Congenital diaphragmatic hernia: current management strategies from antenatal diagnosis to long-term follow-up

Congenital diaphragmatic hernia (CDH) is a developmental birth defect consisting of a diaphragmatic defect and abnormal lung development. CDH complicates 2.3–2.8 per 10,000 live births. Despite efforts to standardize clinical practice, management of CDH remains challenging. Frequent re-evaluation of clinical practices in CDH reveals that management of CDH is evolving from one of postnatal stabilization to prenatal optimization. Translational research reveals promising avenues for in utero therapeutic intervention, including fetoscopic endoluminal tracheal occlusion. These remain highly experimental and demand improved antenatal diagnostics. Timely diagnosis of CDH and identification of severely affected fetuses allow time for delivery planning or in utero therapeutics. Optimal perinatal care and surgical treatment strategies are highly debated. Improved CDH mortality rates have placed increased emphasis on identifying and monitoring the long-term sequelae of disease throughout childhood and into adulthood. We review the current management strategies for CDH, highlighting where progress has been made, and where future developments have the potential to revolutionize care in this vulnerable patient population.     

先天性膈疝35例诊治体会

目的总结先天性膈疝的围手术期处理经验,以提高先天性膈疝患儿的抢救成功率和生存质量。方法回顾性分析2008年1月到2011年12月我们收治的35例新生儿先天性膈疝患儿临床资料。结果35例中,手术31例,术后死亡5例;未手术而于生后1d死亡3例,放弃治疗1例。死亡病例中产前获得确诊而术后死亡2例,其余6例均未获得产前诊断。结论产前诊断可早期发现先天性膈疝,其结果可指导孕妇在产前采取相应的预防措施,并为出生后的及时治疗提供机会。术前积极改善肺功能,待呼吸循环状况稳定后延期手术治疗,可以提高患儿存活率。     

Familial severe congenital diaphragmatic hernia: Left herniation in one sibling and bilateral herniation in another

Familial congenital diaphragmatic hernia (CDH) is extremely rare; it comprises about 2% of all CDH cases. The empirical risk is about 2%, increasing to 10% in a family with two affected children. This report describes severe CDH in two siblings who had been diagnosed prenatally. The female newborn diagnosed with left CDH prenatally was born at 38 weeks of gestation. Despite surgical repair and intensive treatment, she died 10 days after birth. Her younger brother was born at 39 weeks of gestation after being diagnosed with bilateral CDH prenatally, and died 75 min after birth. Both infants had neither other congenital anomaly nor chromosomal abnormalities. Their parents are healthy without consanguinity. Their first daughter and the fourth child have no congenital anomalies.     

Can we improve outcome of congenital diaphragmatic hernia?

This review gives an overview of the disease spectrum of congenital diaphragmatic hernia (CDH). Etiological factors, prenatal predictors of survival, new treatment strategies and long-term morbidity are described. Early recognition of problems and improvement of treatment strategies in CDH patients may increase survival and prevent secondary morbidity. Multidisciplinary healthcare is necessary to improve healthcare for CDH patients. Absence of international therapy guidelines, lack of evidence of many therapeutic modalities and the relative low number of CDH patients calls for cooperation between centers with an expertise in the treatment of CDH patients. The international CDH Euro-Consortium is an example of such a collaborative network, which enhances exchange of knowledge, future research and development of treatment protocols.     

Unilateral agenesis of the diaphragm: a separate entity or an extremely large defect?

Since the mid-1980s, unilateral agenesis of the diaphragm (DA) has attracted the attention of paediatric surgeons as more babies affected by this extreme form of congenital diaphragmatic hernia (CDH) survive. Some authors believe that it represents a separate clinical entity. We undertook a retrospective analysis of all babies with CDH treated in the South-West Regional Paediatric Surgical Centre in Bristol between 1981 and 1995. Of 108 babies 16 (14.8%) were identified as having DA. All presented with severe respiratory distress from birth. In comparison to the group of patients with postero-lateral hernia, neonates with DA had lower Apgar scores and required longer preoperative stabilisation with inotropic support and vasodilators. Nine were subjected to operation and all required diaphragmatic replacement. Only 3 survived; thus, mortality in the DA group was 81.25%, and among those who underwent surgery 66.6% The same data for babies with postero-lateral hernia were 15.2% and 7.2%, respectively. Our results indicate that DA is associated with high morbidity and mortality, but we have not found any evidence that this anomaly is a distinct entity. In addition, we reviewed all post-mortem reports of fetuses with diaphragmatic defects available for the same period. Of 19 fetuses, 10 (52.6%) had DA. The morphological details of the diaphragmatic defect and the presence of associated anomalies were analysed. Our observations support the hypothesis that DA occurs in the very early stages of embryonic life and may be attributed to developmental arrest of the septum transversum. Accepted: 5 January 1999     

The Garbose Family Special Delivery Unit: A new paradigm for maternal–fetal and neonatal care

Birth defects remain the leading cause of infant mortality in the United States according to the Centers for Disease Control. For many anomalies, etiology remains unknown, management and outcome vary widely, and treatment is costly. Great strides have been made in prenatal diagnosis, yet standardized prenatal care and delivery protocols are needed for women carrying fetuses with specific birth defects such as diaphragmatic hernia, lung lesions, abdominal wall defects, congenital heart disease and so forth. In an effort to standardize and improve the overall care for mother and baby with a known birth defect, the Garbose Family Special Delivery Unit was opened at the Children's Hospital of Philadelphia in June 2008. This paper describes an innovative healthcare delivery model focusing on the rationale for developing a specialized delivery unit, the facility design and development process, care model, team and services, and the types of fetal diagnoses and maternal admission criteria for the SDU.     

Recurrent diaphragmatic hernia

Recurrent congenital diaphragmatic hernia (CDH) is a well-known complication, but one that has not been examined systematically. Review of the literature shows a varied incidence as well as a myriad of treatment strategies. Evaluation of the available data is made more difficult by lack of standardized repair techniques and comparable patient groups. As an increasing number of diaphragmatic hernia patients survive the newborn period, a study of the true incidence of recurrent diaphragmatic hernia, its etiologic factors, and the methods of repair is essential to prevent and treat this problem.     

Antenatal treatment of congenital diaphragmatic hernia: an update]

Despite advances in neonatal care, the associated mortality in isolated congenital diaphragmatic hernia remains in the order of 30%. Death is mainly due to consecutive pulmonary hypoplasia and severe associated pulmonary hypertension. This statement led to the implement of fetal therapy in order to improve fetal lung development. The first phase of fetal surgery consisted in open repair with one-stage surgical correction of the anatomic defect. It was followed by tracheal occlusion technique based on the decrease egress of lung fluid in order to improve lung growth. Initial approach of tracheal occlusion used clips on the trachea. It is now performed with intra-tracheal inflatable balloon. The challenge of such prenatal treatment is to establish accurate prenatal prognosis factors in order to offer this therapeutic in the subgroup of patients in whom outcome of postnatal treatment remains dismal. Current factors used for prenatal prognosis evaluation are thoracic liver position and lung-to-head ratio (LHR). The balloon is inserted at 26 to 28 weeks and removed at 34 weeks. First results are encouraging. However, many patients developed premature prelabour rupture of the membrane and paediatric data are sparse. Only few patients were currently treated and long term evaluation is needed. A powered multicentric study is needed to determine the value of fetal tracheal occlusion in the management of fetuses with isolated severe congenital diaphragmatic hernia.     

Ectopic thoracic kidney in a child with congenital diaphragmatic hernia.

Thoracic ectopic kidney with partial or complete renal protrusion above the level of the diaphragma into the posterior mediastinum is the rarest form of all ectopic kidneys with an incidence of less than 1 per 10,000 cases. We present a newborn with right congenital diaphragmatic hernia associated with thoracic ectopic kidney. The diagnosis of ectopia was made prior to surgery. Gerota's fascia of kidney was used to close the diaphragmatic defect. Since this renal anomaly is usually asymptomatic, it does not require any specific treatment. However, a close examination of function and anatomy of the kidney prior to surgery of hernia is important and beneficial. We discuss the embryological context and the importance of renal scintigraphy in patients with ectopic kidney.     

Fetal surgery: for what purpose?]

Widespread use of prenatal ultrasonography allows accurate diagnosis of many fetal malformations. The natural history and pathophysiology of some fetal diseases will undoubtedly induce lethal issue. Prenatal ultrasounds allow to determine prognosis during the second trimester of pregnancy. Experimental model and clinical practice have shown that prenatal surgery could be proposed for some correctable malformations: congenital diaphragmatic hernia, cystic adenomatoid lung disease, sacrococcygeal teratoma, lower urinary tract obstruction. To purpose this fetal therapy, great attention has to be paid to maternal risk and her future fertility, keeping in mind the aim of such fetal surgery: a new hope for improved management of the fetus with life-threatening defect.     

Management of fetal urinary tract anomalies detected by prenatal ultrasonography.

Over a three and a half year period 32 babies were referred with a urinary tract anomaly diagnosed by prenatal ultrasound. This diagnosis was subsequently confirmed in 19 infants by postnatal assessment. Three of 13 infants in whom the original diagnosis was incorrect were subsequently found to have intra-abdominal pathology but no urological anomaly, while the other 10 had lesions in the urinary tract but not those suggested prenatally. Nineteen of the 29 babies with urological abnormalities were clinically normal at birth; 20 underwent surgery. There were three deaths; two from a combination of renal and pulmonary failure secondary to posterior urethral valves, and a third (in an infant who had normal renal function) from diaphragmatic hernia and cardiac anomalies. Prenatal diagnosis was thought to have been of benefit in six patients, of probable benefit in 16, and of no benefit in seven.     

Congenital diaphragmatic hernia: still a moving target

The primary therapeutic target for congenital diaphragmatic hernia (CDH) patients has shifted from emergency surgical repair towards a non-operative emergency of the newborn treated by interdisciplinary teams. The increased understanding of the epidemiological and pathophysiological aspects of CDH have led to an improved knowledge and application of prenatal diagnosis, postnatal ventilation strategies, treatment of associated pulmonary hypertension and the role of extracorporeal membrane oxygenation therapy. In the surgical field, the perspectives have changed with delayed CDH repair, the introduction of minimally invasive surgery and use of prosthetic material for closure of large defects. With decreased mortality, long term multi-organ morbidity has increased in some survivors. In the near future, randomized controlled trials on different aspects of therapy will determine evidence-based optimal care.     

Congenital Diaphragmatic Hernia: Experimental Approach

Congenital diaphragmatic hernia is the only relatively common congenital malformation which requires operative treatment during the neonatal period, and the incidence is reported to be one in 2,000–5,000 births. Although a diaphragmatic defect can be easily corrected by pulling out the herniated viscera of the chest and closing the diaphragma, the mortality rate of infants with congenital diaphragmatic hernia is high despite improvements in neonatal intensive care, because the hypoplastic lungs on the affected side can not provide life support after birth. The severity of associated pulmonary hypoplasia is the most important factor determining survival in an infant with congenital diaphragmatic hernia. From experimental study, it should be emphasized that retardation in the lung growth, regardless of its potential for further growth, just at the time of pleuroperitoneal canal closure, may result in congenital diaphragmatic hernia; the hypoplastic lung on the side of herniation would not result from the compression of the lung by the herniated organs, but it may be induced by the limited space for further growth.     

Congenital diaphragmatic hernia in identical twins

The authors present a pair of identical twins with congenital diaphragmatic hernia (CDH) diagnosed prenatally, who underwent successful surgical repair. They were diagnosed as having CDH at 32 weeks' gestation and showed respiratory distress soon after cesarean section at 33 weeks' gestation. Both survived after scheduled perinatal management followed by surgery, for which the prenatal diagnosis of CDH was valuable. Accepted: 17 June 1999     

The embryology of the diaphragm

Despite the progress in prenatal diagnosis and intervention as well as postnatal therapeutic strategies, congenital diaphragmatic hernia (CDH) is still associated with a meaningful mortality because of the induced pulmonary hypoplasia. An essential key in understanding the pathogenesis of CDH is the underlying embryology, which has been neglected during the last decades. Likewise, the development of the normal diaphragm is still poorly understood. Obsolescent perceptions, mainly formed from histologic sections, are still propagated. In this review we present an atlas of scanning electron microscopy images that depict the normal and defective development of the diaphragm in the nitrofen rat model for CDH. Our findings suggest that the normal diaphragm mainly develops from the posthepatic mesenchymal plate. If the development of the posthepatic mesenchymal plate is impaired, a diaphragmatic defect occurs.     

Networks in Canadian paediatric surgery: Time to get connected

There has been a recent trend of improved outcomes for most infants born with surgically correctable congenital malformations, despite the fact that current surgical treatment is not standardized, with wide variations in practice among institutions. Because care for these infants is multidisciplinary, it is difficult to ascertain with clarity the specific role of neonatal surgery in determining outcomes. Moreover, the lack of validated measures of illness severity for most complex congenital malformations makes risk adjustment difficult. For these reasons, the utility of randomized controlled trials in determining best surgical practice in neonatal surgery for congenital malformations is impractical, and another means of deriving medical evidence to justify ‘optimal’ treatment is necessary.The Canadian Paediatric Surgical Network (CAPSNet) was developed specifically to address these issues. Patterned after the highly successful Canadian Neonatal Network, CAPSNet collects standardized data on every case of gastroschisis and congenital diaphragmatic hernia evaluated in the 16 referral perinatal centres in Canada. These centres serve as provincial referral centres for perinatal care, and, therefore, the data set created is population-based for gastroschisis and congenital diaphragmatic hernia in Canada. In addition to neonatal data fields recorded in the Canadian Neonatal Network, CAPSNet collects specific prenatal data, and details on surgical treatment and outcomes within each of the 16 participating centres. It is hoped that by using advanced analytical techniques, including outcomes modelling and multiple logistic regression analysis of risk-adjusted outcome variations by type of surgery performed, optimal treatment paradigms will be identified that will lead to further outcome improvement in babies born with complex birth defects.     

Neonatal surgical problems of the chest

Neonatal surgical problems of the chest include a wide spectrum of anomalies that extend from chest wall deformities to developmental cardiac malformations. To remain within the scope of this publication, cardiac anomalies and chest wall deformities are excluded.Most neonatal chest conditions have other associated anomalies such as chromosomal anomalies that may form part of more complex syndromes. In the era before prenatal diagnosis many of these conditions would present as fetal loss or asymptomatically and discovered incidentally during postnatal imaging. Prenatal diagnosis has revolutionized the diagnosis and treatment of chest conditions.Congenital cystic lung lesions have a prenatal diagnostic accuracy of almost 100% and are mainly asymptomatic at postnatal presentation. The diagnosis may be confirmed on postnatal computerized tomography (CT) scan, however the treatment of these asymptomatic lesions remains controversial. Most institutions offer surgery to avoid future complications however surveillance with or without imaging an alternate management.More than 60% of cases with prenatally diagnosed congenital diaphragmatic hernia do not make it beyond the neonatal period. Complex associated anomalies and lung hypoplasia are the prime causative factors for this grim outcome. Even those infants that survive post-surgical repair some will have respiratory, gastrointestinal and neurological sequeli.Chylothorax and thoracic teratoma are other thoracic conditions discussed.Diagnosis of oesophageal atresia is less accurate on prenatal scan. Surgery could be challenging and outcomes are dependent on associated anomalies.     

Management of congenital diaphragmatic hernia with transposition of the great arteries

Congenital diaphragmatic hernia (CDH) is a relatively rare malformation, but it has a high mortality rate. Its association with congenital heart disease lowers survival rate due to severe acidosis and desaturation caused by persistent pulmonary hypertension of the neonate. We describe herein a case of CDH with transposition of the great arteries and intact ventricular septum, in a patient who was prenatally diagnosed, managed with extracorporeal oxygenation (ECMO) support and successfully treated with both CDH repair and Jatene procedure, with no respiratory or circulatory sequelae. In conclusion, precise prenatal estimation is essential, and ECMO is a useful therapeutic option in these complex cases.     

Congenital diaphragmatic hernia

Congenital diaphragmatic hernia occurs in approximately 1 in every 2500 live births and is associated with a reported mortality of almost 35% in live-born patients and a higher mortality when in utero deaths are counted. Ventilator-induced lung injury, pulmonary hypoplasia, and other associated anomalies account for the high death rate. Numerous adjunctive measures have been used to treat these patients. Inhaled vasodilators (nitric oxide), intravenous vasodilators, and fetal therapy have no proven benefit. While animal models of congenital diaphragmatic hernia are surfactant deficient, controversy remains over the use of surfactant in infants. There has been no clinical trial showing any clear benefit with the use of exogenous surfactant in these patients. Similarly, prenatal corticosteroids show some improvements in animal models, but again, there is a complete absence of supportive data to show benefit in humans. Mechanical ventilator strategies that limit ventilator-induced lung injury by avoiding hyperventilation and lung over inflation are the strategies currently in use that have been associated with improved survival. Long-term follow-up of these patients is quite important since gastroesophageal reflux, developmental delay, chronic lung disease, and chest wall deformity are all seen with increased frequency in these children.