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Pulmonary arteriovenous malformations (PAVMs) are a common source of morbidity after bidirectional superior cavopulmonary anastomosis (Glenn). The diversion of hepatic venous effluent away from the pulmonary circulation after Glenn appears to play a significant role in the pathogenesis of PAVMs. Although the liver is known to produce factors that regulate vascular development, specific hepatic inhibitors of angiogenesis have not been described in the post-Glenn population. Endostatin, produced from its precursor collagen XVIII, is a potent inhibitor of angiogenesis produced by the liver. This study aimed to investigate the hypothesis that endostatin levels decrease in patients after Glenn. Levels of endostatin and its precursor, long-type collagen XVIII, were determined by enzyme-linked immunoassay and immunoprecipitation, respectively, for serum samples from 38 patients undergoing Glenn, total cavopulmonary anastomosis (Fontan), or biventricular repair of cardiac defects. Samples were obtained before surgery and 24 h afterward. In patients undergoing a bidirectional Glenn procedure, endostatin levels decreased after surgery (n = 17; 4.42 vs 3.34 ng/ml; p < 0.001), and long type-collagen XVIII levels increased by 200 % (n = 10; p = 0.0001). However, endostatin levels did not change after surgery in patients undergoing Fontan (n = 13) or biventricular repair (n = 8). In patients undergoing Fontan, long-type collagen XVIII increased by 18 % (p < 0.01), whereas in control subjects, the levels were unchanged. These data suggest that the diversion of hepatic blood flow away from the pulmonary circulation in patients after the Glenn procedure inhibits endostatin production from collagen XVIII, resulting in decreased circulating serum endostatin levels. A decrease in endostatin may promote angiogenesis. The mechanism whereby the pulmonary circulation processes endostatin and its potential role in the pathogenesis of PAVMs warrant further study.

Endothelin-1 (ET1) is dysregulated in pulmonary hypertension (PH). It may be important in the pathobiology of congenital diaphragmatic hernia (CDH).We hypothesized that ET1 levels in the first month would be higher in infants with CDH who subsequently expired or were discharged on oxygen (poor outcome). We further hypothesized that ET1 levels would be associated with concurrent severity of PH.We sampled plasma at 24 to 48 hours, and 1, 2, and 4 weeks of age in 40 prospectively enrolled newborns with CDH. We performed echocardiograms to estimate pulmonary artery pressure at less than 48 hours of age and weekly to 4 weeks. PH was classified in relationship to systemic blood pressure (SBP): less than 2/3 SBP, 2/3 SBP-systemic is related to pressure, or systemic-to-suprasystemic pressure.ET1 levels at 1 and 2 weeks were higher in infants with poor outcome compared with infants discharged on room air (median and interquartile range: 27.2 [22.6, 33.7] vs. 19.1 [16.1, 29.5] pg/ml, P = 0.03; and 24.9 [17.6, 39.5] vs. 17.4 [13.7, 21.8] pg/ml, P = 0.01 at 1 and 2 weeks, respectively). Severity of PH was significantly associated with increasing ET1 levels at 2 weeks (16.1 [13.7, 21.8], 21.0 [17.4, 31.1], and 23.6 [21.9, 39.5] pg/ml for increasing PH class, P = 0.03). Increasing severity of PH was also associated with poor outcome at that time (P = 0.001).Infants with CDH and poor outcome have higher plasma ET1 levels and severity of PH than infants discharged on room air. Severity of PH is associated with ET1 levels.

Background/purpose The prognosis for multiple vs singleton pregnancies affected by congenital diaphragmatic hernia (CDH) is not known. To improve the counseling of families with multiple gestation pregnancies complicated by CDH, we examined outcomes of a consecutive series of CDH cases occurring in multiple gestation pregnancy referrals. Methods Clinical characteristics and morbidity and mortality data were gathered for a consecutive series of infants with CDH from 16 multiple gestation pregnancies. Outcomes were compared to a cohort of 91 patients with CDH from singleton pregnancies. Multivariate regression was also used in an attempt to determine whether multiple gestation pregnancy was independently predictive of subsequent long-term adverse outcomes. Results Four pregnancies were lost to follow-up, and 1 underwent selective reduction. Overall mortality for live-born multiple gestation fetuses affected by CDH was 30% and was 8% for unaffected siblings. No pregnancy was concordant. Clinical features were not different between the case series and control infants, except median gestational age at delivery, which was significantly lower for the multigestational infants (34 [range, 32-36] vs 38 [range, 28-41] weeks) ( P = .02). Long-term morbidity was comparable between cases and controls. Conclusions In terms of mortality, outcomes of multigestational pregnancies affected by CDH are no worse than for CDH pregnancies in general. Long-term risk may depend more on CDH severity rather than the presence of multiple fetuses.

Surgical complications are common in survivors of congenital diaphragmatic hernia (CDH), but little is known about long-term incidence patterns and associated predictors.A cohort of 99 CDH survivors was prospectively followed at a single-institution multidisciplinary clinic. Data were gathered regarding the adverse surgical outcomes of hernia recurrence, chest and spinal deformity, and operative small bowel obstruction (SBO), and then were retrospectively analyzed in relation to perinatal and perioperative markers of disease severity to determine significant predictors. Statistical methods used included univariate and multivariate regression analysis, hazard modeling, and Kaplan-Meier analysis.At a median cohort age of 4.7 (range, 0.2-10.6) years, 46% of patients with patch repairs and 10% of those with primary repairs had a hernia recurrence at a median time of 0.9 (range, 0.1-7.3) years after repair. Chest deformity was detected in 47%. Small bowel obstruction and scoliosis occurred in 13%. Recurrence and chest deformity were significantly more common with patch repair, liver herniation, age at neonatal extubation greater than 16 days, oxygen requirement at discharge, and prematurity. The strongest predictor of SBO was patch repair. Multivariate analysis showed that patch repair was independently predictive of recurrence and early chest deformity (odds ratios of 5.0 and 4.8, confidence intervals of 1-24 and 1-21, P.05). Use of an absorbable patch was associated with the highest risk of surgical complications.For long-term survivors of CDH, specific perinatal and operative variables, particularly patch repair, are associated with subsequent adverse surgical outcomes.

OBJECTIVE We describe four cases of chronic pulmonary hypertension in infants and children with chronic lung disease and pulmonary hypoplasia due to severe congenital diaphragmatic hernia (CDH) or congenital cystic adenomatoid malformation (CCAM). We report data from cardiac catheterization under various conditions: baseline respiratory support and room air, hyperoxic and inhaled nitric oxide challenge. We further report cardiac catheterization measures after chronic pulmonary vasodilator therapy with sildenafil alone or a combination of sildenafil and inhaled nitric oxide (three patients). DESIGN Case series. SETTING Tertiary academic center. PATIENTS Infants and children ages 0-11 yrs with CDH (n = 3) or CCAM (n = 1) with evidence of chronic pulmonary hypertension by echocardiogram and cor pulmonale (n = 3). INTERVENTIONS Catheterization and pulmonary vasodilator therapy. MEASUREMENTS AND MAIN RESULTS Pulmonary vascular resistance, pulmonary arterial pressure, and changes in these measures were assessed. A 20% change in pulmonary vascular resistance was considered a clinically significant response. Ten catheterizations were performed in four patients. All patients had elevated pulmonary vascular resistance and pulmonary arterial pressures at initial catheterizations and significant vasodilation during inhaled nitric oxide. CONCLUSIONS Chronic lung disease following pulmonary hypoplasia from CDH and CCAM is associated with abnormal pulmonary vascular tone in infants and children with evidence of chronic pulmonary hypertension. Chronic pulmonary vasodilator therapy may improve pulmonary vascular function and enhance lung growth in infants and children who are treated during their period of potential for rapid lung growth.

Introduction: Congenital diaphragmatic hernia (CDH) continues to be a devastating disease in the newborn population, with well-documented morbidity and mortality. Bronchopulmonary sequestration is a separate congenital defect that has been associated with CDH. While the association of sequestration with CDH has been reported to be as high as 30–40%, the prognosis associated with the two simultaneous defects is unknown. We reviewed our experience to evaluate if prognosis was better in the CDH infants with associated bronchopulmonary sequestration. Methods: Institutional approval was obtained. Our institutional database was examined from August 1995 to August 2005, identifying all mothers carrying fetuses with pulmonary masses and/or CDH and all neonates treated with bronchopulmonary sequestration and/or CDH. Patients who had both CDH and sequestration were identified by prenatal ultrasound reports, postnatal radiographs, and operative and pathology reports. Results: 16 patients were identified in the fetal or neonatal period with concomitant diagnoses of CDH and bronchopulmonary sequestration. Of those proceeding to delivery, 6 expired and 6 survived. The presence of liver herniation and low lung-to-head ratio on antenatal ultrasound correlated with mortality. However, 2 patients survived with very low lung-to-head ratio that would usually be associated with 100% mortality at our institution. Two diagnoses of bronchopulmonary sequestration were reversed after final pathology revealed liver tissue. Conclusion: Given the limited series, we cannot conclude that bronchopulmonary sequestration confers an anatomic advantage to patients that have CDH. We did observe survivors in this group that, given their antenatal predictors of CDH severity, would ordinarily have dismal prognosis. The presence of a sequestration may be protective in a subset of patients with severe CDH, or may confound our antenatal predictors of disease severity in these patients.

Objective The purpose of this study was to investigate the relationship between lung-to-head ratio (LHR) and gestational age (GA) in fetuses with isolated left congenital diaphragmatic hernia and to determine the applicability and reliability of LHR to predict postnatal outcome beyond 24-26 weeks of gestation. Study Design The institutional review board approved this retrospective review of the University of California, San Francisco, Fetal Treatment Center database for cases with left congenital diaphragmatic hernia who were referred between March 1995 and June 2004. LHR was determined at the initial evaluation. One hundred seven live-born fetuses at 20-34 weeks of gestation (excluding cases that were lost to follow-up, with factors that potentially could influence the LHR measurement or postnatal outcome, or that were terminated electively). Results The median GA at LHR measurement was 25.6 weeks; the median LHR was 1.01; the median GA at birth was 37.7 weeks; and the overall survival rate was 59% (64/107). The median LHR of nonsurvivors was significantly lower than that of survivors, but neither GA at LHR measurement nor at delivery was significantly different between the groups. Multiple logistic regression analysis confirmed LHR to be an independent predictor of postnatal survival, and receiver-operator characteristic curve analysis demonstrated that an LHR of ≥0.97 has the highest performance in predicting postnatal survival. When fetuses were grouped by GA at initial LHR measurement to determine reliability of LHR, specifically with respect to GA, in the 26-34 and 24-26 weeks of gestation groups, median LHR of survivors was significantly higher than that of nonsurvivors, and receiver-operator characteristic curve analysis confirmed LHR to be a reliable predictor of postnatal survival. However, for fetuses at 20-24 weeks of gestation, there was a trend toward a higher LHR in survivors, although this did not reach statistical significance. Conclusion A significant positive linear relationship exists between LHR and GA at the time of measurement, such that LHR reliably predicts postnatal survival in fetuses with left congenital diaphragmatic hernia at 24-34 weeks of gestation and less reliable at 20-24 weeks. However, given the limitations of a retrospective, cross-sectional study, further prospective longitudinal studies that will investigate the change of LHR with GA and its association with fetal outcome are necessary.

Congenital diaphragmatic hernia (CDH) carries a high mortality risk secondary to pulmonary hypoplasia and respiratory failure. In experimental animals, fetal tracheal occlusion (TO) induces lung growth and morphologic maturation. We measured indicators of pulmonary function in 20 infants who were enrolled in a randomized trial of fetal TO as treatment for severe CDH [nine with conventional treatment (controls); 11 with TO]. We hypothesized that TO would improve lung function. At birth, the TO group had a lower mean gestational age (30.8 +/- 2.0 versus 37.4 +/- 1.0 wk; p=0.0002). All infants required assisted ventilation. Mortality did not differ between groups (64 versus 78%, TO and control, respectively; p=0.64). We measured respiratory mechanics at four study points: 1) first 24 h, 2) before CDH operative repair (5.9 +/- 2.2 d), 3) immediately after repair (7.0 +/- 2.2 d), and 4) before elective extubation (32.5 +/- 16.1 d). We calculated perioperative oxygenation index and alveolar-arterial oxygen difference to assess efficiency of pulmonary gas exchange. Data were analyzed by univariate and repeated measures techniques. Respiratory system compliance (Crs) was low. The rate of increase in Crs over the four study points was greater in the TO group than in control subjects. Crs in the TO group was significantly greater at study 2 (0.28 +/- 0.12 versus 0.17 +/- 0.04 mL.cm H2O(-1).kg(-1); p=0.02) and study 4 (0.93 +/- 0.45 versus 0.51 +/- 0.16 mL.cmH2O(-1).kg(-1); p=0.02). oxygenation index did not differ between groups, but alveolar-arterial oxygen difference was lower in the TO infants. We conclude that fetal TO for severe CDH results in modest improvements in neonatal pulmonary function that are of questionable clinical significance.

Objective We describe a case of chronic pulmonary hypertension in a 7-wk-old infant with congenital diaphragmatic hernia and an oral teratoma. Our patient was dependent on low-dose inhaled nitric oxide and was still very unstable with systemic right ventricular pressures leading to frequent oxygen desaturations. We administered sildenafil therapy to stabilize the infant with discontinuation of inhaled nitric oxide. We describe successful discontinuation of the inhaled therapy as well as a period of stabilization and improvement with continued sildenafil administration. Design Case report. Setting Intensive care nursery in tertiary academic center. Patient A 7-wk-old infant with congenital diaphragmatic hernia who was mechanically ventilated from birth. Intervention Oral sildenafil 0.3 mg/kg/dose every 12 hrs. Measurements and results Right ventricular pressure (from tricuspid valve regurgitant flow) to systemic systolic arterial pressure was measured by echocardiogram. Right ventricular to systemic pressure ratio was marginally improved with the initiation of sildenafil therapy. Inhaled nitric oxide was successfully discontinued, and the patient clinically stabilized temporarily, but he ultimately succumbed to his pulmonary hypertension. Conclusion Sildenafil may be a useful therapy for chronic pulmonary hypertension in congenital diaphragmatic hernia, but further studies of safety and efficacy need to be performed.

Objective. Although indomethacin produces ductus arteriosus constriction in extremely premature newborns, a recurrent symptomatic patent ductus arteriosus (PDA) frequently develops after the initial course of indomethacin. Currently, there is little information available to determine the effectiveness of a second course of indomethacin in producing permanent ductus closure. The objective of this study was to determine the rate of permanent ductus closure after a second course of indomethacin for a recurrent, symptomatic PDA and to identify the factors associated with permanent ductus closure. Methods. We identified 32 infants ( Results. After the second course of indomethacin, 56% (18 of 32) of the infants had persistent or recurrent PDA-related symptoms that were considered to be hemodynamically significant. The only significant predictor of failure of the second indomethacin course was the demonstration (by Doppler echocardiogram) of persistent ductus flow within 24 hours of completing the initial indomethacin course. All of the 9 newborns with persistent Doppler ductus flow after the initial indomethacin course failed the second course of indomethacin. In contrast, only 39% (9 of 23) of newborns with absent Doppler flow after the initial indomethacin course failed the second course of indomethacin. Conclusions. Newborns who are

Background/aims The pathogenesis of BPD is multifactorial. In preterm infants ≤28 wk GA requiring ventilation at 7–14 days, >60% have surfactant dysfunction. Survival without BPD in these infants is Methods Preterm infants ≤28 wk GA requiring mechanical ventilation at 7–14 days were enrolled in a RCT at 25 US centres. All infants received iNO and were randomised to receive surfactant (Infasurf) or sham instillation behind a screen every 1–2 days; maximum of 5 doses. Infants were evaluated by physiologic oxygen/flow reduction at 36 and 40 wk. Pulmonary outcome to 18 months is being collected. Results Between January 2010 and September 2013, 511 of the planned 524 infants were enrolled. There was no difference between groups in mean BW (701 ± 164 grams), GA (25.2 ± 1.2 wk), percentage under 26 wk (70.6%), race, gender, severity of disease at enrollment or co-morbidities of prematurity. Survival without BPD was not different between treated vs. controls at 36 wk (31.3% vs.31.7%; relative benefit 0.98 (0.75, 1.28 p = 0.89) or 40 wk (58.7% vs. 54.1%; relative benefit 1.08 (0.92, 1.27 p = 0.33). Overall survival without BPD at 36wk in African Americans was better than whites (37.2% vs. 25.4%p = 0.008). Conclusions Late treatment with surfactant in ventilated preterm infants did not improve survival without BPD at 36 or 40 weeks PMA. Overall better outcome in African-American infants may be due to a racial response to iNO. Pulmonary and neurodevelopmental assessment are on-going.

Background/aims Inhaled NO (iNO) has been tested for prevention of bronchopulmonary dysplasia in premature infants, however the role of cGMP is not known. We hypothesised that levels of NO metabolites (NOx) and cGMP in urine, as a non-invasive source for biospecimen collection, would reflect the dose of iNO and relate to pulmonary outcome. Methods Studies were performed on 125 infants Results In NO-treated infants there was a significant dose-dependent increase of both urinary NOx and cGMP per creatinine (maximal 3.1- and 2-fold, respectively, at 10–20 ppm iNO) compared to off iNO. The ratio of cGMP to NOx, which may reflect efficiency of NO signalling via guanylate cyclase, was lower (mean 38%) at all doses of iNO compared to off NO. NOx and cGMP concentrations at both 2 ppm and off iNO were inversely related to severity of lung disease (Respiratory Severity Score) during the first month, and the NOx levels were lower in infants who died or developed BPD at term. NOx was higher in Caucasian compared to other infants at all iNO doses. Conclusions Urinary NOx and cGMP are biomarkers of endogenous NO production and lung uptake of iNO, and levels at some doses reflect the severity of lung disease in infants. These results support a role of the NO-cGMP pathway in lung development and repair from injury.

Both patient care and research are fundamental to the missions of academic pediatric medical centers in the US. The value of training physicians to perform basic science, clinical, and translational research is well recognized, and it is supported by the National Institutes of Health (NIH) through several mechanisms, including mentored career development awards (K awards). These awards most often are used to provide physicians the opportunity to develop their scientific skills under the supervision of a mentor at the start of their academic careers. Such time, protected from the burden of clinical duties, is invaluable, given the increasing competition for extramural research funding and the requirements for academic promotion. At the same time, this early career stage comes with the challenge of transitioning to the role of attending physician.

In a randomized multi-center trial, we demonstrated that inhaled nitric oxide begun between 7 and 21 days and given for 24 days significantly increased survival without bronchopulmonary dysplasia (BPD) in ventilated premature infants weighing1250 g. Because some preventative BPD treatments are associated with neurodevelopmental impairment, we designed a follow-up study to assess the safety of nitric oxide.Our hypothesis was that inhaled nitric oxide would not increase neurodevelopmental impairment compared with placebo. We prospectively evaluated neurodevelopmental and growth outcomes at 24 months postmenstrual age in 477 of 535 surviving infants (89%) enrolled in the trial.In the treated group, 109 of 243 children (45%) had neurodevelopmental impairment (moderate or severe cerebral palsy, bilateral blindness, bilateral hearing loss, or score70 on the Bayley Scales II), compared with 114 of 234 (49%) in the placebo group (relative risk, 0.92; 95% CI, 0.75-1.12; P = .39). No differences on any subcomponent of neurodevelopmental impairment or growth variables were found between inhaled nitric oxide or placebo.Inhaled nitric oxide improved survival free of BPD, with no adverse neurodevelopmental effects at 2 years of age.

Background Congenital diaphragmatic hernia (CDH) causes fetal and neonatal lung hypoplasia. Severe fetal CDH has been defined by midgestation ultrasonography (US) and characterized by the presence of liver herniated into the thorax with a low lung-to-head ratio (LHR) (≤ 1.4). LHR is the area of the contralateral lung at the level of the cardiac atria divided by head circumference. We previously performed a single-center randomized study of fetal tracheal occlusion (FTO) versus standard care for severe fetal CDH. The trial was stopped prematurely due to an unexpectedly high survival rate in the control group (compared with historical data). Aim To determine if survival to hospital discharge (DC) in infants receiving neonatal care at a single center (University of California, San Francisco [UCSF]) differs from survival at other centers (Other), after accounting for fetal liver herniation and LHR. Methods We identified all UCSF US evaluations with diagnosis of CDH and LHR at 20 to 296/7 weeks9 gestational age (GA, 1991-2006, n = 237). Patients were excluded if palliative care was elected (n = 37) or survival was unknown (n = 20). The primary outcome was survival to DC. If liver was herniated, fetal CDH severity was defined by LHR group (LHR ≤ 1.0 [LHR 1.0], 1.0 1.4 [LHR1.4]). Data were analyzed by chi square, Fisher9s exact, or rank sum test; p Results Survival for infants with liver herniation and standard care at UCSF versus Other was 26 of 44 (59%) versus 40 of 82 (49%) (p = .27). Evaluation by the LHR group revealed significantly better survival at UCSF in the lowest LHR group only (LHR 1.0: 17 of 30 [57%] vs 8 of 37 [22%], p = .003). In other LHR groups there were no significant survival differences (LHR 1-1.4: 6 of 8 [75%] vs 22 of 33 [67%], p = 1.0; LHR 1.4: 3 of 6 [50%] vs 10 of 12 [77%], p = .27). Without liver herniation, survival was not different by site of neonatal care (UCSF vs Other: 14 of 14 [100%] vs 12 of 16 [75%], p = .10). GA at delivery was comparable by site of care and CDH severity. There was no survival difference among UCSF infants with severe fetal CDH after FTO versus standard care (23 of 37 [62%] vs 23 of 38 [61%], p = .88). There were also no differences by LHR group. Conclusions Survival differences based on fetal CDH severity were significantly different by site of neonatal care only for infants with the most severe fetal CDH (liver herniated, LHR 1.0). This difference may be explained by consistent care at UCSF, a high-volume neonatal referral center. There were no survival differences seen when evaluating only UCSF infants with severe fetal CDH, regardless of whether FTO was performed.

Objective To investigate the potential value of antenatally determined intrathoracic herniation of the liver and the ratio of fetal lung area to head circumference (LHR) in the prediction of postnatal survival in isolated, left-sided congenital diaphragmatic hernia (CDH). Methods In this multicenter study, we searched the antenatal-CDH-Registry for fetuses with isolated leftsided CDH that were liveborn after 30 weeks of gestation and were followed up postnatally for at least 3 months after discharge from hospital. The patients were subdivided into those with and those without intrathoracic herniation of the liver and into subgroups according to the LHR that had been measured between 22 + 0 and 28 + 0 weeks of gestation. The rate of survival in each group and subgroup of patients was determined and compared. Results The registry search identified 184 patients that fulfilled the entry criteria. Logistic regression analysis demonstrated that significant predictors of survival were the presence or absence of intrathoracic herniation of the liver and the LHR. In 86 cases there was liver herniation (Group A) and in 98 the liver was confined to the abdomen (Group B). In Group A, the survival rate was 50.0% and was significantly associated with LHR; in Group B the survival rate was 76.5% and was unrelated to LHR. Conclusion In isolated, left-sided CDH, the postnatal mortality rate is substantially higher if there is intrathoracic herniation of the liver. In fetuses with liver herniation, measurement of LHR at 22–28 weeks of gestation is useful in the prediction of subsequent survival. Copyright  2005 ISUOG. Published by John Wiley & Sons, Ltd.

IN INFANTS WITH CONGENITAL DIAPHRAGMATIC HERNIA? KATHERINE BIANCO (F), AARON B. CAUGHEY, ROBERTA KELLER, MARY E NORTON, KERILYN NOBUHARA, JODY A FARRELL, ROBIN BISGAARD, HANMIN LEE, DIANA FARMER, MICHAEL R. HARRISON, RUTH B. GOLDSTEIN, ROBERT H BALL, University of California, San Francisco, Obstetrics, Gynecology andReproductive Sciences, San Francisco, California, University of California, San Francisco, Neonatology/Pediatrics, San Francisco, California, University of California, San Francisco, Pediatric Surgery, San francisco, California, University of California, San Francisco, Department of Radiology, San Francisco, California OBJECTIVE: To examine the association between single umbilical artery (SUA) and survival in neonates with congenital diaphragmatic hernia (CDH). STUDY DESIGN: This is a retrospective cohort study of all prenatally diagnosed fetuses with CDH referred to the Fetal Treatment Center at the University of California, San Francisco (UCSF), from 1992 to 2004. We compared survival rates for fetuses with CDH and the presence of congenital anomalies to those with isolated CDH. We excluded patients with fetal surgery or an abnormal karyotype. Univariate and multivariate analyses were conducted; Chi-square test was used. RESULTS: There were 230 neonates who met inclusion criteria. The overall survival was 48%. We found a significant decreased survival in the group with SUA compared with isolated CDH: 12.5% vs. 50% Pr = 0.004 (Table). SUA remained predictive when included in an analysis of minor anomalies and survival (e.g. cleft lip, pyelectasis, polydactyly, vertebral abnormalities) (22.9% vs. 53.8%, Pr !0.001). Of the major anomalies (cardiac, GI, or renal), only cardiac was powered to demonstrate a significant decrease in survival (7.15% vs. 50%, Pr = 0.002). We found no differences in ECMO requirements and survival (37.2% vs. 35.7%, Pr =0.841), although the need for supplemental oxygen at the time of discharge was significantly higher in infant with CDH and others anomalies (23.6% vs. 61.9%, Pr =0.02). CONCLUSION: The presence of certain anomalies such as SUA is associated with lower survival in infants affected with CDH. This prognostic information can be utilized to counsel patients with CDH. Survival of infants with CDH with and without congenital anomalies

DIAGNOSED ISOLATED LEFT SIDED DIAPHRAGMATIC HERNIA FETUSES: A MULTICENTER STUDY JACQUES JANI, ALEXANDRA BENACHI, RENE FAVRE, ROBERTA KELLER, HILDE VANDECRUYS, JULIAN DELGADO, MICHAEL HARRISON, JACQUELINE MATIS, EDUARD GRATACOS, KYPROS NICOLAIDES, JAN DEPREST, University Hospital Gasthuisberg, Obstetrics and Gynecology, Leuven, Belgium, Hopital Necker-Enfants Malades, Obstetrics and Gynaecology, Paris, France, CHRU Strasbourg, Obstetrics and Gynecology, Schiltigheim, France, University of California, San Francisco, Neonatology/Pediatrics, San Francisco, California, King’s College London, Harris Birthright Research Centre, London, United Kingdom, Hospital Universitari Vall Hebron, Obstetrics and Gynecology, Barcelona, Spain, University of California, San Francisco, Surgery & Pediatrics, San Francisco, California, CHRU Strasbourg, Neonatology, Schiltigheim, France OBJECTIVE: Congenital diaphragmatic hernia (CDH) is associated to high neonatal mortality. Accurate prediction of outcome is crucial in counselling parents about management options. We evaluated Lung-to-Head Ratio (LHR) and liver position in prediction of outcome of isolated Left CDH. STUDY DESIGN: Retrospective review of consecutive patients diagnosed with isolated LCDH %28 weeks, evaluated at 6 tertiairy units from 1995 onwards. Only patients with LHR measurements by experienced sonographers and with known liver position by ultrasound or MRI, both %28 wks, were included. Outcome measure was survival at discharge from NICU. RESULTS: 134 cases had an LHR obtained at 24.4 G 2.8 wks. 11 patients (8%) opted for termination after evaluation, all with LHR !1.4. There were no postnatal diagnoses of chromosomal anomalies. Overall survival was 43% (58/ 134), after substraction of antenatal losses 47% (58/123). In case of liver herniation survival was 35 %. LHR correlated to survival irrespective of liver position but combination of both variables predicted neonatal outcome better: liver up & LHR !1 predicted a survival of 9%. When LHR !0.8 and liver up, there were no survivors, but with liver down (37% of cases) survival was 40%. When LHR !0.6 there were no survivors irrespective of liver position. CONCLUSION: Combination of liver up& LHR !1 at %28 wks predicts a !10 % chance of survival, dropping to 0% if LHR !0.8. 8% of patients opted for termination after second opinion, all with LHR !1.4, but only in half this coincided with the above poor prognostic indicators.

Objective: In utero diagnosed congenital diaphragmatic hernia (CDH) is associated to high antenatal and neonatal loss rates. Accurate prediction of outcome is crucial in counselling parents about management options. We evaluated Lung-to-Head Ratio (LHR) and liver position in prediction of outcome of isolated Left CDH.

ObjectiveExtracorporeal life support is used in 3% to 8% of infants and children after cardiac surgery. B-type natriuretic peptide may have utility as a biomarker in these patients. The objective of this study was to investigate potential associations between changes in B-type natriuretic peptide during trials off extracorporeal life support and clinical outcome.MethodsTen infants and children requiring extracorporeal life support after cardiac surgery were studied prospectively. Before separation from extracorporeal life support, a shunt was placed in the circuit, allowing for temporary trials off life support. Serum lactate, arterial–venous oxyhemoglobin saturation difference, and B-type natriuretic peptide levels were determined before each trial off life support and at the end of each trial off life support, and the ability to predict postoperative outcome from these data was evaluated.ResultsDuring trials off extracorporeal life support, lactate, the arterial–venous oxyhemoglobin saturation difference, and B-type natriuretic peptide levels increased above pre-trial values (P < .05). Only the arterial–venous oxyhemoglobin saturation difference predicted successful separation from extracorporeal life support after a trial (P < .05). There were no associations between long-term outcome and alterations in lactate and the arterial–venous oxyhemoglobin saturation difference during the final trials off life support. However, an increase in B-type natruiretic peptide levels during the final trial off life support (trial/pre-trial ratio of >1) had a sensitivity of 80% and a specificity of 100% for predicting the need for an unplanned operation or death within 3 months (P < .05).ConclusionB-type natriuretic peptide determinations may be a useful tool for clinicians caring for infants and children requiring extracorporeal life support after cardiac surgery.

ObjectiveB-type natriuretic peptide is used in the diagnosis, risk stratification, and management of adult patients with cardiac disease. However, its use in infants with congenital heart disease has been limited, particularly in the perioperative period. Our objective was to determine the alterations in perioperative B-type natriuretic peptide levels and their predictive value on postoperative outcomes, in infants undergoing congenital heart surgery.MethodsWe prospectively enrolled 115 patients: 24 with univentricular heart disease undergoing a modified Norwood procedure, 11 with d-transposition of the great arteries, 55 with hemodynamically important left-to-right shunt, and 25 with tetralogy of Fallot undergoing primary repair. Clinical data and B-type natriuretic peptide samples were collected before and 2, 12, and 24 hours after cardiopulmonary bypass. Univariate analysis and multivariate linear regression analysis were performed.ResultsThe perioperative B-type natriuretic peptide levels were lesion specific. Patients with d-transposition of the great arteries and univentricular heart disease had high preoperative B-type natriuretic peptide levels that decreased postoperatively, and those with hemodynamically important left-to-right shunts and tetralogy of Fallot had lower preoperative levels that increased during the first 12 hours postoperatively. The patients with univentricular heart disease with an adverse outcome had a significantly greater 24-hour B-type natriuretic peptide level than those without (P