Antenatal exposure to antidepressant drugs and the risk of neurodevelopmental and psychiatric disorders: a systematic review

Abstract: This study investigated whether antenatal exposure to antidepressants (ADs) increases the risks of autism spectrum disorders (ASD), attention deficit/hyperactivity disorders (ADHD), schizophrenia and other mental illnesses, and cognitive and developmental deficits in infants or preschool children. PubMed, EMBASE, BIREME/BVS databases were searched to identify studies examining associations of ADs in pregnancy with neurodevelopmental and psychiatric disorders. Twenty studies addressed ASD and/or ADHD risks while 30 focused on developmental and cognitive deficits in infants or preschool children. Most studies detected no association of antenatal AD with ASD after adjustment of risk ratios for maternal depression or psychiatric disorders. Some studies showed that maternal depression, regardless of whether it is treated or untreated, increased ASD risks. Seven out of 8 studies found no increase in ADHD risk associated with antenatal exposure to selective serotonin reuptake inhibitors, the most commonly used AD. No consistent evidence was found linking AD in pregnancy to neurocognitive developmental deficits in infants or preschool children. A residual confounding by indication (depression severity) remained in almost all studies. This systematic review found no consistent evidence suggesting that ADs in pregnancy increase risks of ASD, ADHD, and neurocognitive development deficits. Some studies, however, found evidence that maternal depression increases ASD risks.摘要：本研究旨在探讨产前暴露于抗抑郁药（antidepressants, ADs）是否会增加婴儿或学龄前儿童罹患自闭症谱系障碍（autism spectrum disorders, ASD）、注意缺陷多动障碍（attention deficit/hyperactivity disorders, ADHD）、精神分裂症及其他精神疾病，同时是否会引发认知与发育缺陷的风险。研究通过检索PubMed、EMBASE、BIREME/BVS数据库，筛选旨在分析妊娠期抗抑郁药暴露与神经发育及精神疾病关联的相关研究。其中20项研究聚焦ASD和/或ADHD的发病风险，另有30项研究关注婴儿或学龄前儿童的发育与认知缺陷情况。多数研究在针对母亲抑郁或精神疾病的风险比进行校正后，未发现产前抗抑郁药暴露与ASD存在显著关联。部分研究显示，无论母亲抑郁是否接受治疗，其后代罹患ASD的风险均会升高。8项相关研究中有7项发现，产前暴露于临床最常用的抗抑郁药——选择性5-羟色胺再摄取抑制剂（selective serotonin reuptake inhibitors），并不会增加ADHD的发病风险。目前尚无一致证据表明妊娠期抗抑郁药暴露与婴儿或学龄前儿童的神经认知发育缺陷存在关联。几乎所有研究均存在指征残留混杂（以抑郁严重程度为混杂来源）的问题。本系统综述未发现一致证据支持妊娠期抗抑郁药暴露会增加ASD、ADHD及神经认知发育缺陷的发病风险。不过部分研究显示，母亲抑郁会增加子代罹患ASD的风险。