Pulmonary Hypoplasia Research Articles

Prediction of neonatal survival according to lung-to-head ratio in fetuses with right congenital diaphragmatic hernia (CDH): A multicentre study from the Latin American CDH Study Group registry.

To evaluate survival outcomes of fetuses with right sided congenital diaphragmatic hernia (CDH) treated in Latin American centres and to assess the utility of left lung area to predict neonatal survival. A retrospective cohort including isolated right sided CDH cases managed expectantly during pregnancy in six tertiary centers from five Latin American countries. The utility of the observed/expected lung-to-head ratio (O/E-LHR) in predicting neonatal survival was assessed, and the best cut-off to predict prognosis was automatically selected by decision tree analysis. A total of 99 right sided CDH cases were recruited, 58 isolated fetuses were selected at a median gestational age of 26.2weeks, showing an overall survival rate of 26.2%. A linear trend was observed between survival and the O/E-LHR, showing that at higher O/E-LHR, the greater probability of survival (r=0.56, p<0.001). O/E-LHR discriminates two groups with different survival outcomes: fetuses with an O/E-LHR ≥65% showed a significantly higher survival rate than those with an O/E-LHR <65% (81.8% vs. 15.6%, p<0.01). Overall survival rate in right sided CDH is lower in Latin American countries. The severity category of pulmonary hypoplasia should be classified according to lung area and the survival rate in such population.

Prenatal Diagnosis of a Lethal Skeletal Dysplasia.

Prenatal Diagnosis of a Lethal Skeletal Dysplasia.

A case of congenital diaphragmatic hernia with malrotation of gut, delayed presentation in adult

Congenital diaphragmatic hernia (CDH), which mainly occurs in the new born or in childhood with severe respiratory distress and is associated with high mortality, is rarely found in adult. Pulmonary hypoplasia and pulmonary hypertension contribute to the high mortality and morbidity due to CDH. These patients adjust their lifestyle to manage symptoms associated with frank herniation of the large bowel, omentum, and other viscera inside the diaphragmatic hernia. We report a 25-year-old male who presented with shortness of breath on exertion diagnosed as having CDH. The disease was detected using chest X-ray (CXR) and was confirmed on contrast enhanced CT scan. A defect was noted in the posterolateral right diaphragm with omentum, small bowel, caecum, appendix, and colon herniating through it with malrotation (incomplete rotation) of gut. CT scan and CXR were the two useful methods in diagnosis of CDH in this patient, but sometimes becomes challenging because of rare incidence and types prior to surgery. For better outcome of CDH patients long term follow up and more investigations are needed. In some cases, where conventional CT scan and ultrasonography fails to diagnose a case of CDH &amp; malrotation of gut, diagnostic laparoscopy plays a key role in facing such situations. Keywords: diaphragmatic hernia; malrotation of gut

Challenging Management of Pulmonary Regurgitation in an Adult Patient With Tetralogy of Fallot and Pulmonary Arterial Hypertension

Abstract Pulmonary regurgitation following correction of tetralogy of Fallot (ToF) is a common postoperative complication associated with progressive right ventricular (RV) enlargement and dysfunction, and is an important determinant of late morbidity and mortality. Usually, pulmonary regurgitation is well tolerated for many years following surgery, but it can lead to progressive exercise intolerance, heart failure, tachyarrhythmias, late sudden death requiring often re-intervention. The appropriate timing of such intervention can be a challenging topic given the risk of prosthetic valve degeneration, the increased risk of reoperation and the decision depends on assessment of right ventricle size and function. Pulmonary hypertension (PH) is not an usual finding in ToF patient and it can be caused by pulmonary agenesis, hypoplasia and/or thrombosis, residual ventricular septal defect, or a large prior systemic-to-pulmonary shunt. Association of pulmonary arterial hypertension in a patient with ToF and pulmonary regurgitation who needs valve correction involves higher surgical risks and the management must be taken in a multidisciplinary team.

Natural history of a complex congenital diaphragmatic hernia

The main complication in the case of congenital diaphragmatic hernia (CDH), which results from the invasion of the abdominal viscera in the thoracic cavity, is represented by the insufficient development of the pulmonary parenchyma (pulmonary hypoplasia, with the increase of the vascular resistance, and finally pulmonary hypertension). Besides pulmonary hypertension, the fetus can also develop cardiac failure in various degrees. Usually, this occurs when the arterial canal closes. We present a completely prenatal diagnosed case of left diaphragmatic hernia of the stomach, liver, and intestinal loops associated with left pulmonary agenesis and stenosis of arterial duct. The important right shifting of the heart in the right hemithorax detected on second trimester ultrasound screening has complicated in the third trimester with pericarditis, pleurisy and heart failure. The magnetic resonance imaging (MRI) examination at 31 weeks of gestation confirmed the ultrasound findings and offered more detailed prognostic elements of the anomaly. Autopsy of the stillbirth sustained MRI diagnosis regarding the absence of the left lung parenchyma and stenosis of the arterial duct. The natural history of this complex malformation underlies the importance of the collaboration of multiple specialists in maternal-fetal medicine, fast fetal MRI, fetal therapy, prenatal genetics, and fetal pathology.

Abstract 12213: Exercise Induced Pulmonary Hypertension in Long Term Survivors of Congenital Diaphragmatic Hernia

Introduction: Survivors of congenital diaphragmatic hernia (CDH) are at risk of pulmonary hypertension (PH) due to pulmonary hypoplasia and other pulmonary vascular abnormalities. Hypothesis: Exercise stress echocardiography (ESE) may detect PH, not apparent on echocardiography at rest, in children and young adults with repaired CDH. Methods: Single center retrospective cohort study of all CDH survivors who underwent ESE at Boston Children’s Hospital (January 2006 – June 2020). Severity of PH was assessed at baseline and after exercise. Patients were assigned to one of two categories based on right ventricular pressure: group 1: no or mild PH after exercise; and group 2: moderate or severe PH after exercise (right ventricular pressure ≥ 60 mmHg or ≥ ½ systemic blood pressure). Results: During the study period 84 CDH patients (70% male) underwent 173 ESE with a median age 8.1 (4.8 – 19.1) years at first ESE. Sixty-four patients were classified as group 1, 11 as group 2, and 9 were unable to be classified due to inconclusive ESE. Moderate to severe PH after exercise was found in 8 (10%) patients with no or mild PH at rest. Risk factors for PH after exercise included larger CDH defect size, patch repair, use of extracorporeal membrane oxygenation, and supplemental oxygen at discharge in univariate analysis (Table 1). Exercise and pulmonary function test parameters associated with a group 2 test included higher VE/VCO2 slope, lower peak oxygen saturation, and lower percent predicted FEV1 and FEV1/FVC ratio. Nine of 11 group 2 patients had a change in management based on ESE. PH was found in all 5 group 2 patients with cardiac catheterization after ESE, including 3 patients with no or mild PH on baseline ESE. Conclusions: Among long term CDH survivors, ESE identified 10% with moderate-severe exercise induced PH indicating ongoing pulmonary vascular abnormalities. Further studies are needed to optimally define screening and treatment for patients with repaired CDH.

Matthew-Wood Syndrome in Monochorionic, Diamnionic Twins.

Matthew-Wood syndrome represents a rare genetic disorder characterized by diaphragmatic defects, pulmonary hypoplasia, micro- or anophthalmia, and cardiac defects. Most cases are lethal with very few infants living beyond a few years of life. Siblings with this diagnosis have been reported but never twins. In this article, we provided a review and discussion of this syndrome following its presentation in monochorionic, diamnionic twin females.

Bi-allelic loss-of-function variants in KIF21A cause severe fetal akinesia with arthrogryposis multiplex

BackgroundFetal akinesia (FA) results in variable clinical presentations and has been associated with more than 166 different disease loci. However, the underlying molecular cause remains unclear in many individuals. We...

Fetal lung development via quantitative biomarkers from diffusion MRI and histological validation in rhesus macaques.

To demonstrate sensitivity of diffusion-weighted MRI (DW-MRI) to pulmonary cellular-space changes during normal in utero development using fetal rhesus macaques, compared to histological biomarkers. In vivo/ex vivo DW-MRI was acquired in 26 fetal rhesus lungs (early-canalicular through saccular stages). Apparent diffusion coefficients (ADC) from MRI and tissue area density (H&E), alveolar type-II cells (ABCA3), and epithelial cells (TTF1) from histology were compared between gestational stages. In vivo/ex vivo ADC correlated with each other (Spearman ρ = 0.47, P = 0.038; Bland-Altman bias = 0.0835) and with area-density (in vivo ρ = -0.56, P = 0.011; ex vivo ρ = -0.83, P < 0.0001). In vivo/ex vivo ADC increased exponentially toward saturation with gestational stage (R2 = 0.49/0.49), while area-density decreased exponentially (R2 = 0.53). ABCA3 and TTF1 stains demonstrated expected fetal cellular development. Fetal DW-MRI provides a non-invasive biomarker for pulmonary structural maturation, with a strong correlation to histological markers during tissue development in rhesus macaques. This method has strong potential for assessing human fetal development, particularly in patients with pulmonary hypoplasia.

Fetal therapy of LUTO (lower urinary tract obstruction) – a follow-up observational study

Purpose Fetal megacystis (MC) can be severe and is mainly caused by fetal lower urinary tract obstruction (LUTO). Mortality of fetal LUTO can be high as a result of pulmonary hypoplasia and/or (chronic) renal insufficiency. Several technical procedures for vesicoamniotic shunting (VAS) were developed to improve fetal MC outcomes. Material and methods We present the outcome of nine fetuses with MC who received VAS in the prenatal period (14 + 6 to 27 + 6 weeks GA) using the Somatex® intrauterine shunt system. MC was defined as an increased longitudinal measurement of the bladder >15 mm. The median follow-up time after birth was 18 months. Results Eight Fetuses had uncomplicated VAS intervention. One case developed PPROM 24 h after VAS leading to abortion. Pregnancy was later terminated in further two cases. All six live-born infants received intensive care treatment. Invasive-mechanical ventilation was necessary in one case who died 24 h post-partum of severe cardiac depression. Five infants who survived the follow-up time developed chronic renal insufficiency (CRI), with one infant developing end-stage renal failure requiring peritoneal dialysis. Conclusion Overall, 5 of 9 LUTO fetuses (55%) undergoing VAS with the Somatex® intrauterine shunt system showed long-term survival beyond the neonatal period of 28 d (5/9; 55%) with varying morbidity.

Right Upper Lobe Pulmonary Hypoplasia

Right Upper Lobe Pulmonary Hypoplasia

Congenital diaphragmatic hernia: asingle-centre experience at Kepler University Hospital Linz.

Congenital diaphragmatic hernia (CDH) is found in about 1 of 3000 live births and is often complicated by pulmonary hypoplasia and alteration of the pulmonary arterial wall with resulting pulmonary hypertension. Since 2005, with the fusion of the children’s hospital and the maternity clinic of the Kepler University Hospital Linz, affected neonates have been treated according to a standard protocol at our perinatal centre. Some prenatally measured parameters have been used to predict mortality, e.g., observed-to-expected lung-to-head ratio or lung volume measurements by nuclear magnetic resonance imaging. We performed a retrospective chart review of 67 new-borns with CDH treated at our institution to detect any predictors of hospital mortality from parameters routinely collected within the first 24 h of life. The term “liver up” was identified as a predictor of hospital mortality; OR 9.2 (95% CI 1.9–51.1, p = 0.002, sensitivity 79%, specificity 71%). In addition, the need for application of high-frequency oscillatory ventilation during the first 24 h was associated with mortality; OR 44.4 (95% CI 6.3–412.1, p = 0.001, sensitivity 85.7%, specificity 88%).

A CASE OF RECURRENT PNEUMOTHORACES IN A NEWBORN

TOPIC: Pediatrics TYPE: Fellow Case Reports INTRODUCTION: Recurrent pneumothroaces (PTX) is an uncommon presentation in the newborn period, often associated with prematurity or ventilator use. This is a case of rapidly progressive cystic disease in the setting of an absent right pulmonary artery. CASE PRESENTATION: Patient is a 18do female, ex-37 weeks gestation, with negative prenatal history. Noted at birth to have meconium aspiration at birth, cyanosis and non-invasive positive pressure ventilation (PPV) at 9 hours of life. CXR showed R PTX, that was resolved with chest tubes and discharged on day of life (DOL) 11. Presented on DOL) 17 with respiratory distress and was found to have a PTX. Chest CT showed R PTX with cystic foci in all three lobes thought to be related to pulmonary interstitial emphysema (PIE). Cardiothoracic surgery felt patient was too young for surgery and recommended more conservative management. Presented on DOL 27 with recurrrent PTX and then again at 3 months of life. Chest CT at this time showed a absent R pulmonary artery not previously recognized. ECHO confirmed absence of R PA. Patient underwent R pneumonectomy with mediastinal tent placement. Pathology showed pneumatoceles in lower lobes, focal areas of dysplastic lung development, absent large hilar pulmonary arteries, lymphangiectasis and pleural fibrosis. Cytology showed few multinucleated giant cells and fibroblastic proliferation along pneumatocele wall. DISCUSSION: Air leak syndromes such as PTX and PIE are more common in neonates with prematurity, need for PPV, meconium aspiration, and pulmonary hypoplasia. The presence of meconium aspiration and need for PPV likely contributed to the initial pulmonary insult that led to her clinical picture. Persistent PIE can associated with multiple large pseudocysts. Presence of multinucleated giant cells with fibroblast proliferation in cytology further supports presence of persistent PIE. In addition the unilateral absence of the R pulmonary artery (UAPA) can contribute to hypoperfusion and hypoplasia. This can subsequently lead to the cystic development especially when there are multiple other insults to the lung as seen in this patient. Post-pneumonectomy complications include concern for development of pulmonary hypertension as well as complication related to the post-pneumonectomy space, such as mediastinal shift causing compression of the airways. CONCLUSIONS: Recurrent PTX can be due to a wide variety of etiologies based on patient's age and presentation. This case highlights recurrent PTX in a neonate in the setting of cystic lung disease that is likely from persistent PIE with further contribution from a unilaterally absent pulmonary artery. REFERENCE #1: Jeng, M.J., Lee, Y.S., Tsao, P.C. & Soong, W.J. Neonatal air leak syndrome and the role of high-frequency ventilation in its prevention. J Chin Med Assoc 75, 551-559 (2012). REFERENCE #2: Agrons, G.A., Courtney, S.E., Stocker, J.T. & Markowitz, R.I. From the archives of the AFIP: Lung disease in premature neonates: radiologic-pathologic correlation. Radiographics 25, 1047-1073 (2005). REFERENCE #3: Kruzliak, P., Syamasundar, R.P., Novak, M., Pechanova, O. & Kovacova, G. Unilateral absence of pulmonary artery: pathophysiology, symptoms, diagnosis and current treatment. Arch Cardiovasc Dis 106, 448-454 (2013). DISCLOSURES: No relevant relationships by Ashish George, source=Web Response no disclosure on file for Robin Ortenberg; No relevant relationships by Swaroop Pinto, source=Web Response

REFRACTORY HYPOXEMIA IN A NONAGENARIAN WITH PATENT FORAMEN OVALE MANAGED MEDICALLY

TOPIC: Pulmonary Vascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Patent foramen ovale (PFO) is a cardiac defect with a prevalence of 25-30%, which notably decreases with age. A study done in 2018 showed an increased incidence of PFO in patients with pulmonary hypertension (pHTN). It is suggested that the presence of PFO in these individuals is a reflection of dilated and dysfunctional right atrium and ventricles, leading to an increased right to left gradient, stretching open a communication between the two atria. CASE PRESENTATION: We present a 96 year old female with heart failure with preserved ejection fraction, chronic respiratory failure secondary to moderate persistent asthma, on 4L of O2 at baseline, recurrent venous thromboembolic disease on apixaban, severe untreated OSA, initially admitted for septic shock due to acute cholecystitis requiring percutaneous cholecystostomy and broad spectrum antibiotics. On admission she also had significant hypoxia with cyanosis requiring intubation. The level of hypoxia was discordant with the clinical picture, with chest x-ray only showing atelectasis. She was extubated to high flow nasal cannula five days later, however we faced challenges in weaning her oxygen requirements. She received systemic steroids, anticoagulation and diuresis without improvement. Subsequently, the patient underwent an echocardiogram that showed a pulmonary artery systolic pressure (PASP) of 79mmHg (previously 47 mmHg in a study done 8 months ago). Given the degree of hypoxia and associated increase in PASP, intracardiac shunting was suspected. A repeat TTE with bubble study confirmed the presence of a small PFO. We discussed surgical closure, however invasive measures were deferred given her advanced age. Instead, the patient was treated with short acting diltiazem every 6 hours and furosemide daily with the goal of reducing pulmonary pressures and R to L shunting of deoxygenated blood. Although diltiazem is associated with negative outcomes in patients with heart failure, there was no evidence of pulmonary vascular congestion, and the immediate benefit outweighed the risk. Many days after initiating our plan, her oxygen requirements suddenly dropped from 60L/min to 4L/min and we were able to discharge her successfully. DISCUSSION: It is postulated that sepsis can lead to pHTN from elevated pulmonary vascular resistance through various mechanisms. Opening of PFO in severe pHTN is a common occurrence - resulting in resistive hypoxemia. Although we lack definitive evidence without right heart catheterization, we were able to exclude other etiologies of hypoxia through trial and error, strengthening our theory that PFO was the main driver of the clinical presentation. CONCLUSIONS: To summarize, hypoxia due to intracardiac shunting is an important cause of hypoxia, not to be missed on our list of differential diagnoses, with timely identification and appropriate therapy being the key to positive outcomes. REFERENCE #1: Sharan L, Stackhouse K, Awerbach JD, Bashore TM, Krasuski RA. Effect of Patent Foramen Ovale in Patients With Pulmonary Hypertension. Am J Cardiol. 2018 Aug 1;122(3):505-510. doi: 10.1016/j.amjcard.2018.04.014. Epub 2018 May 1. PMID: 30201113. REFERENCE #2: William J. Sibbald, NigelA.M. Paterson, Ronald L. Holliday, Richard A. Anderson, Trevor R. Lobb, John H. Duff, Pulmonary Hypertension in Sepsis: Measurement by the Pulmonary Arterial Diastolic-Pulmonary Wedge Pressure Gradient and the Influence of Passive and Active Factors, Chest, Volume 73, Issue 5, 1978, Pages 583-591, ISSN 0012-3692, https://doi.org/10.1378/chest.73.5.583. REFERENCE #3: Islam S, Masiakos P, Schnitzer JJ, Doody DP, Ryan DP. Diltiazem reduces pulmonary arterial pressures in recurrent pulmonary hypertension associated with pulmonary hypoplasia. J Pediatr Surg. 1999 May;34(5):712-4. doi: 10.1016/s0022-3468(99)90361-5. PMID: 10359169. DISCLOSURES: No relevant relationships by Maryam Ahmed, source=Web Response No relevant relationships by Robert McDonald, source=Web Response

Intrapulmonary artery Doppler to predict mortality and morbidity in fetuses with mild or moderate left-sided congenital diaphragmatic hernia.

In fetuses with isolated left-sided congenital diaphragmatic hernia (LCDH), prenatal detection of severe pulmonary hypoplasia is important, as fetal therapy can improve survival. Cases with mild or moderate lung hypoplasia still carry a considerable risk of mortality and morbidity, but there has been less interest in the accurate prediction of outcome in these cases. In this study of fetuses with mild or moderate isolated LCDH, we aimed to investigate: (1) the association between intrapulmonary artery (IPA) Doppler findings and mortality at discharge; (2) whether adding IPA Doppler findings improves the prediction of mortality based on lung size and liver herniation; and (3) the association between IPA Doppler findings and early neonatal morbidity. This was a retrospective study of all consecutive fetuses assessed at the BCNatal and UZ Leuven hospitals between 2008 and 2020 with a prenatal diagnosis of isolated, non-severe LCDH, defined as observed-to-expected lung-to-head ratio (o/e-LHR) > 25%, that were managed expectantly during pregnancy followed by standardized neonatal management. An additional inclusion criterion was the availability of IPA Doppler measurements. The primary outcome was the association between IPA Doppler findings and mortality at discharge. Other predictors included o/e-LHR, liver herniation and gestational age at birth. Secondary outcomes were the association between IPA Doppler findings and the presence of pulmonary hypertension (PHT), need for supplemental oxygen at discharge and need for extracorporeal membrane oxygenation. IPA pulsatility index (PI) values were converted into Z-scores. Logistic regression analysis was performed to investigate the associations between predictor variables and outcome, and the best model was chosen based on the Nagelkerke R2 . Observations for 70 non-severe LCDH cases were available. Fifty-four (77%) fetuses survived until discharge. On logistic regression analysis, higher IPA-PI was associated with an increased risk of mortality (odds ratio (OR), 3.96 (95% CI, 1.62-9.70)), independently of o/e-LHR (OR, 0.87 (95% CI, 0.79-0.97)). An IPA-PI Z-score cut-off of 1.8 predicted mortality with a detection rate of 69% and specificity of 93%. Adding IPA-PI to o/e-LHR improved significantly the model's performance (Nagelkerke R2 , 46% for o/e-LHR + IPA-PI vs 28% for o/e-LHR (P < 0.002)), with a detection rate of 81% at a 10% false-positive rate. IPA-PI was associated with PHT (OR, 2.20 (95% CI, 1.01-4.59)) and need for oxygen supplementation at discharge (OR, 1.90 (95% CI, 1.10-3.40)), independently of lung size. In fetuses with mild or moderate LCDH, IPA-PI was associated with mortality and morbidity, independently of lung size. A model combining o/e-LHR with IPA-PI identified up to four in five cases that eventually died, despite being considered to have non-severe pulmonary hypoplasia. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

VP16.14: Diagnosis of short rib polydactyly syndrome type IV (Beemer‐Langer syndrome): a case report

Short rib-polydactyly syndrome (SRPS) is a rare congenital autosomal recessive inherited disease classified in four subtypes. Prenatal ultrasonography findings and postnatal examinations may help classify in one of four subtypes. We present a case of an infant who presented multiple congenital anomalies and the postnatal radiography helped to classify the SRPS as type IV (Beemer-Langer). A 23-year-old was referred for prenatal ultrasound which showed cystic hygroma, small omphalocele and choledocal cyst. Chromosomal analysis revealed a normal male karyotype. Morphological scan revealed small thorax, short ribs, micromelic shortening of limbs with the tibia slightly longer than the fibula, unilateral clubfoot, hidrocephalus and renal hiperechogenicity. Magnetic Resonance performed at 35 weeks revealed micrognathia and mesenteric lymphangioma. The infant delivered at 38 weeks of gestation and died within 60 minutes due to respiratory failure. Postmortem radiography showed marked shortening of all long bones, strikingly narrow thorax with short and horizontal ribs, highly placed clavicles, small scapulae, small ilia and the tibia was longer then the fibula. Identification of the SRPS subtype can be difficult due to overlap of clinical and pathologic findings. This case may help understanding Beemer-Langer type's phenotypic features such as micrognathia, cleft lip, hydrops, hydrocephalus and omphalocele. The most common radiological findings include narrow thorax with short ribs, short tubular bones, highly placed clavicle, small scapulae and ilia and bowing of radius and ulna with the tibia being longer than the fibula. The prognosis of Beemer-Langer syndrome is poor as infants usually die shortly after birth because of respiratory failure secondary to marked pulmonary hypoplasia.

Deficiency in pigment epithelium-derived factor accelerates pulmonary growth and development in a compensatory lung growth model.

Children with hypoplastic lung disease associated with congenital diaphragmatic hernia (CDH) continue to suffer significant morbidity and mortality secondary to progressive pulmonary disease. Recently published work from our lab demonstrated the potential of Roxadustat (FG-4592), a prolyl hydroxylase inhibitor, as a treatment for CDH-associated pulmonary hypoplasia. Treatment with Roxadustat led to significantly accelerated compensatory lung growth (CLG) through downregulation of pigment epithelium-derived factor (PEDF), an anti-angiogenic factor, rather than upregulation of vascular endothelial growth factor (VEGF). PEDF and its role in pulmonary development is a largely unexplored field. In this study, we sought to further evaluate the role of PEDF in accelerating CLG. PEDF-deficient mice demonstrated significantly increased lung volume, total lung capacity, and alveolarization compared to wild type controls following left pneumonectomy without increased VEGF expression. Furthermore, Roxadustat administration in PEDF-deficient mice did not further accelerate CLG. Human microvascular endothelial lung cells (HMVEC-L) and human pulmonary alveolar epithelial cells (HPAEC) similarly demonstrated decreased PEDF expression with Roxadustat administration. Additionally, downregulation of PEDF in Roxadustat-treated HMVEC-L and HPAEC, a previously unreported finding, speaks to the potential translatability of Roxadustat from small animal studies. Taken together, these findings further suggest that PEDF downregulation is the primary mechanism by which Roxadustat accelerates CLG. More importantly, these data highlight the critical role PEDF may have in pulmonary growth and development, a previously unexplored field.

Predicting neonatal outcomes in infants with giant omphalocele using prenatal magnetic resonance imaging calculated observed-to-expected fetal lung volumes.

To examine the association between prenatal magnetic resonance imaging (MRI) based observed/expected total lung volume (O/E TLV) and outcome in neonates with giant omphalocele (GO). Between 06/2004 and 12/2019, 67 cases with isolated GO underwent prenatal and postnatal care at our institution. MRI-based O/E TLVs were calculated based on normative data from Meyers and from Rypens and correlated with postnatal survival and morbidities. O/E TLV scores were grouped based on severity into <25% (severe), between 25% and 50% (moderate), and >50% (mild) for risk stratification. O/E TLV was calculated for all patients according to Meyers nomograms and for 49 patients according to Rypens nomograms. Survival for GO neonates with severe, moderate, and mild pulmonary hypoplasia based on Meyers O/E TLV categories was 60%, 92%, and 96%, respectively (p=0.04). There was a significant inverse association between Meyers O/E TLV and risk of neonatal morbidities (p<0.05). A similar trend was observed with Rypens O/E TLV, but associations were less often significant likely related to the smaller sample size. Neonatal outcomes are related to fetal lung size in isolated GO. Assessment of Meyers O/E TLV allows identification of GO fetuses at greatest risk for complications secondary to pulmonary hypoplasia.

The novel fetal MRI O/E CLV versus O/E LHR in predicting prognosis in congenital diaphragmatic hernias: can we teach an old dog new tricks?

In congenital diaphragmatic hernia (CDH), ultrasound (U/S) measurements of the contralateral lung commonly provide the observed-to-expected lung-to-head ratio (O/E LHR) and are used to determine the severity of pulmonary hypoplasia. Fetal magnetic resonance imaging (MRI) measurement of the observed-to-expected total lung volume (O/E TLV) has been used as an adjunct to O/E LHR in predicting outcomes. Since O/E LHR only measures the contralateral lung, we sought to investigate if MRI measurements of the contralateral lung volume (O/E CLV) can accurately predict outcomes in CDH. We hypothesize that O/E CLV is a better predictor of CDH outcomes than O/E LHR. We identified all infants with a prenatal diagnosis of CDH at our fetal center who had both MRI and U/S measurements. Using lung volume ratios of right-left 55:45, we calculated O/E CLV from O/E TLV. We used receiver-operating characteristic (ROC) curves to calculate the area under the curve (AUC) to compare the predictive accuracy of O/E CLV to O/E LHR for ECMO support, as well as survival to both discharge and 1 year. Seventy-four patients had complete prenatal imaging with 39% requiring ECMO support. The median O/E CLV was 48.0% and the median O/E LHR was 42.3%. O/E CLV was a better predictor of the need for ECMO support (AUC 0.81 vs. 0.74). O/E CLV was a better predictor of survival to discharge (AUC 0.84 vs. 0.64) and 1-year survival (AUC 0.83 vs. 0.63) than O/E LHR. O/E LHR is a well-validated standard for predicting outcomes and guiding prenatal counseling in CDH. We provide evidence that fetal MRI measurements of the contralateral lung volume corrected for gestational age were more accurate in predicting the need for ECMO and survival. Future prospective studies validating O/E CLV regarding outcomes and ECMO utilization are warranted. Level III, retrospective comparative study.

Bladder outlet obstruction

Bladder outlet obstruction