Galinsky Robert, Bennet Laura, Groenendaal Floris, Lear Christopher A, Tan Sidhartha, van Bel Frank, Juul Sandra E, Robertson Nicola J, Mallard Carina, Gunn Alistair J
Dev Neurosci. 2014;36(2):73-82. doi: 10.1159/000362206.
There is an important unmet need to further improve the outcome of neonatal encephalopathy in term infants. Meta-analyses of large controlled trials now suggest that maternal magnesium sulfate (MgSO4) therapy is associated with a reduced risk of cerebral palsy and gross motor dysfunction after premature birth, but that it has no effect on death or disability. Because of this inconsistency, it remains controversial whether MgSO4 is clinically neuroprotective and, thus, it is unclear whether it would be appropriate to test MgSO4 for treatment of encephalopathy in term infants. We therefore systematically reviewed the preclinical evidence for neuroprotection with MgSO4 before or after hypoxic-ischemic encephalopathy (HIE) in term-equivalent perinatal and adult animals. The outcomes were highly inconsistent between studies. Although there were differences in dose and timing of administration, there was evidence that beneficial effects of MgSO4 were associated with confounding mild hypothermia and, strikingly, the studies that included rigorous maintenance of environmental temperature or body temperature consistently suggested a lack of effect. On balance, these preclinical studies suggest that peripherally administered MgSO4 is unlikely to be neuroprotective. Rigorous testing in translational animal models of perinatal HIE is needed before MgSO4 should be considered in clinical trials for encephalopathy in term infants.
进一步改善足月儿新生儿脑病的治疗效果存在一项重要的未满足需求。对大型对照试验的荟萃分析表明，母亲使用硫酸镁（MgSO4）治疗与早产后脑性瘫痪和严重运动功能障碍风险降低相关，但对死亡或残疾无影响。由于这种不一致性，MgSO4是否具有临床神经保护作用仍存在争议，因此，对于在足月儿中测试MgSO4治疗脑病是否合适尚不清楚。因此，我们系统回顾了足月围产期和成年动物在缺氧缺血性脑病（HIE）之前或之后使用MgSO4进行神经保护的临床前证据。各研究结果高度不一致。虽然给药剂量和时间存在差异，但有证据表明MgSO4的有益作用与混杂的轻度低温有关，而且，那些包括严格维持环境温度或体温的研究一致表明没有效果。总体而言，这些临床前研究表明，外周给予MgSO4不太可能具有神经保护作用。在将MgSO4纳入足月儿脑病的临床试验之前，需要在围产期HIE的转化动物模型中进行严格测试。
