There is an important unmet need to improve long term outcomes of encephalopathy for preterm and term infants. Meta-analyses of large controlled trials suggest that maternal treatment with magnesium sulfate (MgSO4) is associated with a reduced risk of cerebral palsy and gross motor dysfunction after premature birth. However, to date, follow up to school age has found an apparent lack of long-term clinical benefit. Because of this inconsistency, it remains controversial whether MgSO4 offers sustained neuroprotection. We systematically reviewed preclinical and clinical studies reported from January 1 2010, to January 31 2020 to evaluate the most recent advances and knowledge gaps relating to the efficacy of MgSO4 for the treatment of perinatal brain injury. The outcomes of MgSO4 in preterm and term-equivalent animal models of perinatal encephalopathy were highly inconsistent between studies. None of the perinatal rodent studies that suggested benefit directly controlled body or brain temperature. The majority of the studies did not control for sex, study long term histological and functional outcomes or use pragmatic treatment regimens and many did not report controlling for potential study bias. Finally, most of the recent preterm or term human studies that tested the potential of MgSO4 for perinatal neuroprotection were relatively underpowered, but nevertheless, suggest that any improvements in neurodevelopment were at best modest or absent. On balance, these data suggest that further rigorous testing in translational preclinical models of perinatal encephalopathy is essential to ensure safety and best regimens for optimal preterm neuroprotection, and before further clinical trials of MgSO4 for perinatal encephalopathy at term are undertaken.

中文翻译：

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硫酸镁用于围产期神经保护的系统评价：过去十年我们学到了什么？

对于改善早产和足月婴儿的脑病的长期结果，存在未满足的重要需求。大型对照试验的荟萃分析表明，产妇用硫酸镁（MgSO4）治疗可降低早产后脑瘫和总体运动功能障碍的风险。然而，迄今为止，对学龄前的随访发现长期临床获益明显缺乏。由于这种不一致，硫酸镁是否提供持续的神经保护作用仍存在争议。我们系统地回顾了从2010年1月1日至2020年1月31日报告的临床前和临床研究，以评估与MgSO4治疗围生期脑损伤的功效有关的最新进展和知识差距。围产期脑病的早产和足月等效动物模型中MgSO4的结果在研究之间高度不一致。没有一项围产期啮齿类动物研究表明可以直接控制身体或大脑温度。大多数研究没有控制性别，研究长期的组织学和功能结局或使用务实的治疗方案，许多研究没有报告控制潜在的研究偏见。最后，测试MgSO4对围产期神经保护的潜力的大多数近期早产或足月人类研究都相对不足，但是尽管如此，它们表明神经发育的任何改善至多还是适度的。总的来说，