Survival of severe congenital diaphragmatic hernia has morbid consequences

Background/Purpose

Fetal tracheal occlusion (TO) was developed in an attempt to enhance prenatal lung growth and improve survival in fetuses with severe congenital diaphragmatic hernia (CDH). We conducted a randomized, controlled clinical trial in 24 fetuses with severe left CDH (liver herniated into the thorax and low lung-to-head ratio) to compare survival after endoscopic fetal TO vs standard perinatal care (control) and prospectively followed up the 16 survivors (9 control, 7 TO) to compare neurodevelopmental, respiratory, surgical, growth, and nutritional outcomes.

Methods

At 1 and 2 years old, subjects underwent evaluation consisting of medical and neurological history and physical, developmental testing, nutritional assessment, oxygen saturation and pulmonary function testing, chest radiograph, and echocardiogram. Growth and developmental measures were corrected for prematurity. Data were analyzed by Mann-Whitney rank sum test, Fisher's Exact test, and logistic and linear regression.

Results

Infants with TO were significantly more premature at birth (control vs TO, 37.4 ± 1.0 vs 31.1 ± 1.7 weeks; P < .01). Growth failure (z score for weight <2 SDs below mean) was severe in both groups at 1 year of age (control vs TO, 56% vs 86%; P = .31). There was considerable catch-up growth by age 2 years (growth failure: control vs TO, 22% vs 33%; P = .19). There were no differences in other growth parameters. There were also no differences in neurodevelopmental outcome at 1 and 2 years. Supplemental oxygen at hospital discharge was a significant predictor of worse neurodevelopmental outcome at 1 and 2 years old (P = .05 and P = .02, respectively). Hearing loss requiring amplification has been diagnosed in 44% of the group (control vs TO, 44% vs 43%; P = 1.0).

Conclusions

In this group of infants with severe CDH, there were no differences in outcome at 2 years old despite significant prematurity in the TO group. Oxygen supplementation at hospital discharge identified the most vulnerable group with respect to neurodevelopmental outcome, but all infants had significant growth failure, and hearing impairment is a substantial problem in this population. Severe CDH carries significant risk of chronic morbidity.     

Protocolized approach to the management of congenital diaphragmatic hernia: benefits of reducing variability in care

Purpose

Variable approaches to the care of infants with congenital diaphragmatic hernia (CDH) by multiple providers may contribute to inconsistent care. Our institution developed a comprehensive evidence-based protocol to standardize the management of CDH infants. This report reviews patient outcomes before and after the implementation of the protocol.

Methods

Retrospective chart review of CDH infants managed with individualized care (preprotocol group, January 1997-December 2001, n = 22) or on the protocol (Protocol group, January 2002-July 2009, n = 47). Survival and other categorical variables were compared by χ² analysis, and continuous variables were compared using 1-sided analysis of variance analysis, with significance defined as P < .05.

Results

Survival to discharge was significantly greater in the Protocol group (40/47; 85%) than the preprotocol group (12/22; 52%; P = .006), although mean gestational age, mean birth weight, and expected survival were not statistically different between the 2 groups. The use of supportive therapies, including high-frequency jet ventilation, inhaled nitric oxide, and extracorporeal life support, was similar between groups as well.

Conclusions

Since the implementation of a management protocol for infants with CDH, survival has improved significantly compared with expected survival and preprotocol controls. Reduction in the variability of care through use of an evidence-based protocol may improve the survival of CDH infants.     

Prospective, interdisciplinary follow-up of children with prenatally diagnosed giant omphalocele: short-term neurodevelopmental outcome

Purpose

The objective of this study is to determine the short-term neurodevelopmental outcome in infants with giant omphalocele (GO).

Materials and Methods

Between January 2002 and December 2007, 31 consecutive infants with GO received prenatal and postnatal care at our institution. Overall survival was 81% (25/31). Twenty (80%) of the survivors were enrolled in a prospective interdisciplinary follow-up program. Fifteen were at least 6 months of age and received detailed neurodevelopmental evaluation using the Bayley Scales of Infant Development II (BSID-II [before 2006, n = 3]) or BSID-III (after 2006, n = 12). Scores were grouped as average, mildly delayed, and severely delayed by SD intervals (115-85, 71-84, <70). Scores were considered mixed if cognitive or language skills were in different ranges.

Results

Median age at evaluation was 12 months (range, 6-26 months). Average, mildly delayed, and severely delayed scores for cognitive and language skills were found in 6 (40%), 2 (13%), and 6 (40%), respectively. One child had mixed scores (severely delayed for cognitive and mildly delayed for language skills). Motor scores were normal, mildly delayed, and severely delayed in 6 (40%), 2 (13%), and 7 (47%), respectively. The neuromuscular examination was abnormal in 8 patients (62%). Five (33%) scored within the average range, whereas 6 (40%) demonstrated severe delays for cognitive, language, and motor outcome. Of the 6 children with severe delays, 2 (13% of total) have autism, 4 required tracheostomy, and 1 was diagnosed with Williams syndrome.

Conclusions

The presence of GO is associated with deficits in developmental achievements in most of the affected infants ranging from mild to profound delays. These findings underscore the importance of early and standardized neurodevelopmental evaluation throughout childhood for all survivors with GO. Larger studies are warranted for risk factor stratification.     

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.     

Impact of prenatal evaluation and protocol-based perinatal management on congenital diaphragmatic hernia outcomes

Background/Purpose

Although intuitive, the benefit of prenatal evaluation and multidisciplinary perinatal management for fetuses with congenital diaphragmatic hernia (CDH) is unproven. We compared the outcome of prenatally diagnosed patients with CDH whose perinatal management was by a predefined protocol with those who were diagnosed postnatally and managed by the same team. We hypothesized that patients with CDH undergoing prenatal evaluation with perinatal planning would demonstrate improved outcome.

Methods

Retrospective chart review of all patients with Bochdalek-type CDH at a single institution between 2004 and 2009 was performed. Patients were stratified by history of perinatal management, and data were analyzed by Fisher's Exact test and Student's t test.

Results

Of 116 patients, 71 fetuses presented in the prenatal period and delivered at our facility (PRE), whereas 45 infants were either outborn or postnatally diagnosed (POST). There were more high-risk patients in the PRE group compared with the POST group as indicated by higher rates of liver herniation (63% vs 36%, P = .03), need for patch repair (57% vs 27%, P = .004), and extracorporeal membrane oxygenation use (35% vs 18%, P = .05). Despite differences in risk, there was no difference in 6-month survival between groups (73% vs 73%).

Conclusions

Patients with CDH diagnosed prenatally are a higher risk group. Prenatal evaluation and multidisciplinary perinatal management allows for improved outcome in these patients.     

Effect of epidermal growth factor on pulmonary hypoplasia in experimental diaphragmatic hernia

Background/purpose

Currently, tracheal occlusion (TO) is a potent stimulus for fetal lung growth but also a rather invasive and high-risk procedure. The aim of this study was to investigate a new and much less invasive therapeutic strategy, namely the maternal intraperitoneal administration of epidermal growth factor (EGF) and its effect on pulmonary hypoplasia in the nitrofen-induced congenital diaphragmatic hernia (CDH) rat model, especially its effect on type II pneumocytes.

Methods

CDH was induced by maternal administration of a single oral dose (100 mg) of nitrofen on day 8.5 of pregnancy. Four groups of pregnant rats were designed on day 18.5: normal control (n = 4), CDH (n = 4), CDH plus Dex (n = 4), CDH plus EGF (n = 8). All fetuses were delivered by cesarean section on day 21. Accordingly, there were 4 groups of fetuses: normal controls (n = 33), nitrofen-induced CDH (n = 19), CDH plus Dex treatment (n = 15), and CDH plus EGF treatment (n = 24). Lung tissue weight (LW) and body weight (BW) of each fetus were recorded, lung histologic and morphometric evaluations were performed, and image analysis was combined after lung processing. Transmission electron microscopy was used for ultrastructural observation, especially type II pneumocytes.

Results

CDH was observed in 58 of the 94 rat fetuses (61.7%). Lw/Bw of CDH group was significantly lower than those of Dex and EGF (P < .05). The lungs of CDH fetuses showed marked hypoplasia, in contrast to improved mesenchymal differentiation in that of Dex and EGF fetuses. Statistical differences of these morphologic parameters (RAC, MTBD, interstitial%, and alveoli%) were found (P < .05). As to ultrastructural features, type II cells of CDH lungs had few if any lamellar bodies and cytoplasmic organelles, and showed evidence of abundant glycogen granules. The sparse type II cells also showed cytoplasmic degenerative changes. By contrast, type II cells of EGF lungs showed numerous mitochondria, abundant lamellar bodies (surfactant) and deficiency of glycogen granules, and displayed prominent microvillous projections and pitlike depressions. The density of type II pneumocyte were 65 ± 4.5, 31 ± 3.1, and 8 ± 1.5 for EGF, Dex, and CDH, respectively (EGF v Dex, P < .05; EGF v CDH, P < 0.01).

Conclusions

Compared with TO, prenatal EGF administration as a much less-invasive therapeutic strategy had shown marked improvement in pulmonary hypoplasia and promotion of type II pneumocyte differentiation in the nitrofen-induced CDH rat model. Thus, EGF could improve the prognosis of CDH by means of promoting pulmonary hypoplasia and improving the surfactant deficiency, which suggested a potential role in the clinical treatment of CDH.     

Abnormal neuroimaging and neurodevelopmental findings in a cohort of antenatally diagnosed congenital diaphragmatic hernia survivors

Purpose

Prior studies have shown that survivors of congenital diaphragmatic hernia (CDH) repair may have long-term cardiac, pulmonary, and nutritional issues, as well as neurodevelopmental sequelae within the first 3 years of life. In this study, we examined the relationship between neuroimaging abnormalities and neurodevelopmental outcomes in a cohort of antenatally diagnosed CDH survivors.

Methods

Retrospective chart reviews were performed for CDH survivors born from January 2000 to December 2007 who were evaluated antenatally in the Advanced Fetal Care Center at Children's Hospital Boston (Mass). Prenatal and postnatal neuroimaging findings, clinical data, and neurodevelopmental findings were collected for a cohort of 45 patients who were evaluated by a developmental pediatrician at ages 1 and/or 3.

Results

Prenatal neuroimaging studies detected brain anomalies in this cohort with a false-negative rate of 7%. Of the 45 study participants, 87% had left-sided CDH, 22% had cardiac anomalies, and 18% had congenital malformations or genetic syndromes. Nearly all required ventilator management (98%) with a median ventilator time of 17 days (range, 3-56 days). Moreover, 24% required extracorporeal membrane oxygenation. While 84% of patients had medical issues at discharge, 68% and 77% had medical issues at ages 1 and 3, respectively. Pulmonary problems were noted in 32% and 47% of the ages 1 and 3 cohorts, respectively. Motor problems were detected in 46% and 71% of the ages 1 and 3 cohorts, respectively. More patients with motor problems at age 1 had abnormal rather than normal postnatal neuroimaging studies (P = .01). Children with motor problems at age 1 were more apt to have an abnormal postnatal neuroimaging finding (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.5-26.8; P = .01), pulmonary problems at age 1 (OR, 4.0; 95% CI, 0.99-16.6; P = .04), and a history of ventilatory management with a linear ventilator time (OR, 1.1; 95% CI, 1.01-1.12; P = .03).

Conclusions

Prenatal neuroimaging can accurately image the brain of fetuses with CDH. Abnormal postnatal neuroimaging findings, the presence of pulmonary problems at age 1, and the length of ventilator time were predictors of motor problems at age 1. Ongoing follow-up of CDH survivors should include neurodevelopmental evaluations.     

Impact on family of survivors of congenital diaphragmatic hernia repair: a pilot study

Background/Purpose

We hypothesized that long-term impact on the family of survivors of congenital diaphragmatic hernia (CDH) would vary based on the child's current clinical problems and clinical severity, family income, insurance, and out-of-pocket expenses.

Methods

Parents of a retrospective cohort of 53 CDH survivors who underwent repair at Children's Hospital Boston in Massachusetts from 1991 through 1999 completed the Impact on Family Scale (IFS), the Child Health Ratings Inventories General Health Module Parent Report, a rating of their child's clinical severity, an inventory of current clinical problems, and family demographics. Statistical tests of the primary outcome, the IFS total score, were performed.

Results

Survivors of CDH had a median age of 8 years. Most families had private insurance (78%) and annual income levels higher than the federal poverty level (96%). The IFS total score was correlated with child's clinical severity (r = 0.71, P < .001) and was worse among families of children with current clinical problems (P = .01), families with public insurance (P = .01), and those with out-of-pocket expenses of at least $500 (P = .002). Regression analysis identified the independent effect of clinical severity on family impact (P < .001).

Conclusion

Family impact is profound and long-standing at a median of 8 years after surgery for a subset of CDH survivors with more severe conditions and current clinical problems.     

Survival disparities in newborns with congenital diaphragmatic hernia: a national perspective

Purpose

The aim of the study was to examine national outcomes for congenital diaphragmatic hernia (CDH).

Methods

We analyzed the Kids' Inpatient Database for patients admitted at less than 8 days of age.

Results

Overall, 2774 hospitalizations were identified. Most patients were white and had private insurance. Most patients were treated at urban (96%), teaching (75%), and not identified as children's hospital (NIACH) (50%). Birth was the most common admission source at NIACH (91%) and children's unit in general hospital (CUGH) (59%), compared to hospital transfer at children's general hospital (CGH) (81%). Most CDH were repaired through the abdomen (81%), and 25% required extracorporeal membrane oxygenation (ECMO). Most NIACH patients were transferred to another hospital, whereas most at CGH and CUGH were discharged home. Survival to discharge was 66% after excluding hospital transfers. Univariate analysis revealed higher survival for males, birth weight (BW) of 3 kg or more, whites, patients with private insurance, and those in the highest median household income quartile. Survival was 86% after CDH repair but 46% for ECMO. Multivariate analysis identified black race (hazard ratio [HR], 1.536; P = .03) and other race (HR, 1.515; P = .03) as independent predictors of mortality.

Conclusions

Hospital survival for CDH is related to sex, BW, race, and socioeconomic status. Blacks and other non-Hispanic minorities have higher mortality rates.     

Oncologic outcomes after resection of rectal cancer: Laparoscopic versus open approach

Background

This study examined outcomes of laparoscopic and open rectal cancer surgery in a community hospital setting.

Methods

A community health care system cancer registry was reviewed retrospectively (2004-2007) for rectal cancer patients undergoing surgical treatment. Primary end points were rates of recurrence and survival.

Results

Both open and laparoscopic resection groups had similar demographic, treatment, and tumor characteristics. Most patients in the open resection and laparoscopic resection populations experienced no recurrence (79% vs 83%, respectively; P = .5). Overall, the groups had similar mean (88% vs 96%, respectively; P = .4) and disease-free (21 and 23 months, respectively; P = .5) survival.

Conclusions

In a community hospital setting, laparoscopic resection of rectal cancer was found to be as safe and effective as open resection in selected patients.     

Long-term functional impact of congenital diaphragmatic hernia repair on children

Background/Purpose

Congenital diaphragmatic hernia (CDH) is a malformation requiring neonatal surgical repair with in-hospital survival rates above 90%. We examined the long-term functional impact of CDH repair on a cross-sectional cohort of survivors.

Methods

A cohort of 53 CDH families participated in this study. Functional impact was evaluated with parent report of the Functional Status IIR and the Child Health Ratings Inventories General Health Module. Parents also provided a clinical severity score, the child's medical history, and family demographic information. The primary outcome was the effect of medical morbidity on the Functional Status IIR total score.

Results

Congenital diaphragmatic hernia survivors had a median age of 8 years; 50% were in third grade or above. Sixty-six percent had major medical issues at hospital discharge, whereas 48% had current clinical problems. Functional Status IIR total score was strongly correlated with child's clinical severity (r = −0.65; P < .0001) and was lower among children with ongoing medical morbidity, denoting worse functioning (P = .01). Child Health Ratings Inventories General Health Module scores followed a similar pattern.

Conclusions

A subset of long-term CDH survivors continues to have ongoing clinical problems a median of 8 years after surgery, translating to lower functional status. Affected children and their families may benefit from prospective identification and ongoing interventions.     

Fetal lung-head ratio is not related to outcome for antenatal diagnosed congenital diaphragmatic hernia

We asked if fetal lung-to-head ratio (LHR) of 1.0 or lower or liver herniation had a statistical effect on survival or need for extracorporeal membrane oxygenation (ECMO), compared with LHR above 1.0 in patients with congenital diaphragmatic hernia (CDH).

Methods

Antenatal records of all patients diagnosed with CDH from January of 2002 to June of 2005 were examined. Inclusion criteria were isolated left-sided CDH and absence of significant cardiac or other anomalies/syndromes, treated solely at this institution. Lung-to-head ratio values were compared based on the value currently proposed for fetal intervention: LHR of 1.0 or lower vs LHR above 1.0. Outcome was assessed as survival (discharge to home) or need for ECMO.

Results

Twenty-eight patients met inclusion criteria. Overall survival was 86% (24/28). Postnatal survival in fetuses with LHR of 1.0 or lower (8/11) was not statistically different from LHR above 1.0 (16/17) (73% vs 94%, P = .114). The need for ECMO in the group with LHR of 1.0 or lower (3/11) was not significantly different from those with LHR above 1.0 (1/17) (27% vs 6%, P = .114). Herniation of the fetal liver into the chest did not affect survival or need for ECMO (P = .228).

Conclusion

Neither LHR of 1.0 or lower nor liver herniation identified a risk factor significant enough to warrant fetal intervention. Multicenter studies may be more appropriate to investigate this clinical problem.     

Outcomes after muscle flap vs prosthetic patch repair for large congenital diaphragmatic hernias

Background

Repair of large congenital diaphragmatic hernia (CDH) defects still pose a significant challenge, as the defects cannot be repaired primarily. Two techniques have been widely used: autologous anterior abdominal wall muscle flap and prosthetic patch. The latter has been used more often. Our goal was to compare the short-term and long-term outcomes of these 2 approaches.

Methods

This is a retrospective review of all neonates undergoing CDH repair at our institution from 1969 to 2006.

Results

Of 188 children undergoing surgery for CDH, primary repair could not be accomplished in 51 infants (27%). Nineteen had muscle flap repair, and 32 had prosthetic patch repair (Gore-Tex [W.L. Gore and Associates, Flagstaff, AZ], n = 15; Marlex [Bard Inc, Cranston, NJ], n = 9; Surgisis [Cook, Bloomington, IN], n = 5; SILASTIC [Dow Corning, Midland, MI], n = 3). There was no significant difference in gestational age or birth weight between groups. Three patients developed an abdominal wall defect at the muscle flap donor site, but none required surgical intervention. Chest wall deformities were found in 9 patients, 3 after a muscle flap and 6 after a prosthetic patch (P = .7). Postoperative bowel obstruction occurred in 3 muscle flap patients and 1 patch patient (P = .2). There were 10 recurrences among survivors: 2 after a muscle flap and 8 after a prosthetic patch (P = .3) There were 2 deaths among the muscle flap patients (10%), and 3 deaths among the prosthetic patch repair patients (9%) (P = .1). Results were confirmed after controlling for age and comorbidities between both groups in a multivariate logistic regression.

Conclusion

These results suggest that autologous anterior abdominal wall muscle flap and prosthetic patch repairs provide similar short-term and long-term outcomes.     

Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma

Background

The objective of this study was to investigate whether the preoperative platelet-lymphocyte (P/L) ratio represents a significant prognostic index in resected pancreatic ductal adenocarcinoma.

Methods

A total of 110 patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma over a 10-year period were identified from a prospectively maintained database.

Results

The preoperative P/L ratio was found to be a more significant prognostic marker (P < .001) than either the lymphocyte count (P = .007) or platelet count (P = .068) on univariate Cox survival analysis. The median overall survival in patients with a P/L ratio of 150 or less (n = 48) was 19.7 months, 13.7 months in those with a P/L ratio of 151 to 300 (n = 43), and 5.8 months in patients with a value of greater than 300 (n = 19) (log-rank, P = .006). The preoperative P/L ratio retained significance on multivariate analysis (P < .001), along with tumor size (P = .010) and lymph node ratio (P = .013).

Conclusions

The preoperative P/L ratio represents a significant independent prognostic index in patients of resected pancreatic adenocarcinoma.     

Modulating effect of a selective endothelin A receptor antagonist on pulmonary endothelin system protein expression in experimental diaphragmatic hernia

Background/Purpose

Previously, we reported that perinatal administration of atrasentan, a selective endothelin A receptor (ET_A) antagonist, provided a beneficial effect on the cardiopulmonary profile under short-term conditions in newborn lambs with surgically induced congenital diaphragmatic hernia (CDH). We hypothesized that changes in the hemodynamic profile that we observed at birth in treated animals could be influenced by pulmonary modulation of the endothelin (ET) system.

Methods

The effect of atrasentan on protein expression levels of ETs and ET receptors (ET_A and ET_B receptor) was investigated by immunohistochemistry in lung tissues of untreated control (n = 3), treated control (n = 6), untreated CDH (n = 6), and treated CDH newborn lambs (n = 8).

Results

Right lung tissue of treated control lambs showed significantly higher ET_A protein expression levels in both vascular adventitia and airway epithelia when compared with that of untreated control lambs (P < .05). In contrast, protein expression levels of ET_A and ET _B receptor were significantly lower in the vascular smooth muscle cells among other tissue subcompartments of the right lung of treated CDH newborn lambs vs CDH lambs (P < .02 and P = .005, respectively).

Conclusions

We speculate that rapid pulmonary modulation of ET system protein expression levels by atrasentan results from an indirect effect possibly dependent on ventilation and/or perfusion. In CDH groups, this could contribute to the beneficial effect of the treatment.     

Prosthetic patches for congenital diaphragmatic hernia repair: Surgisis vs Gore-Tex

Purpose

The sequelae of congenital diaphragmatic hernia (CDH) continue well beyond the perinatal period. Up to 50% of these patients have subsequent recurrent herniation or small bowel obstruction (SBO). A recent trend has been toward the use of bioactive prosthetic materials. We reviewed different patch closure techniques used for CDH repair at our institution and their association with these sequelae.

Methods

A retrospective review was performed of 152 records for patients with CDH. Newborns that underwent patch repair for CDH and survived for at least 30 days were included in the analysis. Primary outcomes evaluated were recurrent herniation and SBO. Two types of prostheses were examined, Gore-Tex, an artificial material, and Surgisis, a bioactive material.

Results

Twelve (44%) of 27 patients who had Surgisis repair had recurrent herniation. Seventeen (38%) of 45 patients who had a Gore-Tex repair had recurrent herniation. Two additional patients in each group presented with SBO. No significant difference in recurrent herniation rates was observed (P > .5). The time to recurrence was similar in both groups (log-rank, P = .75), with most recurrences (92% Surgisis, 76% Gore-Tex) occurring in the first year.

Conclusion

The rates of recurrent herniation and SBO after neonatal prosthetic patch repair of CDH were similar regardless of the prosthetic material used (Surgisis or Gore-Tex).     

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.     

Fetal tracheal occlusion for severe congenital diaphragmatic hernia in humans: a morphometric study of lung parenchyma and muscularization of pulmonary arterioles

Objective

The aim of this study is to examine structure of lung parenchyma (Pp) and muscularization of pulmonary arterioles (PAs) in human fetuses that underwent tracheal occlusion (TO) therapy for severe congenital diaphragmatic hernia (CDH).

Material

Fifteen fetuses underwent TO, with 5 survivors (Am J Obstet Gynecol. 2000:183;1059-1066). Paraffin-embedded lung specimens from 7 of 10 nonsurvivors (CDH-TO) and 6 age-matched fetuses (CDH) were available for morphometric analysis, which included measurements of point fraction of lung Pp and surface density. The PAs were categorized according to external diameter (<70 μm and 70 ≤ 140 μm). Percent medial wall thickness (%MWT) was calculated by dividing raw measurements of MWT by external diameter.

Results

Gestational age at TO was 27.6 ± 0.9 weeks with a mean duration of TO of 32.6 ± 6.8 days. Gestational age at delivery (CDH-TO 31.9 ± 0.9 vs CDH 35.4 ± 1.8 weeks; P = .18) and postnatal survival time (CDH-TO 20.5 ± 6.0 vs CDH 18.6 ± 7.8 days; P = .85) were not significantly different between groups. Tracheal occlusion significantly increased the lung-to-body weight ratio (CDH-TO 13.0 ± 2.2 vs CDH 6.6 ± 0.9; P = .02). Tracheal occlusion tended to decrease right-lung Pp (CDH-TO 54.6% ± 2.6% vs CDH 65.7% ± 5.9%; P = .05), whereas left-lung Pp was not different between groups (CDH-TO 63.0% ± 3.5% vs CDH 66.7% ± 4.1%; P = .51). Surface density of airspaces was not different between groups in either left (CDH-TO 171.3 ± 16.1 cm⁻¹ vs CDH 151.1 ± 8.1 cm⁻¹; P = .34) or right (CDH-TO 172.0 ± 10.6 cm⁻¹ vs CDH 160.8 ± 3.6 cm⁻¹; P = .33) lungs. The %MWT in small and large PA was similar between groups.

Conclusions

Open prenatal TO in human fetuses increased lung growth, as evidenced by an increase in lung weight, but did not improve parenchymal structure or muscularization of PAs.     

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.