Congenital Diaphragmatic Hernia Registry Research Articles

The Utility of Serial Echocardiography Parameters in Management of Newborns with Congenital Diaphragmatic Hernia (CDH) and Predictors of Mortality

Ventricular dysfunction may be found in 40% of newborns with CDH, and is not only a predictor of disease severity, but also mortality and need for ECMO. We conducted this study to assess the utility of serial echocardiography in management of newborns with CDH and their survival outcomes. This is a retrospective study, wherein the demographic, clinical and echocardiographic data from our local CDH registry and hospital clinical database were analyzed to study the correlation of timed echocardiographic findings with mortality and other outcomes. Fourty-two newborns with CDH were admitted during the study period (M/F:19/23), with median gestation of 38 weeks (IQR:36–39) and birth weight of 2.83 kg (IQR 2.45–3.17). Thirty-one were left-sided, seven right, one central, and three bilateral hernias. Twelve infants (28%) died in early infancy. Three infants were excluded from analysis due to either palliation at birth or significant cardiac anomaly. A total of 137 echos from 39 infants were analyzed. Seventy percent of newborns who died and had an echo within the first 72 h, were noted to have suffered from moderate to severe PH. Birth weight < 2.8 kg, RVSP > 45.5 in the first 72 h and postoperative VIS > 23.5 and RSS > 4.3 were good predictors of mortality. Markers of elevated pulmonary pressures and cardiac function were useful in guiding therapy. Serial timed functional echocardiography (f-Echo) monitoring allows targeted therapy of patients with CDH. Birth weight, initial severity of pulmonary hypertension and postoperative RSS and VIS may be useful in predicting mortality.

Anti-reflux surgery in children with congenital diaphragmatic hernia: A prospective cohort study on a controversial practice

IntroductionGastro-esophageal reflux disease (GERD) is the most frequent long-term morbidity of congenital diaphragmatic hernia (CDH) survivors. Performing a preventive fundoplication during CDH repair remains controversial. This study aimed to: (1) Analyze the variability in practices regarding preventive fundoplication; (2) Identify predictive factors for fundoplication.(3) Evaluate the impact of preventive fundoplication on gastro-intestinal outcomes in children with a CDH patch repair; MethodsThis prospective multi-institutional cohort study (French CDH Registry) included CDH neonates born in France between January 1st, 2010-December 31st, 2018. Patch CDH was defined as need for synthetic patch or muscle flap repair. Main outcome measures included need for curative fundoplication, tube feed supplementation, failure to thrive, and oral aversion. ResultsOf 762 CDH neonates included, 81 underwent fundoplication (10.6%), either preventive or curative. Median follow-up was 3.0 years (IQR: 1.0–5.0).(1) Preventive fundoplication is considered in only 31% of centers. The rates of both curative fundoplication (9% vs 3%, p = 0.01) and overall fundoplication (20% vs 3%, p < 0.0001) are higher in centers that perform preventive fundoplication compared to those that do not.(2) Predictive factors for preventive fundoplication were: prenatal diagnosis (p = 0.006), intra-thoracic liver (p = 0.005), fetal tracheal occlusion (p = 0.002), CDH-grade C-D (p < 0.0001), patch repair (p < 0.0001). After CDH repair, 8% (n = 51) required curative fundoplication (median age: 101 days), for which a patch repair was the only independent predictive factors identified upon multivariate analysis.(3) In neonates with patch CDH, preventive fundoplication did not decrease the need for curative fundoplication (15% vs 11%, p = 0.53), and was associated with higher rates of failure to thrive (discharge: 81% vs 51%, p = 0.03; 6-months: 81% vs 45%, p = 0.008), tube feeds (6-months: 50% vs 21%, p = 0.02; 2-years: 65% vs 26%, p = 0.004), and oral aversion (6-months: 67% vs 37%, p = 0.02; 1-year: 71% vs 40%, p = 0.03). ConclusionsChildren undergoing a CDH patch repair are at high risk of requiring a curative fundoplication. However, preventive fundoplication during a patch repair does not decrease the need for curative fundoplication and is associated with worse gastro-intestinal outcomes in children. Level of evidenceII – Prospective Study.

Emanuel syndrome and congenital diaphragmatic hernia: A systematic review

BackgroundEmanuel Syndrome (ES), a rare chromosomal disorder caused by a supernumerary chromosome 22 derivative (der(22)t(11;22)), was identified in a fetus with congenital diaphragmatic hernia (CDH) at our fetal center. We aimed to identify a precedent for clinical care and patient outcomes to guide family decision-making. MethodsThis non-funded and non-registered study queried the entire CDH Registry (CDHR) including >10,000 patients since 1995 and conducted a systematic literature review for patients with concomitant ES and CDH. ResultsLiterature review captured 12 citations and identified 9 patients with CDH+ES from over 400 known ES cases. Given the rarity of the disease and to reduce bias, there were no exclusion criteria aside from non-English language. Of these 9, two underwent surgical CDH repair with neither surviving. The CDHR identified 6 patients with ES, all reported after 2013 and prenatally diagnosed. Median estimated gestational age was 39 weeks (range 37–40) and median birth weight was 2.72 kg (range 2.4–3.4 kg). 3 patients died within the first few postnatal days; surgical repair was not offered due to “anomalies” and “pulmonary hypertension” in two and one family chose comfort measures. The other 3 patients underwent surgical repair, and 2 were supported with ECMO. Two patients survived to discharge, incurring surgical comorbidities associated with severe CDH including gastrostomy dependence, tracheostomy, and CDH recurrence. ConclusionsES patients with CDH have potential to tolerate repair and survive to discharge, however with significant additional morbidity combined with severe challenges inherent to ES. This represents the largest series of patients with CDH and ES to date. Level of evidenceIV (Case series with no comparison group).

Predicting lethal pulmonary hypoplasia in congenital diaphragmatic hernia (CDH): Institutional experience combined with CDH registry outcomes

BackgroundThe Severe Pulmonary Hypoplasia and Evaluation for Resuscitative Efforts (SPHERE) protocol was developed to attempt to identify CDH patients with likely lethal pulmonary hypoplasia. We present our experience with this protocol and utilize the CDH Registry to critically assess the protocol. MethodsSPHERE patients identified based on prenatal imaging (10/2009–1/2018) were offered ECMO if meeting postnatal physiologic criteria, while others received comfort measures. Within the CDH Registry, patients with suspected severe CDH were identified and separated into “passed” (lowest pCO2 ≤100) versus “failed” (lowest pCO2 >100) groups. ResultsOf 23 SPHERE patients, 57% (13/23) passed criteria for ECMO and survival was 46% (6/13) in that cohort. Of 4912 patients in the CDH Registry, 265 met criteria. There was no difference in survival rates between those that “passed” (122/227; 54%) versus “failed” (18/38; 47%). However, the latter had longer ECMO runs and more required ventilator/ECMO support at 30 days. Amongst survivors, the “failed” group had longer hospital stays and more frequently required tube feeds at discharge. ConclusionsThe SPHERE protocol did not predict mortality in the CDH Registry. However, our data suggest resource utilization is significant when unable to reach pCO2 ≤100 despite resuscitation. Morbidity remains high in this group. Level of evidenceLevel III Annotation of changesInstitutional Review Board Approval at University of Michigan (HUM00031524 and HUM00044010) Type of StudyRetrospective Review

Hepatopulmonary fusion: A rare variant of congenital diaphragmatic hernia

BackgroundHepatopulmonary fusion (HPF), a rare anomaly associated with right congenital diaphragmatic hernia (CDH), is characterized by a fibrovascular fusion between herniated liver and lung parenchyma. We aimed to clarify patient characteristics, management strategies, and outcomes in HPF. MethodsData on infants with HPF were obtained from the Congenital Diaphragmatic Hernia Registry (CDHR). Patient characteristics, management, and outcomes were compared with the results of a literature review. ResultsTen cases of HPF were identified in the CDHR. Five patients survived. The median estimated gestational age was 38 weeks (range 36–40). Median birth weight was 2.7 kg (range 2.0–3.8 kg), but non-survivors had a lower median birth weight (2.3 kg vs. 3.5 kg). All patients had at least 1 congenital anomaly in addition to CDH. Operative approach varied, but most surgeons performed only partial separation of the liver and lung (n = 6). The 2 patients who underwent complete separation both ultimately died, 1 due to significant postoperative complications and 1 due to severe pulmonary hypertension with multiple vascular anomalies. ConclusionPartial separation of liver and lung appears to be the wisest surgical approach in HPF, as complete separation has resulted in catastrophic complications due to frequent underlying vascular anomalies. Level of evidenceIV.

A multicentre study to predict neonatal survival according to lung-to-head ratio and liver herniation in fetuses with left congenital diaphragmatic hernia (CDH): Hidden mortality from the Latin American CDH Study Group Registry.

To evaluate natural history of fetuses congenital diaphragmatic hernia (CDH) prenatally diagnosed in countries where termination of pregnancy is not legally allowed and to predict neonatal survival according to lung area and liver herniation. Prospective study including antenatally diagnosed CDH cases managed expectantly during pregnancy in six tertiary Latin American centres. The contribution of the observed/expected lung-to-head ratio (O/E-LHR) and liver herniation in predicting neonatal survival was assessed. From the total population of 380 CDH cases, 144 isolated fetuses were selected showing an overall survival rate of 31.9% (46/144). Survivors showed significantly higher O/E-LHR (56.5% vs 34.9%; P<.001), lower proportion of liver herniation (34.8% vs 80.6%, P<.001), and higher gestational age at birth (37.8 vs 36.2weeks, P<0.01) than nonsurvivors. Fetuses with an O/E-LHR less than 35% showed a 3.4% of survival; those with an O/E-LHR between 35% and 45% showed 28% of survival with liver up and 50% with liver down; those with an O/E-LHR greater than 45% showed 50% of survival rate with liver up and 76.9% with liver down. Neonatal mortality in CDH is higher in Latin American countries. The category of lung hypoplasia should be classified according to the survival rates in our Latin American CDH registry.

Bilateral congenital diaphragmatic hernia: prognostic evaluation of a large international cohort

BackgroundCongenital diaphragmatic hernia (CDH) is a lethal birth defect, which occurs in 1:2000–3000 live births. Bilateral CDH is a rare form (1%), with a high mortality. This study presents the outcomes of the largest cohort of bilateral CDH patients. MethodsThe records of patients with bilateral CDH from the Congenital Diaphragmatic Hernia Registry born between 1995 and 2015 were retrospectively analyzed to identify parameters associated with mortality. ResultsEighty patients with a bilateral CDH were identified. Overall mortality was 74% (n=59). Apgar scores at 1 and 5min were statistically lower in the non-survivors compared to the survivors (median 3.0 and 5.0, versus 6.5 and 8.0, respectively, p<0.001). All survivors were repaired (n=21), compared to 22% of the non-survivors (n=17). The type of repair was equally divided in the survivors (52% primary versus 48% patch), while non-survivors were mainly patch repaired (82% versus 12%). Nineteen were treated with extracorporeal membrane oxygenation (ECMO) (24%), only three of them survived. When calculating the risk on mortality for the patients who lived until repair, ECMO had an adjusted odds ratio for mortality of 10.8 (95% CI: 2.0–57.7) and patch repair 5.2 (95% CI: 0.8–34.9). ConclusionsThe treatment of bilateral CDH patients remains challenging with a high mortality rate. Lower Apgar-scores, ECMO (probably as a surrogate for the severity of disease), and patch repair were negatively associated with outcome. Level of evidenceLevel IV study

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

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. 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. 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]). 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.

Predictors of neonatal morbidity in fetuses with severe isolated congenital diaphragmatic hernia undergoing fetoscopic tracheal occlusion

To investigate neonatal morbidity in fetuses with severe congenital diaphragmatic hernia (CDH) treated with fetoscopic endoluminal tracheal occlusion (FETO) and compare it with historical controls with less severe forms of CDH that were managed expectantly. This was a prospective, multicenter study on neonatal outcomes and prenatal predictors in 90 FETO survivors (78 left-sided, 12 right) and 41 controls from the antenatal CDH registry with either severe or moderate hypoplasia who were managed expectantly. We also investigated early neonatal morbidity indicators, including the need for patch repair, duration of mechanical ventilation and supplemental oxygen, age at full enteral feeding and incidence of pulmonary hypertension. Gestational age at delivery was predictive of duration of assisted ventilation (P = 0.046), days on supplemental oxygen (P = 0.019) and age at full enteral feeding (P = 0.020). When delivery took place after 34 weeks' gestation, neonatal morbidity of FETO cases was comparable with that of expectantly managed cases with moderate hypoplasia. Fetal intervention for severe CDH is associated with neonatal morbidity that is comparable with that of an expectantly managed group with less severe disease.

Minimally invasive repair of congenital diaphragmatic hernia

Purpose Operative approach, including minimally invasive surgery (MIS) in the repair of congenital diaphragmatic hernia (CDH), is variable among institutions. The short-term recurrent hernia rate is not well described. We evaluated the in-hospital recurrence rate of MIS repairs of infants with CDH from the Congenital Diaphragmatic Hernia Registry. Methods Prospectively collected data from infants with CDH were analyzed from the Congenital Diaphragmatic Hernia Registry from January 1995 to January 2010. Recurrent hernia was defined as reoperations during initial hospitalization. Operative approaches included abdominal, thoracic, laparoscopic, and thoracoscopic techniques. Results Five thousand four hundred eighty infants with CDH were identified, of which 4516 (82.4%) were repaired. Operative data were available in 4390 infants. One hundred fifty-one infants (3.4%) underwent MIS repairs with 12 reported recurrences (7.9%) compared with 114 for open techniques (2.7%, P < .05). Minimally invasive surgery demonstrated a significant increased odds for recurrence (odds ratio, 3.59; 95% confidence interval, 1.92-6.71) after adjusting for gestational age, birth weight, patch repair, and extracorporeal membrane oxygenation. Conclusion Minimally invasive techniques appear to have a significant higher recurrent hernia rate, with thoracoscopy being the highest. Although adjusted for patch repair, other factors with regard to disease severity may contribute to differences in outcomes among centers. This study is limited to short-term recurrence during initial hospitalization.

Protocolized management of infants with congenital diaphragmatic hernia: effect on survival

Background/Purpose In 2006, we introduced a new protocol for congenital diaphragmatic hernia (CDH) management featuring nitric oxide in the delivery room, gentle ventilation, lower criteria for extracorporeal membrane oxygenation (ECMO), and appropriately timed operative repair on ECMO. Our goals were to assess outcomes after institution of this protocol and to compare results with historical controls. Methods Charts were reviewed of all newborns admitted to a large metropolitan children's hospital from 2002 to 2009 with a diagnosis of CDH. Data were recorded regarding delivery, ECMO, operative repair, length of stay, comorbidities/anomalies, complications, and survival. Postprotocol outcomes were compared to those from the preprotocol era and to data from the international CDH Registry. Results Comparison of the protocolized group (n = 43) to the historical group (n = 51) revealed no significant differences in gestational age, birth weight, Apgar scores, or comorbidities. New treatment strategies substantially improved survival to discharge (67% preprotocol, 88% postprotocol; P = .015). Among ECMO patients, survival increased to 82% (20% preprotocol; P = .002). Conclusions Our new protocol significantly improved survival to discharge for newborns with CDH. Institution of such a protocol is valuable in improving outcomes for patients with CDH and merits consideration for widespread adoption.

Congenital diaphragmatic hernia in the preterm infant

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). 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. 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). 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.

Congenital Diaphragmatic Hernia in the Preterm Infant: A Report from the Congenital Diaphragmatic Hernia Study Group

Background: Congenital Diaphragmatic Hernia (CDH) remains a significant cause of death in the newborn. With preoperative stabilization strategies and advances in neonatal critical care, survival in the term infant now approaches 70%.Although prematurity is the most significant risk factor for morbidity and mortality in most neonatal diseases, its impact on infants with CDH has been poorly described. We evaluated the outcomes of preterm (<37 weeks) infants with CDH compared to term infants from the Congenital Diaphragmatic Hernia Registry (CDHR).

Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion

To examine operative and perinatal aspects of fetal endoscopic tracheal occlusion (FETO) in congenital diaphragmatic hernia (CDH). This was a multicenter study of singleton pregnancies with CDH treated by FETO. The entry criteria for FETO were severe CDH on the basis of sonographic evidence of intrathoracic herniation of the liver and low lung area to head circumference ratio (LHR) defined as the observed to the expected normal mean for gestation (o/e LHR) equivalent to an LHR of 1 or less. FETO was carried out in 210 cases, including 175 cases with left-sided, 34 right-sided and one with bilateral CDH. In 188 cases the CDH was isolated and in 22 there was an associated defect. FETO was performed at a median gestational age of 27.1 (range, 23.0-33.3) weeks. The first eight cases were done under general anesthesia, but subsequently either regional or local anesthesia was used. The median duration of FETO was 10 (range, 3-93) min. Successful placement of the balloon at the first procedure was achieved in 203 (96.7%) cases. Spontaneous preterm prelabor rupture of membranes (PPROM) occurred in 99 (47.1%) cases at 3-83 (median, 30) days after FETO and within 3 weeks of the procedure in 35 (16.7%) cases. Removal of the balloon was prenatal either by fetoscopy or ultrasound-guided puncture, intrapartum by ex-utero intrapartum treatment, or postnatal either by tracheoscopy or percutaneous puncture. Delivery was at 25.7-41.0 (median, 35.3) weeks and before 34 weeks in 65 (30.9%) cases. In 204 (97.1%) cases the babies were live born and 98 (48.0%) were discharged from the hospital alive. There were 10 deaths directly related to difficulties with removal of the balloon. Significant prediction of survival was provided by the o/e LHR and gestational age at delivery. On the basis of the relationship between survival and o/e LHR in expectantly managed fetuses with CDH, as reported in the antenatal CDH registry, we estimated that in fetuses with left CDH treated with FETO the survival rate increased from 24.1% to 49.1%, and in right CDH survival increased from 0% to 35.3% (P < 0.001). FETO in severe CDH is associated with a high incidence of PPROM and preterm delivery but a substantial improvement in survival.

The Congenital Diaphragmatic Hernia Study Group: a voluntary international registry

The Congenital Diaphragmatic Hernia Registry (CDHR) was established to collect data on all infants treated at participating institutions with congenital diaphragmatic hernia (CDH) to assess therapy and improve outcome. Since 1995, the CDHR has accumulated data on over 4000 infants. The collective efforts of the CDH Study Group have provided valuable information regarding the efficacy of various therapeutic interventions and have tried to establish predictors of outcome. Because CDH is an uncommon, heterogeneous structural anomaly with a wide spectrum of severity, individual institutions may vary significantly in their experiences and treatment approaches. International multicenter registries, like the CDHR, are useful to provide clinically relevant direction by accumulating far more data on a large patient population than any single institution might.

Corticosteroids for fetuses with congenital diaphragmatic hernia: can we show benefit?

Background and Purpose Prenatal corticosteroids have been used in fetuses with congenital diaphragmatic hernia (CDH). We tested the utility of steroids by 2 methods. Methods Mothers carrying fetuses with CDH were randomized to 3 weekly doses of betamethasone or placebo starting at 34 weeks. Patients were followed until death or discharge. In a separate cohort study, the CDH Registry was used to compare infants who received prenatal steroids to those who had not. Results Thirty-four patients were enrolled at 7 centers, with 32 completing the trial. There were 15 placebo and 17 steroid patients. There was no difference in survival, length of stay, duration of ventilation, or oxygen use at 30 days. For the cohort study, we looked at infants older than 34 weeks who were born after October 2000 when data on prenatal steroids were collected. There were 1093 patients; 390 were evaluable, with 56 receiving steroids. There was no difference in survival, length of stay, ventilator days, or oxygen use at 30 days. Conclusion Neither the trial nor the CDH Registry suggest that late prenatal corticosteroids benefit fetuses with CDH. More than 1700 mothers and fetuses would need to be enrolled in a trial to show a 10% improvement in survival. It is unlikely that late steroids offer benefit to most fetuses with CDH.

Is surfactant therapy beneficial in the treatment of the term newborn infant with congenital diaphragmatic hernia?

To determine the impact of surfactant replacement on survival, need for extracorporeal membrane oxygenation (ECMO), and chronic lung disease in term infants with prenatally diagnosed congenital diaphragmatic hernia (CDH). Prenatally diagnosed infants born at > or =37 weeks' gestation with immediate distress at delivery and no other major congenital anomalies, who were enrolled in the CDH Registry, were analyzed. For univariate analysis, chi 2 tests were used for categoric variables and unpaired t tests for nominal variables. Multiple logistic regression was used to calculate adjusted odds ratios. Eligible infants (n = 522) were identified. Demographic variables were similar between the surfactant-treated (n = 192) and nonsurfactant-treated (n = 330) groups, with the exception of race (white, 88.0% vs 71.2%; P =.0007). The use of ECMO and incidence of chronic lung disease were higher (59.8 vs 50.6, P =.04; 59.9 vs 47.6, P =.0066) and survival lower in the surfactant-treated cohort (57.3 vs 70.0, P =.0033). Adjusted logistic regression for use of ECMO, survival, and chronic lung disease resulted in odds ratios inconsistent with an improved outcome associated with surfactant use. This analysis shows no benefit associated with surfactant therapy for term infants with a prenatal diagnosis of isolated CDH.

Surfactant does not improve survival rate in preterm infants with congenital diaphragmatic hernia

Background Use of exogenous surfactant in congenital diaphragmatic hernia (CDH) patients is routine in many centers. The authors sought to determine the impact of surfactant use in the premature infant with CDH. Methods Data on liveborn infants with CDH from participating institutions were collected prospectively. Surfactant use and timing and outcome data were analyzed retrospectively. The authors evaluated the prenatal diagnosis patients as well. The outcome variable was survival to discharge. Odds ratios with confidence intervals were calculated. Results Five hundred ten infants less than 37 weeks’ gestation were entered in the CDH registry. Infants with severe anomalies (n = 80) were excluded. Information on surfactant use was available for 424 patients. Infants receiving surfactant (n = 209) had a greater odds of death than infants not receiving surfactant (n = 215, odds ratio, 2.17, 95% CI: 1.5 to 3.2; P < .01). In prenatally diagnosed infants with immediate distress, there was a trend toward worse survival rates among those receiving surfactant at 1 hour (52 patients) versus those that did not (93 patients; odds ratio, 1.93, 95% CI: 0.96 to 3.9; P < .07). Conclusions Surfactant, as currently used, is associated with a lower survival rate in preterm infants with CDH. The use of surfactant replacement in premature infants with CDH can be recommended only within the context of a randomized clinical trial.

The Role of ECMO in Neonates with CDH

Source: The Congenital Diaphragmatic Hernia Study Group. Does extracorporeal membrane oxygenation improve survival in neonates with congenital diaphragmatic hernia? J Ped Surg. 1999;34(5):720–724; discussion 724–725.While the benefit from extracorporeal membrane oxygenation (ECMO) in improving survival of neonates with congenital diaphragmatic hernia (CDH) has never been clearly demonstrated with a randomized controlled trial, the lack of alternative therapy and the high mortality rate (approximately one-third) has led to widespread use of this aggressive and costly therapy. This study analyzes data from a CDH registry involving 65 centers with and without ECMO capability to determine if ECMO improved survival after adjusting for overall risk of mortality. Data were available for 632 neonates with birth weight (BW) >2kg, of whom 289 received ECMO. Patients were divided into quintiles based on their predicted risk of death (using BW and 5 minute Apgar). After adjusting for risk of death, ECMO was associated with significantly higher mortality in the 2 quintiles with the lowest risk of death, and lower mortality in the quintile with the highest risk of death, ≥80%. The first 2 groups accounted for 68% of the patients while the latter group for 5%. There was no significant association between ECMO and mortality in the middle 2 quintiles. The authors conclude that ECMO makes a difference in survival for infants at high risk of death. The apparent association of ECMO with lower survival in infants in the 2 lowest quintiles is unexplained, but may be due to a failure of the predictive model to adequately adjust for differences between infants receiving and not receiving ECMO in these groups.This article by the Congenital Diaphragmatic Hernia Group is important because it is one of the first publications from this large, voluntary collaboration of physicians who follow children with diaphragmatic hernia. The important message in this study was that ECMO has value in improving survival for infants with high-risk diaphragmatic hernia. With that in mind, some consideration should probably be given to delivery of infants with congenital diaphragmatic hernia close to an ECMO center.The ability to tell the effect of ECMO on improved survival rests on whether or not the infants with CDH who received ECMO and those who did not were comparable. The authors attempt to do so by stratifying on predicted risk of death (based on birth weight and Apgar), and then comparing survival within those strata. The authors and the commentator point out that ECMO appears to be associated with better survival in the highest risk group. However, survival in the two lowest risk groups was actually poorer in those infants receiving ECMO. The problems in sorting out the effect of ECMO are precisely those seen in studies which are not prospective, controlled clinical trials. In all likelihood, there are underlying differences (eg, degree of congenital lung dysplasia) between the two groups which were not adequately adjusted for in the model. Furthermore, even if the results in the highest risk group were real, and those in the lowest risk groups were not, the overall survival would only increase by 1.4% since the high risk group only accounts for 5% of CDH patients. The optimal use of ECMO in CDH is not yet apparent and almost certainly can only be ascertained by further detailed, analytic reports from this multi-center collaborative study group.

Does extracorporeal membrane oxygenation improve survival in neonates with congenital diaphragmatic hernia?

Background/Purpose: The benefit of extracorporeal membrane oxygenation (ECMO) in improving survival of neonates with congenital diaphragmatic hernia (CDH) has never been clearly demonstrated. This may be due to comparisons made between treatment groups of unequal illness severity and the low statistical power of analyses from previous studies. The authors analyzed the data from the multicenter CDH registry to determine if ECMO improves survival in CDH neonates with a high risk of mortality.Methods: A total of 730 neonates were enrolled in the CDH Registry from January 1995 to November 1997. Of these, 632 neonates had a complete data set and were eligible for ECMO by the weight criterion of greater than 2.0 kg. Multivariate logistic regression analysis was used to assess mortality risk for each neonate based on previously validated independent predictors of survival: birth weight and 5-minute Apgar. Five quintile groups were defined based on increasing predictive mortality risk. Multivariate logistic regression and χ2 analyses with birth weight, Apgar score at 5 minutes, and predictive mortality risk as covariates were then performed to assess survival benefit of ECMO compared with conventional therapy alone. Patient survival rate was defined as survival to discharge from hospital.Results: When analyzing all 632 neonates, ECMO neonates (n = 289) had a decidedly lower survival rate (52.9% v 77.3%, P < .001) than non-ECMO neonates (n = 343) without standardizing for the degree of illness. However, when taking into account the patients' predictive mortality risk, ECMO was associated with improved survival in the neonates with mortality risk ≥80% (P < .05). Furthermore, ECMO was shown to be a positive independent predictor of survival when accounting for the covariates of birth weight, 5-minute Apgar, and mortality risk (P < .05).Conclusions: ECMO significantly improves survival rates for those CDH neonates with a predictive mortality risk ≥80%. Generally, the more critically ill the patient with CDH, the more marked the survival benefit obtained.