David A. Lazar

Prenatal diagnosis and outcome of fetal lung masses

AIM The purpose of this study is to evaluate the accuracy of prenatal diagnostic features, particularly congenital cystic adenomatoid malformation volume ratio (CVR), in predicting outcomes for fetuses with lung masses. METHODS The records and imaging features of all fetuses referred to the Texas Childrens Fetal Center with a fetal lung mass between July 2001 and May 2010 were reviewed retrospectively. Data collected included gestational age (GA) at diagnosis, fetal magnetic resonance imaging findings, CVR, mass size, nature of fetal treatment, surgical findings, pathology, and outcome. Data were analyzed for predicting development of hydrops or the need for fetal therapy using receiver operating characteristic curves. RESULTS Of 82 fetuses (41 male) evaluated for a lung mass, 53 (65%) were left-sided (1 bilateral), and the mean (SD) GA at diagnosis was 21.5 (4.3) weeks. Seventy-three fetuses underwent fetal magnetic resonance imaging at a mean (SD) GA of 26.1 (4.6) weeks. Thirteen fetuses (16%) had fetal treatment. Four fetuses with hydrops underwent open fetal surgical resection, and 3 survived. Six fetuses with large lung masses and persistent mediastinal compression near term underwent ex-utero intrapartum therapy-to-resection procedures, and 3 fetuses with hydrops underwent serial thoracentesis. Congenital cystic adenomatoid malformation volume ratio correlated strongly with the development of hydrops and the need for fetal therapy with an area under the receiver operating characteristic curve of 0.96 (P < .0001) and 0.88 (P < .0001), respectively. Of 18 fetuses with a CVR greater than 2.0 compared with 2 (3%) of 60 with a CVR of 2.0 or less, 10 (56%) required fetal intervention (P < .0001). CONCLUSION Congenital cystic adenomatoid malformation volume ratio correlates strongly with the development of fetal hydrops and the need for fetal intervention. A threshold value of 2.0 yields the most powerful statistical results.

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 Fishers Exact test and Students 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.

Fetal lung volume and quantification of liver herniation by magnetic resonance imaging in isolated congenital diaphragmatic hernia.

To determine associations between fetal lung and liver herniation volumes measured by magnetic resonance imaging (MRI) and mortality/need for extracorporeal membrane oxygenation (ECMO) in cases of isolated congenital diaphragmatic hernia (CDH). A secondary objective was to compare prenatal MRI parameters with two‐dimensional ultrasound lung measurements.

Near-infrared spectroscopy measurement of abdominal tissue oxygenation is a useful indicator of intestinal blood flow and necrotizing enterocolitis in premature piglets

PURPOSE A major objective of necrotizing enterocolitis (NEC) research is to devise a noninvasive method of early detection. We hypothesized that abdominal near-infrared spectroscopy (A-NIRS) readings will identify impending NEC in a large animal model. METHODS Piglets were prematurely delivered and received parenteral nutrition followed by enteral feedings. Serial A-NIRS readings were obtained for 5 days, and animals were monitored for NEC. Separately, A-NIRS readings were obtained in healthy piglets to validate the correlation of A-NIRS with splanchnic oxygen delivery. RESULTS Of 29 piglets, 3 developed NEC. Eleven piglets without NEC died prematurely. Fifteen piglets remained healthy, had normal histologic assessment of their intestines, and served as controls. Abdominal near-infrared spectroscopy readings within 12 hours of birth were significantly lower in animals that developed NEC compared with healthy littermates (4% vs 33%, P = .02). For all time-points measured, A-NIRS readings were significantly lower in the NEC group compared with controls (21% vs 55%, P < .001). Abdominal near-infrared spectroscopy readings correlated with both decreased pulse oximetry readings during apneic episodes (r = 0.96) and increased superior mesenteric artery flow in response to glucagon-like peptide 2 (r = 0.67). CONCLUSION Abdominal near-infrared spectroscopy is capable of detecting alterations in intestinal oxygenation and perfusion in neonatal piglets and may allow early detection of neonates at risk for NEC.

Ex-utero intrapartum treatment procedure for giant neck masses—fetal and maternal outcomes

BACKGROUND/PURPOSE For fetuses with giant neck masses and tracheal obstruction, an ex-utero intrapartum treatment (EXIT) procedure allows for safe nonemergent airway management while on placental support. Our objective was to examine fetal and maternal outcomes after EXIT procedure specifically for giant neck masses. METHODS The medical records of all patients referred to a comprehensive fetal center for a giant neck mass between 2001 and 2010 were reviewed retrospectively. RESULTS Among 24 patients referred, an EXIT procedure was performed in 12 with evidence of tracheal compression. An EXIT procedure was not performed because of minimal tracheal involvement (n = 8), elective abortion (n = 2), fetal demise (n = 1), or obstetric complication (n = 1). In all fetuses, the airway was successfully secured; tracheal intubation was achieved with rigid bronchoscopy (n = 10), direct laryngoscopy (n = 1), and tracheostomy (n = 1). Eleven patients survived to discharge, whereas 1 patient with significant pulmonary hypoplasia died 8 days after emergency EXIT procedure. Of 11 surviving infants, 10 are neurodevelopmentally intact. All mothers who desired future pregnancies have subsequently had uncomplicated deliveries (n = 6). CONCLUSIONS Ex-utero intrapartum treatment procedure for giant neck mass can be performed safely for both mother and child. Most fetuses can be orotracheally intubated with minimal long-term morbidity. The potential for future pregnancies is preserved.

Prenatal MRI Fetal Lung Volumes and Percent Liver Herniation Predict Pulmonary Morbidity in Congenital Diaphragmatic Hernia (CDH)

PURPOSE The purpose of this study was to determine whether prenatal imaging parameters are predictive of postnatal CDH-associated pulmonary morbidity. METHODS The records of all neonates with CDH treated from 2004 to 2012 were reviewed. Patients requiring supplemental oxygen at 30 days of life (DOL) were classified as having chronic lung disease (CLD). Fetal MRI-measured observed/expected total fetal lung volume (O/E-TFLV) and percent liver herniation (%LH) were recorded. Receiver operating characteristic (ROC) curves and multivariate regression were applied to assess the prognostic value of O/E-TFLV and %LH for development of CLD. RESULTS Of 172 neonates with CDH, 108 had fetal MRIs, and survival was 76%. 82% (89/108) were alive at DOL 30, 46 (52%) of whom had CLD. Neonates with CLD had lower mean O/E-TFLV (30 vs.42%; p=0.001) and higher %LH (21.3±2.8 vs.7.1±1.8%; p<0.001) compared to neonates without CLD. Using ROC analysis, the best cutoffs in predicting CLD were an O/E-TFLV<35% (AUC=0.74; p<0.001) and %LH>20% (AUC=0.78; p<0.001). On logistic regression, O/E-TFLV<35% and a %LH>20% were highly associated with indicators of long-term pulmonary sequelae. On multivariate analysis, %LH was the strongest predictor of CLD in patients with CDH (OR: 10.96, 95%CI: 2.5-48.9, p=0.002). CONCLUSION Prenatal measurement of O/E-TFLV and %LH is predictive of CDH pulmonary morbidity and can aid in establishing parental expectations of postnatal outcomes.

Repair of congenital diaphragmatic hernias on Extracorporeal Membrane Oxygenation (ECMO): Does early repair improve patient survival?

INTRODUCTION The optimal timing of repair for congenital diaphragmatic hernia (CDH) patients that require ECMO is controversial. Early repair on ECMO theoretically allows for restoration of normal thoracic anatomy but entails significant bleeding risks. The purpose of this study was to examine the institutional outcomes of early CDH repair on ECMO. METHODS The records of infants with CDH placed on ECMO from 2001 to 2011 were reviewed. Since 2009, a protocol was instituted for early repair while on ECMO. For this study, three cohorts were analyzed: early repair (<72 h), late repair (>72 h), and post-decannulation. These groups were compared for outcomes regarding morbidity and survival. RESULTS Forty-six CDH patients received ECMO support with an overall survival of 53%. Twenty-nine patients (11 early/18 late) were repaired on ECMO, while 17 patients had repair post-decannulation. Survival was 73%, 50%, and 64% for those repaired early, late, or post-decannulation, respectively. Despite significantly worse prenatal factors, patients repaired early on ECMO had a similar survival. When comparing patients repaired on ECMO, the early group patients were decannulated 6 days earlier (p-value=0.009) and had significantly lower circuit complications (p=0.03). CONCLUSION In conclusion, early repair on ECMO was associated with decreased ECMO duration, decreased circuit complications, and a trend towards improved survival.

Abdominal near-infrared spectroscopy measurements are lower in preterm infants at risk for necrotizing enterocolitis.

Objective: Near-infrared spectroscopy is a noninvasive method of measuring local tissue oxygenation (StO2). Abdominal StO2 measurements in preterm piglets are directly correlated with changes in intestinal blood flow and markedly reduced by necrotizing enterocolitis. The objectives of this study were to use near-infrared spectroscopy to establish normal values for abdominal StO2 in preterm infants and test whether these values are reduced in infants who develop necrotizing enterocolitis. Design: We conducted a 2-year prospective cohort study where we prospectively measured abdominal StO2 in preterm infants, to establish reference values for preterm infants, and compared the near-infrared spectroscopy values with preterm infants in the cohort that developed necrotizing enterocolitis. Setting: Two neonatal ICUs: one at Texas Children’s Hospital and the other at Ben Taub General Hospital in Houston, TX. Patients: We enrolled 100 preterm infants (< 32 weeks’ gestation and < 1,500 g birth weight) between January 2007 and November 2008. Interventions: None. Measurements and Main Results: Eight neonates with incomplete data were excluded. Mean abdominal StO2 in normal preterm infants (n = 78) during the first week of life was significantly higher than in those who later developed necrotizing enterocolitis (n = 14) (77.3% ± 14.4% vs 70.7% ± 19.1%, respectively, p = 0.002). An StO2 less than or equal to 56% identified preterm infants progressing to necrotizing enterocolitis with 86% sensitivity, 64% specificity, 96% negative predictive value, and 30% positive predictive value. Using logistic regression, StO2 less than or equal to 56% was independently associated with a significantly increased risk of necrotizing enterocolitis (odds ratio, 14.1; p = 0.01). Furthermore, infants with necrotizing enterocolitis demonstrated significantly more variation in StO2 both during and after feeding in the first 2 weeks of life. Conclusions: This study establishes normal values for abdominal StO2 in preterm infants and demonstrates decreased values and increased variability in those with necrotizing enterocolitis. Abdominal near-infrared spectroscopy monitoring of preterm infants may be a useful tool for early diagnosis and guiding treatment of necrotizing enterocolitis.

Venovenous cannulation for extracorporeal membrane oxygenation using a bicaval dual-lumen catheter in neonates.

PURPOSE Venovenous extracorporeal membrane oxygenation (VV-ECMO) has been used as a management strategy for neonates with refractory pulmonary failure. However, VV-ECMO has been limited in neonates secondary to cannula design and patient size. Herein, we describe the use of a bicaval dual-lumen catheter for VV-ECMO in neonates. METHODS The medical records of all neonates cannulated for ECMO support with a bicaval dual-lumen 13F catheter from 2008 to 2010 were reviewed. RESULTS Nine neonates cannulated with this dual-lumen catheter were identified. The median gestational age was 38 weeks (range, 31-40 weeks), the median weight was 3.4 kg (range, 2.2-5.5 kg), the median age at cannulation was 2 days (range, 1-64 days), and the median duration of ECMO support was 7 days (range, 5-23 days). There were no VV-to-VA conversions. The median pump flow both at 4 and 24 hours postcannulation was 300 mL/min (range, 240-370 mL/min). One patient developed cannula thrombosis, and one required cannula repositioning because of flow recirculation. Overall survival was 56%. CONCLUSION The dual-lumen bicaval catheter can be safely used in neonates with minimal complications and is our preferred method for VV-ECMO support in the neonatal population.

Defining hydrops and indications for open fetal surgery for fetuses with lung masses and vascular tumors

PURPOSE The aim of this study was to identify the most accurate prenatal predictors of outcomes and need for fetal surgery for fetuses with high-risk lung masses and vascular tumors. METHODS The records of all fetuses with high-risk lung mass (congenital cystic adenomatoid malformation-volume ratio > 1.6 or findings of hydrops) and vascular tumor evaluated between July 2001 and March 2011 were reviewed retrospectively. Hydrops was defined as accumulation of fluid in 2 or more compartments. RESULTS Of fetuses with high-risk lung mass, hydrops was identified in 46% (11/24). Fetuses with hydrops and an abnormal echocardiogram (n = 8) demonstrated poor survival without fetal surgery (13%) compared with 100% survival in fetuses with hydrops and a normal echocardiogram (n = 3; P = .02). Of 21 fetuses with vascular tumor (11 sacrococcygeal and 8 cervical teratomas; 2 hemangioendotheliomas), hydrops was identified in 29% and an abnormal echocardiogram in 57%. All fetuses with hydrops had an abnormal echocardiogram and either died (n = 5) or required fetal surgery (n = 1). However, all fetuses with abnormal echocardiograms alone (n = 7) survived without fetal intervention. CONCLUSIONS For fetuses with lung mass, an abnormal echocardiogram in the setting of hydrops is the best predictor of mortality and need for fetal surgery. For fetuses with vascular tumor, hydrops in the setting of high-output physiology best predicts demise and need for fetal surgery.