Congenital diaphragmatic hernia in the neonate

INTRODUCTION — Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that allows abdominal viscera to herniate into the chest. Affected neonates usually present in the first few hours of life with respiratory distress that may be mild or so severe as to be incompatible with life. With the advent of antenatal diagnosis and improvement of neonatal care, survival has improved, but there still remains significant risk of death and complications in infants with CDH.

The clinical manifestations, diagnosis, and management of the neonate with CDH will be reviewed here. The pathogenesis, anatomy, incidence, and prenatal diagnosis and management of CDH are discussed separately. (See "Congenital diaphragmatic hernia: Prenatal issues".)

EFFECT ON PULMONARY DEVELOPMENT — Because herniation occurs during a critical period of lung development, clinical manifestations of CDH result from the pathologic effects of the herniated viscera on lung development. With rising severity of lung compression, there are corresponding decreases in bronchial and pulmonary arterial branching, resulting in increasing degrees of pulmonary hypoplasia. Pulmonary hypoplasia is most severe on the ipsilateral side. However, pulmonary hypoplasia may develop on the contralateral side if the mediastinum shifts and compresses the lung. Arterial branching is reduced, resulting in muscular hyperplasia of the pulmonary arterial tree, which contributes to the increased risk of pulmonary hypertension (PH) [1].

CLINICAL MANIFESTATIONS

Prenatal presentation — Although routine prenatal ultrasound screening may identify CDH at a mean gestational age (GA) of 24 weeks, there is a wide range of reported sensitivity in its detection. Associated other anomalies (eg, cardiac abnormalities) are seen in approximately 50 percent of CDH cases, and their presence improves the sensitivity of detecting CDH. Prenatal presentation and diagnosis are discussed in greater detail separately. (See "Congenital diaphragmatic hernia: Prenatal issues", section on 'Prenatal diagnosis'.)

Postnatal findings — Postnatally, infants with CDH most often present with respiratory distress in the first few hours or days of life. The spectrum can vary from the more common presentation of acute respiratory distress at birth, to minimal or no symptoms, which is observed in a much smaller group of patients who present later in life. (See 'Late CDH presentation' below.)

In patients who present as neonates, the degree of respiratory distress is dependent on the severity of lung hypoplasia and the development of pulmonary hypertension (PH). Postdelivery, hypoxemia and acidosis increase the risk of PH by inducing a reactive vasoconstrictive element to the preexisting fixed arterial muscular hyperplasia component. In some cases, pulmonary hypoplasia is so severe as to be incompatible with life. (See 'Effect on pulmonary development' above and "Persistent pulmonary hypertension of the newborn (PPHN): Clinical features and diagnosis", section on 'Pathogenesis'.)

In most cases of CDH, herniation occurs on the left. Right-sided diaphragmatic hernias occur in approximately 15 percent of cases and bilateral herniation in 1 to 2 percent [2-4]. Although there is no difference in mortality between left- and right-sided lesions, there may be a higher incidence of pulmonary complications associated with right- versus left-sided CDH [3]. Bilateral herniation is associated with a high mortality rate [4].

Adrenal insufficiency is reported to be a common finding in infants with CDH. In one retrospective study of 58 patients, adrenal insufficiency (defined as a cortisol level ≤15 mcg/dL [415 nmol/L]) was demonstrated in two-thirds of the 34 patients who were assessed for adrenal function [5]. In this study, infants with adrenal insufficiency were more likely to have herniation of the liver, and had more severe illness requiring epinephrine for vasopressor support, high-frequency ventilation (HFV), and longer duration of inhaled nitric oxide (iNO) therapy. In our practice, we may administer hydrocortisone therapy in severely ill patients with hypotension. (See "Short-term complications of the preterm infant", section on 'Low blood pressure'.)

Associated anomalies are seen in approximately 50 percent of CDH cases and include chromosomal abnormalities, congenital heart disease, and neural tube defects. (See "Congenital diaphragmatic hernia: Prenatal issues", section on 'Associated fetal abnormalities'.)

Physical findings — Physical findings include a barrel-shaped chest, a scaphoid-appearing abdomen (because of loss of the abdominal contents into the chest), and absence of breath sounds on the ipsilateral side. In patients with a left-sided CDH, the heartbeat is displaced to the right because of a shift in the mediastinum.

DIAGNOSIS

Prenatal — Many cases of CDH are diagnosed prenatally by routine antenatal ultrasound screening. (See "Congenital diaphragmatic hernia: Prenatal issues", section on 'Prenatal diagnosis'.)

Postnatal — For infants with CDH not diagnosed in utero, the diagnosis should be suspected in any term infants with respiratory distress, especially if there are absent breath sounds. The diagnosis is made by chest radiography showing herniation of abdominal contents (usually air- or fluid-containing bowel) into the hemithorax with little or no visible aerated lung on the affected side (image 1). Other radiographic findings include the contralateral displacement of mediastinal structures (eg, heart), compression of the contralateral lung, and reduced size of the abdomen with decreased or absent air-containing intra-abdominal bowel. The diagnosis may be facilitated by placement of a feeding tube, as chest radiography may show the feeding tube within the thoracic cavity or deviation from its expected anatomic course [6]. If the CDH is right sided, the liver may be the only herniated organ and will appear as a large thoracic soft tissue mass with absence of an intra-abdominal liver shadow on chest radiograph.

DIFFERENTIAL DIAGNOSIS

Prenatal — The prenatal differential diagnosis includes other congenital thoracic lesions and is discussed separately. (See "Congenital diaphragmatic hernia: Prenatal issues", section on 'Differential diagnosis'.)

Postnatal — The differential diagnosis for CDH in a term neonate with respiratory distress includes other causes of pulmonary hypoplasia (eg, oligohydramnios from chronic amniotic fluid leak or renal hypoplasia/dysplasia), and persistent pulmonary hypertension of the newborn (PPHN) (eg, meconium aspiration). CDH is differentiated from these conditions by the characteristic chest radiograph finding of herniated abdominal contents into the thorax. (See 'Diagnosis' above and "Persistent pulmonary hypertension of the newborn (PPHN): Clinical features and diagnosis".)

PRENATAL MANAGEMENT — The prenatal management of CDH is discussed separately. (See "Congenital diaphragmatic hernia: Prenatal issues", section on 'Pregnancy management'.)

POSTNATAL MANAGEMENT

Overview — Management of CDH encompasses the following and is associated with survival rates of 70 to 92 percent. (See 'Survival' below.)

●Preoperative medical management, consisting of correction (if needed) and stabilization of the infant's oxygenation, blood pressure, and acid-base status. Acidosis and hypoxia increase the risk of pulmonary hypertension. Hypotension increases the risk of right-to-left shunting that contributes to tissue hypoxia.

●Surgical repair, which includes closure of the diaphragmatic defect and reduction of the viscera into the abdominal cavity (picture 1).

Preoperative medical management — Although there are no randomized clinical trials, case series have shown that initial medical management followed by surgical correction improves survival in neonates with CDH [7-10]. Supportive medical management consists of reducing lung compression, cardiovascular support with fluids and inotropic agents, and ventilatory support using conventional or high-frequency ventilation (HFV). Extracorporeal membrane oxygenation (ECMO) is used in severe cases of patients who are not responsive to the supportive medical interventions.

Initial treatment — The following interventions are initiated in the delivery room when the diagnosis is made or suspected [11]:

●Intubation and ventilation – Prenatally diagnosed patients are intubated in the delivery room. This avoids the use of blow-by oxygen and/or bag-masking that result in gastric/abdominal distension and compression of the lung. The infant should be ventilated with low peak inspiratory pressure (PIP, goal <25 cm H₂O) to minimize lung injury. Delay in securing an adequate airway may contribute to acidosis and hypoxia, which increase the risk of pulmonary hypertension. (See 'Ventilation' below.)

●Nasogastric tube – A nasogastric tube connected to continuous suction is placed in the stomach so as to decompress abdominal contents and reduce lung compression.

●Line placement – The infant should have an umbilical artery line placed for frequent monitoring of blood gases and blood pressure (BP), and if possible an umbilical vein (UV) catheter for administration of fluids and medications. In patients with the liver in the chest, the UV catheter is often difficult to position, and, therefore, once the patient is stabilized, other venous access should be obtained.

●Blood pressure (BP) – BP support should be given to maintain arterial mean BP levels ≥40 mmHg to minimize any right-to-left shunting. Support includes the use of isotonic fluids, inotropic agents such as dopamine and/or dobutamine, and hydrocortisone.

●Surfactant administration – Although administration of surfactant therapy has been suggested in treating infants with CDH [12], it does not appear that surfactant administration improves outcomes [13,14].

However, we do administer surfactant in neonates ≤34 weeks gestation with chest radiographic findings of alveolar atelectasis suggestive of respiratory distress syndrome (RDS) (see "Clinical features and diagnosis of respiratory distress syndrome in the newborn", section on 'Diagnosis').

In addition, we administer surfactant in infants who underwent fetal tracheal occlusion when the release of the occlusion is less than 48 hours prior to delivery. (See "Congenital diaphragmatic hernia: Prenatal issues", section on 'Fetal endoscopic tracheal occlusion (FETO)'.)

●Inhaled nitric oxide (iNO) – Although several studies have shown that iNO does not appear to have long-term benefits, iNO administration is widespread in patients with CDH [15-19]. However, in a retrospective study from our center, iNO administration was associated with improved oxygenation and a decrease in ECMO for infants with normal left ventricular function [20]. As a result, prior to placing the patient on ECMO, we consider iNO in select patients with respiratory failure due to pulmonary hypertension with normal left ventricular systolic function if preductal oxygen saturation is <85 percent or pre/postductal differential is >10 percent despite maximal ventilatory support [20]. (See "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome", section on 'Inhaled nitric oxide (iNO)' and "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome", section on 'Identify and treat underlying conditions'.)

●Other vasodilatory agents (eg, prostaglandin E1, sildenafil, treprostinil, bosentan) are used for severe and persistent PH in the management of CDH [21,22]. (See "Pulmonary hypertension in children: Management and prognosis", section on 'Targeted pulmonary hypertension therapy'.)

Ventilation — As noted above, once the diagnosis of CDH is made, patients are intubated and mechanically ventilated to prevent gastric distension and lung compression. Ventilation strategy is aimed at minimizing lung trauma to hypoplastic lungs, which contributes to mortality and morbidity [17,23]. Our ventilation management uses the minimal settings to maintain preductal oxygen saturations above 85 percent or preductal partial pressure of oxygen (PaO₂) above 30 mmHg, and allows for permissive hypercapnia (defined as partial pressure of carbon dioxide [PaCO₂] between 45 and <65 mmHg and an arterial pH >7.25 to 7.4) [14]. As long as perfusion is maintained, preductal oxygen saturations guide therapy despite significant right-to-left shunting through the ductus arteriosus and lower postductal oxygen saturation levels [24].

Frequent blood gases are important parameters to follow in the adjustment of ventilator settings. Oxygen is started at fractional inspired concentration (FiO₂) of 0.5 and adjusted based on maintaining preductal oxygen saturation above 85 percent [25].

Type of ventilation — Conventional mechanical ventilation (CMV) management consists of pressure-limited ventilation at rates of 30 to 70 breaths per minute at PIP of 20 to 25 cm H₂O [9,26]. PIP exceeding 28 cm H₂O is used transiently as a bridge to ECMO. Positive end-expiratory pressure (PEEP) should be maintained at physiologic levels (3 to 5 cm H₂O) whenever possible. Hyperventilation, hypocarbia, and alkalosis may decrease ductal shunting and control pulmonary hypertension in CDH [27,28], but at the expense of increased barotrauma. Permissive hypercapnia has been used in neonates with CDH, with reports of increased survival compared with hyperventilation and alkalization [7,9,26,29,30]. (See "Overview of mechanical ventilation in neonates", section on 'Conventional mechanical ventilation (CMV)'.)

In our center, high-frequency ventilation (HFV) is reserved for neonates who continue to have hypoxia and hypercarbia (PaCO₂ >65 mmHg) refractory to CMV. Although the indications for HFV are not clearly defined, there are retrospective reports of effective PaCO₂ reduction and good survival rates in neonates with CDH [31-33]. One trial of CMV versus HFV for infants with prenatally-diagnosed CDH reported similar primary outcomes for death and BPD infants regardless of the initial assigned mode of ventilation. [34]. Patients who were randomly assigned to CMV had better secondary outcomes, with fewer ventilator days, decreased use of ECMO and pulmonary vasodilators, and shorter duration of vasoactive drugs. A retrospective study also reported similar outcomes of death, BPD and duration of ventilation between infants initially treated with CMV and those with HFV after adjusting for confounding factors [35]. Further data are needed to determine whether HFV has a preferred initial role in managing neonates with CDH and if so to determine the indications for HFV [17]. (See "Overview of mechanical ventilation in neonates", section on 'High-frequency ventilation (HFV)'.)

Paralysis and sedation — Although paralysis and sedation reduce air swallowing and may enhance compliance and reduce sympathetic vasoconstriction, potentially leading to lower ventilator settings, some experts in the field believe that the loss of the infant's spontaneous contribution to minute ventilation and increased third-space edema negate the benefits of paralysis [26]. In our practice, we avoid the use of paralytic agents, and use sedation and paralytics only when necessary (eg, failure of patient-ventilator synchrony).

Echocardiography — Echocardiography is performed early to detect any associated cardiac anomalies, and to establish the presence and severity of pulmonary hypertension and shunting, and assess ventricular function as these factors impact management decisions (image 2A-B).

Congenital heart disease — The presence of associated severe cardiac anomalies may have an impact on how aggressive subsequent treatment should be, as the survival rate of patients is lower in patients with CDH and major cardiac anomalies (such as hypoplastic left heart syndrome) [36-39]. This was illustrated in the largest case series of 2636 patients from the Congenital Diaphragmatic Hernia Study Group (CDHSG) that reported survival of 41 percent in patients with hemodynamically significant cardiac defects (n = 280, 11 percent of cohort) compared with a 70 percent survival for patients without cardiac defects [37].

It remains unclear whether there is a difference in survival between patients with single ventricle cardiac defects compared with those with two ventricle cardiac lesions. In the CDHSG report, survival was poorer in those with single versus two ventricle anatomy (5 versus 47 percent) [37], whereas in two other studies, there was no difference in survival [38,39].

Pulmonary hypertension and ventricular function — The echocardiographic signs of pulmonary hypertension (PH) include poor contractility of the right ventricle, enlarged right heart chambers, pulmonic and tricuspid valve regurgitation, and presence of ductal shunting. Left ventricular hypoplasia may also be identified. PH with right-to-left shunting, left ventricular dysfunction, or systemic hypotension are indications for prompt administration of inotropic agents. The use of prostaglandin E1 (PGE1) may be a potential intervention for infants with CDH and severe PH, as a retrospective review reported that PGE1 appeared to be well tolerated and was associated with improved BNP and echocardiographic indices of PH, suggesting successful unloading of the RV [22]. Surgical repair is usually delayed until there is resolution of severe pulmonary hypertension (defined as echocardiographic estimated pulmonary artery pressure >80 percent systemic blood pressure) [40]. (See 'Timing' below and "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome" and "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome", section on 'Management approach'.)

Biventricular dysfunction has been reported to be associated with the use of extracorporeal membrane oxygenation (ECMO) therapy and poor outcome [41,42].

Extracorporeal membrane oxygenation — The first CDH survivor treated with ECMO was reported in 1977 [43]. Subsequently, several single-center case series have shown improved survival rates with the use of ECMO in infants with CDH [44-47]. However, the results of ECMO are heavily dependent on selection criteria, which can vary by institution.

Although there are no randomized controlled studies that have demonstrated the efficacy of ECMO in infants with CDH, ECMO, if available, is considered for almost all infants who cannot be managed with maximal conventional medical therapy (maximal ventilatory support, inotropic support for BP and iNO), as these patients would not survive without ECMO. ECMO is advocated as a means to support the patient until the reactive component of pulmonary hypertension resolves, which may take weeks.

Criteria — The primary indication for ECMO is failure of conventional therapy [7,23,48]. In our practice, ECMO is offered to all patients if the infant has initially responded to conventional interventions, irrespective of presence of a heart defect, and meets the following inclusion criteria:

●Inability to maintain preductal PaO₂ saturations >85 percent or postductal PaO₂ >30 mmHg

●PIP >28 cm H₂O or mean airway pressure (MAP) >15 cm H₂O

●Hypotension that is resistant to fluid and inotropic support

●Inadequate oxygen delivery with persistent metabolic acidosis

Exclusionary criteria for ECMO vary between institutions. Most ECMO centers exclude patients with lethal chromosomal abnormalities or severe intracranial hemorrhage.

As a result, traditional inclusion criteria for ECMO, including in our center, also include all of the following [49]:

●Birth weight (BW) >2 kg

●Gestational age (GA) >34 weeks

●Absence of intracranial hemorrhage greater than grade I

●Absence of chromosomal anomalies

There have been reports of patients with cardiac disease, low-grade intracranial hemorrhage, and prematurity who have been placed on ECMO and survived [36,44,50,51].

Weaning — Based upon clinical stability and tolerance to care, we will increase ventilator settings, follow tidal volumes, and perform ECMO turn-down trials guided by echocardiographic findings. When lung fields are opacified, we will check for large pleural effusions which may be drained with tube thoracostomy and consider endotracheal tube change, lavage, and bronchoscopy for clearance of plugs. In some cases, we will administer dexamethasone, which decreases lung inflammation, to help facilitate weaning. Once the lungs are open, if there remains evidence of pulmonary hypertension despite these measures while attempting to withdraw ECMO support, we will consider aggressive pharmacologic treatment with PGE1, iNO, and treprostinil [21,22]. Following optimizing cardiorespiratory support, fluid status, and a time interval, we will again try to wean from ECMO support.

Withdrawal — Criterion for withdrawal of ECMO support at our center includes any extension of intracranial hemorrhage. Infants are at risk for intracranial bleeding due to the need for continuous anticoagulation with heparin.

In our practice, head ultrasounds are performed before initiation of ECMO, daily for the first five days and then every other day while on ECMO support to detect and monitor any extension of intracranial hemorrhage. In addition, head ultrasounds are performed emergently for onset of seizures, change in neurologic status, or following any significant clinical event (eg, surgical repair of CDH, and episodes of hypotension or hypertension). Patients on ECMO are often sedated, and neurologic clinical assessment is difficult. Therefore, we also will use video electroencephalography (EEG) and portable computed tomography (CT) scanning to assist in decisions regarding discontinuation of ECMO when the findings on ultrasound are equivocal for poor prognosis.

Another consideration for withdrawal is worsening clinical status despite optimal therapy. In our practice, we utilize a step-wise approach of interventions to improve pulmonary function and do not set an arbitrary time for pulmonary hypertension resolution [52]. We initially optimize the patient's fluid status and lung aeration while he/she is on ECMO.

Efficacy — It is difficult to accurately assess the benefit of ECMO given the paucity of clinical trials [53]. Although some centers have reported higher survival rates, the survival has decreased for infants in the Extracorporeal Life Support Organization (ELSO) registry, who have received ECMO [54]. In particular, survival decreased over the 10 years between 2001 and 2010 due to a poorer outcome of what is suspected to be a higher-risk patient population. Survival rates may vary because of patient selection.

Once the infant is weaned from ECMO, there remains a risk of recurrent hypoxia secondary to pulmonary hypertension and right-to-left shunting [55]. In a report of patients treated with a second course of ECMO, 16 of 34 (47 percent) CDH patients survived [56]. Systematic reviews of the literature based on limited number of clinical trials have concluded that the available evidence failed to demonstrate a difference in long-term benefit (eg, late mortality) between patients who received ECMO versus those who were not placed on ECMO [53,57,58].

Surgery

Primary versus patch repair — Surgical repair consists of reduction of the abdominal viscera and primary closure of the diaphragmatic defect (picture 1). The diaphragmatic defect may be repaired with sutures alone (primary repair). However, a Gore-Tex patch or split abdominal wall muscle flap [59] repair is often required in patients with large CDHs in whom increased tension using a primary repair compromises total thoracic compliance [60]. Reported patch-related complications include an increased risk of infection, chest wall deformities by tethering of the ribs, and a potential increase in CDH recurrence [61]. However, in our center, the risk of recurrence of CDH was similar in patients who underwent patch repair compared with those with primary repair [60]. The muscle flap is a good alternative when the patient has already had infectious issues to avoid using an implant of Gore-Tex. (See 'Patch-related' below.)

If the abdominal wall is difficult to close following reduction of the hernia, the use of a temporary abdominal wall silo or patch may be helpful [62]. In a retrospective review of CDH repairs at a single institution, delayed abdominal wall closure was required in 9 percent of overall cases, 2 percent of cases off ECMO, and 40 percent of repairs on ECMO [63]. Delayed abdominal wall closure was associated with an increased need for blood transfusions but no significant difference in mortality [63].

Timing — With a better understanding of the pathophysiology and variation in the degree of pulmonary impairment, the timing of surgery has shifted from early surgical intervention to delaying surgical correction until the patient has been stabilized medically [14]. In particular, surgery is usually delayed in neonates with more severe forms of pulmonary hypoplasia and pulmonary hypertension who require additional medical care, which may include ECMO [40]. In our center, we use this approach in the timing of surgery as discussed in the next section.

Reported survival rates in newborns with CDH using this management approach of preoperative stabilization and selective use of ECMO followed by delayed surgical correction range from 79 to 92 percent [7-10,14]. In a review of data from the CDHSG, an analysis adjusted for severity of illness found no differences in mortality based on timing of the surgery stratified as day of life 0 to 3, day of life 4 to 7, and after day of life 8 [64].

Our approach — Our management approach is based on the severity of pulmonary impairment and dictates the timing of surgery. Initial medical treatment as discussed above focuses on stabilizing the neonate, especially those with pulmonary hypertension and hypoplasia.

Once the diagnosis is made or suspected, all patients are intubated and a nasogastric tube connected to continuous suction is placed in the stomach to reduce lung compression. In addition, echocardiography is performed to detect the presence of pulmonary hypertension, cardiac abnormality, and cardiac function. (See 'Initial treatment' above.)

Management including timing of surgery is dependent on the cardiorespiratory status of the patient as follows:

●In patients with only mild symptoms on minimal support, in whom there is no evidence of pulmonary hypertension or pulmonary hypoplasia, repair is typically undertaken at 48 to 72 hours of age.

●In patients with no or mild pulmonary hypoplasia and reversible pulmonary hypertension, the timing of repair is delayed until pulmonary hypertension is resolved and pulmonary compliance improves [65]. The time course is variable and is dependent on the response to medical management (stabilization of blood pressure, oxygenation, and correction of acidosis). The majority of patients will demonstrate initial lability, but then stabilize, allowing repair after 5 to 10 days. (See 'Initial treatment' above and 'Ventilation' above.)

●In patients who require ECMO therapy because of failure to respond to medical management (see 'Criteria' above), there is some controversy about timing of the operative repair. In our center, surgical repair is performed depending upon the individual clinical setting as follows:

•For patients with severe pulmonary hypertension who continue to require ECMO support, one approach is to repair the defect while the infant is on ECMO [66]. Earlier studies reported a high rate of hemorrhagic complications and high mortality once bleeding developed [67,68]. This problem has been partially resolved by administering perioperative aminocaproic acid [66,69], putting fibrin glue on the suture line [70], and avoiding extensive dissection of the diaphragmatic leaves. If the circuit clots secondary to the use of aminocaproic acid or there is excessive bleeding, the infant may be decannulated without significant clinical compromise.

•In our center, an early repair on ECMO is indicated when ECMO flow is compromised secondary to the degree of mediastinal shift, to allow adequate support and when ventilation prior to ECMO is very poor. Other centers advocate for early repair in all cases once ECMO is initiated [71,72]. However, a contra-argument against early repair in all patients is the increased exposure to bleeding complications and mortality, which is a factor on our selective approach to early repair [73].

•In our center, approximately one-half of the patients have evidence of transient adequate gas exchange prior to ECMO, and we will decrease time on ECMO and complications by delaying surgery until off of ECMO after resolution of pulmonary hypertension [74]. In a retrospective review of patients with CDH and ECMO, survival was improved with lower rates of surgical bleeding and total duration of ECMO therapy if patients could be successfully weaned from ECMO prior to repair [75]. Some patients may return to conventional ventilation and decannulation before repair of CDH [49]. This strategy is indicated for neonates who can be weaned from ECMO and when there are coagulation, infectious, or mechanical complications from ECMO.

●In a small group of patients with severe pulmonary hypoplasia and/or pulmonary hypertension, there will be no response to therapy of any kind, including to ECMO. In this group, support is often withdrawn. (See 'Weaning' above.)

COMPLICATIONS

Acute complications — The most serious complication post-repair of CDH is persistent pulmonary hypertension (PH) [76-78]. Some patients may require extracorporeal membrane oxygenation (ECMO) [76-78]. Other complications early in the postoperative course include hemorrhage, chylothorax, and infection (patch infection, sepsis, and urinary tract infection) [79]. (See "Approach to the neonate with pleural effusions", section on 'Traumatic chylothorax'.)

Late complications — Late complications include chronic respiratory disease, recurrent hernia/patch problems, spinal/chest wall abnormalities, gastrointestinal difficulties, and neurological sequelae [80-82].

Readmission — Hospital readmission is common for patients who undergo surgical repair. This was illustrated by a study using the Nationwide Readmissions Database from 2010 to 2014 that reported almost all of the 511 patients identified with neonatal CDH (n = 495) were readmitted within the first year following birth hospital discharge [83]. One-third of the cohort were readmitted within 30 days of birth hospital discharge. The most common complications associated with readmission were gastroesophageal reflux disease (GERD), CDH recurrence, and surgery for gastrostomy tube placement and/or fundoplication.

Pulmonary — Survivors, especially those treated with ECMO, are at risk for respiratory infections and chronic lung disease [84-88]. Pulmonary function tests are abnormal and the severity of impairment increases with increasing degrees of pulmonary hypoplasia and pulmonary hypertension [87-89]. Outcome studies have reported that increasing degrees of airway obstruction detected by pulmonary function studies over time [88,90,91]. It remains uncertain what the impact will be on pulmonary function as survivors reach adulthood.

Recurrent hernia — The reported range of recurrent diaphragmatic hernia varies from 2 to 13 percent of patients undergoing repair [81,92,93]. Reherniation is usually diagnosed by chest or contrast studies prompted by respiratory or gastrointestinal symptoms. The risk of recurrence is greater for those with large defects [92]. In one case series, the risk of recurrence was higher for patients with ECMO [81]. However, data from Congenital Diaphragmatic Hernia Study Group registry found no association with ECMO use and timing of repair [92].

Patch-related — Patches may become chronically infected, requiring removal of the patch and diaphragmatic reconstruction, preferably with native tissue [94]. Although repair using a patch was generally associated with a high rate of recurrence of hernia (up to 40 percent) in earlier case series, subsequently lower recurrence rates of 4 to 5 percent have been reported using Gore-Tex patches [95,96]. In our practice, subsequent surgery is not necessary for patients with patch despite their growth, unless there is a recurrence of CDH or infection.

The need for patch repair has been associated with a higher rate of chest wall deformities such as pectus excavatum, pectus carinatum, and thoracic scoliosis. Chest wall deformities have been reported in up to 50 percent of patients who were initially repaired with a patch [61,90,97,98]. It remains uncertain whether the deformity is directly related to the use of a patch, or a consequence of the severity of the CDH and subsequent incongruent lung growth.

Gastrointestinal — Gastrointestinal complications include GERD and intestinal obstruction.

●GERD – The reported incidence of GERD in patients with CDH ranges from 40 to 50 percent [99-101]. In several case series, antireflux surgery is performed in 15 to 20 percent of all patients with CDH [99-102].

Several anatomic factors that may contribute to the development of reflux include [103-105]:

•Disturbance of normal esophageal and gastroesophageal junction due to mediastinal shift and compression

•Shortened intra-abdominal esophagus

•Obtuse angle of His (angle at which the esophagus intersects the stomach at the cardioesophageal juncture)

•Deformation of the diaphragmatic crus by closure

•Pressure changes related to increased work of breathing

•Enlarged liver with gastric compression in cases with persistent pulmonary hypertension

•Potential neurologic defects

●Intestinal obstruction – Obstruction secondary to adhesions occurs in 10 percent of patients with CDH [98,106,107]. All patients with CDH have malrotation or malfixation of the intestines, and thus, a predisposition to development of volvulus. Rates of this potentially devastating complication vary from 3 to 9 percent [98,108].

Failure to thrive — Subsequent failure to thrive (FTT) has been reported in survivors with CDH, which extends into late childhood and adolescence [109,110]. Risk factors include prematurity, ECMO, prolonged ventilation, and oxygen requirement at discharge [86,110-114]. Increased work of breathing and GERD may also contribute to FTT by making oral feeding and swallowing challenging [109,110]. Affected patients may require supplemental feeding via nasogastric or gastrostomy tubes for adequate caloric intake [109,110]. Oral aversion due to GERD may also require gastrostomy feeding.

Neurodevelopment impairment — Abnormalities detected by cranial imaging include intraventricular hemorrhage (IVH), infarction, periventricular leukomalacia (PVL), and extra-axial fluid collections. Magnetic resonance imaging (MRI) of survivors of severe CDH demonstrates delayed maturation and structural brain abnormalities including PVL and varying degrees of intracranial hemorrhage [115].

These abnormalities likely lead to long-term neurologic complications. Neurodevelopmental impairment has been reported in 30 to 80 percent of patients, and has included both motor and cognitive function [116-125]. Neurocognitive impairment and delay has been reported to persist into school age [116,117,119,126,127]. In particular, hearing loss is common, with reported prevalence of 30 to 50 percent [86,128-130].

One longitudinal study of 47 CDH survivors over the first three years of life demonstrated that most children who had early delays showed improvement in their neurodevelopmental outcome, but children with delays in all domains were the least likely to show improvement [123].

Musculoskeletal deformities — Chest deformities including pectus excavatum, pectus carinatum, and scoliosis are common, particularly in patients with repaired large CDH [90,131,132].

SURVIVAL — The postnatal survival rate at tertiary centers has improved, with reported rates of 70 to 92 percent [133-139]. This increased survival rate appears to be a result of the shift from early surgical intervention to intensive preoperative supportive care aimed at avoiding lung injury, followed by surgical correction. However, these data represent the survival rate of cases of CDH that were full-term infants born or transferred to tertiary care centers with available skilled personnel and access to advanced technology (eg, extracorporeal membrane oxygenation [ECMO]). These survival rates do not account for the cases of CDH that are stillborn or died outside a tertiary center, or fetal loss due to spontaneous or therapeutic abortion [135,140-144]. In a population-based Swedish study, the overall survival was 55 percent when accounting for prenatal loss [144].

Factors associated with decreased survival include [137]:

●Prematurity – Survival is lower for preterm infants with CDH compared with term infants, and survival decreases with decreasing gestation [145,146]. This was illustrated in a review from the Congenital Diaphragmatic Hernia Study Group (CDHSG, formerly called the CDH Registry) that reported a survival rate of 54 percent for preterm infants compared with 73 percent observed in term infants [145]. Preterm infants were less likely to undergo surgical repair (69 versus 86 percent) and be treated with ECMO (26 versus 33 percent). Survival was higher in preterm infants who underwent surgical repair (77 percent), but this was still lower than in term infants with surgical repair (85 percent). Preterm infants were more likely to have chromosomal abnormalities (8 versus 4 percent) and major cardiac defects (12 versus 6 percent).

●Cardiac abnormalities – Data from the CDHSG showed that patients with major complex cardiac defects (eg, single ventricle physiology, left heart obstructive lesions, and transposition of the great arteries) have a significantly lower survival rate (36 percent) compared with those with either minor heart defects (67 percent) or no heart defect (73 percent) [147].

●Persistent and severe pulmonary hypertension [76-78,148].

●Site of care and need for transport – Institutions with greater hospital and surgical volume of caring for infants with CDH have better outcomes with lower mortality and fewer days on mechanical ventilations [149]. In addition, neonatal transport of infants with CDH is associated with poorer survival compared with infants who are inborn at a tertiary center with expertise in the management of CDH [150,151]. As a result, delivery of an affected fetus should be performed at a tertiary center, preferably with ECMO capability. (See "Congenital diaphragmatic hernia: Prenatal issues", section on 'Delivery'.)

●Low preductal oxygen and high carbon dioxide saturation – Survival is poorer in infants whose highest recorded preductal oxygen saturation is below 85 percent in the first 24 hours of life compared with those with higher levels [152,153]. In addition, elevated arterial blood gas PaCO₂ (partial pressure of carbon dioxide) greater than 60 mmHg is associated with decreased survival [153-155].

●Defect size – Infants with very large defects have a poorer outcome [133,156-159]. Reports from the CDHSG from 2007 and 2016 demonstrated that defect size is the most reliable predictor of survival [133,156]. Patients diagnosed prenatally have larger defects and consequently have higher morbidity and mortality [160].

●Right- versus left-sided lesion – It is unclear whether the side of the lesion affects survival. Right-sided lesions are usually larger and often require a patch or muscle repair [3,148,161-164]. However, several large case series have reported similar mortality rates for right- versus left-sided lesions despite the difference in size of defect [3,148,163,164]. Because of the continued postnatal mortality of CDH, research attempts are ongoing to develop in utero therapy to prevent or reverse pulmonary hypoplasia in fetuses with CDH, thereby restoring adequate lung growth for neonatal survival. (See "Congenital diaphragmatic hernia: Prenatal issues", section on 'Fetal endoscopic tracheal occlusion (FETO)'.)

POST-DISCHARGE MANAGEMENT — Because of the associated significant morbidities (ie, pulmonary complications, neurodevelopmental delay, gastroesophageal reflux, hearing loss, and poor growth), care of survivors with CDH following discharge from the hospital is challenging. Structured follow-up, often involving a multidisciplinary team, facilitates recognition and treatment of these complications.

In 2008, the American Academy of Pediatrics (AAP) section on Surgery and the Committee on Fetus and Newborn published a comprehensive plan for the detection and management of the associated morbidities for clinicians who provide care for these patients (table 1) [165]. This plan provides a recommended schedule that includes the following:

●Measurement of growth parameters at each visit

●Chest radiography if a patch was used in repair of the defect or if there are respiratory or gastrointestinal symptoms

●Pulmonary function testing based upon clinical status

●Respiratory syncytial virus (RSV) prophylaxis

●Echocardiography if previously abnormal or supplemental oxygen used

●Brain imaging if previous abnormal head ultrasound, abnormal neurologic status, patch repair, or extracorporeal membrane oxygenation (ECMO) used

●Hearing evaluation

●Developmental screening

●Oral feeding assessment

●Upper gastrointestinal study based upon clinical status

●Scoliosis and chest wall deformity screening

LATE CDH PRESENTATION — Infrequently, CDH will present after the neonatal period. In one case series of 15 children, patients presented with respiratory symptoms (n = 6), gastrointestinal symptoms (n = 6), or both (n = 3) at a mean age of 1.5 years (range 38 days to 9.9 years) [166]. Five patients had failure to thrive. The diagnosis was made by chest radiography in six patients, and the other patients were diagnosed by gastrointestinal contrast series or computed tomography. Primary repair without a patch was successful in all patients with a 100 percent survival rate at a mean follow-up of two years.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pulmonary hypertension in children".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Congenital hernia of the diaphragm (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Introduction and effect on pulmonary development – Congenital diaphragmatic hernia (CDH) is a developmental defect in the diaphragm that allows abdominal viscera to herniate into the chest, thereby compressing the lung and interfering with normal lung development. With increased compression of the developing lung by the herniated abdominal contents, there are corresponding decreases in bronchial and pulmonary arterial branching, resulting in increasing degrees of lung hypoplasia and pulmonary arterial muscle hyperplasia (pulmonary hypertension). (See 'Effect on pulmonary development' above.)

●Clinical manifestations – Patients with CDH most often develop respiratory distress in the first few hours or days of life. The spectrum of presentation can vary from acute, severe respiratory distress at birth, which is common, to minimal to no symptoms, which is observed in a much smaller group of patients. Physical examination will reveal a barrel-shaped chest, a scaphoid-appearing abdomen because of loss of the abdominal contents into the chest, and the absence of breath sounds on the ipsilateral side. (See 'Clinical manifestations' above.)

●Diagnosis – Diagnosis can be made prenatally with ultrasound examination. Among infants in whom CDH is not diagnosed in utero, the diagnosis is made by chest radiography showing herniation of abdominal contents. (See "Congenital diaphragmatic hernia: Prenatal issues", section on 'Prenatal diagnosis' and 'Diagnosis' above.)

●Postnatal management – In our center, management of CDH consists of preoperative management with stabilization of pulmonary and cardiovascular function, and delaying surgery until there is resolution of early pulmonary insufficiency and acute pulmonary hypertension. (See 'Postnatal management' above.)

•In the initial management of all infants with CDH, the following measures are provided (see 'Initial treatment' above):

-Immediate endotracheal intubation to prevent further dilation of abdominal contents. Blow-by oxygen and/or bag-masking should be avoided as they lead to gastric/abdominal distension and compression of the lung.

-Placement of a nasogastric tube connected to continuous suction for decompression of the stomach and intestine.

-Administration of fluids and inotropic agents to maintain mean arterial blood pressure (BP) ≥50 mmHg.

-Administration of surfactant therapy to only preterm infants (gestational age [GA] ≤34 weeks) who also have findings suggestive of respiratory distress syndrome.

•We suggest ventilatory support with minimal airway pressure to maintain preductal oxygen saturations above 85 percent (Grade 2C). Conventional mechanical ventilation (CMV) is first used and high-frequency ventilation (HFV) is reserved for patients who fail CMV. (See 'Ventilation' above.)

•We suggest extracorporeal membrane oxygenation (ECMO) for infants who fail to respond to supportive medical management (Grade 2C). (See 'Extracorporeal membrane oxygenation' above.)

•We suggest that the timing of surgical repair be based on the patient's cardiopulmonary status, which is dependent on the severity of pulmonary hypoplasia and pulmonary hypertension, and his/her response to preoperative medical care (Grade 2C). (See 'Our approach' above.)

●Outcome – The mortality and morbidity of CDH are related to the severity of lung hypoplasia and pulmonary hypertension. Other factors that increase mortality include the presence of associated anomalies (eg, cardiac defects and chromosomal abnormalities) and prematurity. (See 'Survival' above and 'Late complications' above and "Congenital diaphragmatic hernia: Prenatal issues", section on 'Evaluation of prognostic factors' and "Congenital diaphragmatic hernia: Prenatal issues", section on 'Associated fetal abnormalities'.)

Long-term complications in survivors of CDH include chronic respiratory disease, gastroesophageal reflux, failure to thrive, recurrence, neurodevelopmental delay, and musculoskeletal deformities. (See 'Late complications' above.)

●Post-discharge management – Structured follow-up facilitates recognition and treatment of the morbidities associated with CDH as outlined by the American Academy of Pediatrics (AAP)'s recommended schedule for follow-up of these patients (table 1). (See 'Post-discharge management' above.)