宫颈栓在宫颈偏短的孕妇中的使用
一项在宫颈偏短的女性中使用 Arabin® 子宫托(一种有弹性的环形硅胶子宫托)的试验表明,与期待治疗组相比,其能降低早产率(6% vs 27%,比值比为 0.18,95% 置信区间为 0.08-0.37)。作者随后表明其在双胎妊娠女性中存在获益。[102]Goya M, Pratcorona L, Merced C, et al; Pesario Cervical para Evitar Prematuridad (PECEP) Trial Group. Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial. Lancet. 2012;379:1800-1806.http://www.ncbi.nlm.nih.gov/pubmed/22475493?tool=bestpractice.com不过,鉴于期待治疗组的令人难以置信的高事件发生率,在广泛采用这些研究结果之前,需要对其加以证实。另一项研究发现,在多胎妊娠女性中使用子宫托并未改善围产期结局,虽然宫颈偏短的女性可能会有获益。[103]Liem S, Schuit E, Hegeman M, et al. Cervical pessaries for prevention of preterm birth in women with a multiple pregnancy (ProTWIN): a multicentre, open-label randomised controlled trial. Lancet. 2013;382:1341-1349.http://www.ncbi.nlm.nih.gov/pubmed/23924878?tool=bestpractice.com其他研究未能显示单胎或双胎妊娠女性的获益。[104]Nicolaides KH, Syngelaki A, Poon LC, et al. A randomized trial of a cervical pessary to prevent preterm singleton birth. N Engl J Med. 2016;374:1044-1052.http://www.nejm.org/doi/full/10.1056/NEJMoa1511014#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/26981934?tool=bestpractice.com[105]Nicolaides KH, Syngelaki A, Poon LC, et al. Cervical pessary placement for prevention of preterm birth in unselected twin pregnancies: a randomized controlled trial. Am J Obstet Gynecol. 2016;214:3.e1-e9.http://www.ncbi.nlm.nih.gov/pubmed/26321037?tool=bestpractice.com更多试验正在进行中。
硫酸镁
对新生儿神经系统的保护:目前已证实,在分娩前使用硫酸镁可保护胎儿神经系统免受损伤。在针对小于34孕周新生儿的 meta 分析中发现,使用硫酸镁能将脑瘫减少30%(风险减少0.71[0.55-0.91])。[106]Australian Research Centre for Health of Women and Babies, UoA. Antenatal magnesium sulphate prior to preterm birth for neuroprotection of the fetus, infant and child. March 2010. https://www.adelaide.edu.au/arch/ (last accessed 10 May 2017).http://www.adelaide.edu.au/arch/MagnesiumSulphate2010.pdf美国食品药品监督管理局 (FDA) 并不推荐为了阻止早产而给孕妇(超适应症使用)静脉输注硫酸镁超过5至7天,因其可能会导致胎儿或新生儿出现低钙水平和骨骼问题。仍不明确可能会对新生儿造成危害的最短治疗时间,尽管有FDA的推荐意见,在临床实践中使用硫酸镁通常不超过24-48小时。FDA 现已将硫酸镁归入妊娠 D 类药物。[107]US Food and Drug Administration. Magnesium sulfate: drug safety communication - recommendation against prolonged use in pre-term labor. May 2013. http://www.fda.gov/ (last accessed 10 May 2017).https://www.fda.gov/Drugs/DrugSafety/ucm353333.htm没有证据表明硫酸镁是有价值的宫缩抑制剂,且它应仅用作适当女性群体的神经系统保护药物。[98]Crowther CA, Brown J, McKinlay CJ, et al. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database Syst Rev. 2014;(8):CD001060.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001060.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/25126773?tool=bestpractice.com
孕激素疗法
孕激素疗法:在既往有自发性早产的女性中,孕激素治疗可以减少早产的发生率。延长妊娠期:有中等质量的证据表明,孕激素类药物较之安慰剂能够更有效地延长孕周和降低早产率。受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。阴道用制剂(微粒化黄体酮胶囊)可能减少早产。[108]da Fonseca EB, Bittar RE, Carvalho MH, et al. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003;188:419-424.http://www.ncbi.nlm.nih.gov/pubmed/12592250?tool=bestpractice.com一项Cochrane meta 分析发现其能降低不足37周的分娩率,但并不改变围产期的并发症发病率及死亡率。[25]Dodd JM, Jones L, Flenady V, et al. Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth. Cochrane Database Syst Rev. 2013;(7):CD004947.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004947.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23903965?tool=bestpractice.com延长孕周:有高质量的证据表明,根据Cochrane meta 分析,孕激素可有效降低孕周<37周的早产风险。[25]Dodd JM, Jones L, Flenady V, et al. Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth. Cochrane Database Syst Rev. 2013;(7):CD004947.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004947.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23903965?tool=bestpractice.com系统评价或者受试者>200名的随机对照临床试验(RCT)。不过,该结果在随后使用凝胶制剂的试验中并没有得到证实。[109]O'Brien JM, Adair CD, Lewis DF, et al. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007;30:687-696.http://www.ncbi.nlm.nih.gov/pubmed/17899572?tool=bestpractice.com另有报道发现在宫颈偏短的孕妇中使用200 mg栓剂治疗后能减少早产。[110]DeFranco EA, O'Brien JM, Adair CD, et al. Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007;30:697-705.http://onlinelibrary.wiley.com/doi/10.1002/uog.5159/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17899571?tool=bestpractice.com[111]Fonseca EB, Celik E, Parra M, et al. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007;357:462-469.http://www.nejm.org/doi/full/10.1056/NEJMoa067815#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/17671254?tool=bestpractice.com且在宫颈偏短的孕妇阴道内使用孕激素可能还与新生儿并发症发病率及死亡率的降低有关(相对危险度0.57;95% CI:0.40-0.81)。[112]Romero R, Nicolaides K, Conde-Agudelo A, et al. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol. 2012;206:124.e1-124.e19.http://www.ajog.org/article/S0002-9378(11)02358-1/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/22284156?tool=bestpractice.com更大规模的临床试验未能证实这种获益,但已显示无长期不良影响。[113]Norman JE, Marlow N, Messow CM, et al. Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial. Lancet. 2016;387:2106-2116.http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00350-0/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/26921136?tool=bestpractice.com该数据尚未被整合入 meta 分析中。对可能早产的孕妇肌肉注射17α-羟孕酮己酸可以减少早产率及新生儿并发症。[114]Meis PJ, Klebanoff M, Thom E, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348:2379-2385.http://www.nejm.org/doi/full/10.1056/NEJMoa035140#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/12802023?tool=bestpractice.com降低新生儿并发症发病率:中等质量的证据表明,孕激素较之安慰剂,更有效地降低新生儿脑室内出血率,但就降低呼吸窘迫综合征而言效果不佳,对围产儿死亡率也无影响。受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。后续研究未能证实这一结果,[115]Grobman WA, Thom EA, Spong CY, et al; Eunice Kennedy Shriver National Institute of
Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. 17 alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with
cervical length less than 30 mm. Am J Obstet Gynecol. 2012;207:390.e1-390.e8.http://www.ajog.org/article/S0002-9378(12)01016-2/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/23010094?tool=bestpractice.com[116]Winer N, Bretelle F, Senat MV, et al. 17 alpha-hydroxyprogesterone caproate does not prolong pregnancy or reduce the rate of preterm birth in women at high risk for preterm delivery and a short cervix: a randomized controlled trial. Am J Obstet Gynecol. 2015;212:485.e1-485.e10.http://www.ncbi.nlm.nih.gov/pubmed/25448515?tool=bestpractice.com且目前的证据支持阴道内用药优于肌肉注射。[117]Maher MA, Abdelaziz A, Ellaithy M, et al. Prevention of preterm birth: a
randomized trial of vaginal compared with intramuscular progesterone. Acta Obstet
Gynecol Scand. 2013;92:215-222.http://www.ncbi.nlm.nih.gov/pubmed/23016508?tool=bestpractice.com一项4年的随访研究发现对于之后儿童期的成长并没有不良反应。[118]Northern AT, Norman GS, Anderson K, et al. Follow up of children exposed in utero to 17-alpha hydroxyprogesterone caproate compared with placebo. Obstet Gynecol. 2007;110:865-872.http://www.ncbi.nlm.nih.gov/pubmed/17906021?tool=bestpractice.com在美国,FDA为预防单胎早产的发生临时批准使用乙酸羟基孕酮,且待进一步研究。对于双胎妊娠,孕激素治疗并无任何益处,只会增加不良反应。[119]Norman JE, Mackenzie F, Owen P, et al. Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis. Lancet. 2009;373:2034-2040.http://www.ncbi.nlm.nih.gov/pubmed/19523680?tool=bestpractice.com[120]Klein K, Rode L, Nicolaides KH, et al; PREDICT Group. Vaginal micronized progesterone and risk of preterm delivery in high-risk twin pregnancies: secondary analysis of a placebo-controlled randomized trial and meta-analysis. Ultrasound Obstet Gynecol. 2011;38:281-287.http://onlinelibrary.wiley.com/doi/10.1002/uog.9092/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21739499?tool=bestpractice.com[121]Sotiriadis A, Papatheodorou S, Makrydimas G. Perinatal outcome in women
treated with progesterone for the prevention of preterm birth: a meta-analysis.
Ultrasound Obstet Gynecol. 2012;40:257-266.http://onlinelibrary.wiley.com/doi/10.1002/uog.11178/fullhttp://www.ncbi.nlm.nih.gov/pubmed/22611023?tool=bestpractice.com