Development of a multi-institutional registry for children with operative congenital lung malformations.

INTRODUCTION: The purpose of this study was to develop a multi-institutional registry to characterize the demographics, management, and outcomes of a contemporary cohort of children undergoing congenital lung malformation (CLM) resection. METHODS: After central reliance IRB approval, a web-based, secure database was created to capture retrospective cohort data on pathologically-confirmed CLMs performed between 2009 and 2015 within a multi-institutional research collaborative. RESULTS: Eleven children's hospitals contributed 506 patients. Among 344 prenatally diagnosed lesions, the congenital pulmonary airway malformation volume ratio was measured in 49.1%, and fetal MRI was performed in 34.3%. One hundred thirty-four (26.7%) children had respiratory symptoms at birth. Fifty-eight (11.6%) underwent neonatal resection, 322 (64.1%) had surgery at 1-12 months, and 122 (24.3%) had operations after 12 months. The median age at resection was 6.7 months (interquartile range, 3.6-11.4). Among 230 elective lobectomies performed in asymptomatic patients, thoracoscopy was successfully utilized in 102 (44.3%), but there was substantial variation across centers. The most common lesions were congenital pulmonary airway malformation (n = 234, 47.3%) and intralobar bronchopulmonary sequestration (n = 106, 21.4%). CONCLUSION: This multicenter cohort study on operative CLMs highlights marked disease heterogeneity and substantial practice variation in preoperative evaluation and operative management. Future registry studies are planned to help establish evidence-based guidelines to optimize the care of these patients. LEVEL OF EVIDENCE: Level II.

Calculating Observed-to-Expected Total Fetal Lung Volume in CDH Fetuses in Twin Gestation: Is There a Better Way?

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a potentially lethal birth defect, and identifying prenatal predictors of outcome is important. Observed-to-expected total fetal lung volume (o/e TFLV) has been shown to be a predictor of severity and useful in risk stratification but is variable due to different TFLV formulas. OBJECTIVES: To calculate o/e TFLV for CDH patients part of a twin gestation using the unaffected sibling as an internal control and comparing these values to those calculated using published formulas for TFLV. METHODS: Seven twin gestations with one fetus affected by CDH were identified between 2006 and 2017. The lung volume for each twin was calculated using magnetic resonance imaging (MRI), and o/e TFLV was calculated using the unaffected twin's TFLV. This percentage was then compared to the o/e TFLV calculated using published formulas. RESULTS: Lung volumes in the unaffected twins were within normal ranges at the lower end of the spectrum. No single TFLV formula was found to correlate perfectly. Intraclass correlation coefficient estimate was most consistent for o/e TFLV calculated with the Meyers formula and supported by Bland-Altman plots. CONCLUSIONS: O/e TFLV measured in CDH/non-CDH twin gestations using the unaffected sibling demonstrated agreement with o/e TFLV calculated using the Meyers formula. We urge the fetal community to standardize the method, use, and interpretation of fetal MRI in the prenatal evaluation of CDH.

Current operative management of congenital lobar emphysema in children: A report from the Midwest Pediatric Surgery Consortium.

PURPOSE: The purpose of this study was to evaluate the clinical presentation and operative outcomes of patients with congenital lobar emphysema (CLE) within a large multicenter research consortium. METHODS: After central reliance IRB-approval, a retrospective cohort study was performed on all operatively managed lung malformations at eleven participating children's hospitals (2009-2015). RESULTS: Fifty-three (10.5%) children with pathology-confirmed CLE were identified among 506 lung malformations. A lung mass was detected prenatally in 13 (24.5%) compared to 331 (73.1%) in non-CLE cases (p < 0.0001). Thirty-two (60.4%) CLE patients presented with respiratory symptoms at birth compared to 102 (22.7%) in non-CLE (p < 0.0001). The most common locations for CLE were the left upper (n = 24, 45.3%), right middle (n = 16, 30.2%), and right upper (n = 10, 18.9%) lobes. Eighteen (34.0%) had resection as neonates, 30 (56.6%) had surgery at 1-12 months of age, and five (9.4%) had resections after 12 months. Six (11.3%) underwent thoracoscopic excision. Median hospital length of stay was 5.0 days (interquartile range, 4.0-13.0). CONCLUSIONS: Among lung malformations, CLE is associated with several unique features, including a low prenatal detection rate, a predilection for the upper/middle lobes, and infrequent utilization of thoracoscopy. Although respiratory distress at birth is common, CLE often presents clinically in a delayed and more insidious fashion. LEVEL OF EVIDENCE: Level III.

Short-term respiratory outcomes of neonates with symptomatic congenital lung malformations.

INTRODUCTION: The purpose of this study was to evaluate short-term respiratory outcomes in neonates with symptomatic congenital lung malformations (CLM). METHODS: Consecutive newborns who underwent surgical resection of a CLM were retrospectively reviewed. Demographic, prenatal, and outcomes data were analyzed as appropriate (p < 0.05). RESULTS: Twenty-one neonates were managed at a median gestational age of 36.2 weeks [interquartile range (IQR), 33.8-39.0]. Endotracheal intubation was required in 14 (66.7%) for a median of 7.5 days [interquartile range (IQR), 3.0-25.8]. Three (14.3%) children underwent ex utero intrapartum treatment-to-resection, and another 14 (66.7%) had neonatal lung resections performed at a median age of 2.0 days (IQR, 0.08-19.5 days). Excluding one patient who received comfort care at birth, all neonates survived to hospital discharge with a median length of hospitalization of 36.5 days (IQR, 23.8-56.5). More than one-quarter were discharged on supplemental oxygen by nasal cannula. Based on a median follow up of 35.5 months (IQR, 19.0-80.8), CLM-related morbidity was still evident in 55.0%. CONCLUSION: Our study suggests a high incidence of complications and chronic respiratory morbidity after neonatal lung resection for symptomatic CLMs. These data highlight the need to provide realistic expectations in perinatal counseling discussions with families and the importance of coordinating appropriate multidisciplinary follow up for these children. LEVEL OF EVIDENCE: Level IV.

Cutis Marmorata Telangiectatica Congenita Presenting as a Fetal Hemothorax.

We report a case of a fetus diagnosed at 28 weeks' gestation with a spontaneous prenatal hemothorax. Fetal intervention consisted of 2 thoracenteses with analysis of the pleural effusion. The pregnancy was further complicated by recurrence of the hemothorax, with subsequent mediastinal shift, hydrops, and nonreassuring antenatal testing requiring delivery at 31 weeks' gestation. Postnatal workup established the diagnoses of cutis marmorata telangiectatica congenita (CMTC) and pulmonary lymphangiectasia. The child is currently 4 years old and without any active medical issues or sequelae from the CMTC, pulmonary lymphangiectasia, or prenatal interventions.

Diagnostic accuracy of imaging studies in congenital lung malformations.

BACKGROUND: Although fetal ultrasound, fetal MRI and postnatal CT are now widely used in the evaluation of congenital lung malformations (CLM), their diagnostic accuracy remains undefined. OBJECTIVE: To correlate prenatal and postnatal imaging studies with pathological data after CLM resection. DESIGN: Retrospective, descriptive case series study. SETTING: A North American tertiary care centre. PATIENTS: One hundred and three consecutive lung resections for a suspected CLM between 1 January 2005 and 31 December 2015. MAIN OUTCOME MEASURES: Diagnostic accuracy of imaging diagnosis compared with pathological evaluation. RESULTS: Pathological diagnoses included congenital pulmonary airway malformation ((CPAM) n=45, 44%), bronchopulmonary sequestration (BPS; n=25, 24%), CPAM/BPS hybrid lesions (n=22, 21%) and pleuropulmonary blastoma (n=2, 2%). Fetal ultrasound detected 85 (82.5%) lesions and correctly diagnosed whether or not a lesion was a CPAM in 75% of cases (sensitivity 93%, specificity 32%). Fetal MRI had a similar concordance rate (73%) but was superior in correctly determining whether a systemic feeding vessel was present in 80% of cases (sensitivity 71%, specificity 88%) compared with an ultrasound accuracy rate of 72% (sensitivity 49%, specificity 93%). By comparison, postnatal CT correctly diagnosed whether a CPAM was present in 84% of cases (sensitivity 86%, specificity 77%) and whether a systemic feeding vessel was present in 90% of cases (sensitivity 92%, specificity 88%). CONCLUSIONS: Fetal ultrasound remains an important tool in the detection and evaluation of congenital lung malformations. However, it does not correctly predict histology in approximately 25% of prenatally detected CLMs and remains limited by relatively poor sensitivity for systemic feeding vessels pathognomic for a bronchopulmonary sequestration. These data suggest the importance of obtaining additional cross-sectional imaging, preferably a postnatal CT scan, in all patients to help counsel families and to guide in the optimal management of these lesions.

Fetal intervention for congenital chylothorax is associated with improved outcomes in early life.

BACKGROUND: Congenital chylothorax (CC) can have devastating consequences for neonates. We sought to determine the outcomes of cases treated at our institution and evaluate the role of fetal intervention. MATERIALS AND METHODS: With Institutional Review Board approval, patients treated at our institution 09/2006-04/2016 with CC were reviewed. History and outcomes were compared between patients undergoing fetal intervention (fetal group) and patients who did not (control group). RESULTS: Twenty-three patients were identified. Mean gestational age at birth was 35 wk. Overall mortality was 30% (7 patients). Nineteen patients (83%) were prenatally diagnosed, and 10 patients (43%) underwent fetal intervention. Birth weight was significantly lower in the fetal group compared to the control group (median interquartile range [IQR]; 2.5 [2.3-3.0] versus 3.3 [2.6-3.7] kg, P = 0.02). Apgar scores were significantly higher in the fetal group than the control group at 1 and 5 min (median [IQR]; 6 [4-8] versus 1 [1-2], P = 0.005 and 8 [7-9] versus 2 [2-6], P = 0.008, respectively). For those patients with prenatal diagnosis of CC and hydrops fetalis, thrombosis and lymphopenia were both improved in the fetal group (thrombosis 0% versus 40%, P = 0.03; lymphocyte nadir [median {IQR}] 1.5 [0.6-2.9] versus 0.1 [0.05-0.2], P = 0.02). Duration of support with mechanical ventilation was significantly shorter in the fetal group (median [IQR]; 1 [0-40] versus 41 [29-75] d, P = 0.04). CONCLUSIONS: Fetal intervention for CC is associated with improved Apgar scores and decreased ventilator days and complications in patients with hydrops fetalis. Fetuses with chylothorax, especially those with hydrops, should be referred to a fetal center for evaluation.

Outcomes of fetuses with primary hydrothorax that undergo prenatal intervention (prenatal intervention for hydrothorax).

BACKGROUND: Primary hydrothorax is a congenital anomaly affecting 1 in 10,000-15,000 pregnancies. The natural history of this condition is variable with some fetuses having spontaneous resolution and others showing progression. The associated pulmonary hypoplasia leads to increased perinatal morbidity and mortality. Optimal prenatal intervention remains controversial. METHODS: After obtaining the Institutional Review Board approval, a retrospective review of all patients evaluated for a fetal pleural effusion in the Fetal Diagnosis and Treatment Center at The University of Michigan, between 2006 and 2016 was performed. Cases with secondary etiologies for an effusion or when families decided to pursue elective termination were excluded. RESULTS: Pleural effusions were identified in 175 patients. Primary hydrothorax was diagnosed in 15 patients (8%). The effusions were bilateral in 13/15 cases (86%) and 10/15 (66%) had hydrops at presentation. All 15 patients with primary hydrothorax underwent prenatal intervention. Thoracentesis was performed in 14/15 cases (93%). Shunt placement was performed in 10/15 cases (66%). Shunt migration was seen in four patients (40%) and all of these underwent prenatal shunt replacement. Overall survival was 76%. The rates of prematurity and preterm premature rupture of membranes were 69% and 35%, respectively. CONCLUSIONS: Fetal intervention for the treatment of primary hydrothorax is effective, and it appears to confer a survival advantage. Both the fetuses and the mothers tolerated the procedures well. Preterm labor and preterm premature rupture of membranes remain an unsolved problem. Further studies are needed to understand the mechanisms behind the development of fetal hydrothorax.

Comparison of early versus delayed strategies for repair of congenital diaphragmatic hernia on extracorporeal membrane oxygenation.

PURPOSE: For the last seven years, our institution has repaired infants with CDH that require ECMO early after cannulation. Prior to that, we attempted to decannulate before repair, but repaired on ECMO if we were unable to wean after two weeks. This study compares those strategies. METHODS: From 2002 to 2016, 65 infants with CDH required ECMO. 67.7% were repaired on ECMO, and 27.7% were repaired after decannulation. Data were compared between patients repaired ≤5days after cannulation ("early protocol", n=30) and >5days after cannulation or after de-cannulation ("late protocol", n=35). We used Cox regression to assess differences in outcomes between groups. RESULTS: Survival for the early and late protocol groups was 43.3% and 68.8%, respectively (p=0.0485). For patients that were successfully decannulated before repair, survival was 94.4%. Moreover, the early repair protocol was associated with prolongation of ECMO (16.8±7.4 vs. 12.6±6.8days, p=0.0216). After multivariate regression, the early repair protocol was an independent predictor of both mortality (HR=3.48, 95% CI=1.28-9.45, p=0.015) and days on ECMO (IRR=1.39, 95% CI=1.07-1.79, p=0.012). All bleeding occurred in patients repaired on ECMO (29.5%, 13/44). CONCLUSIONS: Our data suggest that protocolized CDH repair early after ECMO cannulation may be associated with increased mortality and prolongation of ECMO. However, early repair is not necessarily harmful for those patients who would otherwise be unable to wean from ECMO before repair. Further work is needed to better move towards individualized patient care. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: Level III.

Steroid use for refractory hypotension in congenital diaphragmatic hernia.

PURPOSE: Guidelines for diagnosis and treatment of adrenal insufficiency (AI) in newborns with congenital diaphragmatic hernia (CDH) are poorly defined. METHODS: From 2002 to 2016, 155 infants were treated for CDH at our institution. Patients with shock refractory to vasopressors (clinically diagnosed AI) were treated with hydrocortisone (HC). When available, random cortisol levels <10 µg/dL were considered low. Outcomes were compared between groups. RESULTS: Hydrocortisone was used to treat AI in 34% (53/155) of patients. That subset of patients was demonstrably sicker, and mortality was expectedly higher for those treated with HC (37.7 vs. 17.6%, p = 0.0098). Of the subset of patients with random cortisol levels measured before initiation of HC, 67.7% (21/31) had low cortisol levels. No significant differences were seen in survival between the high and low groups, but mortality trended higher in patients with high cortisol levels that received HC. After multivariate analysis, duration of HC stress dose administration was associated with increased risk of mortality (OR 1.11, 95% CI 1.02-1.2, p = 0.021), and total duration of HC treatment was associated with increased risk of sepsis (OR 1.04, 95% CI 1.005-1.075, p = 0.026). CONCLUSION: AI is prevalent amongst patients with CDH, but prolonged treatment with HC may increase risk of mortality and sepsis.

Staphylococcus aureus infections in adolescents.

Staphylococcus aureus infections are important causes of morbidity and mortality in the pediatric population. Over the past decade, community-associated methicillin-resistant S. aureus has emerged as an adolescent pathogen with disease ranging from mild skin and soft tissue infections to severe sepsis syndrome. Various conditions and behaviors common to adolescents render them more susceptible to staphylococcal infections. This review focuses on the problem of S. aureus in the adolescent population, including an outline on the approach, treatment, and prevention of these infections.