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We aimed to investigate the clinical characteristics and outcomes of patients with isolated left-sided congenital diaphragmatic hernia (CDH) who developed preoperative pneumothorax and determine its risk factors. We performed an international cohort study of patients with CDH enrolled in the Congenital Diaphragmatic Hernia Study Group registry between January 2015 and December 2020. The main outcomes assessed included survival to hospital discharge and preoperative pneumothorax development. The cumulative incidence of pneumothorax was estimated by the Gray test. The Fine and Gray competing risk regression model was used to identify the risk factors for pneumothorax. Data for 2858 neonates with isolated left-sided CDH were extracted; 224 (7.8%) developed preoperative pneumothorax. Among patients with a large diaphragmatic defect, those with pneumothorax had a significantly lower rate of survival to discharge than did those without. The competing risks model demonstrated that a patent ductus arteriosus with a right-to-left shunt flow after birth (hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.21–2.63; p = 0.003) and large defects (HR: 1.65; 95% CI: 1.13–2.42; p = 0.01) were associated with an increased risk of preoperative pneumothorax. Significant differences were observed in the cumulative incidence of pneumothorax depending on defect size and shunt direction (p < 0.001). Pneumothorax is a significant preoperative complication associated with increased mortality in neonates with CDH, particularly in cases with large defects. Large diaphragmatic defects and persistent pulmonary hypertension were found to be risk factors for preoperative pneumothorax development. LEVEL Ⅲ Retrospective Comparative Study. What is currently known about this topic? • The few cohort studies assessing the impact of pneumothorax on mortality and morbidity have demonstrated that pneumothorax is more likely to develop in patients with CDH with large defects and is a fatal complication. What new information is contained in this article? • Large diaphragmatic defects and persistent pulmonary hypertension were found to be risk factors for preoperative pneumothorax development. • Pneumothorax is significantly associated with a large diaphragmatic defect and adverse outcomes. [ABSTRACT FROM AUTHOR]

Neonates with symptomatic tetralogy of Fallot (sTOF) with hypoplastic pulmonary arteries (hPA) are considered high risk. Data are needed to inform the impact of hPA on outcomes, and the ideal management strategy. The objectives of this study were to quantify the impact of hPA on outcomes in neonates with sTOF and measure the impact of strategy on pulmonary artery (PA) growth in this population. Neonates with sTOF from 2005 to 2017 were reviewed from the Congenital Cardiac Research Collaborative. Criteria for hPA included a unilateral PA z score <−2.0 and contralateral PA z score <0. Primary outcome was mortality. Secondary outcomes included reintervention and PA growth. We included 542 neonates with sTOF, including 188 (35%) with hPA and 354 (65%) with normal PA, with median follow-up of 4.1 years. Median right and left hPA z scores were −2.19 (25th-75th percentile: −2.55 to −1.94) and −2.23 (25th-75th percentile: −2.64 to −1.91), respectively. Staged repair (vs primary TOF repair) was less common in the hPA cohort (36 vs 44%; P = 0.07). Survival was similar between groups (unadjusted P = 0.16; adjusted P = 0.25). Reintervention was more common in the hPA group (HR: 1.28; 95% CI: 1.01-1.63; P = 0.044); there was no difference after definitive repair (HR: 1.21; 95% CI: 0.93-1.58; P = 0.16). PA growth at 1 year was greater in the hPA cohort, particularly for the right PA (P < 0.001). Despite perception, the presence of hPA in neonates with sTOF conferred no increase in overall hazard of mortality or reintervention after definitive repair. PA growth was superior in the hPA cohort. These findings suggest that the presence of hPA does not adversely impact outcomes in sTOF. [Display omitted] [ABSTRACT FROM AUTHOR]

Lower urinary tract obstruction (LUTO) is a rare birth defect with a prevalence between 1 in 5,000 and 1 in 25,000 pregnancies. LUTO is one of the most common causes of congenital abnormalities of the renal tract. Several genetic conditions have been associated with LUTO. Most common causes of LUTO are posterior urethral valves and urethral atresia. Despite available prenatal and postnatal treatments, LUTO is a significant cause of morbidity and mortality in newborns causing significant end stage renal disease and pulmonary hypoplasia. [ABSTRACT FROM AUTHOR]

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Objective: While preterm premature rupture of membranes complicates an estimated 3 % of pregnancies, rupture near the limit of fetal viability is rarer (estimated 0.04 %). This study aimed to analyze maternal and neonatal outcomes in patients with premature preterm rupture of membranes (PPROM) before 20 0/7 weeks of pregnancy with the goal of identifying potential outcome predictors.Study Design: This retrospective cohort study examined 60 patients with preterm premature rupture of membranes before 20 0/7 weeks of pregnancy from 01/01/2008 through 12/31/2018 in a university hospital setting. Two patients were excluded from analysis due to fetal kidney dysplasia. Multiples (5 twins, 2 triplets) were excluded. The remaining 51 cases were analyzed.Results: Thirty-three patients (Range 12 5/7 weeks to 19 2/7 weeks) medically terminated pregnancy (64.7 %). Ten patients spontaneously aborted (19.6 %). Fifteen patients were diagnosed with intraamniotic infection (29.4 %). Neonatal mortality was 28.6 %% (one case of pulmonary hypoplasia). The baby take home rate was 9.8 % (27.8 % after excluding medical terminations) after a mean prolongation of 92.9 days. Neonatal morbidity included respiratory distress syndrome (57.1 %), infection (100 %, including all cases (direct postpartum and during admission), one case of sepsis), pulmonary hypoplasia (42.9 %), pulmonary hypertension (28.6 %), bronchopulmonary dysplasia (14.3 %), and sepsis combined pneumonia (14.3 %). 57.1 % of the infants could be discharged without severe morbidity and 80 % of the survivors had normal development at two and four years.Conclusion: Anhydramnios combined with low gestational age at PPROM appear to negatively influence neonatal outcome after pre-viable preterm premature rupture of membranes. The incidence of neonatal complications decreased with increasing gestational age. Survival without long term severe morbidity is possible. Maximal therapy is an interdisciplinary decision and the patients should be counseled accordingly. Delivery in centers where potential postnatal complications including pulmonary hypoplasia, severe bronchopulmonary dysplasia and respiratory distress syndrome can be aggressively treated is recommended. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) is a life-threatening birth defect with significant morbidity and mortality. The prenatal management of a pregnancy with a fetus affected with CDH is complex and requires a multi-disciplinary team approach. An improved understanding of prenatal diagnosis and management is essential to developing strategies to optimize outcomes for these patients. In this review, we explore the current knowledge on diagnosis, severity stratification, prognostic prediction, and indications for fetal intervention in the fetus with CDH. [ABSTRACT FROM AUTHOR]

• Fetuses with congenital diaphragmatic hernia may have abnormal cerebral perfusion from decreased left-ventricular cardiac output. • Children with congenital diaphragmatic hernia are four times more likely to have neurodevelopmental impairment compared to the general population. • The fetal lamb model of congenital diaphragmatic hernia has decreased perfusion on contrast enhanced ultrasound. Neurodevelopmental impairment is common in survivors of congenital diaphragmatic hernia (CDH). Altered cerebral perfusion in utero may contribute to abnormal brain development in CDH patients. 5 fetal lambs with surgical left-CDH and 5 controls underwent transuterine cranial Doppler and contrast enhanced ultrasound (CEUS). Global and regional perfusion metrics were obtained. Biometric and perfusion data were compared between groups via nonparametric Mann Whitney U test and Spearman's rank order correlation. No significant differences in cerebral Doppler measurements were identified between groups. By CEUS, CDH animals demonstrated significantly decreased global brain perfusion and increased transit time. With focal regions-of-interest (ROIs), there was a tendency towards decreased perfusion in the central/thalamic region in CDH but not in the peripheral brain parenchyma. Transit time was significantly increased in both ROIs in CDH, whereas flux rate was decreased in the central/thalamic region but not the peripheral brain parenchyma. Biometric CDH severity was correlated to perfusion deficit. There was no difference in cardiomyocyte histology. The fetal lamb model of CDH shows altered cerebral perfusion as measured by CEUS, correlating to disease severity. This suggests a physiological abnormality in fetal cerebrovascular perfusion that may contribute to abnormal brain development and neurodevelopmental impairment in survivors. [ABSTRACT FROM AUTHOR]

Objectives: To assess the feasibility of magnetic resonance imaging (MRI) for postnatal assessment of pulmonary vascularity in infants with congenital diaphragmatic hernia (CDH).Study Design: Infants with prenatally diagnosed CDH (n = 24) received postnatal pulmonary MRI. Infants with nonpulmonary birth defects served as controls (n = 5). Semiautomatic segmentation was performed to obtain total vascular volume using time of flight images to assess vascularity.Results: Average vascular density (vascular volume/lung volume) in control infants was 0.23 ± 0.06 mm3/mm3 compared with 0.18 ± 0.06 mm3/mm3 in infants with CDH is (P = .09). When stratified further based on CDH severity, the difference between control infants and moderate CDH group was statistically significant. (0.23 mm3/mm3 vs 0.15 mm3/mm3, P = .01). Ipsilateral vascular density on MRI in infants with CDH significantly correlated with the prenatal pulmonary hypertensive index (P = .0004, Spearman R = +0.87) and with number of days on mechanical ventilation (P = .04, Spearman R = -0.44), total days on inhaled nitric oxide (P = .02, Spearman R = -0.47), use of epoprostenol for acute pulmonary hypertension (PH) (0.14 mm3/mm3 vs 0.20 mm3/mm3, P = .005), and use of sildenafil for chronic PH (0.15 mm3/mm3 vs 0.19 mm3/mm3, P = .03).Conclusions: Our results suggest that postnatal pulmonary vascularity assessed by MRI strongly correlates with prenatal and postnatal markers of PH severity and that pulmonary vascularity may serve as a direct measure of pulmonary vascular hypoplasia in infants with CDH. [ABSTRACT FROM AUTHOR]

The combination of a giant omphalocele (GO) and congenital diaphragmatic hernia (CDH) is extremely rare and results in high mortality and morbidity rates in neonates. The most difficult period for survival is the immediate postnatal period, with approximately one-third of newborns dying within the first 48 h after birth. We present the case of a newborn girl with a GO and congenital left-sided Bochdalek hernia who survived beyond the neonatal period and underwent radical surgery. The female neonate, weighing 2946 g, was delivered by scheduled Cesarean section at 37 weeks gestation. She had a left-sided Bochdalek CDH containing a small portion of the small bowel and a GO containing a large portion of the liver. There were no other associated malformations, and the pulmonary hypoplasia and pulmonary hypertension in the neonatal period were not fatal. We performed an operation to repair the diaphragmatic hernia, initially approaching it from her abdominal wall defect. We performed multiple operations to close the abdominal wall. Initially, during the neonatal period, we closed it with a skin layer; however, poor weight gain occurred afterward. Considering gastroesophageal reflux as a complication, we performed mesh-assisted abdominal wall closure and fundoplication at 10 months of age, successfully resolving the underlying disease and complications. Repair of the CDH from the abdominal wall defect provided good visual field and safer primary direct closure. Without using artificial materials in the CDH until closure of the GO avoided infection and resulted in a favorable outcome in this case. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) represents a developmental anomaly that profoundly impacts the embryonic development of both the respiratory and cardiovascular systems. Understanding the influences of developmental defects, their origins, and clinical consequences is of paramount importance for further research and the advancement of therapeutic strategies for this condition. In recent years, groundbreaking studies in the fields of metabolomics and genomics have significantly expanded our knowledge regarding the pathogenic mechanisms of CDH. These investigations introduce novel diagnostic and therapeutic avenues. CDH implies a scarcity of available information within this domain. Consequently, a comprehensive literature review has been undertaken to synthesize existing data, providing invaluable insights into this rare disease. Improved comprehension of the molecular underpinnings of CDH has the potential to refine diagnostic precision and therapeutic interventions, thus potentially enhancing clinical outcomes for CDH patients. The identification of potential biomarkers assumes paramount significance for early disease detection and risk assessment in CDH, facilitating prompt recognition and the implementation of appropriate interventions. The process of translating research findings into clinical practice is significantly facilitated by an exhaustive literature review. It serves as a pivotal step, enabling the integration of novel, more effective diagnostic and therapeutic modalities into the management of CDH patients. • Lung hypoplasia and pulmonary hypertension constitute the hallmark features of CDH. • MiRNAs may play a role in the pathogenesis of pulmonary vascular dysfunction in CDH. • MiRNAs may be possible early prenatal biomarkers of CDH. • Novel research on specific miRNAs or mitochondria as potential therapeutic targets [ABSTRACT FROM AUTHOR]

The purpose of this review is to provide ECMO outcome data for medical personnel who counsel families of patients with pulmonary hypoplasia (PH), often secondary to renal abnormalities. We report diagnoses and outcomes associated with PH in neonates that were treated with ECMO over the past 35 years. Retrospective cohort study using the ELSO database for neonates born between 1981 and 2016 with a primary or secondary diagnosis of PH. Five patient groups were created based on ICD-9 codes. Mortality rates were compared and trends over time were investigated. Thirty-three percent of the 1385 patients survived to discharge. Congenital diaphragmatic hernia (CDH) patients had significantly higher mortality than PH patients secondary to renal dysplasia (p < 0.001). Mortality decreased significantly over time for all groups (p < 0.001). The proportion of patients alive at discharge increased over time for CDH patients (p < 0.001), whereas survival decreased for patients with PH secondary to renal dysplasia (p = 0.012). Neonates with PH that require ECMO have high mortality rates, which have generally decreased over the past 35 years; however, mortality for neonates with PH secondary to renal dysplasia continues to increase. We speculate that the apparent rise in mortality for these patients is because of changes in patient selection subsequent to improvements in non-ECMO ventilatory support. II [ABSTRACT FROM AUTHOR]

Esophageal lung is rare bronchopulmonary foregut malformation where a main stem bronchus is connected anomalously to the esophagus. We present a challenging diagnostic workup of a 14-month-old who was referred following multiple complicated hospitalizations for recurrent respiratory distress. A male infant born at 37 weeks was noted to be hypoxemic at birth and subsequently diagnosed with right-sided pulmonary hypoplasia, absent right main stem bronchus, a left-sided non-obstructive pulmonary artery sling, and possible tracheal stenosis via computed tomographic angiography (CTA). After a stay in the neonatal intensive care unit for persistent hypoxemia, he was discharged home on oxygen. At 4.5 months, the patient developed severe respiratory distress requiring extracorporeal membrane oxygenation, which was complicated by a stroke. During this admission, repeat CTA showed a broncho-esophageal fistula, concerning for esophageal lung. The patient was seen in consultation at our institution at 14 months given persistent respiratory insufficiency. He underwent repeat endoscopy with our multi-disciplinary Aerodigesive Clinic, confirming mild tracheal stenosis and esophageal lung. A right pneumonectomy was recommended. During the pneumonectomy, the right bronchus was confirmed to originate from the distal esophagus on endoscopy. Intraoperative bronchoscopy showed a patent central airway and left bronchopulmonary tree. The patient recovered well post-operatively without complications and was discharged home on room air. Diagnosing esophageal lung can be difficult and requires thorough evaluation of the adjacent anatomy, oftentimes requiring multidisciplinary evaluation with multiple radiologic and endoscopic modalities. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) is a congenital malformation characterized by pulmonary hypoplasia, pulmonary hypertension, and cardiac dysfunction. Pulmonary hypertension represents the major cause of neonatal mortality and morbidity. Prenatal diagnosis allows assessment of severity and selection of foetal surgery candidates. We have shown that treprostinil, a prostacyclin analogue with an anti-remodelling effect, attenuates the relative hypermuscularization of the pulmonary vasculature in rats with nitrofen-induced CDH. Here we confirm these observations in a large animal model of surgically-created CDH. In the rabbit model, subcutaneous maternal administration of treprostinil at 150 ng/kg/min consistently reached target foetal concentrations without demonstrable detrimental foetal or maternal adverse effects. In pups with CDH, prenatal treprostinil reduced pulmonary arteriolar proportional medial wall thickness and downregulated inflammation and myogenesis pathways. No effect on alveolar morphometry or lung mechanics was observed. These findings provide further support towards clinical translation of prenatal treprostinil for CDH. • Treprostinil's antiremodeling receptors are expressed at relevant foetal age. • Treprostinil administration is well tolerated by the mother and the foetus. • Prenatal treprostinil reduces pulmonary arteriolar muscularization in pups with CDH. [ABSTRACT FROM AUTHOR]

To determine the prevalence and identify risk factors of autism spectrum disorders (ASDs) and neurodevelopmental delays in giant omphalocele (GO) survivors. The study cohort consists of 47 GO survivors enrolled in our follow-up program between 07/2004 and 12/2015. All patients underwent assessments at 2 years of age or older. Outcomes were assessed by either the Bayley Scales of Infant Development II (prior 2006) or III (after 2006), or the Wechsler Preschool and Primary Scale of Intelligence (children older than 4 years). ASD diagnosis was made based on the Diagnostic and Statistical Manual of Mental Disorders IV (prior to 2014) or 5 criteria. The prevalence of ASD in GO children is 16 times higher than the general population (P = 0.0002). ASD patients were more likely to be diagnosed with neurodevelopmental and neurofunctional delays, language disorders, and genetic abnormalities (P < 0.01). While 53.2% of GO children scored within the average range for all developmental domains, 19.1% scored within the mildly delayed and 27.7% in the severe delayed range in at least one domain. Prolonged respiratory support, pulmonary hypertension, gastroesophageal reflux disease, feeding problems, prolonged hospitalization, abnormal BAER hearing screen, presence of delayed motor coordination, and hypotonicity were associated with delayed scores (P < 0.05). There is a significant rate of ASD in GO survivors. Neurodevelopmental delays, language delays, and genetic abnormalities were strongly associated with ASD. Neurological impairments were present in nearly half of GO children. Surrogate markers of disease severity were associated with below average neurodevelopmental scores. Level of evidence Level IV [ABSTRACT FROM AUTHOR]

Microtia is a congenital malformation of the out ear, occurring either as an isolated defect or part of a specific pattern of multiple congenital anomalies. The etiology of microtia is poorly understood. Four patients with microtia and lung hypoplasia were reported by our team in a previous article. The purpose of this study was to identify the underlying genetic basis, mainly focusing on de novo copy number variations (CNVs) embedded in the noncoding region, in the four subjects. DNA samples from all four patients and their unaffected parents were extracted for whole-genome sequencing on the Illumina platform. All variants were obtained through data quality control, variant calling and bioinformatics analysis. De novo strategy was used to prioritize the variants, and candidate variants were verified by PCR amplification combined with Sanger sequencing and visual inspection of bam file. Whole gene sequencing following bioinformatics analysis showed no potential de novo pathogenic variants in the coding region. Nonetheless, four de novo CNVs in the non-coding region, intronic or intergenic, were identified in each subject, ranging in size from 10 Kb to 12.5 Kb, and all are deletions. Case 1 had a de novo deletion of 10 Kb on chromosome10q22.3, located in the intronic region of the LRMDA gene. The other three cases all had a de novo deletion in intergenic regions, located on chromosome 20q11.21, 7q31.1 and 13q12.13, respectively. This study reported multiple long-lived cases of microtia with pulmonary hypoplasia and provided genome-wide genetic analysis focusing on de novo mutations. Whether the de novo CNVs identified are responsible for the rare phenotypes remains an open question. However, the results of our study provided a new perspective that the unsolved etiology of microtia might involve in non-coding sequences, which have long been ignored. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia is surgically correctable, yet the poor lung development determines mortality and morbidity. In isolated cases the outcome may be predicted prenatally by medical imaging. Cases with a poor prognosis could be treated before birth. However, prenatal modulation of lung development remains experimental. Fetoscopic endoluminal tracheal occlusion triggers lung growth and is currently being evaluated in a global clinical trial. Prenatal transplacental sildenafil administration may in due course be a therapeutic approach, reducing the occurrence of persistent pulmonary hypertension, either alone or in combination with fetal surgery. [ABSTRACT FROM AUTHOR]

Pulmonary hypoplasia, although rare, is associated with significant neonatal morbidity and mortality. Conditions associated with pulmonary hypoplasia include those which limit normal thoracic capacity or movement, including skeletal dysplasias and abdominal wall defects; those with mass effect, including congenital diaphragmatic hernia and pleural effusions; and those with decreased amniotic fluid, including preterm, premature rupture of membranes, and genitourinary anomalies. The ability to predict severe pulmonary hypoplasia prenatally aids in family counseling, as well as obstetric and neonatal management. The objective of this review is to outline the imaging techniques that are widely used prenatally to assess pulmonary hypoplasia and to discuss the limitations of these methods. [ABSTRACT FROM AUTHOR]

Introduction The investigators hypothesized that patients with Crouzon syndrome and premature fusion of the spheno-occipital synchondrosis (SOS) more often have, or have more severe midface hypoplasia and obstructive sleep apnea (OSA). Methods A prospective cohort study was performed among patients with Crouzon syndrome to analyze SOS closure, midface hypoplasia represented by the sella-nasion angle (SNA) and OSA. Results Forty patients were included in whom the OSA-prevalence was 65%. Kaplan Meier analyses suggest a trend towards earlier closure of synchondrosis in patients with OSA (p = 0.066). The mean SNA was 74.7°. There was a positive effect of age on the SNA (p = 0.020). There was no difference in SNA for patients with an open SOS as compared to patients with a closed SOS after correction for age. Conclusions The longitudinal data are suggestive of a trend towards earlier fusion of the SOS in patients with Crouzon syndrome and OSA as compared to patients with Crouzon syndrome without OSA. Although the SNA increases with age, our results suggest that this increase in independent closure of the SOS. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) remains a major challenge and associated mortality is still significant. Patients have benefited from current therapeutic options, but most severe cases are still associated to poor outcome. Regenerative medicine is emerging as a valid option in many diseases and clinical trials are currently happening for various conditions in children and adults. We report here the advancement in the field which will help both in the understanding of further CDH development and in offering new treatment options for the difficult situations such as repair of large diaphragmatic defects and lung hypoplasia. The authors believe that advancements in regenerative medicine may lead to increase of CDH patients׳ survival. [ABSTRACT FROM AUTHOR]

Despite wide use and decades of experience, survival of congenital diaphragmatic hernia (CDH) patients treated with extra-corporeal membrane oxygenation (ECMO), as reported by the extra-corporeal life support organization (ELSO), remains unchanged at 50%. High-survival rates both with and without utilizing ECMO have been reported, fueling questions about the utility of ECMO support in this difficult population. This review looks at data from the Congenital Diaphragmatic Hernia Study Group and individual center reports, to evaluate the role of ECMO in CDH, focusing on defining the patients most likely to benefit, and discussing how those benefits can best be achieved. These data show that ECMO improves survival in those CDH patients who are most severely affected, but potential complications of ECMO delivery outweigh benefit in patients with less severely affected. Improved results can be expected by minimizing ECMO complications, and by improving rates of CDH repair in patients that require ECMO. [ABSTRACT FROM AUTHOR]

Neonates with congenital diaphragmatic hernia are among the more complex patients to support with mechanical ventilation. They have particular features that add to the difficulties already present in the neonatal patient. A ventilation strategy tailored to the patient's underlying physiology rather than mode of ventilation is a crucial issue for clinicians treating these delicate patients. [ABSTRACT FROM AUTHOR]

The outcomes of patients diagnosed with congenital diaphragmatic hernia (CDH) have recently improved. However, mortality and morbidity remain high, and this is primarily caused by the abnormal lung development resulting in pulmonary hypoplasia and persistent pulmonary hypertension. The pathogenesis of CDH is poorly understood, despite the identification of certain candidate genes disrupting normal diaphragm and lung morphogenesis in animal models of CDH. Defects within the lung mesenchyme and interstitium contribute to disturbed distal lung development. Frequently, a disturbance in the development of the pleuroperitoneal folds (PPFs) leads to the incomplete formation of the diaphragm and subsequent herniation. Most candidate genes identified in animal models have so far revealed relatively few strong associations in human CDH cases. CDH is likely a highly polygenic disease, and future studies will need to reconcile how disturbances in the expression of multiple genes cause the disease. Herein, we summarize the available literature on abnormal lung development associated with CDH. [ABSTRACT FROM AUTHOR]

Background/purpose Pulmonary hypoplasia (PH), characterized by incomplete alveolar development, remains a major therapeutic challenge associated with congenital diaphragmatic hernia (CDH). Follistatin-like 1 (Fstl1) is a crucial regulator of alveolar formation and maturation, which is strongly expressed in distal airway epithelium. Fstl1 -deficient mice exhibit reduced airspaces, impaired alveolar epithelial cell differentiation, and insufficient production of surfactant proteins similar to PH in human CDH. We hypothesized that pulmonary Fstl1 expression is decreased during alveolarization in the nitrofen-induced CDH model. Methods Timed-pregnant rats received nitrofen or vehicle on gestational day 9 (D9). Fetal lungs were harvested on D18 and D21 and divided into control −/nitrofen-exposed specimens. Alveolarization was assessed using morphometric analysis techniques. Pulmonary gene expression of Fstl1 was determined by qRT-PCR. Immunofluorescence-double-staining for Fstl1 and alveolar epithelial marker surfactant protein C (SP-C) was performed to evaluate protein expression/localization. Results Radial alveolar count was significantly reduced in hypoplastic lungs of nitrofen-exposed fetuses with significant down regulation of Fstl1 mRNA expression on D18 and D21 compared to controls. Confocal-laser-scanning-microscopy revealed strikingly diminished Fstl1 immunofluorescence and SP-C expression in distal alveolar epithelium of nitrofen-exposed fetuses with CDH-associated PH on D18 and D21 compared to controls. Conclusions Decreased expression of Fstl1 in alveolar epithelium may disrupt alveolarization and pulmonary surfactant production, thus contributing to the development of PH in the nitrofen-induced CDH model. Level of evidence 2b (Centre for Evidence-Based Medicine, Oxford). [ABSTRACT FROM AUTHOR]

Background: Appropriate post-natal growth remains a mainstay of therapeutic goals for infants with CDH, with the hypothesis that optimizing linear growth will improve survival through functional improvements in pulmonary hypoplasia. However, descriptions of growth and the effect on survival are limited in affected infants.Objective: Describe in-hospital weight gain related to survival among infants with CDH.Design/methods: Children's Hospitals Neonatal Database (CHND) identified infants with CDH born ≥34weeks' gestation (2010-14). Exclusion criteria were: admission age>7days, death/discharge age<14days, or surgical CDH repair prior to admission. Weight gain velocity (WGV: g/kg/day) was calculated using an established exponential approximation and the cohort stratified by Q1: <25%ile, Q2-3: 25-75%ile, and Q4: >75%ile. Descriptive measures and unadjusted Kaplan-Meier analyses describe the implications of WGV on mortality/discharge.Results: In 630 eligible infants, median WGV was 4.6g/kg/day. After stratification by WGV [Q1: (n=156; <3.1g/kg/day); Q2-3 (n=316; 3.1-5.9g/kg/day), and Q4 (n=158, >5.9g/kg/day)] infants in Q1 had shortest median length of stay, less time on TPN and intervention for gastro-esophageal reflux relative to the other WGV strata (p<0.01 for all). Unadjusted survival estimates revealed that Q1 [hazard ratio (HR)=9.5, 95% CI: 5.7, 15.8] and Q4 [HR=2.9, 95% CI: 1.7, 5.1, p<0.001 for both] WGV were strongly associated with NICU mortality relative to Q2-3 WGV.Conclusion: Variable WGV is evident in infants with CDH. Highest and lowest WGV appear to be related to adverse outcomes. Efforts are needed to develop nutritional strategies targeting optimal growth. [ABSTRACT FROM AUTHOR]

Objective To evaluate neurodevelopmental sequelae in congenital diaphragmatic hernia (CDH) children at 5 years of age. Materials and methods The study cohort of 35 CDH patients was enrolled in our follow-up program between 06/2004 and 09/2014. The neurodevelopmental outcomes assessed at a median of 5 years (range, 4–6) included cognition (Wechsler Preschool and Primary Scale of Intelligence [WPPSI], n = 35), Visual-Motor-Integration (n = 35), academic achievement (Woodcock-Johnson Tests of Achievement, n = 25), and behavior problems (Child Behavior Check List [CBCL], n = 26). Scores were grouped as average, borderline, or extremely low by SD intervals. Results Although mean Full (93.9 ± 19.4), Verbal (93.4 ± 18.4), and Performance (95.2 ± 20.9) IQ were within the expected range, significantly more CDH children had borderline (17%) and extremely low (17%) scores in at least one domain compared to normative cohorts ( P < 0.02). The Visual-Motor-Integration score was below population average ( P < 0.001). Academic achievement scores were similar to expected means for those children who were able to complete testing. CBCL scores for the emotionally reactive (23%) and pervasive developmental problems scales (27%) were more likely to be abnormal compared to normal population scores ( P = 0.02 and P = 0.0003, respectively). Autism was diagnosed in 11%, which is significantly higher than the general population ( P < 0.01). Univariate analysis suggests that prolonged NICU stay, prolonged intubation, tracheostomy placement, pulmonary hypertension, autism, hearing impairment, and developmental delays identified during infancy are associated with worse cognitive outcomes ( P < 0.05). Conclusion The majority of CDH children have neurodevelopmental outcomes within the average range at 5 years of age. However, rates of borderline and extremely low IQ scores are significantly higher than in the general population. CDH survivors are also at increased risk for developing symptoms of emotionally reactive and pervasive developmental problems. Risk of autism is significantly elevated. Disease severity and early neurological dysfunction appear to be predictive of longer-term impairments. [ABSTRACT FROM AUTHOR]

We present a case of diffuse distal congenital pulmonary artery hypoplasia with elevated right ventricular systolic pressures, successfully treated with pulmonary artery stenting. A 35-year-old female presented with increasing exertional dyspnoea, on a background of diffuse distal congenital pulmonary artery hypoplasia due to an elastin gene mutation and morbid obesity.There was evidence of mild right heart failure on examination and oxygen saturations were normal. Her transthoracic echocardiogram showed right ventricular (RV) hypertrophy with moderately impaired systolic function, moderate tricuspid regurgitation and an estimated RV systolic pressure (RVSP) of 120 mmHg. Her right atrial pressure was 8 mmHg on right heart catheterisation, RVSP was 138 mmHg, mean pulmonary artery pressure (mPAP) was 84 mmHg, with a normal cardiac output and pulmonary capillary wedge pressure. A decision was made for an experienced interventional radiologist to proceed initially with balloon pulmonary angioplasty (BPA). Her obesity made her an unsuitable candidate for lung transplantation. BPA to the left and right lower lobe pulmonary artery basal segments was performed, without clinical improvement. One week later, cutting BPA was performed to the left lower lobe pulmonary artery and its A7/8 and A9/10 trunks, without improvement. Finally, PA stenting was undertaken to the left lower lobe main branch and the proximal A7/8 and A9/10 trunks, right lower lobe PA and the right middle lobe A4/5 trunk. Completion angiography showed improved flow to all stented segments, except A4. The mPAP was 36 mmHg and there were no complications.The patient experienced a marked improvement in exercise tolerance at six months follow-up with normal RV contractility. We present a rare case of congenital pulmonary artery hypoplasia treated with BPA and subsequent successful PA stenting. Treatments for this condition not well characterised, highlighting the importance of this case. [ABSTRACT FROM AUTHOR]

The respiratory difficulties experienced by infants with omphalocele are being appreciated with greater frequency. These problems represent self-limited difficulties related to omphalocele closure or are the result of severe pulmonary disease including pulmonary hypoplasia and pulmonary hypertension. Infants with giant omphalocele represent a unique group that may experience increased respiratory morbidity which may lead to chronic respiratory problems extending into childhood and adolescence. Importantly, respiratory insufficiency at birth is an independent predictor of mortality for patients with omphalocele. In this review, we will provide a summary of the respiratory difficulties experienced by patients with omphalocele as well as insight into management and surveillance. [ABSTRACT FROM AUTHOR]

• The new porcine model well replicates the clinical features of EOS + TIS. • A total of 432 DE-mRNAs were identified in the porcine EOS + TIS model. • DE-mRNAs may involve in the regulation of immunity, inflammation and cell cycle. • CCL2, ATF3, BTG2, DUSP1 and THBS1 are hub genes of pulmonary dysplasia in EOS + TIS. Early-onset scoliosis (EOS) is a scoliosis deformity caused by various reasons before the age of 10 years and is often combined with thoracic insufficiency syndrome (TIS) causing patients with difficulty in securing lung growth in the thoracic cage. Currently, there is a shortage of effective large animal models for evaluating EOS + TIS in therapeutic studies. Consequently, we propose to construct a porcine EOS + TIS model and evaluate its transcriptome changes by RNA sequencing. Piglets were constructed using unilateral posterior spine-tethering and ipsilateral rib-tethering in the EOS + TIS model, and X-ray and computed tomography (CT) were performed to assess growth changes in the spine, thoracic cage and lungs. The H&E and Masson staining was performed for pathological analysis of lung tissue. After RNA sequencing of lung tissues, data were analyzed for differential expression of mRNA, functional enrichment analysis (GO, KEGG and GSEA) and protein–protein interaction (PPI) network construction, and differential expression of hub gene was verified by RT-qPCR. In the model group, growth (body weight and length) of piglets was significantly delayed; fusion of ribs occurred and cobb angle changes in the coronal and sagittal planes were significantly enlarged; total lung volume (TLV) was significantly reduced, especially at the T7-T10 level. Pathological analysis revealed that, in the model lung tissue, the alveolar wall of was poorly perfused, the alveolar space was enlarged, the number and size of alveoli were significantly reduced, and it was accompanied by collagen fiber deposition. Moreover, a total of 432 differentially expressed mRNAs (DE-mRNAs) were identified in model lung tissues, which contained 262 down-regulated and 170 up-regulated DE-mRNAs, and they were mainly involved in the regulation of immunity, inflammation, cell cycle and extracellular matrix. A PPI network containing 71 nodes and 158 edges was constructed based on all DE-mRNAs, and JUN, CCL2, EGR1, ATF3, BTG2, DUSP1 and THBS1 etc. were hub gene. Overall, we constructed a porcine model that was capable of replicating the common clinical features of EOS + TIS such as rib fusion, asymmetric thoracic cage, increased cobb angle, decreased TLV, and pulmonary hypoplasia. Also, we revealed transcriptomic changes in the EOS + TIS model that may cause pulmonary hypoplasia. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) is characterized by a diaphragmatic defect with herniation of abdominal organs into the thoracic cavity. Outcomes are largely dependent on the degree of pulmonary hypoplasia and pulmonary hypertension, with the most severe cases associated with approximately 50% mortality. Long term pulmonary complications are well known, however, development of lobar emphysema leading to hemodynamic instability is exceedingly rare. We report the case of a patient with severe left-sided CDH who underwent successful diaphragmatic hernia repair but subsequently developed emphysematous bullous disease of the left lung with hemodynamic compromise, requiring emergent lung volume reduction surgery. [ABSTRACT FROM AUTHOR]

A subset of omphalocele infants has respiratory decompensation after the first week of life and PHN is diagnosed. Infection may initiate decompensation. In some, PHN is distinct from pulmonary hypoplasia as they oxygenate on room air for some time after birth. With aggressive treatment and follow-up, PHN can resolve. The late diagnosis of PHN in infants with omphalocele is previously unappreciated and deserves further study. [ABSTRACT FROM AUTHOR]

Body stalk anomaly is composed of a set of genetic component abnormalities that are still rather unknown. This anomaly consists of a large defect in the abdominal wall closure, anatomical defects of the pelvis and lower limbs, severe scoliosis, and pulmonary hypoplasia. In addition to these deformities are heart disease and neural tube closure defects. Because of the association of these severe deformities, the cases described in the literature have proven to be almost entirely incompatible with life, resulting in abortion and stillborn fetuses. Therefore, the present article describes a case of body stalk anomaly that survived for nearly three months, the first of its kind in Latin America. [ABSTRACT FROM AUTHOR]

Background The purpose of the study was to investigate the impact of gestational age (GA) on short-term neurodevelopmental (ND) outcomes in congenital diaphragmatic hernia survivors. Materials Between 6/2004 and 2/2013, 135 consecutive CDH patients underwent ND assessment using the Bayley Scales of Infant Development-III at a median follow-up age of 13 months (range, 5–36). ND delay was defined by a score of ≤ 85 in any of the composite scales. Severe impairment was defined as a score of ≤ 69 in at least one domain. The effect of GA was evaluated as continuous and categorical variables. GA at delivery was grouped into full term (39–41 weeks), near term (37–38), late preterm (34–36), and preterm (24–33). Results Median GA at delivery was 38 weeks (range, 24–41). Fifty (37%) patients were delivered full term, 59 (44%) near term, 16 (12%) late preterm, and 10 (7%) preterm. CDH children born before 39 weeks’ gestation were more likely to score below average (P = 0.005) with corrected age for at least one composite score compared to full term peers. Cognitive (P = 0.06) and language (P = 0.08) scores tended to be lower in the near-term and late-preterm group compared to full-term CDH infants. Patients born near term and late preterm had significantly lower motor composite and fine motor scores compared to full-term children (P = 0.009 and P < 0.01, respectively). Preterm children scored the lowest in all composite scales (P < 0.05). Conclusions Compared to term infants, not only preterm but also late preterm and near-term CDH children carry an increased risk of ND delays. Motor performance appears most susceptible to earlier delivery. [ABSTRACT FROM AUTHOR]

Background/Purpose Monocarboxylate transporters (MCTs) are crucial for the maintenance of intracellular pH homeostasis in developing fetal lungs. MCT1/4 is strongly expressed by epithelial airway cells throughout lung branching morphogenesis. Functional inhibition of MCT1/4 in fetal rat lung explants has been shown to result in airway defects similar to pulmonary hypoplasia (PH) in congenital diaphragmatic hernia (CDH). We hypothesized that pulmonary expression of MCT1/4 is decreased during lung branching morphogenesis in the nitrofen model of CDH-associated PH. Methods Timed-pregnant rats received nitrofen or vehicle on gestational day 9 (D9). Fetuses were harvested on D15, D18, and D21, and divided into control and nitrofen-exposed group. Pulmonary gene expression levels of MCT1/4 were analyzed by qRT-PCR. Immunofluorescence staining for MCT1/4 was combined with E-cadherin in order to evaluate protein expression in branching airway tissue. Results Relative mRNA levels of MCT1/4 were significantly reduced in lungs of nitrofen-exposed fetuses on D15, D18, and D21 compared to controls. Confocal laser scanning microscopy confirmed markedly decreased immunofluorescence of MCT1/4 in distal bronchial and primitive alveolar epithelium of nitrofen-exposed fetuses on D15, D18, and D21 compared to controls. Conclusion Decreased expression of MCT1/4 in distal airway epithelium may disrupt lung branching morphogenesis and thus contribute to the development of PH in the nitrofen-induced CDH model. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) occurs as 1/3000–1/4000 live births. The main pathology associated with the diaphragmatic defect is pulmonary hypoplasia and hypertension. Occasionally gastrointestinal symptoms may also be present due to obstruction and incarceration of herniated bowel loops. Here we present a case of a term male neonate with an antenatal diagnosis of CDH. While on the intensive care unit he developed symptoms of acute bowel obstruction on day 14 of life. An emergency laparotomy was done with a partial gastrectomy for gastric perforation. A concomitant splenectomy was carried out due to an iatrogenic injury. The defect was closed primarily. The patient made a full recovery and was discharged on day 27 post operatively. [ABSTRACT FROM AUTHOR]

Recently, two randomized controlled, prospective trials, the Tracheal Occlusion to Accelerate Lung Growth (TOTAL) trials, reported the outcomes on fetal endoluminal tracheal occlusion (FETO) for isolated left congenital diaphragmatic hernia (CDH). FETO significantly improved outcomes for severe hypoplasia. The effect in moderate cases, where the balloon was inserted later in pregnancy, did not reach significance. In a pooled analysis investigating the effect of the heterogeneity of the treatment effect by the time point of occlusion and severity, the difference may be explained by a difference in the duration of occlusion. Nevertheless, FETO carries a significant risk of preterm birth. The primary objective of this review is to provide an overview of the rationale for fetal intervention in CDH and the results of the randomized trials. The secondary objective is to discuss the technical aspects of FETO. Finally, recent developments of potential alternative fetal approaches will be highlighted. [ABSTRACT FROM AUTHOR]

Background We evaluated the neurodevelopmental (ND) outcome at one year of age for congenital diaphragmatic hernia (CDH) children who have not undergone extracorporeal membrane oxygenation (ECMO) treatment during the neonatal period. Material and methods Between 01/2005 and 06/2012, 63 consecutive CDH patients underwent ND assessment using the BSID-III at a median age of 12 months. ND delay was defined by a score of ≤ 85 in any of the composite scales. Severe impairment was defined as a score of ≤ 69 in at least one domain. Results Mean ± SD cognitive, language, and motor functions were 94 ± 14, 86 ± 14, 90 ± 15, respectively (normal 100 ± 15, P < 0.01 for each). Forty-three-percent scored within the average range for all scales. Forty-four-percent had mild, and 13% had severe delays in at least one domain. Prolonged NICU stay, intubation and O 2 requirement, fundoplication, abnormal BAERs, and tracheostomy were associated with lower scores in all domains. Right-sided CDH, male gender, lower 5 min APGAR, pulmonary hypertension, and delayed start of enteral feeding were predictive of lower cognitive and/or language scores. Conclusion At one year of age, a high percentage of CDH children whose illness did not necessitate ECMO have below normal ND scores. Modifiable and non-modifiable factors are significant determinants of adverse outcomes. [ABSTRACT FROM AUTHOR]

We describe a Danish family with an, until recently, unknown X-linked disease with muscular dystrophy (MD), facial dysmorphology and pulmonary artery hypoplasia. One patient died suddenly before age 20 and another was resuscitated from cardiac arrest at the age of 28. Linkage analysis pointed to a region of 25 Mb from 123.6 Mb to 148.4 Mb on chromosome X containing over 100 genes. Exome sequencing identified a single nucleotide splice site mutation c.502-2A > T, which is located 5' to exon 6 in the gene encoding four and a half LIM domain 1 (FHL1) protein. FHL1 expresses three main splice variants, known as FHL1A, FHL1B and FHL1C. In healthy individuals, FHL1A is the predominant splice variant and is mainly found in skeletal and cardiac muscle. The FHL1 transcript profiles from two affected individuals were investigated in skin fibroblasts with quantitative real-time PCR. This demonstrated loss of isoform A and B, and an almost 200-fold overexpression of isoform C confirming that lack of FHL1A and overexpression of FHL1C results in an extended phenotype of EDMD as recently shown by Tiffin et al. [2013] . [ABSTRACT FROM AUTHOR]

Objective To examine patient-specific factors as potential predictors of neurodevelopmental (ND) outcome in children with giant omphalocele (GO). Materials Between 06/2005 and 07/2012, 31 consecutive GO survivors underwent ND assessment using the BSID-III at a median of 24 months (range 6–35). ND delay was defined by a score of ≤ 84 in any composite score. Severe impairments were defined as a score of ≤ 69 in at least one domain. Correlations between ND outcome and patient-specific factors were analyzed by one-way ANOVA, chi-square, or logistic regression as appropriate. Results The mean cognitive score (86.8 ± 16.8) was in the low average range. Mean language (83.2 ± 21.1) and motor (81.5 ± 16.2) scores were below average. Forty-six-percent scored within the average range for all scales. Mild deficits were found in 19%, and 35% had severe delays in at least one domain. Hypotonicity was present in 55%. Autism was suspected/confirmed in 13%. Predictors of lower ND scores were prolonged ventilator support (P < 0.01), high-frequency oscillatory ventilation (P < 0.01), tracheostomy placement (P < 0.001), O 2 supplementation at day of life 30 (P < 0.02), pulmonary hypertension (P < 0.02), delayed enteral feeding (P = 0.01), need for feeding tube (P < 0.001), GERD (P = 0.05), abnormal BAER hearing screen (P < 0.006), prolonged hospitalization (P = 0.01), and failure to thrive (P = 0.001). Autism was associated with delays in cognitive and language outcomes (P < 0.03). Delayed staged closure (P = 0.007), older age at final repair (P = 0.03), and hypotonicity (P = 0.02) were associated with motor dysfunction. Conclusions Neurological impairments were present in more than half of GO survivors. Disease severity was associated with ND dysfunction. Autism and hypotonicity were often co-morbidities with ND delays and poor motor function. [ABSTRACT FROM AUTHOR]

Purpose Hydrops and pulmonary hypoplasia are associated with significant morbidity and mortality in the setting of a congenital lung lesion or pleural effusion (PE). We reviewed our experience using in utero thoracoamniotic shunts (TA) to manage fetuses with these diagnoses. Methods A retrospective review of fetuses diagnosed with a congenital lung lesion or pleural effusion who underwent TA shunt placement from 1998–2013 was performed. Results Ninety-seven shunts were placed in 75 fetuses. Average gestational age (± SD) at shunt placement and birth was 25 ± 3 and 34 ± 5 weeks. Shunt placement resulted in a 55 ± 21% decrease in macrocystic lung lesion volume and complete or partial drainage of the PE in 29% and 71% of fetuses. 69% of fetuses presented with hydrops, which resolved following shunt placement in 83%. Survival was 68%, which correlated with GA at birth, % reduction in lesion size, unilateral pleural effusions, and hydrops resolution. Surviving infants had prolonged NICU courses and often required either surgical resection or tube thoracostomy in the perinatal period. Conclusion TA shunts provide a therapeutic option for select fetuses with large macrocystic lung lesions or PEs at risk for hydrops and/or pulmonary hypoplasia. Survival following shunting depends on GA at birth, reduction in mass size, and hydrops resolution. [ABSTRACT FROM AUTHOR]

Summary Congenital diaphragmatic hernia (CDH) may be isolated or associated with other structural anomalies, the latter with poor prognosis. The defect allows viscera to herniate through the defect into the chest, competing for space with the developing lungs. At birth, pulmonary hypoplasia leads to respiratory insufficiency and persistent pulmonary hypertension that is lethal in up to 30% of patients. When isolated, survival chances can be predicted by antenatal measurement of lung size and liver herniation. Chromosomal microarrays and exome sequencing contribute to understanding genetic factors underlying isolated CDH. Prenatal intervention aims at stimulating lung development, clinically achieved by percutaneous fetal endoscopic tracheal occlusion (FETO) under local anesthesia. The Tracheal Occlusion To Accelerate Lung growth trial ( www.totaltrial.eu ) is an international randomized trial investigating the role of fetal therapy for severe and moderate pulmonary hypoplasia. Despite an apparent increase in survival following FETO, the search for lesser invasive and more potent prenatal interventions must continue. [ABSTRACT FROM AUTHOR]

Background Pulmonary hypoplasia has been described in cases of giant omphalocele (GO), although pulmonary hypertension (PH) has not been extensively studied in this disorder. In the present study, we describe rates and severity of PH in GO survivors who underwent standardized prenatal and postnatal care at our institution. Methods A retrospective chart review was performed for all patients in our pulmonary hypoplasia program with a diagnosis of GO. Statistical significance was calculated using Fisher's exact test and Mann–Whitney test ( p < 0.05). Results Fifty-four patients with GO were studied, with PH diagnosed in twenty (37%). No significant differences in gender, gestational ages, birth weight, or Apgar scores were associated with PH. Patients diagnosed with PH were managed with interventions, including high frequency oscillatory ventilation, and nitric oxide. Nine patients required long-term pulmonary vasodilator therapy. PH was associated with increased length of hospital stay ( p < 0.001), duration of mechanical ventilation ( p = 0.008), and requirement for tracheostomy ( p = 0.0032). Overall survival was high (94%), with significantly increased mortality in GO patients with PH ( p = 0.0460). Prenatal imaging demonstrating herniation of the stomach into the defect was significantly associated with PH ( p = 0.0322), with a positive predictive value of 52%. Conclusions In this series, PH was observed in 37% of GO patients. PH represents a significant complication of GO, and management of pulmonary dysfunction is a critical consideration in improving clinical outcomes in these patients. [ABSTRACT FROM AUTHOR]

Arthrogryposis has been the term used to describe multiple congenital contractures for over a century. It is a descriptive term and present in over 400 specific conditions. Responsible gene abnormalities have been found for more than 150 specific types of arthrogryposis. Decreased fetal movement is present in all affected individuals which leads to a variety of secondary deformations. Decreased fetal movement (fetal akinesia) is associated with increased connective tissue around the immobilized joint, skin dimpling overlying the immobilized joint, disuse atrophy of the muscles that mobilize the joint and abnormal surface of the joint depending on the immobilized position. Other frequently observed features include: micrognathia, mildly shortened limbs, intrauterine growth restriction, pulmonary hypoplasia and short and/or immature gut. Primary etiologies include neuropathic processes; myopathic processes; end-plate abnormalities; maternal illness, trauma and drugs; limitation of fetal space; vascular compromise; and metabolic disorders to the developing embryo/fetus. [ABSTRACT FROM AUTHOR]

Background/purpose Accessory hemi diaphragm (AHD) is an uncommon condition. Its clinical features, diagnosis and management have not been clearly defined. Methods We reviewed the world literature and added a case of our own. Results There are 40 proven cases in the literature. The lesion occurs almost exclusively in the right hemithorax. Twenty seven cases presented with cardiovascular and/or respiratory symptoms while 3 had symptoms pertaining to other systems. In the remaining 10 patients the diagnosis was either made accidentally or information pertaining to their presentation is missing. Abnormalities of pulmonary and systemic blood vessels often accompany the abnormality. The diagnosis is usually suspected because of an abnormal chest radiograph and confirmed by a variety of tests. Conclusions If the AHD prevents proper aeration of the lung it should be excised. If vascular abnormalities coexist they should be treated along with the AHD. Asymptomatic patients may be observed after confirming the diagnosis. [ABSTRACT FROM AUTHOR]

Background/Purpose The purpose of this study was to clarify the relationship between the lung to thorax transverse area ratio (L/T ratio) and the observed to expected lung area to head circumference ratio (O/E LHR), based on the results of a nationwide Japanese survey conducted in 2011, and to evaluate the compatibility of these prognostic predictors of fetal CDH. Methods Two hundred and forty-two prenatally diagnosed isolated CDH patients born between 2006 and 2010 were included in the present analysis. A regression analysis was conducted to investigate the relationship between the L/T ratio and the O/E LHR based on 191 simultaneous measurements of these parameters in 120 patients. Results The linear regression equation between the L/T ratio and the O/E LHR was: L/T ratio = 0.0233 + (0.00222 x O/E LHR), (R = 0.847, p < 0.0001). According to this equation, 25% of the O/E LHR, the cut-off value used in the fetal intervention for CDH, was equivalent to an L/T ratio of 0.08, a commonly accepted cut-off value for identifying the most severe cases of fetal CDH. Conclusions As there is a positive correlation between the L/T ratio and the O/E LHR, these two parameters proved to be used interchangeably according to the linear regression equation. [ABSTRACT FROM AUTHOR]

Abstract: Background/purpose: Prenatal administration of all-trans retinoic acid (ATRA) has been shown to stimulate alveolarization in nitrofen-induced pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH). Lipid-containing interstitial lipofibroblasts (LIFs), characterized by adipocyte differentiation-related protein (ADRP), play a critical role in alveolar development by coordinating lipid homeostasis. Previous studies have demonstrated that ATRA positively affects LIF expression in developing lungs. We hypothesized that pulmonary LIF expression is increased after prenatal ATRA treatment in the nitrofen model of CDH-associated PH. Methods: Timed-pregnant rats were treated with nitrofen or vehicle on E9.5, followed by injection of ATRA or placebo on E18.5, E19.5, and E20.5. Fetal lungs were dissected on E21.5 and divided into Control+Placebo, Control+ATRA, Nitrofen+Placebo, and Nitrofen+ATRA. Pulmonary gene expression levels of ADRP were analyzed by quantitative real-time polymerase chain reaction, and LIF expression was investigated by ADRP immunohistochemistry, oil-red-O-, and immunofluorescence-double-staining. Results: Relative mRNA expression of pulmonary ADRP was significantly increased in Nitrofen+ATRA compared to Nitrofen+Placebo (0.31±0.02 vs. 0.08±0.01; P <0.0001). ADRP immunoreactivity and oil-red-O-staining were markedly increased in alveolar interstitium of Nitrofen+ATRA compared to Nitrofen+Placebo. Immunofluorescence-double-staining confirmed markedly increased LIF expression in alveolar walls of Nitrofen+ATRA compared to Nitrofen+Placebo. Conclusions: Increased LIF expression after prenatal treatment with ATRA in nitrofen-induced PH suggests that ATRA may have a therapeutic potential in attenuating CDH-associated PH by stimulating alveolar development. [Copyright &y& Elsevier]

Abstract: Purpose: Recent experimental work suggests the therapeutic role of mesenchymal stromal cells (MSCs) during lung morphogenesis. The purpose of this study was to investigate the potential paracrine effects of amniotic fluid-derived MSCs (AF-MSCs) on fetal lung growth in a nitrofen explant model. Methods: Pregnant Sprague–Dawley dams were gavage fed nitrofen on gestational day 9.5 (E9.5). E14.5 lung explants were subsequently harvested and cultured ex vivo for three days on filter membranes in conditioned media from rat AF-MSCs isolated from control (AF-Ctr) or nitrofen-exposed (AF-Nitro) dams. The lungs were analyzed morphometrically and by quantitative gene expression. Results: Although there were no significant differences in total lung surface area among hypoplastic lungs, there were significant increases in terminal budding among E14.5+3 nitrofen explants exposed to AF-Ctr compared to explants exposed to medium alone (58.8±8.4 vs. 39.0±10.0 terminal buds, respectively; p<0.05). In contrast, lungs cultured in AF-Nitro medium failed to augment terminal budding. Nitrofen explants exposed to AF-Ctr showed significant upregulation of surfactant protein C to levels observed in normal fetal lungs. Conclusions: AF-MSCs can augment branching morphogenesis and lung epithelial maturation in a fetal explant model of pulmonary hypoplasia. Cell therapy using donor-derived AF-MSCs may represent a novel strategy for the treatment of fetal congenital diaphragmatic hernia. [Copyright &y& Elsevier]

Résumé: Objectif: Évaluer le devenir à court terme des grossesses compliquées d’une rupture prématurée des membranes (RPDM) avant 26 semaines d’aménorrhée (SA). Patientes et méthodes: Étude rétrospective incluant 40 patientes prises en charge entre 1998 et 2008. Résultats: La moitié des RPDM a eu lieu avant 23SA. Un pourcentage de 21,4 des enfants ont survécu lorsque la RDPM a eu lieu avant 22SA versus 54,5 % lorsqu’elle a eu lieu entre 22 et 23SA+six jours et 80 % après 24SA (p =0,006). Les patientes primigestes ont été plus fréquemment confrontées à un décès périnatal (OR=5,16 ; IC95 %[0,99–36,59]). La réalisation d’un geste invasif avant la RPDM n’a pas modifié le taux de survie. Le tabagisme a induit un raccourcissement de la latence (19,1±13,8 jours vs 40,5±32,3 jours ; p =0,01). Une chorioamniotite a compliqué toutes les grossesses interrompues avant 26SA versus 50 % des grossesses après 26SA (p =0,02). Soixante-dix pour cent des germes à l’origine d’une chorioamniotite étaient identifiés en anténatal. Les patientes dont la CRP était supérieure à 6mg/L lors de la RPDM ont eu un taux de mortalité fœtale supérieur (63,6 % vs 27,8 % ; p =0,02 ; OR=4,3 ; IC95 %[0,99–22,1]). Il n’a pas été retrouvé de différence significative pour la fréquence de survenue d’une chorioamniotite en fonction de l’âge gestationnel à la rupture, du résultat du prélèvement vaginal à l’admission ou de la quantité de liquide amniotique (LA). Discussion et conclusion: L’âge gestationnel de la RPDM et celui de la naissance restent les facteurs pronostiques majeurs. Les patientes primigestes sont plus exposées au décès périnatal. La CRP apparaît comme un facteur prédictif de décès périnatal. [ABSTRACT FROM AUTHOR]