmental confounds associated with more severe illness (rather than the antidepressant exposure by itself) may be responsible for the increased risk of ASD.
在过去一年中，至少有5项新的研究（均为观察性设计）探讨了子宫内接触抗抑郁药物的儿童患自闭症谱系障碍（ASD）的风险。这些研究未被纳入过去一年中发表的众多系统评价和荟萃分析。
总结了这些新研究的显著方法和结果。详细分析其中一项研究，以帮助读者理解该领域至关重要的方法学和概念性问题。还讨论了文献解读中的一些一般性注意事项。
为减少与观察性设计相关的局限性，这些新研究采用了许多创新方法，包括患有精神疾病的母亲作为对照、倾向评分匹配对照、孕前抗抑郁药物暴露对照、兄弟姐妹对照、父亲使用抗抑郁药物的对照以及对未知混杂因素存在情况的建模。两项研究发现孕期母亲使用抗抑郁药物与后代患ASD的风险之间存在关联；即使在进行协变量调整后，这些关联在统计学上仍具有显著性。另外三项研究发现，在进行统计调整后，抗抑郁药物暴露与ASD风险之间的显著关联消失；孕前抗抑郁药物暴露也与ASD风险增加有关；抗抑郁药物暴露情况不一致的兄弟姐妹患ASD的风险相似；父亲使用抗抑郁药物也与风险增加有关。
这些新研究并未改变现有荟萃分析的结论。事实上，至少一些新数据强化了以下结论：孕期使用抗抑郁药物可能是更严重疾病的一个标志，与更严重疾病相关的未充分测量、未测量或未知的遗传、行为和环境混杂因素（而非抗抑郁药物暴露本身）可能是ASD风险增加的原因。
