早产

对于明显早产出现宫缩的孕妇的初始评估应包括所有有关孕龄的资料进行全面细致的回顾，因为孕龄与预后密切相关。胎儿纤连蛋白检测可以找出高危孕妇，从而影响后续治疗，最终减少早产率。[65]Berghella V, Hayes E, Visintine J, et al. Fetal fibronectin testing for reducing the risk of preterm birth. Cochrane Database Syst Rev. 2008;(4):CD006843.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006843.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/18843732?tool=bestpractice.com对胎儿的监测包括间断听诊或持续胎心宫缩监护 (CTG)； [ ]For women in labor, what are the benefits and harms of continuous cardiotocography (CTG) as a form of electronic fetal monitoring (EFM)?http://cochraneclinicalanswers.com/doi/10.1002/cca.1644/full显示答案但在妊娠早期进行此类监测可能并不合适。应事先考虑好分娩方式，尤其是对需要进行剖宫产者，在这方面几乎没有指导决策的证据，且应将决定权交于有经验的产科医生，并咨询新生儿学专家。如果可能，应让双亲参观NICU。在处于关键孕周（23-26周）的孕妇中，入院治疗可以防止意外分娩时新生儿远离复苏设施。

未足月胎膜早破 (PPROM)的孕妇应住院并密切监测有无感染征象包括孕妇有无心率增快或发热、子宫有无压痛、阴道分泌物是否增多、白细胞或CRP是否升高。然而，这些母体血液检测对于临床诊断绒毛膜羊膜炎的敏感性和特异性很少超过50%。[75]Watts DH, Krohn MA, Hillier SL, et al. Characteristics of women in preterm labor associated with elevated C-reactive protein levels. Obstet Gynecol. 1993;82:509-514.http://www.ncbi.nlm.nih.gov/pubmed/8377973?tool=bestpractice.com应对胎儿进行胎心监测，胎心率增快（＞160 bpm）也是绒毛膜羊膜炎的征象之一。如果需要对胎儿进行监测，建议使用持续胎心监护 (CTG)，不推荐多普勒或生物物理评分作为一线监测方法。[76]Lewis DF, Adair CD, Weeks JW, et al. A randomized clinical trial of daily nonstress testing versus biophysical profile in the management of preterm premature rupture of membranes. Am J Obstet Gynecol. 1999;181:1495-1499.http://www.ncbi.nlm.nih.gov/pubmed/10601934?tool=bestpractice.com

经过谨慎选择的脐带脱垂风险低且炎性标志物正常的未足月胎膜早破 (PPROM)孕妇，可以在住院观察48至72小时后继续门诊随诊监测。这些孕妇仍应每天监测两次体温，并知晓需要住院的感染症状和体征。

针对经选择患者组全部患者的治疗推荐

确诊为未足月胎膜早破 (PPROM) 之后应使用抗生素。可选择红霉素证据 C延长妊娠期：有质量较差的证据表明，在48小时或7天的治疗时间内，红霉素较之安慰剂可能更为有效地减少未足月胎膜早破 (PPROM)后早产儿的比例。低质量的观察性（队列）研究或者受试者＜200名且方法学存在缺陷的随机对照临床试验（RCT）。或青霉素类药物证据 C延长妊娠期：有质量较差的证据表明，青霉素类（除外阿莫西林-克拉维酸）可能较之安慰剂能更有效地减少未足月胎膜早破 (PPROM)后48小时及7天内早产儿的比例。低质量的观察性（队列）研究或者受试者＜200名且方法学存在缺陷的随机对照临床试验（RCT）。。不推荐使用阿莫西林/克拉维酸，因其可能会增加新生儿坏死性小肠结肠炎的风险。

疗程：10天。

针对经选择患者组全部患者的治疗推荐

在妊娠24周至34周时，应常规予皮质类固醇。一旦胎膜破裂，早产不可避免，皮质类固醇对新生儿有益。证据 A降低围产儿并发症发病率和死亡率：有高质量的证据表明，在出生最初的48小时内，较之安慰剂或未干预组，如能在产前使用皮质类固醇，更能有效地减少新生儿呼吸窘迫综合征、脑室内出血、坏死性肠炎和新生儿感染的发生，但就降低慢性肺疾病的发生率而言未更有效。皮质类固醇亦能有效降低围产儿死亡率。倍他米松和地塞米松就结局而言并无差别。系统评价或者受试者＞200名的随机对照临床试验（RCT）。并无证据显示皮质类固醇会增加感染风险。[64]Brownfoot FC, Gagliardi DI, Bain E, et al. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2013;(8):CD006764.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006764.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23990333?tool=bestpractice.com[77]Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev. 2013;(12):CD001058.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001058.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24297389?tool=bestpractice.com

美国妇产科医师协会 (ACOG) 现在建议，在妊娠 23 周时有即将分娩风险的女性中考虑使用皮质类固醇。[83]American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice; Society for Maternal-Fetal Medicine. Committee opinion no.677: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol. 2016;128:e187-e194.http://www.ncbi.nlm.nih.gov/pubmed/27661658?tool=bestpractice.com这个选择取决于家属对复苏的意愿。[83]American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice; Society for Maternal-Fetal Medicine. Committee opinion no.677: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol. 2016;128:e187-e194.http://www.ncbi.nlm.nih.gov/pubmed/27661658?tool=bestpractice.com

有证据表明，在早产妊娠后期（即 35-36 周），给予皮质类固醇可能会减少新生儿呼吸系统并发症，但这些获益必须与可能的不良反应加以权衡。[83]American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice; Society for Maternal-Fetal Medicine. Committee opinion no.677: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol. 2016;128:e187-e194.http://www.ncbi.nlm.nih.gov/pubmed/27661658?tool=bestpractice.com[85]Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374:1311-1320.http://www.ncbi.nlm.nih.gov/pubmed/26842679?tool=bestpractice.com[86]Saccone G, Berghella V. Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials. BMJ. 2016;355:i5044.http://www.bmj.com/content/355/bmj.i5044.longhttp://www.ncbi.nlm.nih.gov/pubmed/27733360?tool=bestpractice.com

可以使用倍他米松或地塞米松。

可考虑对无明显感染迹象的妊娠女性行期待治疗，直至 37 周。[79]Morris JM, Roberts CL, Bowen JR, et al. Immediate delivery compared with expectant management after preterm pre-labour rupture of the membranes close to term (PPROMT trial): a randomised controlled trial. Lancet. 2016;387:444-452.http://www.ncbi.nlm.nih.gov/pubmed/26564381?tool=bestpractice.com

美国妇产科医师大会 (ACOG) 建议自妊娠 34 周起的早产胎膜早破以及妊娠 34 周至 37 周且伴有共病（例如，羊水过少、胎儿多普勒显示异常、先兆子痫、慢性高血压）的情况可分娩。[81]American Congress of Obstetricians and Gynecologists. Medically indicated late-preterm and early-term deliveries. Committee opinion 560. April 2013. http://www.acog.org/ (last accessed 10 May 2017).http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Obstetric_Practice/Medically_Indicated_Late-Preterm_and_Early-Term_Deliveries

没有医学指征时不建议引产，胎儿肺成熟度的评估也不应用于判断是否可以引产。[82]American Congress of Obstetricians and Gynecologists. Nonmedically indicated early-term deliveries. Committee opinion 561. April 2013. http://www.acog.org/ (last accessed 10 May 2017).http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Obstetric_Practice/Nonmedically_Indicated_Early-Term_Deliveries

除此之外，保守治疗是可能的且胎儿能获得进一步成熟，但感染的风险会增加。

绒毛膜羊膜炎会导致胎儿神经系统受损。[72]Yoon BH, Park CW, Chaiworapongsa T. Intrauterine infection and the development of cerebral palsy. BJOG. 2003;110(suppl 20):124-127.http://www.ncbi.nlm.nih.gov/pubmed/12763129?tool=bestpractice.com一旦有感染证据即应分娩，以避免母体及胎儿出现并发症。

妊娠24至34周时即将分娩的高危因素包括规律宫缩、宫颈扩张或胎儿纤连蛋白阳性。

对于有明显早产出现宫缩的孕妇的初始评估应包括对所有有关孕龄的资料进行全面细致的回顾，因为孕龄与预后密切相关。对胎儿的监护包括间断听诊及持续胎心监护 (CTG)，尽管在妊娠极早期监护可能并不恰当。应事先考虑好分娩方式，尤其是对需要进行剖宫产者，在这方面几乎没有指导决策的证据，且应将决定权交于产科医生，并咨询新生儿学专家。如果可能，应鼓励双亲参观NICU。

针对经选择患者组全部患者的治疗推荐

两项最重要的改善早产结局的干预措施为产前使用皮质类固醇，以及当地新生儿救治水平不足时，将早产儿宫内转运至专科中心。[53]Shlossman PA, Manley JS, Sciscione AC, et al. An analysis of neonatal morbidity and mortality in maternal (in utero) and neonatal transports at 24-34 weeks' gestation. Am J Perinatol. 1997;148:449-456.http://www.ncbi.nlm.nih.gov/pubmed/9376004?tool=bestpractice.com[64]Brownfoot FC, Gagliardi DI, Bain E, et al. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2013;(8):CD006764.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006764.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23990333?tool=bestpractice.com证据 A降低围产儿并发症发病率和死亡率：有高质量的证据表明，在出生最初的48小时内，较之安慰剂或未干预组，如能在产前使用皮质类固醇，更能有效地减少新生儿呼吸窘迫综合征、脑室内出血、坏死性肠炎和新生儿感染的发生，但就降低慢性肺疾病的发生率而言未更有效。皮质类固醇亦能有效降低围产儿死亡率。倍他米松和地塞米松就结局而言并无差别。系统评价或者受试者＞200名的随机对照临床试验（RCT）。

在妊娠24至34周时，出现规律宫缩及宫颈扩张，即存在短期内分娩的风险，无论胎膜是否早破，均应给予其单疗程倍他米松或地塞米松，[83]American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice; Society for Maternal-Fetal Medicine. Committee opinion no.677: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol. 2016;128:e187-e194.http://www.ncbi.nlm.nih.gov/pubmed/27661658?tool=bestpractice.com且地塞米松可能会降低新生儿脑室内出血率。[64]Brownfoot FC, Gagliardi DI, Bain E, et al. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2013;(8):CD006764.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006764.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23990333?tool=bestpractice.com

美国妇产科医师协会 (ACOG) 现在建议，在妊娠 23 周时有即将分娩风险的女性中考虑使用皮质类固醇。[83]American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice; Society for Maternal-Fetal Medicine. Committee opinion no.677: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol. 2016;128:e187-e194.http://www.ncbi.nlm.nih.gov/pubmed/27661658?tool=bestpractice.com这个选择取决于家属对复苏的意愿。[83]American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice; Society for Maternal-Fetal Medicine. Committee opinion no.677: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol. 2016;128:e187-e194.http://www.ncbi.nlm.nih.gov/pubmed/27661658?tool=bestpractice.com

有证据表明，在早产妊娠后期（即 35-36 周）给予皮质类固醇可能会减少新生儿呼吸系统并发症，但这些获益必须与可能的不良反应加以权衡。[83]American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice; Society for Maternal-Fetal Medicine. Committee opinion no.677: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol. 2016;128:e187-e194.http://www.ncbi.nlm.nih.gov/pubmed/27661658?tool=bestpractice.com[85]Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374:1311-1320.http://www.ncbi.nlm.nih.gov/pubmed/26842679?tool=bestpractice.com[86]Saccone G, Berghella V. Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials. BMJ. 2016;355:i5044.http://www.bmj.com/content/355/bmj.i5044.longhttp://www.ncbi.nlm.nih.gov/pubmed/27733360?tool=bestpractice.com

产前皮质类固醇发挥最佳临床效果的时间为给药后的24小时到7至14天。多个剂量使用与胎儿宫内生长受限以及理论上的远期并发症发病率有关。[87]Murphy KE, Hannah ME, Willan AR, et al. Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial. MACS Collaborative Group. Lancet. 2008;372:2143-2151.http://www.ncbi.nlm.nih.gov/pubmed/19101390?tool=bestpractice.com不过，如果仍处于妊娠关键期，则 7 天后再给予一个重复疗程的用药可能会有益处，[88]Crowther CA, Haslam RR, Hiller JE, et al; Australasian Collaborative Trial of Repeat Doses of Steroids (ACTORDS) Study Group. Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial. Lancet. 2006;367:1913-1919.http://www.ncbi.nlm.nih.gov/pubmed/16765760?tool=bestpractice.com[89]Crowther CA, McKinlay CJ, Middleton P, et al. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease. Cochrane Database Syst Rev. 2015;(7):CD003935.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003935.pub4/abstracthttp://www.ncbi.nlm.nih.gov/pubmed/26142898?tool=bestpractice.com [ ]How do repeated doses of corticosteroids compare with a single course in women at risk of preterm birth?http://cochraneclinicalanswers.com/doi/10.1002/cca.1496/full显示答案 且一项在超过 4000 名儿童中进行的 meta 分析显示，并没有在 2-3 年时出现损伤的证据。[90]McKinlay CJ, Crowther CA, Middleton P, et al. Repeat antenatal glucocorticoids for women at risk of preterm birth: a Cochrane Systematic Review. Am J Obstet Gynecol. 2012;206:187-194.http://www.ajog.org/article/S0002-9378%2811%2900959-8/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/21982021?tool=bestpractice.com

在中低收入国家/地区，产前使用皮质类固醇已增加了总体新生儿死亡率，但必须注意不要将临床试验的研究结果推及到所有人群。[91]Althabe F, Belizán JM, McClure EM, et al. A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: the ACT cluster-randomised trial. Lancet. 2015;385:629-639.http://www.ncbi.nlm.nih.gov/pubmed/25458726?tool=bestpractice.com

如果当地医疗护理条件不足以对新生儿进行监护和支持，应进行转诊。

针对经选择患者组全部患者的治疗推荐

在美国，对出现规律子宫收缩或进行性宫颈扩张的早产活跃妊娠女性，均会静脉内使用针对 B 族链球菌 (GBS) 的抗生素进行预防治疗。[101]Royal College of Obstetricians and Gynaecologists. Prevention of early onset neonatal group B streptococcal disease. Green top Guideline no. 36. July 2012. http://www.rcog.org.uk (last accessed 10 May 2017).https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_36.pdf英国对B族链球菌 (GBS) 并不进行常规筛查，只对那些具有高危因素的孕妇（例如，如果前次分娩新生儿感染GBS，阴道拭子或尿培养提示GBS，或分娩时母体发热）在分娩时给予静脉用抗生素。除非患者过敏，否则首选青霉素。

针对经选择患者组全部患者的治疗推荐

使用宫缩抑制剂可以将孕期延长2至7天。建议短期内使用，从而为使用皮质类固醇及转诊至配置良好的新生儿监护室争取时间。[53]Shlossman PA, Manley JS, Sciscione AC, et al. An analysis of neonatal morbidity and mortality in maternal (in utero) and neonatal transports at 24-34 weeks' gestation. Am J Perinatol. 1997;148:449-456.http://www.ncbi.nlm.nih.gov/pubmed/9376004?tool=bestpractice.com

一项纳入17项临床试验的系统评价证实，宫缩抑制剂可减少24小时内、48小时内和7天内的分娩。必须慎重考虑宫缩抑制剂的使用，因目前尚无明确证据显示其能改善结局。且在选择特定药物时应将其不良反应考虑在内。[54]Royal College of Obstetricians and Gynaecologists. Tocolytic drugs for women in preterm labour. Green-top Guideline no. 1b. February 2011. http://www.rcog.org.uk (last accessed 10 May 2017).https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg1b/

住院用药期间，在用药的第一个24小时内，在最初的4个小时应每30分钟监测一次母体的心率和血压，随后改为每2小时监测一次。

禁忌证包括致命的胎儿畸形、绒毛膜羊膜炎、胎儿窘迫、阴道出血明显或存在母体合并症。

硝苯地平（钙离子通道阻滞剂）是常用药物之一。钙通道阻滞剂较其他宫缩抑制剂而言，可更有效地减少妊娠 34 周前的分娩 [ ]What are the effects of calcium channel blockers for inhibiting preterm labor and birth?http://cochraneclinicalanswers.com/doi/10.1002/cca.521/full显示答案 和新生儿并发症发病率。证据 A降低新生儿并发症发病率：有高质量的证据表明，钙离子通道阻滞剂较之其他宫缩抑制剂，能有效降低新生儿并发症发病率，包括呼吸窘迫综合征、脑室内出血和坏死性肠炎。系统评价或者受试者＞200名的随机对照临床试验（RCT）。硝苯地平的副作用与剂量有关，往往在总剂量达到60 mg 之后发生。[97]Khan K, Zamora J, Lamont RF, et al. Safety concerns for the use of calcium channel blockers in pregnancy for the treatment of spontaneous preterm labour and hypertension: a systematic review and meta-regression analysis. J Matern Fetal Neonatal Med. 2010;23:1030-1038.http://www.ncbi.nlm.nih.gov/pubmed/20180735?tool=bestpractice.com阿托西班（催产素拮抗剂）和硝苯地平的疗效相当，且副作用较少，围产期结局相似。[94]Flenady V, Wojcieszek AM, Papatsonis DN, et al. Calcium channel blockers for inhibiting preterm labour. Cochrane Database Syst Rev. 2014;(6):CD002255.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002255.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24901312?tool=bestpractice.com[95]Flenady V, Reinebrant HE, Liley HG, et al. Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database Syst Rev. 2014;(6):CD004452.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004452.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24903678?tool=bestpractice.com[96]van Vliet EO, Nijman TA, Schuit E, et al. Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial. Lancet. 2016;387:2117-2124.http://www.ncbi.nlm.nih.gov/pubmed/26944026?tool=bestpractice.com证据 C延长孕周：有质量较差的证据表明，硝苯地平和阿托西班就减少早产率、延长孕周48小时或7天似乎同样有效。低质量的观察性（队列）研究或者受试者＜200名且方法学存在缺陷的随机对照临床试验（RCT）。阿托西班在某些国家/地区使用，但在美国尚不可用。证据 A延长孕周和减少围产儿死亡：有高质量的证据表明，治疗开始后的48小时及7天内，阿托西班和β受体激动剂在减少＜37孕周时的早产率方面同样有效。二者在降低围产儿死亡率上亦同样有效。系统评价或者受试者＞200名的随机对照临床试验（RCT）。β受体激动剂似乎不再是最佳选择，虽然其可延长妊娠期，[93]Neilson JP, West HM, Dowswell T. Betamimetics for inhibiting preterm labour. Cochrane Database Syst Rev. 2014;(2):CD004352.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004352.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24500892?tool=bestpractice.com [ ]In women in spontaneous preterm labor, what are the benefits and harms of betamimetics compared with placebo or each other?http://cochraneclinicalanswers.com/doi/10.1002/cca.574/full显示答案 但是更容易引起导致治疗终止的母体不良反应。FDA 现已警告针对早产，不得超适应症使用特布他林。 [ ]Is there randomized controlled trial evidence to support the use of betamimetics for maintenance therapy after threatened preterm labor?http://cochraneclinicalanswers.com/doi/10.1002/cca.177/full显示答案 [ ]Do prophylactic betamimetics given to women with a singleton pregnancy at risk of preterm delivery improve outcomes?http://cochraneclinicalanswers.com/doi/10.1002/cca.180/full显示答案