A Case of Congenital Hepatoblastoma Coexisting with Pulmonary Hypertension.

Hepatoblastoma (HBL) is the most frequently detected malignant tumor of the liver in childhood. HBLs detected antenatally or up to 3 months after birth are considered congenital HBLs. We report a five-day-old female infant in whom a hepatic mass was detected at 20 weeks' gestation. At birth (36 weeks), the hepatic mass measured 12x6 cm, and she had respiratory distress. Pulmonary hypertension (PHT) was detected on echocardiographic evaluation. Despite dual medical therapy, her PHT did not improve. Histologically, the biopsy demonstrated a mixed epithelial-mesenchymal HBL with predominance of fetal morphology in the epithelial component. Chemotherapy was initiated on postnatal day 15; however, the baby died of respiratory failure on postnatal day 23. Conclusion: HBL is an embryonal tumor which can develop early in the intrauterine period. Although the mechanism is not known, it may cause PHT which would affect the prognosis negatively.

Severe persistent pulmonary hypertension of the newborn and dysmorphic features in neonate with a deletion involving TWIST1 and PHF14: a case report.

BACKGROUND: Persistent pulmonary hypertension is a well-known disease of the newborn that in most cases responds well to treatment with nitric oxide and treatment of any underlying causes. Genetic causes of persistent pulmonary hypertension of the newborn are rare. The TWIST1 gene is involved in morphogenetics, and deletions are known to cause Saethre-Chotzen syndrome. Deletions of PHF14 have never been reported in neonates, but animal studies have shown a link between severe defects in lung development and deletions of this gene. There have not, to the best of our knowledge, been any publications of a link between the genes TWIST1 and PHF14 and persistent pulmonary hypertension of the newborn, making this a novel finding. CASE PRESENTATION: We describe a white male neonate born at term to non-consanguineous white parents; he presented with dysmorphic features and a therapy-refractory persistent pulmonary hypertension. Array-based comparative genomic hybridization revealed the presence of a 14.7 Mb interstitial deletion on chromosome 7, encompassing the genes TWIST1 and PHF14. CONCLUSIONS: The TWIST1 gene can explain our patient's dysmorphic features. His severe persistent pulmonary hypertension has, however, not been described before in conjunction with the TWIST1 gene, but could be explained by involvement of PHF14, consistent with findings in animal experiments showing lethal respiratory failure with depletion of PHF14. These findings are novel and of importance for the clinical management and diagnostic workup of neonates with severe persistent pulmonary hypertension of the newborn and dysmorphic features.

Two Cases of Late Shone Syndrome With Pulmonary Hypertension: Heart-Lung Transplant or Valve Surgery?

Two cases of Shone syndrome with severe mitral and aortic valve problems and pulmonary hypertension were referred for heart-lung transplantation. Severely elevated pulmonary vascular resistance (PVR) was confirmed as was severe periprosthetic mitral and aortic regurgitation. Based on the severity of the valve lesions in both patients, surgery was decided upon and undertaken. Both experienced early pulmonary hypertensive crises, one more than the other, that gradually subsided, followed by excellent recovery and reversal of pulmonary hypertension and PVR. These cases illustrate Braunwald's concept that pulmonary hypertension secondary to left-sided valve disease is reversible.

Transient neonatal hyperinsulinism with adaptation disorders: a report of three cases.

Transient hyperinsulinism can occur in neonates following exposure to perinatal stress, such as intrauterine growth restriction and birth asphyxia. However, little is known about its pathophysiology and clinical manifestations. We report three neonatal cases of transient severe hyperinsulinism complicated with cardiopulmonary problems, thrombocytopenia, and marked erythroblastosis at birth. All cases showed signs of placental insufficiency, indicating that chronic hypoxia and malnutrition during fetal development might be associated with characteristic clinical features after birth. Perinatal stress-associated hyperinsulinism can be regarded as a systemic syndrome characterized by cardiopulmonary and hematological problems due to fetal chronic hypoxia.

Congenital chylothorax and pulmonary hypertension complicated with heart failure and hepatopathy.

Respiratory difficulty resulting from congenital chylothorax is usually relieved by postnatal thoracentesis, closed chest drainage, and oxygen therapy. However, early occurrence of congenital chylothorax or accumulation of a large amount of chylous fluid sometimes leads to pulmonary hypoplasia or persistent pulmonary hypertension of the newborn, which requires further customized mechanical ventilatory support. In these cases, conventional mechanical ventilation is primarily used during initial treatment and is later replaced by high-frequency ventilation, but the advantages of inhaled nitric oxide treatment have rarely been described. This case suggests the benefits of inhaled nitric oxide in patients with congenital chylothorax, even when mechanical ventilation cannot improve respiratory distress because of severe pulmonary hypertension of the newborn leading to right cardiac dysfunction and possibly cholestasis.

Stability prior to surgery in Congenital Diaphragmatic Hernia: is it necessary?

BACKGROUND: Delaying surgery for infants with CDH until they achieve clinical stability is common practice. Stability, however, is inconsistently defined, and many infants fail to reach pre-established criteria. We sought to determine if infants undergoing surgery without meeting pre-established criteria could achieve meaningful survival. METHODS: All infants in the CAPSNet database were analyzed (2005-2010). Patients undergoing operative repair were divided into two groups based on whether they met strict (FiO2<0.40, conventional ventilation, preductal saturation >92%, no inotropes or vasodilators), or lenient (FiO2 <0.60, conventional ventilation, preductal saturation >88%, no vasodilators) criteria. Univariate analyses were performed comparing characteristics of those who survived after surgery (N=273) with those who did not (N=21). RESULTS: 294 patients (85%) survived to surgery. Predictors of post-operative survival included prenatal liver position (p=0.003), preoperative oxygen requirements (p=0.008), preoperative inotropes (p<0.0001), and non-conventional ventilation (p=0.004). Infants meeting strict criteria had increased survival (99%; p<0.0001). Infants meeting lenient criteria constituted 70% of survivors. Nearly one-third of survivors met neither strict nor lenient criteria. CONCLUSIONS: Infants with CDH can achieve good survival even when criteria for pre-operative stability are not met. We suggest that all infants should be repaired even if lenient criteria for ventilatory, inotrope, or vasodilator requirements are not achieved.

Congenital diaphragmatic hernia (CDH) mortality without surgical repair? A plea to clarify surgical ineligibility.

PURPOSE: Little is known about liveborn CDH patients who die without surgery. We audited a national CDH cohort to determine whether these patients were different from patients who received CDH repair. METHODS: A national CDH database was analyzed (2005-2009). After excluding infants with severe physiologic instability and genetic/congenital malformations, a potential surgical candidate (PSC) subgroup was identified. PSCs were compared to the operative group (OG) and the operative non-survivor (ONS) subgroup. Standard statistical analyses were performed. RESULTS: Of 275 liveborns, 35 (13%) died without surgery. The PSC subgroup (n=11) had a median survival of 10 days (range: 3-18). Ten of 11 PSC infants were treated in ECMO centers, with 4 receiving ECMO. No differences in BW, GA, and rates of minor malformation were observed between PSC and OG patients. While neonatal illness severity (SNAP-II) predicted overall mortality, SNAP-II scores were similar between PSC and ONS groups (34 vs. 29; p=0.431). Furthermore, greater than 80% of infants with SNAP-II scores between 30 and 39 survived in the OG cohort. CONCLUSION: Our analysis demonstrated that PSCs were similar to infants offered surgery based on illness severity and the presence of congenital malformations. We suggest that criteria for surgical ineligibility be developed to standardize the selection of surgical candidates.

Recurrent severe oligohydramnios and fetal pulmonary hypoplasia associated with ErbB4 mutation.

BACKGROUND: Pulmonary hypoplasia resulting from oligohydramnios or anhydramnios can cause severe respiratory compromise in newborn patients. We report a case of recurrent oligohydramnios in a mother with an ErbB4 mutation and speculate that the effects on the placenta through decreased vascularization contributed to oligohdyramnios and subsequent pulmonary hypoplasia in the newborn. CASE: The pregnant mother in this case had two subsequent term pregnancies complicated by severe oligohydramnios. Both pregnancies resulted in live born female neonates with pulmonary hypoplasia, pneumothoraces, and pulmonary hypertension. The mother and second newborn, who died, were found to have the ErbB4 mutation. Examination of the placenta with that pregnancy showed decreased vascularity. CONCLUSION: ErbB4 may have important effects on placental development and hydramnios that also may affect neonatal pulmonary hypoplasia.

Pulmonary interstitial glycogenosis associated with pulmonary hypertension and hypertrophic cardiomyopathy.

A neonate with pulmonary interstitial glycogenosis, pulmonary hypertension, and hypertrophic cardiomyopathy is described. The fatal outcome for this patient contrasts with the reported favorable prognosis associated with isolated pulmonary interstitial glycogenosis. To the authors' knowledge, the association of pulmonary interstitial glycogenosis and hypertrophic cardiomyopathy has not been reported previously. The authors have broadened the phenotype of pulmonary interstitial glycogenosis and demonstrate the diagnostic value of lung biopsy in cases of unexplained neonatal pulmonary hypertension.

Potts shunt in children with idiopathic pulmonary arterial hypertension: long-term results.

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) remains a progressive fatal disease. Palliative Potts shunt has been proposed in children displaying suprasystemic IPAH. METHODS: A retrospective multicenter study was performed to evaluate Potts shunt in pediatric IPAH. RESULTS: Between 2003 and 2010, 8 children with suprasystemic IPAH and in World Health Organization functional class IV despite medical pulmonary arterial hypertension therapy underwent Potts shunt. Age at IPAH diagnosis ranged from 4 to 180 months (median age, 64 months). Surgical procedure was performed in a mean delay of 41.9±54.3 months (range, 4 to 167 months; median delay, 20 months) after IPAH diagnosis. Mean size of the Potts shunt was 9.25±3.30 mm. Two patients, whose medical pulmonary arterial hypertension therapy had been interrupted just after surgery, died at postoperative days 11 and 13 of acute pulmonary hypertensive crisis. After a mean follow-up of 63.7±16.1 months, the 6 children who were discharged from the hospital were alive. Functional status improved markedly in the 6 survivors, with a World Health Organization functional class I (n=4) or II (n=2) at last follow-up, consistent with significant improvement of 6-minute-walk distance (302±95 m [51%±20% of theoretical values] versus 456±91 m [68%±10% of theoretical values]; p=0.038) and decrease of brain natriuretic peptide levels (608±109 pg/mL versus 76±45 pg/mL; p=0.035). No Potts shunt was found to be restrictive at last echocardiography. CONCLUSIONS: Palliative Potts shunt constitutes a new alternative to lung transplantation in severely ill children with suprasystemic IPAH, carrying a prolonged survival and persistent improvement in functional capacities.

Open vertical vein in non-obstructed supracardiac TAPVC: merits and fate.

Data of 18 patients who underwent surgical repair of non-obstructed supracardiac total anomalous pulmonary venous connection between January 2007 and March 2011 were reviewed. The vertical vein was left patent in all patients as an elective surgical strategy. There was no operative mortality in patients with or without preoperative pulmonary infection, but there were significant differences in postoperative airway pressures, ventilation time, intensive care unit and hospital stay between the 2 groups. None of the patients demonstrated any flow in the vertical vein over a 30-day follow-up period. One patient had a mild anastomotic stricture and pulmonary venous hypoplasia. Operative repair of supracardiac total anomalous pulmonary venous connection can be carried out successfully without ligation of the vertical vein, and this strategy possibly reduces early postoperative morbidity and mortality, with no adverse effects detected in the short to midterm follow-up.

Right-sided congenital diaphragmatic hernia, hepatic pulmonary fusion, duodenal atresia, and imperforate anus in an infant.

We present a case of a neonate with VACTERL-like association, with the VACTERL association defined as the non-random association of vertebral, anal, cardiac, esophageal, renal/kidney, and limb defects, as manifested by a hemivertebra, imperforate anus, and digit anomalies, in rare association with duodenal atresia and right-sided diaphragmatic hernia. This constellation is previously undescribed and may offer insight into the pathogenesis of VACTERL and associated birth defects.

Neonatal pulmonary hypertension.

When the normal cardiopulmonary transition fails to occur, the result is persistent pulmonary hypertension of the newborn. Severe persistent pulmonary hypertension of the newborn is estimated to occur in 2 per 1000 live-born term infants, and some degree of pulmonary hypertension complicates the course of >10% of all neonates with respiratory failure. This review article discusses the vascular abnormalities that are associated with neonatal pulmonary hypertension, including recognition of its role in severe bronchopulmonary dysplasia in preterm infants. A systematic review of the evidence for common therapies including inhaled nitric oxide, high-frequency ventilation, surfactant, and extracorporeal life support is included. Finally, this field is rapidly evolving, and the rationale for promising new treatment approaches is reviewed, including inhibition of phosphodiesterases and scavengers of reactive oxygen species.

Perinatal profile of ventricular overload markers in congenital diaphragmatic hernia.

BACKGROUND: In congenital diaphragmatic hernia (CDH), pulmonary hypertension increases right ventricle (RV) afterload, which could impair heart function and contribute to poor outcome for most affected infants. Nevertheless, the real significance of vascular pulmonary alterations in perinatal hemodynamics is largely unknown. It is defined that ventricular pressure overload induces increased myocardium gene expression of B-type natriuretic peptide (BNP) and components of the renin-angiotensinogen and endothelin (ET)-1 systems. Our aim was to evaluate perinatal myocardium expression of these genes associated with ventricular pressure overload in a nitrofen-induced CDH rat model. METHODS: In the nitrofen-induced CDH rat model, fetuses from dated pregnant Sprague-Dawley rats at 15.5, 17.5, 19.5 and 21.5 days postcoitum as well as newborn pups were assigned to 3 experimental groups: control, nitrofen (exposed to nitrofen, without CDH), and CDH (exposed to nitrofen, with CDH). Myocardial samples collected from the RV and left ventricle (LV) were processed for quantification of messenger RNA (mRNA) of BNP, angiotensinogen, and ET-1. RESULTS: The perinatal expression of BNP, angiotensinogen, and ET-1 mRNA in the RV and LV of the control group revealed daily changes. During gestation, the expression of BNP and angiotensinogen mRNA underwent significant oscillation compared with control in both nitrofen-exposed fetuses, although we cannot identify significant differences between the nitrofen and CDH groups. After birth, we found a significant increasing expression of all studied genes only in the RV of CDH pups. CONCLUSIONS: Perinatal myocardial quantification of BNP, angiotensinogen, and ET-1 mRNA levels suggests that both nitrofen-exposed and control pups revealed prenatal variations of expression of the studied genes. Moreover, CDH is associated with significant molecular alterations only in the RV after birth.

Robotic repair of a Bochdalek congenital diaphragmatic hernia in a small neonate: robotic advantages and limitations.

Minimally invasive repair for a Bochdalek congenital diaphragmatic hernia has been performed over the last few years with mixed results. Although the anomaly has been approached from both the abdomen and the chest, the defect can be difficult to close as the posterolateral region may be difficult to reach with precise suturing using standard rigid laparoscopic instruments. The articulating instruments of robotic surgery offer a substantial improvement in degrees of freedom and may help over come these obstacles. However, other limitations including instrument length in relation to patient size need to be accounted for when planning a robotic procedure in small children. We present a robotic repair of a foramen of Bochdalek congenital diaphragmatic in a 2.2 kg neonate using and abdominal approach with the Da Vinci Surgical Robot (Intuitive Surgical, Sunnyvale, CA).

Therapy of pulmonary hypertension in neonates and infants.

Pulmonary hypertension (PH) in newborns and infants can present in its idiopathic form or complicate a long list of other diseases. Most of these conditions are either pulmonary or cardiovascular in origin. In the present review our current knowledge regarding pathophysiology, structural changes, diagnosis, and available treatment options for PH in the age group below 1 year of age is summarized. New treatment options available in adults including endothelin receptor antagonists (ETRA) and phosphodiesterase (PDE) inhibitors are presented and the need for randomized controlled trials in newborns and infants is emphasized. Future candidates for pharmacotherapy of PH in infants include among others vasoactive intestinal polypeptide (VIP), PDE-3 and PDE-4 inhibitors, hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, and adrenomedullin (ADM).

Milrinone improves oxygenation in neonates with severe persistent pulmonary hypertension of the newborn.

BACKGROUND: Many neonates with severe persistent pulmonary hypertension of the newborn (PPHN) are nonresponders to inhaled nitric oxide (iNO). Milrinone is a promising adjunctive therapy because of its pulmonary vasodilator properties and cardiotropic effects. DESIGN: Case series of neonates with severe PPHN (defined as oxygenation index [OI] >20, failure of iNO therapy, and echocardiographic confirmation of PPHN). SETTING: Tertiary neonatal intensive care unit. SUBJECTS: Full-term (> or =37 weeks) neonates with severe PPHN who received intravenous milrinone. MEASUREMENTS: The primary end point was the effect of intravenous milrinone on OI and hemodynamic stability over a 72-hour study period. Secondary end points examined included duration of iNO and degree of cardiorespiratory support. RESULTS: Nine neonates at a mean gestation of 39.25 +/- 2.76 weeks, birth weight of 3668 +/- 649.1 g, and baseline OI of 28.1 +/- 5.9 received milrinone treatment after a poor initial response to iNO treatment. Intravenous milrinone was commenced at a median age of 21 hours (range, 18-49 hours), and patients were treated for median of 70 hours (range, 23-136). Oxygenation index was significantly reduced after milrinone treatment, particularly in the immediate 24 hours of treatment (8.0 +/- 6.6, P < .001). There was a significant improvement in heart rate (179 +/- 15.2 vs 149.6 +/- 22.4, P < .001) over the same period. Infants who received milrinone did not develop systemic hypotension; in fact, there was a nonsignificant trend toward improved blood pressure. CONCLUSIONS: Intravenous milrinone produces early improvements in oxygenation without compromising systemic blood pressure.

Hypoplastic left heart syndrome with intact atrial septum--attempt of an interventional palliation by ductal and interatrial stent implantation.

In patients with hypoplastic left heart syndrome (HLHS) and intact atrial septum, the blood entering the left atrium cannot egress. Emergency treatment interventionally or surgically is mandatory immediately after birth. We describe a patient with HLHS and intact atrial septum who underwent successful transvenous atrial septostomy immediately after birth. When the interatrial communication became restrictive, stent implantation into the arterial duct and into the atrial septum was performed on the 7th day of life. Despite good hemodymanic response, the lung damage was severe and persistent, rendering staged surgical correction impossible. The child died on the 23rd day of life. Autopsy showed patent and correct placed stents in the duct and the atrial septum. There was severe dilatation of pulmonary lymphatic and venous vessels, suggestive of long-standing pulmonary venous hypertension. In conclusion, this form of HLHS has a poor prognosis despite early and aggressive interventional treatment.

Serendipitous diagnosis of infracardiac total anomalous pulmonary venous return by umbilical venous catheter blood gas samples.

Total anomalous pulmonary venous return (TAPVR) is a rare congenital heart defect that occurs when all four pulmonary veins connect to the systemic venous circulation. We describe a full-term male neonate who presented with cyanosis and mild tachypnea shortly after birth. One umbilical artery and the umbilical vein were catheterized, and oxygen treatment was provided. Four echocardiograms indicated severe pulmonary hypertension and were negative for any congenital heart defects. After the umbilical artery catheter was removed, high partial pressure of oxygen was detected in blood samples drawn from the umbilical venous catheter that was positioned below the diaphragm. Based on this finding, TAPVR was suspected and confirmed with angiography through a central venous catheter. The neonate underwent a successful surgical repair to correct the cardiac defect.