Pamela A. Lally

Defect size determines survival in infants with congenital diaphragmatic hernia

OBJECTIVES. Congenital diaphragmatic hernia is a significant cause of neonatal mortality. The objective of this study was to evaluate the clinical factors associated with death in infants with congenital diaphragmatic hernia by using a large multicenter data set. METHODS. This was a prospective cohort study of all liveborn infants with congenital diaphragmatic hernia who were cared for at tertiary referral centers belonging to the Congenital Diaphragmatic Hernia Study Group between 1995 and 2004. Factors thought to influence death included birth weight, Apgar scores, size of defect, and associated anomalies. Survival to hospital discharge, duration of mechanical ventilation, and length of hospital stay were evaluated as end points. RESULTS. A total of 51 centers in 8 countries contributed data on 3062 liveborn infants. The overall survival rate was 69%. Five hundred thirty-eight (18%) patients did not undergo an operation and died. The defect size was the most significant factor that affected outcome; infants with a near absence of the diaphragm had a survival rate of 57% compared with infants having a primary repair with a survival rate of 95%. Infants without agenesis but who required a patch for repair had a survival rate of 79% compared with primary repair. CONCLUSIONS. The size of the diaphragmatic defect seems to be the major factor influencing outcome in infants with congenital diaphragmatic hernia. It is likely that the defect size is a surrogate marker for the degree of pulmonary hypoplasia. Future research efforts should be directed to accurately quantitate the degree of pulmonary hypoplasia or defect size antenatally. Experimental therapies can then be targeted to prospectively identify high-risk patients who are more likely to benefit.

Risk factors for chronic lung disease and mortality in newborns with congenital diaphragmatic hernia.

Background: Congenital diaphragmatic hernia (CDH) is associated with a mortality rate of 10–35% in live-born infants. Moreover, CDH survivors have a substantial risk of developing long-term pulmonary sequelae, such as bronchopulmonary dysplasia (BPD). Objectives: This study aims to evaluate risk factors associated with BPD and mortality in neonates with CDH, with particular focus on the initial ventilation mode. Methods: Eligible for inclusion were live-born infants with CDH born from 2001 through 2006 at the centers participating in the CDH Study Group. BPD (defined as oxygen dependency at day 30) and/or mortality by day 30 served as the primary endpoint. Results: A total of 2,078 neonates were included in the analysis. At day 30, 56% of the patients had either died or met the criteria for BPD. In infants who survived until day 30, the prevalence of BPD was 41%. The overall mortality rate was 31%. High-frequency oscillatory ventilation as initial ventilation mode, a right-sided defect, a prenatal diagnosis, a lower Apgar score at 5 min, a cardiac anomaly, a chromosomal anomaly and a lower gestational age were all associated with BPD and/or mortality by day 30. Conclusions: Despite improvements in neonatal care, the rates of BPD and early mortality in newborns with CDH are still considerable. Several important risk factors for a worse outcome are reported in this nonrandomized prospective observational study.

Standardized reporting for congenital diaphragmatic hernia – An international consensus

BACKGROUND/PURPOSE Congenital diaphragmatic hernia (CDH) remains a significant cause of neonatal death. A wide spectrum of disease severity and treatment strategies makes comparisons challenging. The objective of this study was to create a standardized reporting system for CDH. METHODS Data were prospectively collected on all live born infants with CDH from 51 centers in 9 countries. Patients who underwent surgical correction had the diaphragmatic defect size graded (A-D) using a standardized system. Other data known to affect outcome were combined to create a usable staging system. The primary outcome was death or hospital discharge. RESULTS A total of 1,975 infants were evaluated. A total of 326 infants were not repaired, and all died. Of the remaining 1,649, the defect was scored in 1,638 patients. A small defect (A) had a high survival, while a large defect was much worse. Cardiac defects significantly worsened outcome. We grouped patients into 6 categories based on defect size with an isolated A defect as stage I. A major cardiac anomaly (+) placed the patient in the next higher stage. Applying this, patient survival is 99% for stage I, 96% stage II, 78% stage III, 58% stage IV, 39% stage V, and 0% for non-repair. CONCLUSIONS The size of the diaphragmatic defect and a severe cardiac anomaly are strongly associated with outcome. Standardizing reporting is imperative in determining optimal outcomes and effective therapies for CDH and could serve as a benchmark for prospective trials.

Treatment evolution in high-risk congenital diaphragmatic hernia: ten years' experience with diaphragmatic agenesis.

Objective:The objective of this study was to evaluate the impact of newer therapies on the highest risk patients with congenital diaphragmatic hernia (CDH), those with agenesis of the diaphragm. Summary Background Data:CDH remains a significant cause of neonatal mortality. Many novel therapeutic interventions have been used in these infants. Those children with large defects or agenesis of the diaphragm have the highest mortality and morbidity. Methods:Twenty centers from 5 countries collected data prospectively on all liveborn infants with CDH over a 10-year period. The treatment and outcomes in these patients were examined. Patients were followed until death or hospital discharge. Results:A total of 1569 patients with CDH were seen between January 1995 and December 2004 in 20 centers. A total of 218 patients (14%) had diaphragmatic agenesis and underwent repair. The overall survival for all patients was 68%, while survival was 54% in patients with agenesis. When patients with diaphragmatic agenesis from the first 2 years were compared with similar patients from the last 2 years, there was significantly less use of ECMO (75% vs. 52%) and an increased use of inhaled nitric oxide (iNO) (30% vs. 80%). There was a trend toward improved survival in patients with agenesis from 47% in the first 2 years to 59% in the last 2 years. The survivors with diaphragmatic agenesis had prolonged hospital stays compared with patients without agenesis (median, 68 vs. 30 days). For the last 2 years of the study, 36% of the patients with agenesis were discharged on tube feedings and 22% on oxygen therapy. Conclusions:There has been a change in the management of infants with CDH with less frequent use of ECMO and a greater use of iNO in high-risk patients with a potential improvement in survival. However, the mortality, hospital length of stay, and morbidity in agenesis patients remain significant.

Timing of Delivery and Survival Rates for Infants With Prenatal Diagnoses of Congenital Diaphragmatic Hernia

OBJECTIVES. The goal of the study was to test the hypothesis that infants with known congenital diaphragmatic hernias born at early term gestation (37–38 weeks) rather than later (39–41 weeks) had greater survival rates and less extracorporeal membrane oxygenation use. Primary outcomes were survival to hospital discharge or transfer and extracorporeal membrane oxygenation use. METHODS. A retrospective cohort study of term infants with prenatal diagnoses of congenital diaphragmatic hernia was performed with the Congenital Diaphragmatic Hernia Study Group Registry of patients with congenital diaphragmatic hernias who were treated between January 1995 and December 2006. RESULTS. Among 628 term infants at 37 to 41 weeks of gestation who had prenatal diagnoses of congenital diaphragmatic hernia and were free of major associated anomalies, early term birth (37 vs 39–41 weeks) and greater birth weight were associated independently with survival, whereas black race was related inversely to survival. Infants born at early term with birth weights at or above the group mean (3.1 kg) had the greatest survival rate (80%). Among infants born through elective cesarean delivery, infants born at 37 to 38 weeks of gestation, compared with 39 to 41 weeks, had less use of extracorporeal membrane oxygenation (22.0% vs 35.5%) and a trend toward a greater survival rate (75.0% vs 65.8%). CONCLUSIONS. The timing of delivery is an independent, potentially important factor in the consideration of elective delivery for infants diagnosed prenatally as having congenital diaphragmatic hernias. Among fetuses with prenatally diagnosed congenital diaphragmatic hernias and without major associated anomalies, early term delivery may confer advantage.

Congenital diaphragmatic hernia in the preterm infant

BACKGROUND Congenital diaphragmatic hernia (CDH) remains a significant cause of death in newborns. With advances in neonatal critical care and ventilation strategies, survival in the term infant now exceeds 80% in some centers. Although prematurity is a significant risk factor for morbidity and mortality in most neonatal diseases, its associated risk with infants with CDH has been described poorly. We sought to determine the impact of prematurity on survival using data from the Congenital Diaphragmatic Hernia Registry (CDHR). METHODS Prospectively collected data from live-born infants with CDH were analyzed from the CDHR from January 1995 to July 2009. Preterm infants were defined as <37 weeks estimated gestational age at birth. Univariate and multivariate logistic regression analysis were performed. RESULTS During the study period, 5,069 infants with CDH were entered in the registry. Of the 5,022 infants with gestational age data, there were 3,895 term infants (77.6%) and 1,127 preterm infants (22.4%). Overall survival was 68.7%. A higher percentage of term infants were treated with extracorporeal membrane oxygenation (ECMO) (33% term vs 25.6% preterm). Preterm infants had a greater percentage of chromosomal abnormalities (4% term vs 8.1% preterm) and major cardiac anomalies (6.1% term vs 11.8% preterm). Also, a significantly higher percentage of term infants had repair of the hernia (86.3% term vs 69.4% preterm). Survival for infants that underwent repair was high in both groups (84.6% term vs 77.2% preterm). Survival decreased with decreasing gestational age (73.1% term vs 53.5% preterm). The odds ratio (OR) for death among preterm infants adjusted for patch repair, ECMO, chromosomal abnormalities, and major cardiac anomalies was OR 1.68 (95% confidence interval [CI], 1.34-2.11). CONCLUSION Although outcomes for preterm infants are clearly worse than in the term infant, more than 50% of preterm infants still survived. Preterm infants with CDH remain a high-risk group. Although ECMO may be of limited value in the extremely premature infant with CDH, most preterm infants that live to undergo repair will survive. Prematurity should not be an independent factor in the treatment strategies of infants with CDH.

A Clinical Prediction Rule for the Severity of Congenital Diaphragmatic Hernias in Newborns

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a condition with a highly variable outcome. Some infants have a relatively mild disease process, whereas others have significant pulmonary hypoplasia and hypertension. Identifying high-risk infants postnatally may allow for targeted therapy. METHODS: Data were obtained on 2202 infants from the Congenital Diaphragmatic Hernia Study Group database from January 2007 to October 2011. Using binary baseline predictors generated from birth weight, 5-minute Apgar score, congenital heart anomalies, and chromosome anomalies, as well as echocardiographic evidence of pulmonary hypertension, a clinical prediction rule was developed on a randomly selected subset of the data by using a backward selection algorithm. An integer-based clinical prediction rule was created. The performance of the model was validated by using the remaining data in terms of calibration and discrimination. RESULTS: The final model included the following predictors: very low birth weight, absent or low 5-minute Apgar score, presence of chromosomal or major cardiac anomaly, and suprasystemic pulmonary hypertension. This model discriminated between a population at high risk of death (∼50%) intermediate risk (∼20%), or low risk (<10%). The model performed well, with a C statistic of 0.806 in the derivation set and 0.769 in the validation set and good calibration (Hosmer-Lemeshow test, P = .2). CONCLUSIONS: A simple, generalizable scoring system was developed for CDH that can be calculated rapidly at the bedside. Using this model, intermediate- and high-risk infants could be selected for transfer to high-volume centers while infants at highest risk could be considered for advanced medical therapies.

Congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation: does timing of repair matter?

PURPOSE Severe congenital diaphragmatic hernia (CDH) requiring extracorporeal membrane oxygenation (ECMO) is associated with high mortality. Timing of CDH repair relative to ECMO therapy remains controversial. Our hypothesis was that survival would significantly differ between those who underwent repair during ECMO and those who underwent repair after ECMO therapy. METHODS We examined deidentified data from the CDH study group (CDHSG) registry from 1995 to 2005 on patients who underwent repair and ECMO therapy (n = 636). We used Cox regression analysis to assess differences in survival between those who underwent repair during and after ECMO. RESULTS Five covariates were significantly associated with mortality as follows: timing of repair relative to ECMO (P = .03), defect side (P = .01), ECMO run length (P < .01), need for patch repair (P = .03), birth weight (P < .01), and Apgar score at 5 minutes (P = .03). Birth year, inborn vs transfer status, diaphragmatic agenesis, age at repair, and presence of cardiac or chromosomal abnormalities were not associated with survival. Repair after ECMO therapy was associated with increased survival relative to repair on ECMO (hazard ratio, 1.407; P = .03). CONCLUSION These data suggest that CDH repair after ECMO therapy is associated with improved survival compared to repair on ECMO, despite controlling for factors associated with the severity of CDH.

Clinical Characteristics and Outcomes of Patients with Cardiac Defects and Congenital Diaphragmatic Hernia

OBJECTIVE To evaluate the impact of associated heart defects on outcomes to discharge, and identify factors affecting survival of all infants born with congenital diaphragmatic hernia (CDH) in last decade using Congenital Diaphragmatic Hernia Study Group data. STUDY DESIGN This was a retrospective review of all infants with CDH enrolled in Congenital Diaphragmatic Hernia Study Group database from January 2000 to December 2010. The study cohort was divided into 3 groups (GRP): GRP 1, CDH with major heart defects; GRP 2, CDH with minor heart defects; and GRP 3, CDH with no reported heart defects. RESULTS The 4268 enrolled infants included 345 (8%) in GRP 1, 412 (10%) in GRP 2, and 3511 (82%) in GRP 3. Survival was significantly lower in GRP 1 compared with GRP 2 and GRP 3 (36% vs 73%). In GRP 1, the most common defects were left heart obstructive lesions (34%). Survival was lowest in infants with transposition of great arteries (0%) and single ventricle physiology (16%). There was no change in survival rate for any group between 2000-2005 and 2006-2010. In GRP 1, factors that predicted lower survival were birth weight <2.5 kg, associated noncardiac anomalies, single ventricle physiology, no sildenafil therapy, no CDH repair, and no cardiac repair. CONCLUSION Survival is significantly lower in patients with CDH and major heart defects compared with patients with minor or no heart defects. Outcomes of newborns with CDH and major heart defects have not improved over the last decade.

A risk-stratified analysis of delayed congenital diaphragmatic hernia repair: does timing of operation matter?

BACKGROUND Congenital diaphragmatic hernia (CDH) remains a significant cause of death in newborns and, despite improved outcomes with multimodality therapies, optimal timing of repair remains undefined. We sought to evaluate the influence of surgical timing on patient outcomes and hypothesized that delayed repair does not improve survival in CDH. METHODS Prospectively collected data from 1,385 CDH Registry infants without preoperative extracorporeal membrane oxygen therapy (ECMO) were evaluated. Patients were stratified by timing of repair: Day of life (DOL) 0-3 (group 1), 4-7 (group 2), or >8 (group 3), and the effect of surgical timing on mortality was determined by logistic regression and risk-adjusted for severity of illness. RESULTS The unadjusted odds ratio (OR) for mortality increased significantly with delayed repair (group 2, 1.73 [95% CI, 1.00-2.98; group 3, 3.42 [95% CI, 1.97-5.96]). However, when adjusted for severity of illness, delay in repair did not predict increased mortality (group 2, 1.2 [95% CI, 0.7-2.2]; group 3, 1.4 [95% CI, 0.8-2.6]), nor did it portend an increased need for postoperative ECMO (group 2, 1.1 [95% CI, 0.5-2.4]; group 3, 0.5 [95% CI, 0.2-1.4]). CONCLUSION After adjustment for known risk factors, the timing of CDH repair in low-risk infants does not seem to influence mortality. However, specific clinical parameters guiding timing of elective CDH repair remain unknown.