病因学提示脑瘫的形成是多因素的,因此预防脑瘫需要根据精确的病因学支持的多种手段。 通过对危险因素的诊断和治疗预防是有效的。
母体孕期有高危因素如碘缺乏、甲状腺疾病、孕期感染等应进行早期筛查及治疗。 孕期应尽早预防/治疗TORCH感染。 应避免不必要的放射线照射及使用不必要的药物。 Rh阴性的母亲应进行免疫治疗,新生儿高胆红素血症应进行蓝光治疗和换血治疗。
应尽可能避免早产,尽可能积极治疗早产的并发症。 目前的治疗是通过尝试阻止在严重不良事件如窒息或新生儿卒中的炎症改变,来最大程度减少神经结构的损伤。[40]Nelson KB, Chang T. Is cerebral palsy preventable? Curr Op Neurol. 2008 Apr;21(2):129-35.http://www.ncbi.nlm.nih.gov/pubmed/18317269?tool=bestpractice.com 有高质量的证据支持在有早产风险的患者中进行硫酸镁输注,因为硫酸镁可以预防早产儿发生脑瘫。[41]Shepherd E, Salam RA, Middleton P, et al. Antenatal and intrapartum interventions for preventing cerebral palsy: an overview of Cochrane systematic reviews. Cochrane Database Syst Rev. 2017 Aug 8;(8):CD012077.http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD012077.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28786098?tool=bestpractice.com[42]Conde-Agudelo A, Romero R. Antenatal magnesium sulfate for the prevention of cerebral palsy in preterm infants less than 34 weeks' gestation: a systematic review and metaanalysis. Am J Obstet Gynecol. 2009 Jun;200(6):595-609.http://www.ncbi.nlm.nih.gov/pubmed/19482113?tool=bestpractice.com[43]Doyle LW, Crowther CA, Middleton P, et al. Antenatal magnesium sulfate and neurologic outcome in preterm infants: a systematic review. Obstet Gynecol. 2009 Jun;113(6):1327-33.http://www.ncbi.nlm.nih.gov/pubmed/19461430?tool=bestpractice.com[44]Doyle LW, Crowther CA, Middleton P, et al. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD004661.http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD004661.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19160238?tool=bestpractice.com[45]Gilbert GE, Wahlquist AH, eds. InfoPOEMS: antenatal magnesium neuroprotective for premies. J Natl Med Assoc. 2009;101(8):824.[46]Costantine MM, Weiner SJ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants: a meta-analysis. Obstet Gynecol. 2009 Aug;114(2 Pt 1):354-64.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761069/http://www.ncbi.nlm.nih.gov/pubmed/19622997?tool=bestpractice.com[47]Rouse DJ, Hirtz DG, Thom E, et al; Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med. 2008 Aug 28;359(9):895-905.http://www.nejm.org/doi/full/10.1056/NEJMoa0801187http://www.ncbi.nlm.nih.gov/pubmed/18753646?tool=bestpractice.com 数项研究已证实此疗法的作用机制在于产前使用硫酸镁的神经保护作用。[48]Wolf HT, Hegaard HK, Greisen G, et al. Treatment with magnesium sulphate in pre-term birth: a systematic review and meta-analysis of observational studies. J Obstet Gynaecol. 2012 Feb;32(2):135-40.http://www.ncbi.nlm.nih.gov/pubmed/22296422?tool=bestpractice.com[49]Doyle LW. Antenatal magnesium sulfate and neuroprotection. Curr Opin Pediatr. 2012 Apr;24(2):154-9.http://www.ncbi.nlm.nih.gov/pubmed/22227787?tool=bestpractice.com[50]American College of Obstetricians and Gynecologists Committee on Obstetric Practice; Society for Maternal-Fetal Medicine. Committee opinion no. 455: magnesium sulfate before anticipated preterm birth for neuroprotection. Obstet Gynecol. 2010 Mar;115(3):669-71.http://www.ncbi.nlm.nih.gov/pubmed/20177305?tool=bestpractice.com[51]Magee L, Sawchuck D, Synnes A, et al; Magnesium Sulphate for Fetal Neuroprotection Consensus Committee; Maternal Fetal Medicine Committee. SOGC clinical practice guideline: magnesium sulphate for fetal neuroprotection. J Obstet Gynaecol Can. 2011 May;33(5):516-29.https://sogc.org/wp-content/uploads/2013/01/gui258CPG1106E.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/21639972?tool=bestpractice.com 南澳大利亚孕产妇和新生儿实践社区 (South Australia Maternal and Neonatal Community of Practice) 发表了一份关于硫酸镁用于胎儿神经保护的临床指南。[52]SA Maternal & Neonatal Community of Practice. Magnesium sulphate for neuroprotection of the fetus in women at risk of preterm birth. Apr 2016 [internet publication].http://www.sahealth.sa.gov.au/wps/wcm/connect/86f3f2804ee4f45294189dd150ce4f37/magnesium+sulphate+neuroprotect+fetus+risk+preterm_27042016.pdf 美国食品药品监督管理局 (FDA) 并不推荐为了阻止早产而连续使用胃肠外硫酸镁超过 5-7 天。长期使用(超过 5-7 天)可能导致发育中的婴儿或胎儿出现低钙水平和骨骼问题,包括骨量减少和骨折。[53]US Food and Drug Administration. Drug safety communications: FDA recommends against prolonged use of magnesium sulfate to stop pre-term labor due to bone changes in exposed babies. May 2013 [internet publication].https://www.fda.gov/downloads/Drugs/DrugSafety/UCM353335.pdf
在学龄期进行随访,比较硫酸镁和安慰剂对极早产儿的治疗效果,结果并未证实早期儿童研究的发现,但也没有显示任何有害影响。 不能排除死亡率优势。[54]Doyle LW, Anderson PJ, Haslam R, et al; Australasian Collaborative Trial of Magnesium Sulphate (ACTOMgSO4) Study Group. School-age outcomes of very preterm infants after antenatal treatment with magnesium sulfate vs placebo. JAMA. 2014 Sep 17;312(11):1105-13.https://jamanetwork.com/journals/jama/fullarticle/1904828http://www.ncbi.nlm.nih.gov/pubmed/25226476?tool=bestpractice.com 一项 Cochrane 综述未能证实硫酸镁对足月儿的保护作用。[55]Nguyen TM, Crowther CA, Wilkinson D, et al. Magnesium sulphate for women at term for neuroprotection of the fetus. Cochrane Database Syst Rev. 2013 Feb 28;(2):CD009395.http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD009395.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23450601?tool=bestpractice.com 低温疗法可阻止炎性因子的级联反应对缺血缺氧脑病的足月儿造成的永久性脑损伤。[56]Edwards AD, Brocklehurst P, Gunn AJ, et al. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ. 2010 Feb 9;340:c363.https://www.bmj.com/content/340/bmj.c363.longhttp://www.ncbi.nlm.nih.gov/pubmed/20144981?tool=bestpractice.com[57]Shah PS. Hypothermia: a systematic review and meta-analysis of clinical trials. Semin Fetal Neonatal Med. 2010 Oct;15(5):238-46.http://www.ncbi.nlm.nih.gov/pubmed/20211588?tool=bestpractice.com[58]Rizzotti A, Bas J, Cuestas E. Efficacy and security of therapeutic hypothermia for hypoxic ischemic encephalopathy: a meta-analysis [in Spanish]. Rev Fac Cien Med Univ Nac Cordoba. 2010;67(1):15-23.http://www.ncbi.nlm.nih.gov/pubmed/21192128?tool=bestpractice.com[59]Wu L, Yi B, Hu Y, et al. The efficacy of hypothermia in hypoxic-ischemic encephalopathy at 18 mo or more. Indian J Pediatr. 2012 Oct;79(10):1342-6.http://www.ncbi.nlm.nih.gov/pubmed/22231774?tool=bestpractice.com 推荐患有缺血缺氧脑病的足月或近足月儿应尽可能在生后6小时之内应用低温疗法。[60]Jacobs SE, Morley CJ, Inder TE, et al. Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial. Arch Pediatr Adolesc Med. 2011 Aug;165(8):692-700.https://jamanetwork.com/journals/jamapediatrics/fullarticle/1107569http://www.ncbi.nlm.nih.gov/pubmed/21464374?tool=bestpractice.com[61]Tagin MA, Woolcott CG, Vincer MJ, et al. Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. Arch Pediatr Adolesc Med. 2012 Jun 1;166(6):558-66.https://jamanetwork.com/journals/jamapediatrics/fullarticle/1149494http://www.ncbi.nlm.nih.gov/pubmed/22312166?tool=bestpractice.com[62]Pfister RH, Soll RF. Hypothermia for the treatment of infants with hypoxic-ischemic encephalopathy. J Perinatol. 2010 Oct;30 Suppl:S82-7.http://www.ncbi.nlm.nih.gov/pubmed/20877413?tool=bestpractice.com[63]Thoresen M. Hypothermia after perinatal asphyxia: selection for treatment and cooling protocol. J Pediatr. 2011 Feb;158(2 Suppl):e45-9.http://www.ncbi.nlm.nih.gov/pubmed/21238705?tool=bestpractice.com [
]What are the benefits and harms of cooling in newborns with hypoxic ischemic encephalopathy?https://cochranelibrary.com/cca/doi/10.1002/cca.301/full显示答案 重组人促红素已经显示出在出生后 72 小时内给予时可改善极早产儿的结果。 死亡或中度至重度神经功能障碍的风险从 26.9% 降至 13.0%。 单独神经功能障碍的发生率从 18.8% 降至 7.1%,并且未观察到过多不良事件。[64]Song J, Sun H, Xu F, et al. Recombinant human erythropoietin improves neurological outcomes in very preterm infants. Ann Neurol. 2016 Jul;80(1):24-34.https://onlinelibrary.wiley.com/doi/full/10.1002/ana.24677http://www.ncbi.nlm.nih.gov/pubmed/27130143?tool=bestpractice.com
已经证实,预防性抗生素(用于羊水未破裂的早产患者,以及刚出生的怀疑损伤的早产儿)可能无效,并可能造成损害。早产前接受一个或多个疗程的皮质类固醇治疗,似乎对儿童患脑瘫的几率没有明确影响。[41]Shepherd E, Salam RA, Middleton P, et al. Antenatal and intrapartum interventions for preventing cerebral palsy: an overview of Cochrane systematic reviews. Cochrane Database Syst Rev. 2017 Aug 8;(8):CD012077.http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD012077.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28786098?tool=bestpractice.com 一项 Cochrane 评价试图研究母体使用褪黑素对胎儿神经保护的作用,但未发现可纳入该评价的任何随机临床试验,因此作者无法提出任何实践建议。[65]Wilkinson D, Shepherd E, Wallace EM. Melatonin for women in pregnancy for neuroprotection of the fetus. Cochrane Database Syst Rev. 2016 Mar 29;(3):CD010527.http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD010527.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27022888?tool=bestpractice.com