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To investigate the clinical value of echocardiographic detection in the prenatal early diagnosis of Scimitar syndrome (SS) in fetuses, and to develop better and more accurate management strategies for improved prognosis.

Abstract Introduction Congenital lung anomalies (CLA) are a group of anomalies, including congenital cystic adenomatoid malformation (CCAM), bronchopulmonary sequestrations (BPS), congenital lobar emphysema (CLE), and bronchogenic cysts (BC). The prevalence of these rare anomalies has risen in recent years, according to various population-based studies due to advances in fetal ultrasound technology. Method This retrospective study examines the diagnosis of CLA, and was conducted on 72 patients between March 2014 and March 2024 at Taleghani Pediatric Hospital in Gorgan, Iran. Result The average age was 18.8 ± 30.3 months, with the majority being boys (62.5%). Most participants had CCAM (41.7%), followed by CLE (18.1%), BPS (16.7%), pulmonary hypoplasia (9.7%), BC (8.3%), and hybrid lesion (5.6%). The majority of patients were Fars (62.5%), and the average hospitalization days was 9.4 ± 4.5 days. Cardiac anomalies were observed in 19.4% of the patients. 62 patients (86.1%) exhibited respiratory symptoms, and prenatal screening during pregnancy led to the diagnosis in 51 patients (70.8%). Most patients had left lung anomalies (43; 59.7%), and the majority (90.3%) survived. There is a statistically significant relation between needed for surgical treatment and patients’ type of pulmonary lesions (p-value: 0.02). In addition, there was a significant relation between the Fars ethnicity and the presence of cardiac anomalies (p-value: 0.04). Conclusion Some CLAs remain undiagnosed or untreated due to the rare nature of congenital lung anomalies. Nevertheless, improvements in ultrasound and other imaging methods will make diagnosing and managing these anomalies during the prenatal period more prevalent, resulting in enhanced understanding.

Abstract Background Pulmonary typical carcinoid occurring in hypoplasia of the right middle lobe is very rare. Case presentation A routine examination's chest X-ray revealed an abnormal shadow in the right middle lung field of an 82-year-old Japanese woman. A chest computed tomography scan showed a solid 2.5 × 2.0-cm nodule in the very small right middle lobe. A trans-bronchial lung biopsy of the mass in the right middle lobe was performed; it revealed atypical cells with round nuclei growing in multiple foci, and immunostaining was positive for chromogranin A, synaptophysin and CD56, suggesting pulmonary carcinoid. The preoperative clinical diagnosis of primary lung cancer, cT1cN0M0 stage IA3 was considered. A right middle lobectomy and mediastinal lymph node dissection were performed by video-assisted thoracic surgery. Intraoperatively, the middle lobe of the right lung was very small, with 1- to 2-mm-dia. pulmonary arteries and veins that were considered hypoplastic. The final histopathological diagnosis was typical carcinoid, pT2aN0M0 stage IB based on the presence of pleural invasion. Conclusions Including the present patient, only nine cases of lung cancer occurring within pulmonary hypoplasia have been reported, most of which were typical carcinoid.

Key Clinical Message Isolated agenesis of pulmonary arteries with congenital lung hypoplasia is rare. It can be found in childhood or adulthood if asymptomatic. We present a patient with congenital right lung hypoplasia with an absent right pulmonary artery.

Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm resulting in herniation of viscera into the chest. This condition is characterized by pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac ventricular dysfunction. PH is a key component of the pathophysiology of CDH in neonates and contributes to morbidity and mortality. Traditionally, PH associated with CDH (CDH-PH) is thought to be secondary to increased pulmonary arterial resistance and vasoreactivity resulting from pulmonary hypoplasia. Additionally, there is increasing recognition of associated left ventricular hypoplasia, dysfunction and elevated end diastolic pressure resulting in pulmonary venous hypertension in infants with CDH. Thus, hemodynamic management of these infants is complex and cautious use of pulmonary vasodilators such as inhaled nitric oxide (iNO) is warranted. We aim to provide an overview of different phenotypic profiles of CDH associated PH and potential management options based on current evidence and pathophysiology.

Background: The posterior procedure utilizing growth-friendly techniques is the golden standard for patients with early-onset scoliosis combined with thoracic insufficiency syndrome (EOS + TIS). Pulmonary hypoplasia is the main cause of dying prematurely in the EOS + TIS. This study assessed the therapeutic impact of a novel growth-friendly system on the pulmonary development of piglet's EOS + TIS model. Methods: The animal procedure period lasts 12 weeks, of which the construction of the EOS + TIS was performed at 0–8 weeks, and implantation of a novel growth-friendly system was applied at 8–12 weeks. During the animal procedure, X-rays and CT were performed to observe scoliosis, thorax, and lungs. After 12 weeks, pathological changes in lung tissue were assessed using HE and IHC staining. RNA-seq characterized novel growth-friendly system-associated differentially expressed genes (DEGs) and validated using RT-qPCR, western blotting, and IHC. Results: Implantation of the novel growth-friendly system increased body weight, body length, and total lung volume, as well as decreased the coronal and sagittal Cobb angles for the EOS + TIS model. It also ameliorated EOS + TIS-induced thickening of the alveolar wall, increased alveolar spaces, and decreased alveolar number and diameter. In lung tissue, a total of 790 novel growth-friendly system-associated DEGs were identified, and they were mainly involved in the regulation of immune, inflammatory, calcium transport, and vascular development. Among these DEGs, BDKRB1, THBS1, DUSP1, IDO1, and SPINK5 were hub genes, and their differential expression was consistent with RNA-seq results in lung tissues. Conclusion: The novel growth-friendly system has mitigated scoliosis and pulmonary hypoplasia in the EOS + TIS model. We further elucidate the molecular mechanisms underlying the amelioration of pulmonary hypoplasia.

Oligohydramnios is both a consequence of fetal malformations and of uteroplacental insufficiency. Its existence is associated with a high rate of both antepartum and intrapartum complications. It is vital that its occurrence is detected as early as possible so that we can manage it correctly. The main causes of its occurrence are identified and described in this review. The management of oligohydramnios is most often expectant, the timing of delivery also being determined by Doppler examination and changes in parameters measuring fetal growth and development.

Objectives. Congenital diaphragmatic hernia (CDH) represents a developmental defect of the diaphragm, which allows the protrusion of the abdominal viscera into the thoracic cavity. In view of the fact that herniation occurs during a critical period of lung development, the pathological effect is pulmonary hypoplasia in different degrees, usually more severe on the ipsilateral side of the hernia, and also may be present contralateral if the mediastinum is bulged, compressing the lung. Material and methods. We present the case of a patient hospitalized in the Neonatology Department of “St. Andrew” County Emergency Clinical Hospital of Constanta, diagnosed with left CDH at birth. Outcomes. Full-term male newborn, gestational age (GA) 39 weeks, birth weight (BW) 3300g, Apgar Score 6. The 35-year-old mother, Gravida-VI, Para-III, has a pregnancy with inadequate prenatal care, with no structural abnormalities of the fetus detected by the 3rd-semester ultrasound. At birth, the newborn needed neonatal resuscitation, initially with positive pressure ventilation (on mask and bag) and after that, intubated and mechanical ventilated. Chest X-Ray showed a left diaphragmatic hernia, and the pediatric surgery team was called for further therapeutic management. Approximately 48 hours postoperatively, the chest X-Ray identified right upper lobe pneumothorax, with complete remission in 24 hours, under mechanical ventilation. Conclusions. CDH represents a condition with a challenging diagnosis and management. In the best cases, newborns have a very good clinical outcome with neonatal care and surgical treatment after birth. The management of infants with congenital diaphragmatic hernia requires the services of an interprofessional team. After the diagnosis in the antenatal period, parents should be allowed to discuss with a team, including maternal-fetal medicine, pediatric surgery, neonatology, and social work as appropriate. Genetic evaluation and counseling are recommended to identify risks in future pregnancies. Following the repair in the postnatal period, a standardized and interdisciplinary follow-up to provide surveillance, screening, and clinical care is recommended to improve outcomes.

IntroductionCongenital diaphragmatic hernia (CDH) is a rare condition characterized by pulmonary hypoplasia, vascular dystrophy, and pulmonary hypertension at birth. Validation of the lamb model as an accurate representation of human CDH is essential to translating research findings into clinical practice and understanding disease mechanisms. This article emphasizes the importance of validating the lamb model to study CDH pathogenesis and develop innovative therapeutics.Material and methodsAt 78 days of gestation, the fetal lamb's left forelimb was exposed through a midline laparotomy and hysterotomy, and a supra diaphragmatic thoracotomy was performed to allow the digestive organs to ascend into the thoracic cavity. At 138 ± 3 days of gestation, lambs were delivered via a cesarean section; then, with umbilical cord intact during 1 hour, the lambs were mechanically ventilated with gentle ventilation in a pressure-controlled mode for 2 h.ResultsCDH lambs exhibited a lower left lung-to-body weight ratio of 5.3 (2.03), p

This is a retrospective study investigating biometric measurements using magnetic resonance imaging (MRI) examinations in congenital diaphragmatic hernia (CDH). CDH is one of the more common causes of pulmonary hypoplasia, with grave consequences for the fetus. Inclusion criteria were patients diagnosed with CDH as the only observed anomaly, who underwent MRI examination after the second-trimester morphology ultrasound. The patients came from three university hospitals in Bucharest, Romania. In total, 19 patients were included in the study after applying exclusion criteria. Comparing the observed values of the thoracic transverse diameter, the thoracic anterior–posterior diameter, the thoracic circumference, the thoracic area, and the thoracic volume with values from the literature, we observed a predictive alteration of these parameters, with most showing Gaussian distribution. We observed statistical significance for most of our correlations, except between the observed and expected thoracic anterior–posterior diameters and the observed and expected thoracic volume values. This is very helpful when complex studies that can calculate the pulmonary volume cannot be obtained, as in the case of movement artifacts, and allows the clinicians to better assess the severity of the disease. MRI follow-up in CDH cases is a necessity, as it offers the most accurate thoracic biometry.

Abstract Background Isolated right upper lobe pulmonary agenesis is a highly uncommon congenital anomaly, usually detected at adulthood when the patient is evaluated for an incidental abnormal chest radiograph. Chest radiography findings are non-specific. Chest computed tomography with pulmonary angiography is the modality of choice for diagnosing pulmonary agenesis. Case presentation We describe a case of isolated right upper lobe agenesis in a young man who presented with mild shortness of breath and an abnormal chest radiograph. High-resolution computed tomography chest showed right upper lobe pulmonary agenesis which was initially erroneously diagnosed as right lower lobe collapse on chest X-ray. Abnormal segmentation of the middle lobe was also seen which has not been described earlier according to our literature search. Conclusions There should be a high index of suspicion for congenital anomalies on chest X-ray to recommend further imaging studies. This case highlights the importance of computed tomography with pulmonary angiography to adequately assess and characterize the congenital lung anomalies.

Abstract Pulmonary hypoplasia is diagnosed during the perinatal period and is a cause of death in newborns. However, these developmental abnormalities are diagnosed in adulthood in some cases. A 70‐year‐old male smoker was diagnosed with stage IIIA pulmonary adenocarcinoma in the right upper lobe with right middle lobe hypoplasia. He subsequently underwent right upper and middle lobectomy with lymph node dissection by video‐assisted thoracoscopic surgery. In addition to an invasive adenocarcinoma in the right upper lobe, pathological examination of the hypoplastic lobe revealed neuroendocrine hyperplasia, as well as tumorlets and a typical carcinoid. Eight cases of pulmonary neuroendocrine tumors that developed from pulmonary hypoplasia have been reported to date. Interestingly, all but one case occurred in the right middle lobe. Neuroendocrine cell hyperplasia has been reported to develop in hypoplastic lungs postnatally; therefore, we speculated that the lesion was the origin of these neuroendocrine tumors. Moreover, the pathological findings suggested that atelectasis was involved in the pathogenesis of this rare condition. In adults, when lobar hypoplasia is diagnosed, neuroendocrine tumors should be anticipated.

(1) Background: There is no reliable way to assess antenatal fetal pulmonary hypoplasia; however, the biological parameters of the fetal lung can help in evaluating fetal lung development. This study aimed to establish the reference intervals for normal fetal lung biological parameters at 21–40 weeks among the Chinese population. (2) Methods: This was a cross-sectional study of Chinese groups, and included a total of 1388 normal single pregnant women at 21–40 weeks’ gestation. We selected 2134 images of a standard four-chamber view (4CV). ImageJ software (Release 2.14.0) was used to measure the left and right lung areas using a manual tracing method; the elliptic function key was used to measure the fetal thoracic circumference (TC), thoracic area (TA), head circumference (HC), heart area (HA), and abdominal circumference (AC). Based on the above measurements, the following parameters were calculated: lung area to head circumference ratio (LHR), total lung area (TLA), TLA/Weight (mm2/g), cardiothoracic ratio (CTR), lung–thoracic area ratio (TLA/TA), lung–heart area ratio (TLA/HA), TC/AC, and TC/HC. (3) Results: The left and right lung areas and LHRs positively correlated with gestational age (R2 = 0.85, 0.88, 0.66, 0.71, p < 0.001). From 21–40 weeks, the left and right lung areas and TLA increased by about 3.33 times, 3.16 times, and 3.22 times, respectively. The means of left and right LHRs increased by about 1.94 times and 1.84 times, respectively. TLA/Weight (mm2/g) was weakly correlated with gestational age, while CTR, TLA/TA, TLA/HA, TC/AC, and TC/HC had no significant correlation with gestational age. There was no statistically significant difference in fetal lung parameters between different genders of newborns, p > 0.05. (4) Conclusions: Our study establishes the reference intervals for normal Chinese fetal lung biological parameters at 21–40 weeks. Moreover, the reference intervals apply to fetuses of different genders. This paper can provide a reference for the prenatal non-invasive assessment of fetal pulmonary hypoplasia.

Introduction. Potter’s sequence is a very rare and severe syndromic complex that includes congenital kidney defects leading to oligohydramnios, lung hypoplasia and structural skeletal disorders. Clinical case presentation: observation of a boy born from the 5th pregnancy to the mother at 37 weeks. Antenatally, the fetus was found to have bilateral renal and urinary bladder agenesis, malformations of the limbs, but the parents refused to terminate the pregnancy. After birth, the child was diagnosed with Potter’s syndrome with severe hypoplasia of the lungs, which required mechanical ventilation. In 2 hours after birth, the child developed a tension pneumothorax, which was arrested by performing drainage of the pleural cavity. During the day, the patient received complex treatment in the intensive care unit, despite which, by the 2nd day of life, the death of the child occurred. Currently, there are no guidelines for the treatment of Potter syndrome with proven positive long-term outcomes.Discussion. Children with Potter syndrome do not have the same set of symptoms, but they develop a chain of events leading to a common ultimate result - decreased amount of amniotic fluid. Abnormalities leading to oligohydramnios may include severe hypoplasia, dysplasia, polycystic, obstructive uropathy or renal agenesis. In most cases, the disease occurs sporadically, but there are also forms with transmission of the disorder through successive generations: autosomal dominant or recessive inheritance of polycystic disease, hereditary renal dysplasia caused by mutations in RET, UPK3A genes and other chromosomal abnormalities.Conclusion. Potter syndrome is a set of severe syndromes manifested by abnormalities in the development of kidneys, oligohydramnios, leading to lung hypoplasia, skeletal disorders and other congenital anomalies. The severity of congenital defects included in the set depends on the time periods when oligohydramnios occurred. Despite the availability of experimental therapies, the disease is now considered to be fatal.

Lung endothelial cells comprise the pulmonary vascular bed and account for the majority of cells in the lungs. Beyond their role in gas exchange, lung ECs form a specialized microenvironment, or niche, with important roles in health and disease. In early development, progenitor ECs direct alveolar development through angiogenesis. Following birth, lung ECs are thought to maintain their regenerative capacity despite the aging process. As such, harnessing the power of the EC niche, specifically to promote angiogenesis and alveolar regeneration has potential clinical applications. Here, we focus on translational research with applications related to developmental lung diseases including pulmonary hypoplasia and bronchopulmonary dysplasia. An overview of studies examining the role of ECs in lung regeneration following acute lung injury is also provided. These diseases are all characterized by significant morbidity and mortality with limited existing therapeutics, affecting both young children and adults.

ObjectiveLiver herniation is a known risk factor for increased severity in CDH and is associated with clinically significant pulmonary hypoplasia and pulmonary hypertension. Better studies are needed to understand the growth of the herniated liver compared to the liver that remains in the abdomen and how this liver growth then affects lung development. Serial hi-resolution fetal MRI enables characterization of liver growth throughout gestation and examination of macroscopic features that may regulate liver growth. Here, we hypothesized that the nature of liver herniation affects liver growth and, in turn, affects lung growth.MethodsClinical data were retrospectively collected from consecutive cases of prenatally diagnosed isolated left-sided or right-sided CDH from June 2006 to August 2021. Only those cases with MRI lung volumetry for both mid-gestation and late-gestation time points were recruited for analysis. Cases with fetal chromosomal abnormalities and other major structural abnormalities were excluded. Fractional liver volume and liver growth was indexed to estimated fetal weight and compared to lung growth.ResultsData was collected from 28 fetuses with a left liver-down CDH (LLD), 37 left liver-up CDH (LLU) and 9 right liver-up CDH (RLU). Overall, RLU fetuses had greater overall and fractional (intra-thoracic vs. intra-abdominal) liver growth when compared to LLD and LLU fetuses. Additionally, intra-thoracic liver growth was consistently slower than intra-abdominal liver growth for either right- or left-sided CDH. When the liver was not herniated, a positive correlation was seen between liver growth and lung growth. However, when the liver was herniated above the diaphragm, this positive correlation was lost.ConclusionRight-sided CDH fetuses exhibit greater liver growth compared to left-sided CDH. Liver herniation disrupts the normal positive correlation between liver and lung growth that is seen when the liver is entirely within the abdomen.

Congenital diaphragmatic hernia (CDH) is a complex disease associated with pulmonary hypoplasia and pulmonary hypertension. Great strides have been made in our ability to care for CDH patients, specifically in the prenatal improvement of lung volume and morphology with fetoscopic endoluminal tracheal occlusion (FETO). While the anatomic effects of FETO have been described in-depth, the changes it induces at the cellular and molecular level remain a budding area of CDH research. This review will delve into the cellular and molecular effects of FETO in the developing lung, emphasize areas in which further research may improve our understanding of CDH, and highlight opportunities to optimize the FETO procedure for improved postnatal outcomes.

Objective: Pulmonary hypoplasia is common in the perinatal period and causes death in newborn infants. It is commonly associated with a number of malformation syndromes. Various parameters are used to estimate pulmonary hypoplasia at fetal autopsy including Lung Weight Body Weight ratio (LW:BW), Radial Alveolar Count (RAC) and DNA estimation. Material and Method: This study was carried out as a retrospective analysis of 108 lung specimens of fetuses with congenital anomalies for a period of five years. All terminated fetuses with anomalies were received with 10% formalin. An inverted Y-shaped incision was made on the fetus to remove the lungs. Lung weight and body weight were measured and the ratio was calculated. Morphometric estimation of RAC was done microscopically by counting the number of alveoli using the Q capture software. RAC was calculated based on gestational age. Results: Among the restrictive lung diseases, pulmonary hypoplasia by the LW:BW ratio was prevalent in 43% while the same by RAC was 19%. Similarly, pulmonary hypoplasia by the LW:BW ratio was prevalent in 35% while the same by RAC was 26% among cases with non restrictive lung diseases. Oligohydramnios showed the highest prevalence of pulmonary hypoplasia (23.7%), followed by renal anomalies (16.9%) and CNS anomalies (15.2%). Conclusion: Pulmonary hypoplasia is a common occurrence in many congenital anomalies, premature rupture of membranes, and hydrops fetalis. Identifying the anomaly during the intrauterine period will help to anticipate and accordingly manage the baby in the postpartum period. Early diagnosis of correctable condition like oligohydramnios will also help in the early intervention and prevention of pulmonary hypoplasia.

Background. Obstructive lesion of upper respiratory tract in fetus is extremely rare pathology with adverse perinatal outcomes.Clinical Case Description. Ultrasound examination of fetus (gestational age 21 weeks 6 days) has revealed one-sided isolated main bronchus atresia. Atresia was presented as enlargement of right lung due to mucus accumulation, its increased echogenicity, mediastinal displacement to the left and left lung size reduction. We performed differential diagnosis with cystic-adenomatous lung malformation type III, congenital lobar emphysema and pulmonary sequestration. These conditions are also characterized by lung echogenicity and volume increase but they are usually limited to one lung lobe or segment, and pulmonary sequestration has a systemic blood supply. The use of high-frequency transducers, lung vessels Doppler imaging and volume echography allow us to investigate in detail the lung structure of the fetus, correctly calculate the lungs volume and timely the main bronchus atresia at the second trimester of pregnancy.Conclusion. The ultrasound diagnosis of isolated main bronchus atresia is based on revealing of increased lung volume on ipsilateral side, its increased echogenicity, presence of hypoechogenic linear tubular structures (bronchocele), mediastinal displacement to the opposite side and extreme hypoplasia of the contralateral lung. Prognosis for the life is unfavorable.

Congenital diaphragmatic hernia (CDH) is an emergency case in neonates. The prevalence of CDH is 1 in 2500 births and occurs 4–8 times more commonly on left side than right side. CDH is usually worsened by pulmonary hypoplasia and pulmonary hypertension. It is characterized by respiratory failure and bowel sound in the chest area and mostly requires surgical procedure. This case report discusses a neonate with congenital left diaphragmatic hernia who underwent surgical procedure to close the defect. Patients present with cyanosis and shortness of breath, are early intubated, and are mechanically ventilated in neonatal intensive care unit (NICU). In the present case, the surgical procedure lasted approximately 2 h with general anesthesia, with hemodynamic stability during the surgery. The patient was thereafter intubated and treated at the NICU for close monitoring.

he authors present the latest data on the hypophosphatasia (HPP) management in children. Hypophosphatasia is a rare genetic disease caused by deficiency of tissue-specific alkaline phosphatase due to mutation in the ALPL gene. The article covers all the features of epidemiology, etiology and pathogenesis, detailed stages of differential diagnostics. Treatment guidelines for pediatric patients are provided, they are based on the principles of evidence-based medicine. Special attention was given to the only effective method of hypophosphatasia management —enzyme replacement therapy (ERT). This material is the clinical guideline draft for the management of patients with hypophosphatasia prepared by the Union of Pediatricians of Russia and the Association of Medical Geneticists.

Congenital diaphragmatic hernia (CDH) is a relatively common and life-threatening birth defect, characterized by an abnormal opening in the primordial diaphragm that interferes with normal lung development. As a result, CDH is accompanied by immature and hypoplastic lungs, being the leading cause of morbidity and mortality in patients with this condition. In recent decades, various animal models have contributed novel insights into the pathogenic mechanisms underlying CDH and associated pulmonary hypoplasia. In particular, the generation of genetically modified mouse models, which show both diaphragm and lung abnormalities, has resulted in the discovery of multiple genes and signaling pathways involved in the pathogenesis of CDH. This article aims to offer an up-to-date overview on CDH-implicated transcription factors, molecules regulating cell migration and signal transduction as well as components contributing to the formation of extracellular matrix, whilst also discussing the significance of these genetic models for studying altered lung development with regard to the human situation.

Scimitar syndrome is a rare congenital heart defect characterized by the combination of vascular, bronchial, and parenchymal malformations. This syndrome includes anomalous right pulmonary venous drainage to the inferior caval vein, hypoplastic right pulmonary artery, right lung hypoplasia and the presence of aortopulmonary collaterals to the right lung. In this study, we evaluate the different surgical approaches of 3 cases with Scimitar syndrome who was corrected successfully.

Oligohydramnios secondary to mid-trimester preterm premature rupture of the membranes can result in a range of abnormalities from functional hypoplasia of the lungs to structural hypoplasia and fetal compression syndrome. Here, we discuss two infants born at 24-week gestation with a history of severe oligohydramnios requiring extensive resuscitation with high ventilation pressures at birth. One had dry lung syndrome (DLS) and after adequate resuscitation did well. The second case had severe pulmonary hypoplasia complicated by recurrent air leaks and succumbed to it. Management of DLS is primarily supportive; these neonates require adequate respiratory support to open the collapsed airway at birth and optimal ventilation in the early neonatal period to facilitate smooth recovery.

Mechanical forces are increasingly recognized as important determinants of cell and tissue phenotype and also appear to play a critical role in organ development. During the fetal stages of lung morphogenesis, the pressure of the fluid within the lumen of the airways is higher than that within the chest cavity, resulting in a positive transpulmonary pressure. Several congenital defects decrease or reverse transpulmonary pressure across the developing airways and are associated with a reduced number of branches and a correspondingly underdeveloped lung that is insufficient for gas exchange after birth. The small size of the early pseudoglandular stage lung and its relative inaccessibility in utero have precluded experimental investigation of the effects of transpulmonary pressure on early branching morphogenesis. Here, we present a simple culture model to explore the effects of negative transpulmonary pressure on development of the embryonic airways. We found that negative transpulmonary pressure decreases branching, and that it does so in part by altering the expression of fibroblast growth factor 10 (Fgf10). The morphogenesis of lungs maintained under negative transpulmonary pressure can be rescued by supplementing the culture medium with exogenous FGF10. These data suggest that Fgf10 expression is regulated by mechanical stress in the developing airways. Understanding the mechanical signaling pathways that connect transpulmonary pressure to FGF10 can lead to the establishment of novel non-surgical approaches for ameliorating congenital lung defects.

Pulmonary underdevelopment is a rare congenital disease which manifests as persistent hemithorax opacification at chest radiography. We present three patients with different types of pulmonary underdevelopment, their imaging features and associated anomalies. Case 1 is a premature neonate with persistent respiratory distress. Further imaging confirmed right pulmonary hypoplasia, associated with a patent foramen ovale, patent ductus arteriosus and vertebral anomalies. Case 2 is a 6-year-old child with corrected anorectal malformation, and recurrent pneumonia. Further imaging confirmed left pulmonary aplasia, associated with an aberrant right subclavian artery and vertebral anomaly. Case 3 is a full term neonate who developed excessive drooling of saliva and respiratory distress. Further imaging confirmed right pulmonary agenesis, associated with an atrial septal defect, patent ductus arteriosus and tracheo-oesophageal fistula. Pulmonary underdevelopment is classified into three types: hypoplasia, aplasia and agenesis. The majority of them have associated anomalies. This condition should be considered a differential diagnosis in paediatric patients with an opaque hemithorax on chest radiography.

Unilateral pulmonary agenesis or aplasia (UPA) in combination with congenital heart defects is rare and has not been reported in connection with transposition of the great arteries. This case demonstrated dextroposition of the fetal heart, and subsequent scans could not clearly visualize the right pulmonary artery. UPA should be considered in the workup and counseling for a family in the setting of fetal heart malposition, as there is a significant clinical impact.

Abstract Background Survival of neonates with intrauterine renal insufficiency and oligo- or anhydramnios correlates with the severity of secondary pulmonary hypoplasia. Early prenatal diagnosis together with repetitive amnioinfusions and modern intensive care treatment have improved the prognosis of these neonates. Extracorporeal membrane oxygenation is an established treatment option, mainly applied to neonates with pulmonary hypoplasia caused by congenital diaphragmatic hernia. However, a few case reports of extracorporeal membrane oxygenation in neonates with lower urinary tract obstruction have been published. Case presentation We describe a case of a Caucasian male infant with prenatally diagnosed lower urinary tract obstruction and secondary pulmonary hypoplasia who was delivered spontaneously at 36 + 2 weeks of gestation. Venovenous extracorporeal membrane oxygenation was initiated on the first day of life for severe respiratory failure and consecutive hypoxemia despite treatment with inhaled nitric oxide and high-frequency oscillation. The patient was supported by extracorporeal membrane oxygenation for 10 days and extubated 6 weeks later. Hemofiltration was required on the second day of life because of renal insufficiency and was later replaced by peritoneal dialysis. The child was discharged after 4 months with nasal high-flow mild oxygen therapy and peritoneal dialysis. Conclusion Neonatal extracorporeal membrane oxygenation support is a possible treatment option for neonates with lower urinary tract obstruction and pulmonary hypoplasia.

Fetal pericardiocentesis is a safe and effective procedure that is used to drain pericardial effusion in selected fetuses. The aim of the procedure is to reduce the risk of pulmonary hypoplasia, the development of cardiac tamponade and fetal hydrops, and in some cases to allow fetal lung maturity, improving fetal extraction with a better haemodynamic and respiratory condition. In this review, we discuss the indications, technical procedure, and the outcomes of the fetal pericardiocentesis reported in the literature.

Congenital diaphragmatic hernias (CDHs) and structural anomalies of the diaphragm are a common class of congenital birth defects that are associated with significant morbidity and mortality due to associated pulmonary hypoplasia, pulmonary hypertension and heart failure. In ∼30% of CDH patients, genomic analyses have identified a range of genetic defects, including chromosomal anomalies, copy number variants and sequence variants. The affected genes identified in CDH patients include transcription factors, such as GATA4, ZFPM2, NR2F2 and WT1, and signaling pathway components, including members of the retinoic acid pathway. Mutations in these genes affect diaphragm development and can have pleiotropic effects on pulmonary and cardiac development. New therapies, including fetal endoscopic tracheal occlusion and prenatal transplacental fetal treatments, aim to normalize lung development and pulmonary vascular tone to prevent and treat lung hypoplasia and pulmonary hypertension, respectively. Studies of the association between particular genetic mutations and clinical outcomes should allow us to better understand the origin of this birth defect and to improve our ability to predict and identify patients most likely to benefit from specialized treatment strategies.

Eventration of the diaphragm is a rare entity, characterised by abnormal elevation of a dome of diaphragm. In this condition, the diaphragm is composed of fibrous tissue with few or no interspersed muscle fibres. Eventration can be congenital or acquired. Congenital eventration results from inadequate development of muscles or absence of phrenic nerve. The common cause of acquired eventration is injury to the phrenic nerve from traumatic birth injury or surgery for heart disease. The perioperative anaesthetic management of diaphragmatic eventration along with ventricular septal defect with severe pulmonary hypertension makes this case both challenging and unique.

Purpose: To analyze the correlation and agreement between three dimensional (3D) US and MRI in the assessment of pulmonary volumes of fetuses with different types of urinary tract malformations (UTM) and high-risk of pulmonary hypoplasia (PH). Patients and methods: Thirty-nine fetuses with various UTM, at risk for PH were involved in this cross-sectional study. 3D volume US data sets of the fetal lungs were acquired. The right, left and total lung volumes were calculated separately using the virtual organ computer-aided analysis (VOCAL) method with a 30° rotation. MRI of fetal lung was obtained with assessment of signal intensity and lung volumetry. Comparison between mean lung volumes was performed using unpaired t test. Agreement between the 3D-US and MRI methods was done using Cohen kappa test. Results: Good agreement was detected between the two methods (Kappa = 0.629, p = 0.001). The measured lung volumes by 3D-US were smaller than those measured by MRI (p > 0.05, non-significant). MRI showed greater specificity, PPV and diagnostic accuracy (100% each) than 3D-US (50%, 88.9% and 90% respectively). Conclusion: There is a good concordance between 3D-US and MRI in the evaluation of PH in fetuses with UTM. MRI could be reserved for borderline cases of pulmonary hypoplasia and the difficult diagnostic situations.

Congenital diaphragmatic hernia (CDH) is a malformation leading to pulmonary hypoplasia, which can be treated in utero by fetal tracheal occlusion (TO). However, the changes of gene expression induced by TO remain largely unknown but could be used to further improve the clinically used prenatal treatment of this devastating malformation. Therefore, we aimed to investigate the pulmonary transcriptome changes caused by surgical induction of diaphragmatic hernia (DH) and additional TO in the fetal rabbit model. Induction of DH was associated with 378 upregulated genes compared to controls when allowing a false-discovery rate (FDR) of 0.1 and a fold change (FC) of 2. Those genes were again downregulated by consecutive TO. But DH+TO was associated with an upregulation of 157 genes compared to DH and controls. When being compared to control lungs, 106 genes were downregulated in the DH group and were not changed by TO. Therefore, the overall pattern of gene expression in DH+TO is more similar to the control group than to the DH group. In this study, we further provide a database of gene expression changes induced by surgical creation of DH and consecutive TO in the rabbit model. Future treatment strategies could be developed using this dataset. We also discuss the most relevant genes that are involved in CDH.

Introduction: Potter’s syndrome, also known as Potter’s sequence, is an uncommon and fatal disorder. Potter’s sequence in a multiple pregnancy is uncommon, and its frequency remains unknown. Worldwide in a diamniotic twin pregnancy, there are only a few cases described. Case report: We present an unusual case discordance for Potter’s syndrome in a dichorionic diamniotic twin pregnancy. Twin A had the typical physical and histological Potter’s findings. Twin B had normal respiratory function and normal physical examination findings. There are many controversies about this condition in diamniotic twin pregnancy. One case report concluded that that the presence of a normal co-twin in diamniotic pregnancy prevented the cutaneous features seen in Potter’s syndrome and ameliorated the pulmonary complications, whereas two other case studies reported that the affected twin had extrarenal features typical of the syndrome. Conclusion: We performed an autopsy and calculated lung weight/body weight ratio to diagnose pulmonary hypoplasia. Histopathologic examination of lungs and kidneys was performed. We concluded that the appearance of extrarenal features in the affected twin depends on the amniocity.

Prelabor rupture of the membranes (PROM) near the limit of viability is associated with significant risks for both mother and fetus. Preterm labor, intra-amniotic infection, and placental abruption are the immediate risks to the pregnancy; however, the fetus incurs additional risks related to the sequela of persistent oligohydramnios. Transabdominal intra-amniotic infusions have been studied. Results, suggesting that this intervention may prolong the latency period, and potentially, decrease pulmonary hypoplasia in surviving neonates without evidence of increasing risk of intra-amniotic infection. To our knowledge, the use of antibiotic-infused fluid has not been reported in this clinical scenario. Therefore, we present a case of a patient with PROM before the limit of viability who underwent serial transabdominal amnioinfusions with oxacillin-containing normal saline, which resulted in membrane resealing and neonatal survival with no additional maternal morbidity.

Pulmonary hypoplasia (PH) is a developmental anomaly of the lung parenchyma, characterized by a decrease in the number and size of airways, alveoli and vessels. We present a case of a 31-year-old patient with a history of chronic productive cough and frequent respiratory infections, who was referred for investigation of abnormal chest x-ray. The combination of chest computed tomography (CT) and bronchoscopy set the diagnosis of left pulmonary hypoplasia and the patient was treated surgically with a left pneumonectomy. PH is usually diagnosed immediately after birth, causing severe respiratory failure with high mortality. The less severe, unilateral forms can possibly survive by causing compensatory hyperinflation of the other lung and remain undiagnosed until adulthood, presenting either asymptomatic or with symptoms of chronic bronchitis and recurrent respiratory infections. Chest CT is considered the imaging technique of choice for the diagnosis and for the differential diagnosis from other congenital or acquired conditions. The treatment is usually conservative, although surgical resection is indicated in cases of severe cystic changes and intense symptomatology.

In this article, we report an up-to-date summary on tracheal occlusion (TO) as an approach to drive accelerated lung growth and strive to review the different maternal- and fetal-derived local and systemic signals and mechanisms that may play a significant biological role in lung growth and formation of heterogeneous topological zones following TO. Pulmonary hypoplasia is a condition whereby branching morphogenesis and embryonic pulmonary vascular development are globally affected and is classically seen in congenital diaphragmatic hernia. TO is an innovative approach aimed at driving accelerated lung growth in the most severe forms of diaphragmatic hernia and has been shown to result in improved neonatal outcomes. Currently, most research on mechanisms of TO-induced lung growth is focused on mechanical forces and is viewed from the perspective of homogeneous changes within the lung. We suggest that the key principle in understanding changes in fetal lungs after TO is taking into account formation of unique variable topological zones. Following TO, fetal lungs might temporarily look like a dynamically changing topologic mosaic with varying proliferation rates, dissimilar scale of vasculogenesis, diverse patterns of lung tissue damage, variable metabolic landscape, and different structures. The reasons for this dynamic topological mosaic pattern may include distinct degree of increased hydrostatic pressure in different parts of the lung, dissimilar degree of tissue stress/damage and responses to this damage, and incomparable patterns of altered lung zones with variable response to systemic maternal and fetal factors, among others. The local interaction between these factors and their accompanying processes in addition to the potential role of other systemic factors might lead to formation of a common vector of biological response unique to each zone. The study of the interaction between various networks formed after TO (action of mechanical forces, activation of mucosal mast cells, production and secretion of damage-associated molecular pattern substances, low-grade local pulmonary inflammation, and cardiac contraction-induced periodic agitation of lung tissue, among others) will bring us closer to an appreciation of the biological phenomenon of topological heterogeneity within the fetal lungs.

We report two cases of pulmonary hypoplasia due to fetal ascites in symptomatic congenital cytomegalovirus (CMV) infections despite fetal therapy. The patients died soon after birth. The pathogenesis of pulmonary hypoplasia in our cases might be thoracic compression due to massive fetal ascites as a result of liver insufficiency. Despite aggressive fetal treatment, including multiple immunoglobulin administration, which was supposed to diminish the pathogenic effects of CMV either by neutralization or immunomodulatory effects, the fetal ascites was uncontrollable. To prevent development of pulmonary hypoplasia in symptomatic congenital CMV infections, further fetal intervention to reduce ascites should be considered.

Abstract Background Congenital diaphragmatic hernia (CDH) is fatal in severe cases of pulmonary hypoplasia. We experienced a fatal case of pulmonary hypoplasia due to CDH, thoracic myelomeningocele (MMC), and thoracic dysplasia. This constellation of anomalies has not been previously reported. Case Report A male infant with a prenatal diagnosis of thoracic MMC with severe hydrocephalus and scoliosis was born at 36 weeks of gestation. CDH was found after birth and the patient died of respiratory failure due to pulmonary hypoplasia and persistent pulmonary hypertension of the newborn at 30 hours of age despite neonatal intensive care. An autopsy revealed a left CDH without herniation of the liver or stomach into the thoracic cavity, severe hydrocephalus, Chiari malformation type II, MMC with spina bifida from Th4 to Th12, hemivertebrae, fused ribs, deformities of the thoracic cage and legs, short trunk, and agenesis of the left kidney. Conclusion We speculate that two factors may be associated with the severe pulmonary hypoplasia: decreased thoracic space due to the herniation of visceral organs caused by CDH and thoracic dysplasia due to skeletal deformity and severe scoliosis.

Objective: To establish a reference of normal fetal lung volume using three-dimentional ultrasonography in the second half of pregnancy. Methods: A prospective longitudinal study was conducted in 53 Thai healthy singleton pregnant women at 22-37 weeks of gestation. By using 3-D ultrasonography with Virtual Organ Computer-Aided Analysis (VOCAL), the whole fetal thorax was obtained as volume data and then calculated in each participant for 3-6 successions. Our method showed excellent intraclass correlation coefficients (ICC = 0.990-0.991) among three operators and validity ranged within 3% of the actual volume. Multivariate analysis was used to identify the relationship between lung volume and gestational age. This longitudinal data set was then analysed by mixed model regression analysis. Results: A total of 260 fetal lung volumes were obtained. Average maternal age, gestational age and birth weight were 26.9 ± 4.7 years, 38.9 ± 1.3 weeks and 3,007.5 ± 349.3 grams. With mixed model of regression analysis, the relationship between lung volume and GA was demonstrated as follows: left lung volume (ml.) = (-12.19) + (0.22*GA) + (0.03*GA2), right lung volume (ml.) = (-24.91) + (1.19*GA) + (0.02*GA2), total lung volume (ml.) = (-37.32) + (1.43*GA) + (0.05*GA2). Conclusion: This is the normal fetal lung volume in the Thai population using the rotational technique (VOCAL). It could be considered as a reference for prenatal diagnosis of pulmonary hypoplasia.

Abstract Objective Describe a case of congenital acinar dysplasia and review the literature. Study Design Retrospective chart review and literature search. Results Congenital acinar dysplasia is a rare malformation of growth arrest of the lower respiratory tract resulting in critical respiratory insufficiency at birth. It is a form of pulmonary hypoplasia that is characterized by diffuse maldevelopment and derangement of the acinar and alveolar architecture of the lungs, resulting in the complete absence of gas exchanging units. The growth-arrested lung tissue resembles the pseudoglandular phase of 16 weeks' gestation. The etiology is unknown. It is diagnosed by exclusion of all other causes of pulmonary hypoplasia and a summation of clinical, imaging, and histopathologic findings. Conclusion There is no cure and clinical treatment is supportive until death of the infant. We present a case of congenital acinar dysplasia in a male infant who lived 20 days with intensive support.

Objective: Our purpose was to review our experience with congenital diaphragmatic hernia emphasizing diagnosis, management, and outcome. Study Design: We conducted a retrospective review of all cases of babies with congenital diaphragmatic hernia diagnosed and treated in our centre from 1998 to 2010. Results: There were 28 congenital diaphragmatic hernia cases, 13 girls and 15 boys with a mean weight birth of 3 kg. Three patients (10, 6% of cases) died within a few hours after admission. In the remaining cases, surgery was performed after a stabilization period of 2 days. The diaphragmatic defect was sitting in the posterolateral left in 23 cases and right in 2 cases. Its dimensions were on average 4,5 cm, tow cases of agenesis of the cupola were seen and required the placement of gortex prosthesis. The remaining cases are treated by direct closure of defect. Postoperative course was marked by an early death in context of respiratory distress in six cases and later with sepsis in tow cases. The outcome was favourable in 17 cases (60, 7%), despite the occurrence of sepsis in four cases and evisceration in two cases. Conclusions: Congenital diaphragmatic hernia remains a serious disease with high mortality and morbidity despite advances in prenatal diagnosis and neonatal resuscitation.

Hypogenetic lung syndrome is more popularly known as a scimitar syndrome (SS). It is a rare developmental lung malformation which almost always occurs on the right side. The two most constant features of this syndrome are anomalous pulmonary venous return into systemic circulation, most frequently via inferior vena cava (IVC), and lung hypoplasia. We are reporting such a case illustrating most typical and some uncommon features on chest radiograph and multislice computer tomography (MSCT) of chest. Focal herniation of liver through a diaphragmatic defect presenting as an ovoid soft tissue mass in right lower paraspinal region on chest X ray mimicking sequestration is an interesting but rare finding.

Congenital diaphragmatic hernia results from the anomalous closure of pericardioperitoneal canal. There are various challenges faced by anesthesiologists during management of such cases which include intraoperative complications including hypoxia and hypercarbia, which leads to pulmonary hypertension and right to left shunt. Mortality remains high because of associated pulmonary hypoplasia and pulmonary hypertension. Here, we describe anesthetic management of a 2-month-old female child with difficulty in breathing since birth following feeding, due to congenital diaphragmatic hernia.

Aims: To evaluate the usefulness of intravesical pressure as a prognostic indicator in congenital diaphragmatic hernia. Material and Methods: In 25 cases, bladder pressure was measured intraoperatively during repair. Results: Cases were divided into three groups according to the intravesical pressure. Group 1: pressure 15 cm (n.5). Number of ventilated days was tabulated against these groups. Median number of ventilated days for Group 1, with the lowest pressure, was 3 days, while that for Group 2 was 5 and for Group 3, with the highest pressure, was 10 days. This was significant, with a P-value of 0.016. Conclusion: Measurement of intravesical pressure is a reliable prognostic indicator in newborns with congenital diaphragmatic hernia. It also helps in predicting postoperative ventilatory requirement.

Background/Purpose: The molecular pathophysiology of lung hypoplasia in congenital diaphragmatic hernia (CDH) remains poorly understood. The Wnt signaling pathway and downstream targets, such as bone morphogenetic proteins (BMP) 4 and other factors such as late gestation lung protein 1 (LGL1), are essential to normal lung development. Nitrofen-induced hypoplastic CDH rodent lungs demonstrate down regulation of the Wnt pathway including BMP4 and reduced LGL1 expression. The aim of the current study was to examine the molecular pathophysiology associated with a surgically induced CDH in an ovine model. Methods: Left thoracotomy was performed at 80 days in 14 fetal sheep; CDH was created in 7 experimental animals. Lungs were harvested at 136 days (term=145d). Lung weight and mean terminal bronchiole density (MTBD) were measured to determine the degree of pulmonary hypoplasia. Quantitative real time PCR was undertaken to analyze Wnt2, Wnt7b, BMP4 and LGL1 mRNA expression. Results: Total lung weight was decreased while MTBD was increased in the CDH group (p

In recent decades, new research into the developmental defects and pathophysiological basis of congenital diaphragmatic hernia has revealed opportunities for the development of innovative therapies. Importantly, the use of animal models to represent this anomaly in the laboratory has resulted in the discovery of many important genetic, epigenetic and other molecular contributors to this condition. In this review, the most commonly used and newly devised animal models of CDH are presented to familiarize the reader with the latest innovations in the basic sciences.

Objective: To report a rare congenital anomaly, a right diaphragmatic hernia, in a near-term baby Case Report: A 40-year-old female, gravida 3, para 2, had undergone regular prenatal care in our department since the early second trimester. She underwent amniocentesis at 16 weeks of gestation. The result showed normal 46,XY. Fetal growth was appropriate throughout the pregnancy. A small heart with marked left-side deviation was noted in the third trimester. The heart rate was less than 25% of normal. A homogenous mass with centralized vessels was noted in the fetus's right chest. The baby showed respiratory distress immediately after delivery. Imaging studies after birth proved there was a right diaphragmatic hernia with severe pulmonary hypertension and poor lung function. Conclusion: Right congenital diaphragmatic hernia is rare. A prenatal diagnosis is difficult to make in the second trimester. Prognosis is greatly influenced by the associated abnormalities.

Hypomelanosis of Ito (HI) is a neurocutaneous syndrome characterized by hypopigmented cutaneous lesions and extracutaneous manifestations frequently affecting the nervous system and the musculoskeletal system. Dysmorphic features, dental, ophthalmic, gastrointestinal, cardiac, and renal abnormalities are described in a minority of patients. The authors describe a 4-month-old infant having HI with unusual pulmonary hypoplasia that has not been reported so far.

Los quistes congénitos del pulmón son un grupo diverso de anomalías que pueden ser únicos o múltiples y variar grandemente en su volumen. Por lo regular están confinados a un segmento o lóbulo y son asiento frecuente de infección. Se presenta el caso de un quiste broncogénico intrapulmonar gigante acompañado de hipoplasia de la arteria pulmonar izquierda y del lóbulo pulmonar superior ipsilateral. Se hacen consideraciones relacionadas con el origen del quiste, su relación con la hipoplasia arterial y pulmonar y se discuten las posibles causas de la atelectasia y edema posoperatorios, que llevaron a la necesidad de completar la neumonectomía ante un cuadro séptico severoThe congenital lung cysts are a group of diverse abnormalities, unique or multiple, and of different volumes. Generally, they are confined to a segment or lobe and they are a frequent site of infection. The case of a bronchogenic intrapulmonary giant cyst accompanied with hypoplasia of the left pulmonary artery and of the upper ipsilateral pulmonary lobe, is reported. Considerations are made on the origin of the cyst, and on its connection with arterial and pulmonary hypoplasia. The possible causes of postoperative atelactasis and edema, leading to the need of completing pneumonectomy in the face of a severe septic picture, are discussed