【罂粟摘要】妊娠期全麻对胎儿神经认知发育影响的系统评价及Meta分析
妊娠期全麻对胎儿神经认知发育影响的系统评价及Meta分析
贵州医科大学 高鸿教授课题组
翻译：牛振瑛 编辑：佟睿 审校：曹莹
背景
美国食品和药物管理局警告中提出，孕妇暴露在全身麻醉剂中可能会损害胎儿的大脑发育。这篇综述系统地评估了这一警告背后的证据。
方法
检索PubMed、EMBASE和Web of Science从建库到2020年4月3日的所有文献。临床前和临床研究均符合纳入标准。排除标准包括病例报告、体外模型、慢性暴露和仅在分娩期间暴露的研究。本综述对标准化平均数差异进行了Meta分析。主要观察指标是对学习/记忆的总体影响。次要观察指标包括神经元损伤的标记物(凋亡、突触形成、神经元密度和增殖)和亚组分析。
结果
共纳入65项临床前实验研究，未发现临床研究。孕期麻醉会损害学习和记忆(标准化均值差-1.16，95%可信区间-1.46~-0.85)，并导致所有实验模型的神经元损伤，但与麻醉药物和孕期无关。在大多数研究中，偏倚的风险很高。尽管它们的大脑发育与人类有很大的不同，啮齿动物仍是最常用的动物物种。在少数研究中，未区分麻醉与手术的影响。在许多研究中，生理稳态的监测和严格控制均低于临床前和临床标准。暴露的时间和频率以及麻醉剂量往往比临床常规高得多。
结论
在临床前研究中，麻醉可引起孕期神经毒性的结论是一致的，但将这些结果转化为临床情况仍受到几个因素的限制。需要进一步的临床观察研究。
原始文献来源
Bleeser T, et al.Effects of general anaesthesia during pregnancy on neurocognitive development of the fetus: a systematic review and meta-analysis [J].Br J Anaesth. 2021 Jun;126(6):1128-1140. doi: 10.1016/j.bja.2021.02.026.
Effects of general anaesthesia during pregnancy on neurocognitive development of the fetus: a systematic review and meta-analysis
Background: The US Food and Drug Administration warned that exposure of pregnant women to general anaesthetics may impair fetal brain development. This review systematically evaluates the evidence underlying this warning.
Methods: PubMed, EMBASE, and Web of Science were searched from inception until April 3, 2020. Preclinical and clinical studies were eligible. Exclusion criteria included case reports, in vitro models, chronic exposures, and exposure only during delivery. Meta-analyses were performed on standardised mean differences. The primary outcome was overall effect on learning/memory. Secondary outcomes included markers of neuronal injury (apoptosis, synapse formation,neurone density, and proliferation) and subgroup analyses.
Results: There were 65 preclinical studies included, whereas no clinical studies could be identified. Anaesthesia during pregnancy impaired learning and memory (standardised mean difference -1.16, 95% confidence interval -1.46 to -0.85) and resulted in neuronal injury in all experimental models, irrespective of the anaesthetic drugs and timing in pregnancy. Risk of bias was high in most studies. Rodents were the most frequently used animal species, although their brain development differs significantly from that in humans. In a minority of studies, anaesthesia was combined with surgery. Monitoring and strict control of physiological homeostasis were below preclinical and clinical standards in many studies. The duration and frequency of exposure and anaesthetic doses were often much higher than in clinical routine.
Conclusion:Anaesthesia-induced neurotoxicity during pregnancy is a consistent finding in preclinical studies, but translation of these results to the clinical situation is limited by several factors. Clinical observational studies are needed.