Management of prenatally diagnosed congenital diaphragmatic hernia

doi:10.1053/j.sempedsurg.2012.10.007

Seminars in Pediatric Surgery

Volume 22, Issue 1, February 2013, Pages 37-43

https://doi.org/10.1053/j.sempedsurg.2012.10.007 Get rights and content

Abstract

Congenital diaphragmatic hernia (CDH) is a congenital anomaly that presents with a broad spectrum of severity that is dependent upon components of pulmonary hypoplasia and pulmonary hypertension. While advances in neonatal care have improved the overall survival of CDH in experienced centers, mortality and morbidity remain high in a subset of CDH infants with severe CDH. Prenatal predictors have been refined for the past two decades and are the subject of another review in this issue. So far, all randomized trials comparing prenatal intervention to standard postnatal therapy have shown no benefit to prenatal intervention. Although recent non-randomized reports of success with fetoscopic endoluminal tracheal occlusion (FETO) and release are promising, prenatal therapy should not be widely adopted until a well-designed prospective randomized trial demonstrating efficacy is performed. The increased survival and subsequent morbidity of CDH survivors has resulted in the need to provide resources for the long-term follow up and support of the CDH population.

Introduction

Congenital diaphragmatic hernia (CDH) is a developmental defect in the diaphragm that allows abdominal viscera to herniate into the chest. It is estimated to occur in 1 out of 2200 births. The majority of affected neonates present, in the first few hours of life, with respiratory distress that may be mild or so severe to be incompatible with life. With prenatal diagnosis and advancements in neonatal care, survival has improved but there remains a significant risk of death and complications in infants with severe CDH. Fetal diagnosis of CDH has revolutionized postnatal care by both educating the families and preparing the health care teams towards eventual delivery of the CDH patient, but the spectrum of severity in CDH has made standardization of prenatal and postnatal care and patient selection for prenatal intervention persistent challenges.

Section snippets

Pathogenesis

CDH is a simple anatomic defect, i.e., an opening in the diaphragm that leads to devastating physiologic consequences. The pathophysiology of CDH is comprised of both fixed (pulmonary and vascular hypoplasia) and reversible (pulmonary vascular reactivity) components. Because the herniation of abdominal contents through this opening coincides with a critical period of lung development when bronchial and pulmonary artery branching occurs, lung compression by the herniated viscera and bowel

Prenatal diagnosis

Most cases of CDH are diagnosed prenatally. Thoracic lesions that should also be considered when the diagnosis of CDH is made prenatally by ultrasound include diaphragmatic eventration, congenital cystic adenomatoid malformation, bronchopulmonary sequestration, bronchogenic cysts, bronchial atresia, enteric cysts, and teratomas. The definitive sonographic diagnosis of fetal CDH relies on the visualization of abdominal organs in the fetal chest. The sonographic hallmark of a left CDH is a

Prenatal prediction of CDH severity

A complete and accurate assessment of the fetal patient with CDH includes high-resolution ultrasound, fetal MRI scan, echocardiography and genetic testing between 20 and 24 weeks gestation. This allows for maximal information to be obtained from the imaging studies and allows comprehensive non-directive counseling regarding CDH, including the option of elective termination. In order to provide optimal counseling, accurate prenatal prognostication is essential. Much effort has been directed

Associated anomalies

The fetus with CDH in association with another major anomaly has a very poor prognosis. While there are recent reports of survivors of CDH associated with congenital heart disease, all of these reports are of patients with a relatively mild CDH and biventricular cardiac anatomy.5, 6 The infant with severe CDH and univentricular CHD has a near 100% mortality and should be offered comfort care. Familial CDH, bilateral CDH, syndromic CDH and CDH associated with specific genetic abnormalities are

Liver herniation and lung volumes (subgroup of prenatal DX)

In addition to patients with associated anomalies, the next clear poor prognostic factor is the presence of liver herniation. This is the single most reliable predictor of severity and mortality in CDH and has been validated by multiple centers.7, 8, 9, 10, 11 The presence of liver in the chest associated with a left-sided CDH is indicative of a large defect with early herniation of viscera resulting in severe pulmonary hypoplasia. In our most recent series, mortality of patients with “liver

Pre- and perinatal management

The first component of prenatal management involves the non-directive counseling process, which is dependent upon accurate prenatal diagnosis. Counseling is best performed by a multidisciplinary team that has extensive experience with the pre-, peri-, and postnatal issues related to CDH, and usually includes obstetrics, genetics, pediatric surgery and neonatology. The family must understand the severity of this anomaly and the expected pre- and postnatal events that may transpire. They should

ECMO for CDH

The first CDH survivor treated with extracorporeal membrane oxygenation (ECMO) was reported in 1977.²⁵ Subsequently, several single institution series reported an improved survival rate with the use of ECMO.26, 27, 28, 29, 30 ECMO became widely used on the sickest of neonates. The use of ECMO has now shifted to lung preservation when standard therapy has failed. With the widespread dissemination of the gentle ventilation techniques,21, 22 the use of ECMO has decreased in some centers (Toronto),

Fetal intervention for CDH

CDH was one of the first anomalies considered for prenatal intervention. Despite years of effort by many investigators, the subject remains highly controversial. The rationale for prenatal therapy is to prevent or reverse pulmonary hypoplasia and restore adequate lung growth for neonatal survival.41, 42 The initial prenatal approach consisted of patch closure of the diaphragmatic defect with abdominal silo placement to prevent an increase in intra-abdominal pressure and compromise of umbilical

Long-term follow up of CDH

The postnatal survival rate at tertiary centers has improved with reported rates of 70% to 92%.23, 78, 79, 80, 81, 82 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

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Cited by (48)

Birth Admission Length-of-Stay and Hospital Readmission in Children With Congenital Diaphragmatic Hernia
2023, Journal of Pediatric Surgery
The objective of this study was to identify factors associated with prolonged birth admission length of stay (LOS) and to evaluate the association between these characteristics and readmission in the year following discharge for children with congenital diaphragmatic hernia (CDH).
This was a single-center retrospective cohort study of children with isolated CDH born in the Special Delivery Unit and admitted to the Newborn/Infant Intensive Care Unit at Children's Hospital of Philadelphia from April 2008 to August 2019. Birth admission hospitalization was categorized into 3 groups (≤35, 36–75, and >76 days) based on the data distribution. Participant factors included gestational age (days), side of CDH (right/left), liver position (up/down), CDH repair technique (open/minimally invasive), exposure to extracorporeal membrane oxygenation, lung-to-head circumference ratio, and feeding tube at discharge. Chi-squared, t-tests and analysis of variance were used to examine bivariable associations between participant characteristics, birth admission LOS and readmission in the year following initial hospital discharge. Multivariable logistic regression was used to evaluate factors associated with readmission.
Children hospitalized ≥76 days at birth had 4.33 (95% CI: 1.2, 15.2) higher odds of readmission than those admitted for ≤35 days. Children with a non-operative feeding tube at discharge had 4.12 (895% CI: 1.6, 10.5) higher odds of readmission when compared to those with no feeding tube at discharge.
Longer birth hospitalization and non-operative feeding tube are associated with increased readmissions in the year after discharge.
Level III.
Inborn Versus Outborn Delivery in Neonates With Congenital Diaphragmatic Hernia
2022, Journal of Surgical Research
Citation Excerpt :
In turn, this permits for comprehensive non–directive counseling and optimal planning for the perinatal and postnatal periods. Parents and providers can make appropriate decisions regarding location and timing of delivery.12 Prenatal diagnosis and multidisciplinary peri- and postnatal management have been shown to improve outcomes, even in high-risk neonates with CDH.13
Congenital diaphragmatic hernia (CDH) is a morbid and potentially fatal condition that challenges providers. The aim of this study is to compare outcomes in neonates with prenatally diagnosed CDH that are inborn (delivered in the institution where definitive care for CDH is provided) versus outborn.
Prenatally diagnosed CDH cases were identified from the Congenital Diaphragmatic Hernia Study Group (CDHSG) database between 2007 and 2019. Using risk adjustment based on disease severity, we compared inborn versus outborn status using baseline risk and multivariable logistic regression models. The primary endpoint was mortality and the secondary endpoint was need for extracorporeal life support (ECLS).
Of 4195 neonates with prenatally diagnosed CDH, 3087 (73.6%) were inborn and 1108 (26.4%) were outborn. There was no significant difference in birth weight, gestational age, or presence of additional congenital anomalies. There was no difference in mortality between inborn and outborn infants (32.6% versus 33.8%, P = 0.44) or ECLS requirement (30.9% versus 31.5%, P = 0.73). Among neonates requiring ECLS, outborn status was a risk factor for mortality (OR 1.51, 95% CI 1.13-2.01, P = 0.006). After adjusting for post-surgical defect size, which is not known prenatally, outborn status was no longer a risk factor for mortality for infants requiring ECLS.
Risk of mortality and need for ECLS for inborn CDH patients is not different to outborn infants. Future studies should be directed to establishing whether highest risk infants are at risk for worse outcomes based on center of birth.
Fetal Surgery
2019, Pediatric Clinics of North America
Lung function and pulmonary artery blood flow following prenatal maternal retinoic acid and imatinib in the nitrofen model of congenital diaphragmatic hernia
2018, Journal of Pediatric Surgery
Citation Excerpt :
Significant advances in neonatal and surgical care have improved outcomes for many patients with CDH. Despite these advances, survival rates of CDH infants remain low at 68%–92% with significant morbidity and mortality attributed to pulmonary hypertension and hypoplasia [34–36]. The ability to prenatally diagnose a CDH as well as predict its severity [37–40] offers the potential to introduce therapies for fetuses with the most severe defects prior to birth.
Lung and pulmonary vascular maldevelopment in congenital diaphragmatic hernia (CDH) results in significant morbidity and mortality. Retinoic acid (RA) and imatinib have been shown to improve pulmonary morphology following prenatal administration in the rat nitrofen-induced CDH model. It remains unclear if these changes translate into improved function. We evaluated the effect of prenatal RA and imatinib on postnatal lung function, structure, and pulmonary artery (PA) blood flow in the rat CDH model.
Olive oil or nitrofen was administered alone or in combination with RA or imatinib to pregnant rats. Pups were assessed for PA blood flow by ultrasound and pulmonary function/morphology following delivery, intubation, and short-term ventilation.
Neither RA nor imatinib had a negative effect on lung and body growth. RA accelerated lung maturation indicated by increased alveoli number and thinner interalveolar septa and was associated with decreased PA resistance and improved oxygenation. With the exception of a decreased PA pulsatility index, no significant changes in morphology and pulmonary function were noted following imatinib.
Prenatal treatment with RA but not imatinib was associated with improved pulmonary morphology and function, and decreased pulmonary vascular resistance. This study highlights the potential of prenatal pharmacologic therapies, such as RA, for management of CDH.
Fetal imaging and therapy for CDH—Current status
2017, Seminars in Pediatric Surgery
In congenital diaphragmatic hernia (CDH), herniation of the abdominal organs into the fetal chest causes pulmonary hypoplasia and pulmonary hypertension, the main causes of neonatal mortality. As antenatal ultrasound screening improves, the risk of postnatal death can now be better predicted, allowing for the identification of fetuses that might most benefit from a prenatal intervention. Fetoscopic tracheal occlusion is being evaluated in a large international randomized controlled trial. We present the antenatal imaging approaches that can help identify fetuses that might benefit from antenatal therapy, and review the evolution of fetal surgery for CDH to date.
Percent predicted lung volume changes on fetal magnetic resonance imaging throughout gestation in congenital diaphragmatic hernia
2017, Journal of Pediatric Surgery
Citation Excerpt :
The Youden J-index indicates an optimal last PPLV cutoff value of < 15%, which has a sensitivity of 64% (i.e., correctly classifies 21 of 33 patients requiring ECMO use) and a specificity of 92% (i.e., correctly classifies 22 of 24 patients not requiring ECMO) (Fig. 3). The management of high-risk CDH remains very challenging, despite a multitude of diverse management strategies, with continued high mortality and morbidity [1–3,13]. Over the past several decades, efforts have been made to identify prenatal predictors in this high-risk cohort to better predict prognosis and counsel expectant mothers, guide selection for potential fetal intervention, and anticipate the need for postnatal ECMO support.
Percent predicted lung volume (PPLV) < 15% on fetal MRI predicts high-risk CDH. Potential changes in PPLV throughout gestation and impact on risk stratification are unknown. We reviewed CDH patients with serial fetal MRIs to follow PPLV and determine correlation with postnatal outcomes.
CDH patients with serial fetal MRIs from 2005 to 2015 were included. We recorded prenatal MRI gestational age (GA) and PPLV, postnatal ECMO use, and survival. Data were analyzed by logistic regression and Fisher's exact test.
57 patients had 127 fetal MRI studies. PPLV decreased from mean 25.4% to 19.6% between GA 22.1 and 32.6 weeks. A steeper decline in PPLV, regardless of final PPLV, was independently predictive of higher ECMO use (p = 0.046) and death (p = 0.045). All patients with first PPLV < 15% remained high-risk with poor outcomes. Of those with first PPLV > 15%, 31% dropped below 15%, having similar ECMO use as the high-risk cohort, but trending toward greater survival (p = 0.09). Those with first and final PPLV > 15% had significantly less ECMO use (p = 0.015) and greater survival (p < 0.001) than the high-risk cohort.
On average, PPLV decreases throughout gestation in fetuses with CDH. Serial MRI is recommended for those with initial PPLV > 15%, as clinical outcomes tend to mirror the lowest PPLV.
Treatment study
III

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Management of prenatally diagnosed congenital diaphragmatic hernia

Abstract

Introduction

Section snippets

Pathogenesis

Prenatal diagnosis

Prenatal prediction of CDH severity

Associated anomalies

Liver herniation and lung volumes (subgroup of prenatal DX)

Pre- and perinatal management

ECMO for CDH

Fetal intervention for CDH

Long-term follow up of CDH

Semin Pediatr Surg

J Pediatr

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

Am J Obstet Gynecol

J Pediatr Surg

J Pediatr

J Pediatr Surg

Semin Neonatol

J Pediatr Surg

J Pediatr Surg

Ann Thorac Surg

J Pediatr Surg

J Pediatr Surg

Semin Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surgery

J Pediatr Surg

Am J Obstet Gynecol

Eur J Obstet Gynecol Reprod Biol

Semin Perinatol

J Pediatr Surg

Sem Pediatr Surg

Am J Obstet Gynecol

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg

Early Hum Dev

Persistent hypoplasia of the lung after repair of congenital diaphragmatic hernia

Thorax

Lung hypoplasia in congenital diaphragmatic hernia. A quantitative study of airway, artery, and alveolar development

Br J Surg