《先天性膈疝的围产期临床管理指南》推荐意见调查问卷

推荐依据： 对于先天性膈疝的分娩时机及首选分娩方式，目前的研究尚无定论。2010年一项队列研究[1]将分娩孕周分为＜37周分娩、37-38周分娩、39-41周分娩，三者的新生儿的存活率分别为66.6%、87.1%、72%（P=0.12），而大多数队列研究[2-6]显示先天性膈疝的早产儿存活率明显低于足月儿存活率。因此，建议无并发症时，尽量延长妊娠至足月，但对于足月后的最佳孕周的研究争议较大。2009年一篇队列研究（n=628）[1]显示，对于孤立性先天性膈疝足月分娩患者，随着孕周增加新生儿存活率呈现降低的趋势，37-38周分娩者较39周-41周分娩者有更高存活率（72.6% vs 67.1%; OR=1.57, 95% CI [1.07, 2.31]）。而2021年的一篇队列研究（n=213）[2]显示，在中度CDH患儿中，37-38+6周分娩的比39周及以后分娩的28天存活率（81.5% vs 61.5%，P=0.03）及6个月存活率（80% vs 55.9%，P=0.01）均高，且使用ECMO、吸入性NO等高级通气的比例有降低趋势（P=0.1；P=0.33）。虽然关于在37-38周分娩还是在39周以后分娩新生儿的存活率有争议，但研究结果的共同点是妊娠40周后先天性膈疝新生儿的存活率降低。同时，2015年欧洲联盟更新的关于CDH的共识[8]建议在证据不充足的条件下，于39周后在大型三级分娩中心计划分娩。因此，目前对于具体分娩时机尚存在争议，需要与新生儿外科及NICU医师联合确定分娩时机，在充分准备下进行分娩。 对于先天性膈疝患儿的分娩方式，2017年的一篇队列研究（n=3906）[9]显示，在先天性膈疝患者中，自然阴道分娩、引产、择期剖宫产、急症剖宫产这四种分娩方式在新生儿的体外膜肺氧合要求、住院时间、插管时间、及总生存率等方面均无明显差异。另有三项队列研究的结果也相似，但其中2007年的一篇队列研究（n=548）[10]显示，在无ECMO存活率方面，剖宫产患者存活率（60%）要高于自然分娩（49%）及阴道引产（49%）（P0.05）。同时2009年的一篇队列研究（n=628）[11]也显示，选择性剖宫产虽然与新生儿存活率无关，但可减少新生儿出生后ECMO使用率（OR=0.55, 95% CI [0.38, 0.80]），且在使用ECMO患儿中经选择性剖宫产的有更高的存活率（OR=1.46, 95% CI [1.02, 2.09]）。2015年欧洲联盟更新的关于CDH的共识[8]提到分娩方式取决于孕妇的适应证。因此，胎儿先天性膈疝不是剖宫产指征，需要综合考虑母胎情况来确定具体分娩方式。 先天性膈疝患儿的分娩地点也会影响孕妇和CDH患儿的安全和预后。2011年的一篇队列研究（n=140）[12]显示，分娩地点是影响先天性膈疝患者死亡率的一个重要因素，与提前入住于具备新生儿抢救条件三级医院待产分娩的孕妇相比，分娩时转院至具备新生儿抢救条件的三级医院的新生儿死亡率更高（OR=2, P=0.04）。2004年的一篇队列研究（n=88）[13]显示，高容量三级中心（在研究22个月内能接诊12例及以上的胎儿先天性膈疝患者的具有儿科手术条件及ECMO资源的医疗中心）的CDH患儿的生存率显著高于低容量中心（（在研究22个月内能接诊12例以下的胎儿先天性膈疝患者的医疗中心））(90% vs 77%; P0.01)。因此选择具有新生儿外科条件及术后监护的三级医院或胎儿医学中心进行分娩对新生儿存活率有重要意义。

基于以上证据并结合该干预／因素的临床成本及中远期的安全性、患者偏好及价值观，您对本问题的推荐意见有何建议：

参考文献1．McAteer JP, Hecht A, De Roos AJ, et al. Maternal medical and behavioral risk factors for congenital diaphragmatic hernia[J]. J Pediatr Surg. 2014, 49(1): 34-38.2．Burgosa CM, Ehréna H, Connerb P. Maternal Risk Factors and Perinatal Characteristics in Congenital Diaphragmatic Hernia: A Nationwide Population-Based Study[J]. Fetal Diagn Ther. 2019, 46:385–391.3．Carmen Mesas Burgosa Henrik Ehréna Peter Connerb, et al. Maternal Risk Factors and Perinatal Characteristics in Congenital Diaphragmatic Hernia: A Nationwide Population-Based Study[J]. Fetal Diagn Ther2019;46:385–391.4．Beurskens WLJE, Schrijver LH, Tibboel D, et al. Dietary Vitamin A Intake below the Recommended Daily Intake during Pregnancy and the Risk of Congenital Diaphragmatic Hernia in the Offspring[J]. Birth Defects Research (Part A) 97:6066 (2013).5．Auger N, Côté-Daigneault J, Bilodeau-Bertrand M, et al. Inflammatory Bowel Disease and Risk of Birth Defects in Offspring[J]. Journal of Crohns and Colitis, 2020, 588–594.6．Yang W, Shaw GM , Suzan L, et al. Nutrient Intakes in Women and Congenital Diaphragmatic Hernia in Their Offspring[J]. Defects Research (Part A) 82:131–138, 2008.7．Turkmen GG, Timur H, Tokmak A, et al. Levels of serum vitamin D and calcium in pregnancies complicated with fetal congenital diaphragmatic hernia and normal pregnancies[J]. Matern Fetal Neonatal Med, 2017; 30(8): 990–994.8．Caspers KM, Oltean C, Romitti PA, et al. Maternal Periconceptional Exposure to Cigarette Smoking and Alcohol Consumption and Congenital Diaphragmatic Hernia[J]. Birth Defects Res A Clin Mol Teratol. 2010 December ; 88(12): 1040–1049.9．Balayla J, Abenhaim H A. Incidence, predictors and outcomes of congenital diaphragmatic hernia: a population-based study of 32 million births in the United States. J Matern Fetal Neonatal Med, 2014; 27(14): 1438–1444.10．Lan Yu, Sawle AD, Wynn J, et al. Increased burden of de novo predicted deleterious variants in complex congenital diaphragmatic hernia[J]. Molecular Genetics, 2015, Vol. 24, No. 16 4764–4773.11．Zhua QH, High FA, Zhang QS, et al. Systematic analysis of copy number variation associated with congenital diaphragmatic hernia[J]. PNAS | May 15, 2018 | vol. 115 | no. 20 | 5247–5252.12．Shanmugam H, Brunelli L, BottoLD,et al. Research Article Epidemiology and Prognosis of Congenital Diaphragmatic Hernia: A Population-Based Cohort Study in Utah[J]. Birth Defects Research 109:1451–1459, 2017.13．Bahado-Singh RO, Schenone M, Cordoba M, et al. Male gender significantly increases risk of oxidative stress related congenital anomalies in the non-diabetic population[J]. The Journal of Maternal-Fetal and Neonatal Medicine, May 2011; 24(5): 687–691.14．Paoletti M, Raffler G, Gaff MS, et al. Prevalence and risk factors for congenital diaphragmatic hernia: A global view[J]. Journal of Pediatric Surgery 55 (2020) 2297–2307.15．Duong HT, Hoyt AT, Carmichael SL, et al. Is Maternal Parity an Independent Risk Factor for Birth Defects[J]? Birth Defects Res A Clin Mol Teratol. 2012 April ; 94(4): 230–236. 16．Ramakrishnan R, Salemi JL, Stuart AL, et al. Trends, correlates, and survival of infants with congenital diaphragmatic hernia and its subtypes[J]. Birth Defects Research. 2018;110:1107–1117.17．Ramakrishnan R, Stuart AL ,Salemi JL, et al. Maternal exposure to ambient cadmium levels, maternal smoking during pregnancy, and congenital diaphragmatic hernia[J]. Birth Defects Research. 2019;111:1399–1407.18．Dawson1 AL, Riehle-Colarusso1 T, ReefhuisMaternalJ,et al. Exposure to Methotrexate and Birth Defects: a Population-Based Study[J]. Am J Med Genet A. 2014 September ; 0(9): 2212–2216. 19. Green RF, Devine O, Crider KS, et al. Association of Paternal Age and Risk for Major Congenital Anomalies from the National Birth Defects Prevention Study[J], 1997–2004 Ann Epidemiol. 2010 March ; 20(3): 241–249.

基于以上证据并结合该干预／因素的临床成本及中远期的安全性、患者偏好及价值观，您对本问题的推荐意见有何建议：

参考文献1.SAFAVI A, LIN Y, SKARSGARD E D, et al. Perinatal management of congenital diaphragmatic hernia: when and how should babies be delivered? Results from the Canadian Pediatric Surgery Network [J]. Journal of Pediatric Surgery. 2010, 45(12): 2334-2339.2.BOUCHGHOUL H, DUMERY G, RUSSO F M, et al. Optimal gestational age at delivery in isolated left-sided congenital diaphragmatic hernia [J]. Ultrasound in obstetrics gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, 2021, 57(6): 968-973.3.CANNON C, DILDY G A, WARD R, et al. A population-based study of congenital diaphragmatic hernia in Utah: 1988-1994 [J]. Obstetrics and gynecology, 1996, 87(6): 959-963.4.TSAO K, ALLISON N D, HARTING M T, et al. Congenital diaphragmatic hernia in the preterm infant [J]. Surgery, 2010, 148(2): 404-410.5.EDMONDS L, BONIFACE C, ALCOCK G, et al. Congenital diaphragmatic hernia in Northern Queensland [J]. Journal of Paediatrics and Child Health, 2013, 49(6): 475-479.6.BARRIèRE F, MICHEL F, LOUNDOU A D, et al. One-Year Outcome for Congenital Diaphragmatic Hernia: Results From the French National Register [J]. Journal of Pediatrics, 2018, 193: 204-210.7.HUTCHEON J A, BUTLER B, LISONKOVA S, et al. Timing of delivery for pregnancies with congenital diaphragmatic hernia [J]. BJOG : an international journal of obstetrics and gynaecology, 2010, 117(13): 1658-1662.8.SNOEK K G, REISS I K M, GREENOUGH A, et al. Standardized Postnatal Management of Infants with Congenital Diaphragmatic Hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update [J]. Neonatology, 2016, 110(1): 66-74.9.BURGOS C M, FRENCKNER B, LUCO M, et al. Prenatally diagnosed congenital diaphragmatic hernia: optimal mode of delivery? [J]. Journal of perinatology : official journal of the California Perinatal Association, 2017, 37(2): 134-138.10.FRENCKNER B P, LALLY P A, HINTZ S R, et al. Prenatal diagnosis of congenital diaphragmatic hernia: how should the babies be delivered? [J]. Journal of Pediatric Surgery, 2007, 42(9): 1533-1538.11.STEVENS T P, VAN WIJNGAARDEN E, ACKERMAN K G, et al. Timing of Delivery and Survival Rates for Infants With Prenatal Diagnoses of Congenital Diaphragmatic Hernia [J]. Pediatrics, 2009, 123(2): 494-502.12.NASR A, LANGER J C. Influence of location of delivery on outcome in neonates with congenital diaphragmatic hernia [J]. Journal of pediatric surgery, 2011, 46(5): 814-816.13.JAVID P J, JAKSIC T, SKARSGARD E D, et al. Survival rate in congenital diaphragmatic hernia: the experience of the Canadian Neonatal Network [J]. Journal of pediatric surgery, 2004, 39(5): 657-660.