出生缺陷是备受政府和社会关注的公共卫生问题。提高对出生缺陷的早期诊断和干预救治能力，可对目前三胎国策的实施提供医疗技术支撑和保障，具有重大的积极意义。先天性膈疝(Congenital diaphragmatic hernia, CDH)是一种严重的出生缺陷，是国际上出生缺陷疾病研究的热点，其主要成因是胎儿膈肌发育不完整，使得腹腔内脏器进入胸腔压迫肺脏。CDH发病的遗传因素占10%，80%以上并未找到明确病因。过去，受限于对CDH的认识不足、新生儿手术等救治手段尚不成熟等原因，CDH的病死率在30％以上，重症CDH的病死率可达70％，引产率高达61.5%。近年来随着产前诊断技术、遗传筛查技术的推广以及重症监护技术和手术方式的进展，极大地提升了CDH患儿的救治成功率。在临床实践中，成功行先天性膈肌修补手术的患儿，经过术后呼吸功能锻炼及长期随访，其远期预后可以达到与健康同龄儿相仿。

CDH的主要病理生理改变为胎儿肺发育不良。因其发育过程中，腹腔内脏器疝入胸腔后压迫肺脏，影响支气管分支分化，小动脉数量减少、管壁增厚，致使肺发育不全、肺血管发育异常，最终表现为新生儿出生后的低氧血症、高碳酸血症，患儿持续性肺动脉高压(Persistent pulmonary hypertension of the newborn, PPHN)。体循环血液流经未闭合的动脉导管和卵圆孔形成右向左分流，使新生儿呈持续处于胎儿循环状态，最终引起低氧血症、呼吸循环衰竭、患儿死亡。因此，如能对CDH患儿进行早期精确的诊断评估，及时干预与治疗，将为这类患儿带来更多生存的机会。

产时宫外治疗(Ex utero intrapartum treatment，EXIT)是一种在分娩时通过维持胎盘循环，为新生儿提供心肺支持的技术。EXIT程序的优势在于，在胎盘循环支持下让医师有足够的时间执行一些挽救生命的操作，如支气管镜检查、喉镜检查、气管内插管、气管切开术等，甚至插管行ECMO治疗，在分娩时给予患儿安全的气道保护，减少发生缺氧、酸中毒甚至缺血性脑病的相关风险。国际上已有研究支持将EXIT应用于CDH患儿救治是安全可行的，美国费城儿童医院Foglia教授团队的研究显示EXIT组患儿的第一次测量血红蛋白含量及生后一小时平均动脉压等短期指标优于对照组患儿。但至今尚无研究探讨EXIT-气管插管（EXIT-to-Airway）是否可以改善CDH患儿的生存率及复发率等预后指标。

本论文第一部分首次评估将EXIT-气道建立（EXIT-to-Airway）用于新生儿膈疝对患儿预后的影响。通过对2011年1月1日至2020年12月31日期间在首都儿科研究所附属儿童医院接受治疗的新生儿先天性膈疝进行回顾性研究，对其中22例产前诊断为先天性膈疝、经评估病情较重、出生后呼吸困难的新生儿应用EXIT,对患者的临床特征、手术相关参数、临床结局等资料进行比较。共95例纳入研究，获随访6个月至10年。EXIT组共22例，其中21例接受手术治疗，存活19例（术后存活率为90.5%)；非EXIT组共73例，其中60例接受手术治疗，存活43例（术后存活率为71.7%)。Logistic回归分析显示，行产时宫外治疗[OR=0.104,(95%CI:0.022-0.493)]、产前诊断时间[OR=0.863,(95%CI:0.783-0.952)]与肝脏疝入胸腔[OR=9.657,(95%CI:3.094-30.137)]三个因素为先天性膈疝患者预后状况的独立影响因素。根据ROC曲线结果可知，产前诊断时间最优诊断效能对应的cutoff值为24.5周。最终结论为EXIT安全可行，可有效改善先天性膈疝新生儿患者预后，产时宫外治疗、产前诊断胎龄及肝脏疝入胸腔是新生儿先天性膈疝的预后相关因素。

由于患儿疾病严重程度的显著差异可能会导致选择偏倚，根据出生时是否行EXIT将患儿分为EXIT组和非EXIT组，采用倾向性评分匹配(Propensity score matching，PSM)可最大限度降低其他可能影响患儿预后的因素的干扰，我们希望借此模拟RCT的研究条件，进一步探讨EXIT对CDH新生儿预后的影响。本论文第二部分通过回顾性分析1992年9月至2021年6月首都儿科研究所附属儿童医院收治的116例CDH患儿的临床资料，根据出生时是否行EXIT将患儿分为EXIT组和非EXIT组，采用倾向评分匹配方法(PSM)，比较两组患儿的预后，采用Logistic回归分析探讨EXIT对患儿生存的影响。研究期间30例患儿接受EXIT，86例被纳入非EXIT组。临床数据经PSM处理后，两组的存活率分别为82.76%(24/29)和48.28%(14/29)(P=0.006)。EXIT[OR=0.083 (95%CI:0.013-0.525)，P=0.008]、肝脏疝入胸腔[OR=16.955 (95%CI:2.342-122.767)，P=0.005]、诊断时胎龄[OR=0.662 (95%CI:0.497-0.881)，P=0.005]是所有CDH患儿的存活的独立影响因素。有99名患儿接受手术治疗。经PSM处理后，EXIT组和非EXIT组的术后生存率分别为84.6%(22/26)和76.9%(20/26)(P=0.754)。肝脏疝入胸腔[OR=10.451 (95%CI:1.641-66.544)，P=0.013]和诊断时胎龄[OR=0.736 (95%CI:0.577-0.938)，P=0.013]是CDH患儿术后存活的独立影响因素。最终结论为对于先天性膈疝新生儿，EXIT是安全可行的，具有降低死亡率的倾向，且不会造成相对于标准剖宫产手术更多的并发症。

过去三年，新型冠状病毒肺炎(COVID-19)疫情肆虐全球，也是目前全世界关注的最重要议题。对潜在感染风险的担忧及严格执行疫情防控措施可能会导致常规诊断和治疗的延误。在疫情期间，小儿外科医生应该如何应对疫情对医疗工作的影响仍然是一个巨大的挑战。论文第三部分通过评估新型冠状病毒肺炎(COVID-19)疫情流行期间执行一定的防护措施对先天性膈疝患儿救治的影响。本研究回顾性收集2020年1月1日至2021年12月31日期间入院的先天性膈疝患者的数据；对照组为2018年1月1日至2019年12月31日期间入院的先天性膈疝患者。对比分析两组患者临床数据。结果显示，疫情期间，41名产前诊断的先天性膈疝患者转运至我院，40例接受手术治疗,转运至我院并进行治疗患者数量较疫情前增加24.2%。疫情期间患者的总存活率，术后存活率及复发率分别为85.4%，87.5%和7.3%，对照组分别为75.8%，83.3%和9.1%，两组相比无显著差异（P>0.05）。疫情期间收治的CDH患者平均住院时间长于对照组，院感发生率高于对照组。截止本文撰写时，本科室没有患者或医务人员感染SARS-CoV-2。我们的数据表明，在SARS-CoV-2大流行期间实施一定的保护措施，以及适当的筛查和病例评估，对患儿预后没有负面影响。我们希望借此为处于抗击疫情前线的全球小儿外科医生提供一些可参考的建议。

Birth defect is a public health problem which is concerned by the government and society. Improving the ability of early diagnosis, intervention and treatment of birth defects can provide medical technical support for the implementation of the current three-children policy, which is of great positive significance. Congenital diaphragmatic hernia (CDH) is a serious birth defect, which is a hot topic of research on birth defect diseases in the world. It is mainly caused by dysplasia of fetal diaphragm, which makes the abdominal viscera enter the chest cavity and compress the lung. Genetic factors account for 10% of CDH morbidity, and more than 80% have not found clear etiology. In the past, due to insufficient understanding of CDH and limited treatment methods such as neonatal surgery, the mortality of CDH was over 30%, the mortality of severe CDH was up to 70%, and the induced labor rate was as high as 61.54%. In recent years, with the promotion of prenatal diagnosis and genetic screening technology and the progress of intensive care technology and surgical methods, the prognosis of children with CDH has been greatly improved. In clinical practice, the long-term prognosis of children with successful congenital diaphragm repair can be similar to that of healthy children of the same age after postoperative respiratory exercise and long-term follow-up.

The main pathophysiological changes of CDH were fetal lung dysplasia. During fetal development, the abdominal viscera herniated into the thoracic cavity and compressed the lungs, affecting the growth of bronchial branches, reducing the number of small arteries and thickening the blood vessel wall, resulting in lung hypoplasia and abnormal development of pulmonary blood vessels. The final manifestations are hypoxemia, hypercapnia and persistent pulmonary hypertension of the newborn (PPHN). The systemic circulation blood flows through the unclosed arterial duct and foramen ovale to form right-left shunt, which causes the newborn to remain in the fetal circulation state, and eventually causes hypoxemia, respiratory circulation failure, and death of the child. Therefore, early and accurate diagnostic evaluation, timely intervention and treatment of children with CDH will bring more chances of survival for this population.

Ex utero intrapartum treatment (EXIT) is a technique used to provide cardiopulmonary support to newborns during delivery by maintaining placental circulation. EXIT procedure has the advantage that the placental circulation support let physicians have enough time to perform some action to save lives, such as bronchoscopy, laryngoscopy, endotracheal intubation and tracheotomy, even ECMO treatment, giving children a safe airway protection during childbirth, and reduce the risks associated with hypoxia, acidosis, and even of ischemic encephalopathy. International studies have supported the safe and feasible application of EXIT in the treatment of children with CDH. The study by Foglia's team at the Children's Hospital of Philadelphia showed that the children in EXIT group had better short-term indicators such as the hemoglobin content measured at the first time and the mean arterial pressure one hour after birth than the control group. But there have been no studies on whether EXIT-to-Airway can improve the survival rate and recurrence rate of children with CDH.

The effect of EXIT-to-Airway treatment on the prognosis of neonatal diaphragmatic hernia was first evaluated in our center (Part 1). From January 1, 2011 to December 31, 2020, a retrospective review was performed for 95 CDH neonates. Among them, 22 cases with severe disease and postnatal dyspnea received ex utero intrapartum treatment (EXIT), 21 were operated and 19 survived with a postoperative survival rate of 90.5%. Clinical characteristics, surgical parameters and outcomes were compared. There were 73 cases in non-EXIT group, 60 cases were operated and 43 cases survived with a postoperative survival rate of 71.7%. Logistic regression analysis showed that EXIT during labor (OR=0.104, [95% CI:0.022-0.493]), gestational age at prenatal diagnosis(OR=0.863,[95%CI:0.783-0.952]) and liver herniation into chest (OR = 9.657,[95%CI: 3.094- 30.137]) were independent prognostic factors for CDH children. According to the receiver operating characteristic (ROC) curve, the cutoff value of maximizing the diagnostic efficiency of prenatal diagnostic age was 24.5 weeks. The final conclusion is that both safe and feasible, EXIT may improve the prognosis of neonatal CDH effectively. EXIT, gestational age of prenatal diagnosis and liver herniation into thoracic cavity are independent prognostic factors for CDH neonates.

Since selection bias might exist due to the significant difference in disease severity, here, we applied propensity score matching (PSM) to minimise the effect of other confounding factors for prognosis, and simulate the research conditions of an RCT. To further explore the influence of EXIT on the prognosis of CDH neonates. Clinical data of 110 children with CDH treated in Children's Hospital of Capital Institute of Pediatrics from 2012 to 2021 were retrospectively analyzed (Part 2). Children were divided into EXIT group and non-EXIT group according to whether EXIT was performed at birth. The outcomes of the two groups were compared, applying propensity score matching. Logistic regression analysis was carried out to explore the efficacy of EXIT on survival. During the study period 30 of 116 children received EXIT. After PSM, the survival rates of the EXIT group and the non-EXIT group were 82.76%(24/29) and 48.28%(14/29), respectively (P=0.006). EXIT (OR=0.083, 95%CI=0.013–0.525, P=0.008), liver herniation (OR=16.955, 95%CI=2.342–122.767, P=0.005), and gestational age at diagnosis (OR=0.662, 95%CI=0.497–0.881, P=0.005) were independent mortality related risk factors of all children with CDH. Ninety-nine of 116 children underwent surgery. After PSM, the postoperative survival rates of the EXIT group and non-EXIT group were 84.6%(22/26) and 76.9%(20/26), respectively (P=0.754). Liver herniation (OR=10.451, 95%CI=1.641–66.544, P=0.013] and gestational age at diagnosis (OR=0.736, 95%CI=0.577–0.938, P=0.013) were independent mortality related risk factors of children after surgery. The final conclusion is that, for selected neonates with CDH, EXIT is safe and feasible with potentially better survival than traditional delivery mode, and does not cause more complications than traditional cesarean section.

Over the past three years, the COVID-19 pandemic has ravaged the world and is the most important issue for the world right now. Concerns about the potential risk of infection and the strict implementation of containment measures can lead to delays in routine diagnosis and treatment. How pediatric surgeons should respond to the impact of the pandemic on health care remains a huge challenge. To investigate the impact of COVID-19 on the treatment of children with congenital diaphragmatic hernia (CDH), we retrospectively collected and compared the data of patients with CDH admitted between January 1, 2020 and December 31, 2021(study group) with the CDH patients admitted before the pandemic between January 1, 2018 and December 31, 2019 (control group) (Part 3). During the pandemic, 41 patients with CDH diagnosed prenatally were transferred to our hospital, and 40 underwent surgical repair. The number of patients treated in our hospital increased by 24.2% compared with the 33 patients before the pandemic. During the pandemic, the overall survival rate, postoperative survival rate and recurrence rate were 85.4%, 87.5% and 7.3%, respectively, and there were no significant differences compared with the control group(75.8%, 83.3% and 9.1%, respectively). The average length of hospital stay in patients admitted during the pandemic was longer than that in the control group (31 days vs. 16 days, P<0.001), and the incidence of nosocomial infection was higher than that in the control group (19.5% vs. 3%, P=0.037). We came to the conclusion that CDH patients confirmed to be SARS-CoV-2 infection-free can receive routine treatment. Our data indicate that the implementation of protective measures during the COVID-19 pandemic, along with appropriate screening and case evaluation, do not have a negative impact on the prognosis of children. We hope to offer some advice to pediatric surgeons around the world who are on the front lines of fighting the epidemic.