Search

Although Bochdalek hernias are uncommon in adults and difficult to diagnose, such congenital diaphragmatic hernias (CDHs) are some of the most serious malformations among newborns. In particular, CDHs are accompanied by high mortality and marked disability later in life due to concomitant morbidity (i.e., caused by pulmonary lung hypoplasia and persisting pulmonary hypertension of neonates) and require long-lasting neonatal treatment in an intensive care unit. Late-diagnosed CDHs are extremely rare and always show small defects that justify a better prognosis than CDHs with large defects. In most cases, such CDHs go undiagnosed due to their mild, delayed symptoms. In the case described here, an 18-year-old Asian male presented with abdominal pain and a bowel contour in the epigastric region and left upper quadrant. A chest X-ray and thoracoabdominal computerized tomography scan confirmed the diagnosis of bowel obstruction due to a left diaphragmatic hernia. Moreover, a defect was revealed in the posterolateral left diaphragm, and the transverse colon, spleen, and half of the stomach had herniated through it. A segmentectomy was performed on the transverse colon, followed by an end-to-end anastomosis, a diaphragmatic plasty, and the placement of an intrapleural catheter. In conclusion, diagnosing a diaphragmatic hernia before surgery can be difficult due to its rarity and wide range of symptoms. Although prenatal diagnosis using ultrasonography is possible in up to 80% of fetuses, that method may not be available in all regions in Indonesia or in all countries, where doctors thus continue to face a diagnostic challenge when dealing with CDHs. [ABSTRACT FROM AUTHOR]

Introduction: Midtrimester prelabor rupture of membranes (PROM) between 16 and 24 weeks of gestational age is a major obstetric complication with high rates of perinatal morbidity and mortality. Amnioinfusion has been proposed in women with midtrimester PROM to target oligohydramnios and subsequently enhance pulmonary development and perinatal outcomes. Material and Methods: The purpose of this study was to perform a systematic review and meta-analysis including all randomized clinical trials investigating amnioinfusion versus no intervention in women with PROM between 16+0 and 24+0 weeks of gestational age. Databases Central, Embase, Medline, ClinicalTrials.gov and references of identified articles were searched from inception of database to December 2021. The primary outcome was perinatal mortality. Secondary outcomes included neonatal, maternal, and long-term developmental outcomes as defined in the core outcome set for preterm birth studies. Summary measures were reported as pooled relative risk (RR) or mean difference with corresponding 95% confidence interval (CI). Results: Two studies (112 patients, 56 in the amnioinfusion group and 56 in the no intervention group) were included in this review. Pooled perinatal mortality was 66.1% (37/56) in the amnioinfusion group compared with 71.4% (40/56) in no intervention group (RR 0.92, 95% CI: 0.72–1.19). Other neonatal and maternal core outcomes were similar in both groups, although due to the relatively small number of events and wide CIs, there is a possibility that amnioinfusion can be associated with clinically important benefits and harms. Long-term healthy survival was seen in 35.7% (10/28) of children assessed for follow-up and treated with amnioinfusion versus 28.6% (8/28) after no intervention (RR 1.30, 95% CI: 0.47–3.60, "best case scenario"). Conclusions: Based on these findings, the benefits of amnioinfusion for midtrimester PROM <24 weeks of gestational age are unproven, and the potential harms remain undetermined. [ABSTRACT FROM AUTHOR]

Lethal congenital contracture syndrome 11 (LCCS11) is caused by homozygous or compound heterozygous variants in the GLDN gene on chromosome 15q21. GLDN encodes gliomedin, a protein required for the formation of the nodes of Ranvier and development of the human peripheral nervous system. We report a fetus with ultrasound alterations detected at 28 weeks of gestation. The fetus exhibited hydrops, short long bones, fixed limb joints, absent fetal movements, and polyhydramnios. The pregnancy was terminated and postmortem studies confirmed the prenatal findings: distal arthrogryposis, fetal growth restriction, pulmonary hypoplasia, and retrognathia. The fetus had a normal chromosomal microarray analysis. Exome sequencing revealed two novel compound heterozygous variants in the GLDN associated with LCCS11. This manuscript reports this case and performs a literature review of all published LCCS11 cases. [ABSTRACT FROM AUTHOR]

This is a retrospective study investigating the relationship between ultrasound and magnetic resonance imaging (MRI) examinations in congenital diaphragmatic hernia (CDH). CDH is a rare cause of pulmonary hypoplasia that increases the mortality and morbidity of patients. Inclusion criteria were: patients diagnosed with CDH who underwent MRI examination after the second-trimester morphology ultrasound confirmed the presence of CDH. The patients came from three university hospitals in Bucharest, Romania. A total of 22 patients were included in the study after applying the exclusion criteria. By analyzing the total lung volume (TLV) using MRI, and the lung to head ratio (LHR) calculated using MRI and ultrasound, we observed that LHR can severely underestimate the severity of the pulmonary hypoplasia, even showing values close to normal in some cases. This also proves to be statistically relevant if we eliminate certain extreme values. We found significant correlations between the LHR percentage and herniated organs, such as the left and right liver lobes and gallbladder. MRI also provided additional insights, indicating the presence of pericarditis or pleurisy. We wish to underline the necessity of MRI follow-up in all cases of CDH, as the accurate measurement of the TLV is important for future treatment and therapeutic strategy. [ABSTRACT FROM AUTHOR]

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.

This article, titled "EP09.115: Partial anomalous pulmonary venous connection scimitar type: clues to prenatal diagnosis," discusses the rare congenital anomaly known as scimitar syndrome, which involves abnormal connections and drainage of pulmonary veins into the systemic venous circulation. The authors present two cases of scimitar syndrome that were detected prenatally using fetal echo and MRI, with confirmation after birth. The article emphasizes the challenges of prenatal diagnosis and reviews the findings that may lead to a successful diagnosis. [Extracted from the article]

This article discusses the case of a 39-year-old pregnant woman who was diagnosed with both congenital diaphragmatic hernia (CDH) and Pallister-Killian Syndrome (PKS) during a first trimester ultrasound. CDH is a severe malformation where abdominal organs enter the chest cavity through a hole in the diaphragm, while PKS is a rare chromosomal disorder characterized by the presence of extra copies of chromosome 12. The article highlights the importance of early diagnosis and genetic counseling for these conditions, as they can have significant implications for the health and development of the fetus. [Extracted from the article]

This article, published in the journal Ultrasound in Obstetrics & Gynecology, discusses the fetal diagnosis of agenesis of the ductus venosus (ADV) and its corresponding perinatal outcomes. The study included 17 patients diagnosed with ADV out of 2,775 patients evaluated at a fetal cardiology unit. The most common type of ADV was the intrahepatic variety, and only two patients had chromosomal abnormalities. The article highlights the high prevalence of pulmonary hypertension in patients with extrahepatic ADV and the higher mortality rates associated with this condition. The authors emphasize the importance of early diagnosis and the need for further research on ADV. [Extracted from the article]

This article discusses the prenatal diagnosis and outcomes of meso/dextrocardia, a cardiac axis abnormality. The study reviewed 29 cases of fetal meso/dextrocardia diagnosed in a single hospital between January 2014 and February 2024. The results showed that there were eight cases of mesocardia and 21 cases of dextrocardia, with different complications associated with each. The study emphasizes the importance of evaluating the entire fetal body for anomalies when meso/dextrocardia is detected. [Extracted from the article]

This article, published in the journal Ultrasound in Obstetrics & Gynecology, discusses the Fetal Akinesia Deformation Sequence (FADS), a disorder characterized by limited fetal movement. The authors describe a new case of FADS in a non-consanguineous European couple, where the fetus exhibited lung hypoplasia, camptodactyly, and Talipes equinovarus. The pregnancies were terminated, and postmortem examination confirmed the prenatal findings and identified facial dysmorphism. The authors also identify ultrasound markers, such as reduced lung-to-head ratio and elevated diaphragmatic domes, that can indicate lung hypoplasia in FADS. [Extracted from the article]

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]

Bilateral renal agenesis (BRA) is a fetal anomaly which leads to anhydramnios and resultant pulmonary hypoplasia. Historically, this anomaly was universally fatal early in the neonatal period due to the severity of the associated lung disease. Over the last 30 years, innovations in fetal therapies—specifically, serial amnioinfusions—have led to instances of infant pulmonary survival and initiation of postnatal dialysis, raising the possibility that early neonatal death may not be inevitable. Amnioinfusions are not without risk, and maternal complications can include prelabor rupture of membranes, preterm labor, infection, and bleeding. The data detailing neonatal outcomes are still limited and actively being collected. Two case series and one non-randomized clinical trial have supplied most of the known outcome data for infants with BRA after prenatal amnioinfusion. Although there are survivors reported in the literature, mortality remains high, with many deaths in infancy due to dialysis-associated sepsis. In addition, previously unknown morbidities have been documented in these infants, including neurologic injury. These challenges, in addition to the mechanical difficulties of providing dialysis to extremely small infants, can result in significant burdens for patients and their caregivers and moral distress for the health care team. The present review aims to explain the pathophysiology of BRA, detail the historical context and rationale for serial amnioinfusions to treat the pulmonary insufficiency associated with BRA, describe the available data regarding outcomes of infants born following prenatal amnioinfusions, discuss ethical issues surrounding this fetal intervention, and describe critical aspects of prenatal counseling for patients considering the intervention.A higher resolution version of the Graphical abstract is available as Supplementary informationA higher resolution version of the Graphical abstract is available as Supplementary informationGraphical abstract: Bilateral renal agenesis (BRA) is a fetal anomaly which leads to anhydramnios and resultant pulmonary hypoplasia. Historically, this anomaly was universally fatal early in the neonatal period due to the severity of the associated lung disease. Over the last 30 years, innovations in fetal therapies—specifically, serial amnioinfusions—have led to instances of infant pulmonary survival and initiation of postnatal dialysis, raising the possibility that early neonatal death may not be inevitable. Amnioinfusions are not without risk, and maternal complications can include prelabor rupture of membranes, preterm labor, infection, and bleeding. The data detailing neonatal outcomes are still limited and actively being collected. Two case series and one non-randomized clinical trial have supplied most of the known outcome data for infants with BRA after prenatal amnioinfusion. Although there are survivors reported in the literature, mortality remains high, with many deaths in infancy due to dialysis-associated sepsis. In addition, previously unknown morbidities have been documented in these infants, including neurologic injury. These challenges, in addition to the mechanical difficulties of providing dialysis to extremely small infants, can result in significant burdens for patients and their caregivers and moral distress for the health care team. The present review aims to explain the pathophysiology of BRA, detail the historical context and rationale for serial amnioinfusions to treat the pulmonary insufficiency associated with BRA, describe the available data regarding outcomes of infants born following prenatal amnioinfusions, discuss ethical issues surrounding this fetal intervention, and describe critical aspects of prenatal counseling for patients considering the intervention.A higher resolution version of the Graphical abstract is available as Supplementary informationA higher resolution version of the Graphical abstract is available as Supplementary information [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]

Background: Autosomal‐recessive renal tubular dysgenesis (AR‐RTD) is a rare genetic disorder caused by defects in the renin‐angiotensin system that manifests as fetal anuria leading to oligohydramnios and Potter sequence. Although the most common outcome is neonatal death from renal failure, pulmonary hypoplasia, and/or refractory arterial hypotension; several cases have been reported that describe survival past the neonatal period. Methods: Herein, we report the first family with biallelic ACE variants and more than one affected child surviving past the neonatal period, as well as provide a review of the previously reported 18 cases with better outcomes. Results: While both siblings with identical compound heterozygous ACE variants have received different treatments, neither required renal replacement therapy. We show that both vasopressin and fludrocortisone in the neonatal period may provide survival advantages, though outcomes may also be dependent on the type of gene variant, as well as other factors. Conclusion: While AR‐RTD is most often a lethal disease in the neonatal period, it is not universally so. A better understanding of the factors affecting survival will help to guide prognostication and medical decision‐making. [ABSTRACT FROM AUTHOR]

The Hedgehog (HH) signaling pathway plays an essential role in mouse lung development. We hypothesize that the HH pathway is necessary for branching during human lung development and is impaired in pulmonary hypoplasia. Single-cell, bulk RNA-sequencing data, and human fetal lung tissues were analyzed to determine the spatiotemporal localization of HH pathway actors. Distal human lung segments were cultured in an air-liquid interface and treated with an SHH inhibitor (5E1) to determine the effect of HH inhibition on human lung branching, epithelial-mesenchymal markers, and associated signaling pathways in vitro. Our results showed an early and regulated expression of HH pathway components during human lung development. Inhibiting HH signaling caused a reduction in branching during development and dysregulated epithelial (SOX2, SOX9) and mesenchymal (ACTA2) progenitor markers. FGF and Wnt pathways were also disrupted upon HH inhibition. Finally, we demonstrated that HH signaling elements were downregulated in lung tissues of patients with a congenital diaphragmatic hernia (CDH). In this study, we show for the first time that HH signaling inhibition alters important genes and proteins required for proper branching of the human developing lung. Understanding the role of the HH pathway on human lung development could lead to the identification of novel therapeutic targets for childhood pulmonary diseases. [ABSTRACT FROM AUTHOR]

Purpose: We previously demonstrated that absence of miR-200b results in abnormal lung development in congenital diaphragmatic hernia due to imbalance between epithelial and mesenchymal cells. Tenascin C is a highly conserved extracellular matrix protein involved in epithelial to mesenchymal transition, tissue regeneration and lung development. Considering the involvement of Tenascin C and miR-200b and their potential interaction, we aimed to study Tenascin C during lung development in the absence of miR-200b. Methods: We collected lungs of miR-200b−/− mice (male, 8 weeks). We performed Western blot (WB) analysis (N = 6) and immunofluorescence (N = 5) for Tenascin C and alpha smooth muscle actin and RT-qPCR for Tenascin C gene expression (N = 4). Results: Using WB analysis, we observed a decreased total protein abundance of Tenascin C in miR-200b−/− lungs (miR-200b+/+: 3.8 × 107 ± 1 × 107; miR-200b−/−: 1.9 × 107 ± 5 × 106; p = 0.002). Immunofluorescence confirmed decreased total Tenascin C in miR-200b−/− lungs. Tenascin C was significantly decreased in the mesenchyme but relatively increased in the airways of mutant lungs. Total lung RNA expression of Tenascin C was higher in miR-200b−/− lungs. Conclusion: We report dysregulation of Tenascin C in lungs of miR-200b−/− mice. This suggests that absence of miR-200b results in abnormal Tenascin C abundance contributing to the lung hypoplasia observed in miR-200b−/− mice. [ABSTRACT FROM AUTHOR]

Background: Congenital diaphragmatic hernia (CDH) is a birth defect associated with abnormal lung development. Yes-associated protein (YAP) is a core kinase of the Hippo pathway, which controls organ size during development. The absence of YAP protein during lung development results in hypoplastic lungs comparable to the lung phenotype in CDH (Mahoney, Dev Cell 30(2):137–150, 2014). We aimed to describe the expression of YAP during normal and nitrofen-induced abnormal lung development. Methods: Intra-gastric administration of dams with 100 mg of nitrofen was used to induce CDH and abnormal lung development in the embryos. Immunofluorescence was performed to visualize the localization of YAP and p-YAP during lung development (E15, E18, E21). Western Blotting was used to determine the abundance of YAP and p-YAP in E21 control and nitrofen-induced hypoplastic CDH lungs. Results: Immunofluorescence demonstrated cytoplasmic localization of YAP protein in airway epithelial and mesenchymal cells of nitrofen-induced hypoplastic lungs compared to nuclear localization in control lungs. Western Blotting showed a decrease (p = 0.0188) in abundance of YAP (active form) and increase in p-YAP (inactive form) in hypoplastic lungs compared to control lungs. Conclusion: Our results demonstrate that YAP protein is mostly phosphorylated, inactive, and expressed in the cytoplasm at the later stages of nitrofen-induced hypoplastic lung development indicating that the alteration in regulation of YAP can be associated with the pathogenesis of abnormal lung development in experimental CDH. [ABSTRACT FROM AUTHOR]

Variants involving TBX4 are associated with a wide variety of disorders, including pulmonary arterial hypertension, ischiocoxopodopatellar syndrome (ICPPS)/small patella syndrome (SPS), lethal lung developmental disorders (LLDDs) in neonates, heart defects, and prenatally lethal posterior amelia with pelvic and pulmonary hypoplasia syndrome. The objective of our study was to elucidate the wide variable phenotypic expressivity and incomplete penetrance in a three‐generation family with a truncating variant in TBX4. In addition to exome and genome sequencing analyses, a candidate noncoding regulatory single nucleotide variant (SNV) within the lung‐specific TBX4 enhancer was functionally tested using an in vitro luciferase reporter assay. A heterozygous frameshift variant c.1112dup (p.Pro372Serfs*14) in TBX4 was identified in patients with mild interstitial lung disease (1), bronchiolitis obliterans (1), recurrent pneumothorax (1), ICPPS/SPS (1), LLDD (2), and in unaffected individuals (4). In two deceased neonates with LLDD, we identified a noncoding SNV rs62069651‐C located in trans to the mutated TBX4 allele that reduced the TBX4 promoter activity by 63% in the reporter assay. Our findings provide a functional evidence for the recently reported model of complex compound inheritance in which both TBX4 coding and in trans noncoding hypomorphic variants in the lung‐specific enhancer of TBX4 contribute to LLDD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Lung volume measurement on fetal MRI is a component of the imaging workup for various prenatal conditions, but its use as a prognosticator has been most heavily studied in congenital diaphragmatic hernia (CDH). Pediatric radiologists who perform and interpret fetal MRI must be familiar with the technical aspects of lung volume measurement to guarantee accurate measurement and reporting. Variability in timing and type of measurement at different fetal centers also requires pediatric radiologists to be up-to-date with the literature and aware of their center's internal data. This paper provides both a how-to guide for measuring fetal lung volumes on MRI and a comprehensive review of the CDH outcome literature to serve as a convenient reference for the pediatric radiologist. [ABSTRACT FROM AUTHOR]

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.

Background: Profound pulmonary arterial hypertension with end-stage right heart failure is considered to be the main cause of death in children with un-repaired congenital heart disease, and the traditional surgical treatment is heart-lung transplantation. We performed bilateral lung transplantation (LTx) with concomitant cardiac repair, and the patient has uplifting outcome.Case Presentation: We have reported the case of a patient with congenital hypoplasia of the bilateral pulmonary arteries and patent ductus arteriosus. The patient's clinical condition was gradually worsening and severely limited his ability to perform the activities of daily life. Bilateral LTx with concomitant patent ductus arteriosus repair was performed at the age of 11 years. The postoperative course was smooth and cardiopulmonary function nearly returned to normal according to radiological and laboratory examinations.Conclusions: Bilateral LTx with concomitant cardiac repair may be superior to heart-lung transplantation in the case of the specific congenital heart disease. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia can be diagnosed in the prenatal period and its severity can be measured by fetal imaging. There is now level I evidence that, in selected cases, Fetoscopic Endoluminal Tracheal Occlusion with a balloon increases survival to discharge from the neonatal unit as well as the risk for prematurity. Both effects are dependent on the time point of tracheal occlusion. Fetoscopic Endoluminal Tracheal Occlusion may also lead to iatrogenic death when the balloon cannot be timely retrieved. The implementation of the findings from our clinical studies, may also vary based on local conditions. These may be different in terms of available skill set, access to fetal therapy, as well as outcome based on local neonatal management. We encourage prior benchmarking of local outcomes with optimal postnatal management, based on large enough numbers and using identical criteria as in the recent trials. We propose to work further on prenatal prediction methods, and the improvement of fetal intervention. In this manuscript, we describe a research agenda from a fetal medicine perspective. This research should be in parallel with innovation in neonatal and pediatric (surgical) management of this condition. [ABSTRACT FROM AUTHOR]

Purpose: To report the longitudinal lung growth and prognosis of fetuses with severe left sided congenital diaphragmatic hernia (CDH) treated with fetoscopic tracheal occlusion (FETO) in a single institution. Methods: Fetal lung size (observed‐to‐expected lung area to head circumference [o/e‐LHR]) was measured in seven consecutive fetuses with isolated severe left‐sided CDH who underwent FETO. Fetal lung growth was used to prognosticate survival and need for ECMO. Results: Seven consecutive fetuses had a FETO procedure in the timeframe of this study. A total of 44 longitudinal ultrasound were performed to evaluate lung development. FETO was performed at GA 28.5 ± 0.5 weeks. Five (71.4%) infants survived to one‐year follow‐up and ECMO was needed in three patients (42.8%). Fetal lung response was observed in all fetuses; mean o/e‐LHR increased from 22.5% ± 1.4 before FETO to 44.4% ± 9.8 before delivery. Infants who survived had a higher percentage of fetal lung growth (21.8%) than those who died (8.25%). Conclusion: Our study supports the hypothesis that FETO promotes fetal lung growth in fetuses with severe left‐sided CDH, and the fetal pulmonary response seems to be associated with improved outcomes after the procedure. [ABSTRACT FROM AUTHOR]

To compare ultrasound (US) and magnetic resonance imaging (MRI) in the assessment of mediastinal shift angles (MSAs) in fetuses affected by isolated left congenital diaphragmatic hernia (CDH). The use of MRI-MSA and US-MSA as prognostic factor for postnatal survival in fetal left CDH was also explored. This was an observational study of 29 fetuses with prenatally diagnosed isolated left CDH, assessed with both US and MRI examinations between January 2015 and December 2018. The US-MSA measurements performed within 2 weeks from the MRI assessment were considered for the analysis. The primary outcome was the postnatal survival rate. No significant difference between US and MRI MSAs was detected (p =.419). Among the 29 cases, there were 21 alive infants, for an overall postnatal survival rate of 72.41%. After stratifying for postnatal survival, the best cutoffs with the highest discriminatory power in terms of sensibility and specificity were 42.1° for the US-MSA and 39.1° for the MRI-MSA. The performance of MRI-MSA in predicting postnatal survival was close to that of US-MSA in terms of sensitivity (62.5 versus 50.0%), specificity (80.9 versus 90.5%), positive predictive value (55.6 versus 66.7%), negative predictive value (85.0 versus 82.6%) and accuracy (75.9 versus 79.3%). There was no statistically significant difference between the two modalities (p >.05 for all). MRI and US can be interchangeably used for the assessment of MSA in prenatally diagnosed isolated left CDH. Moreover, MSA measured by both US and MRI was confirmed to be correlated with perinatal outcome in terms of survival. [ABSTRACT FROM AUTHOR]

Introduction: Congenital diaphragmatic hernia (CDH) is a defect involving herniation of the abdominal organs into the pleural cavity through an incompletely closed diaphragm. This defect is also accompanied by various types of pulmonary and bronchial hypoplasia and serious anomalies in the pulmonary vascular bed and pulmonary hypertension. Extracorporeal membrane oxygenation (ECMO) is used in extreme cases resistant to standard treatment. There are no reports clearly indicating the optimal time to make a decision about the repair of CDH in paediatric patients on ECMO. In high-risk neonates (with severe hypoplasia and pulmonary hypertension), this repair procedure is postponed until the cardiopulmonary parameters are stabilized and pulmonary pressure reduced. Aim: To present the experience of paediatric surgeons regarding congenital diaphragmatic hernia repair in neonates on extracorporeal membrane oxygenation. Material and methods: CDH was surgically repaired in 17 neonates, and of these 7 were on ECMO. Results: Surgical problems were encountered intraoperatively: positioning of the patient forced by the cannulae inserted in the carotid vessels, significant generalized oedema, significant capillary bleeding from the surgical wound, difficulties with closing the abdominal cavity. The most common postoperative complications included bleeding from various areas. Conclusions: Each surgery in a neonate with CDH on ECMO is a challenge for the whole medical team involved in the procedure. [ABSTRACT FROM AUTHOR]

Copyright of Folia Cardiologica is the property of VM Medica-VM Group (Via Medica) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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.

Purpose: Mediastinal position varies in neonates with congenital diaphragmatic hernia (CDH), reflecting contralateral shift due to mass effect. We aimed to create and validate a postnatal measurement of mediastinal positioning using chest radiographs in neonates with CDH who require extracorporeal membrane oxygenation., Methods: Chart review identified neonates with CDH who required veno-arterial extracorporeal membrane oxygenation between 2017 and 2022. Mediastinal shift index (MSI) is the ratio of the distance between the venous cannula tip and the contralateral chest wall divided by the total width of the contralateral hemithorax. Three raters completed MSI measurements at designated timepoints: after cannulation, post- CDH repair, and immediately before decannulation. Intraclass correlation coefficients (ICC) assessed inter-rater agreement. Initial MSI and observed/expected lung head ratio (O/E LHR) were correlated and compared between survivors and non-survivors. Receiver operative characteristic (ROC) curve analysis evaluated the ability of MSI and O/E LHR to predict survival., Results: 38 neonates were included. MSI demonstrated excellent agreement (ICC>0.98) amongst raters. Initial MSI and O/E LHR had a moderate positive correlation (Spearman correlation = 0.47, p = 0.014). Initial MSI differed significantly between survivors and non-survivors (0.52 vs. 0.33, p = 0.035) as did O/E LHR (0.36 vs. 0.26, p = 0.036). ROC analysis revealed initial MSI >0.35 was predictive of survival with 73% sensitivity and 70% specificity., Conclusion: Mediastinal shift index is reliable and predicted survival with a higher specificity than O/E LHR. Future studies will elucidate the role of trending MSI over a patient's course to inform interventions to optimize mediastinal position., Competing Interests: Conflict of interest None to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Fryns syndrome is an extremely rare autosomal recessive disorder and is characterized by congenital diaphragmatic hernia (CDH), dysmorphic facial features, distal limb hypoplasia, pulmonary hypoplasia, and characteristic-associated anomalies that lead to a high mortality rate. We present a prenatally diagnosed new case of Fryns "anophthalmia-plus" syndrome (FAPS) in a 41-year-old pregnant woman. An ultrasonographic examination at 22 weeks of gestation demonstrated left CDH with mediastinal shift, hypoplastic thorax with presumptive pulmonary hypoplasia, craniofacial anomalies, left anophthalmia, and distal limb hypoplasia. A genetic analysis of the fetal karyotype was held, which was negative for any known chromosomal or single gene abnormalities. After genetic counseling about the risks associated with these ultrasonographic findings, the parents opted for pregnancy termination. Timely identification or suspicion of Fryns syndrome during the early stages of pregnancy could facilitate parental guidance and enable the development of suitable strategies for prenatal treatment and/or perinatal care., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Maritsa et al.)

Scimitar syndrome is characterized by the anomalous connection of the right pulmonary venous return to the hepatic portion of the inferior vena cava. Its name is derived from the characteristic image observed in chest X-ray, CT scan, or during pulmonary angiography in cardiac catheterization. It is more common among females and rarely affects the left lung. The importance of knowing its symptoms and presentation allows for a high diagnostic suspicion, thus avoiding the underdiagnosis of the disease. The prognosis is generally good, and timely diagnosis can prevent the occurrence of complications such as pulmonary hypertension or portal hypertension. We present the case of an eight-year-old female patient, who was previously evaluated for episodes of lower respiratory tract infections at 18 months of age, detecting only dextroposition, without any diagnostic workup. She was then sent to our office at eight years of age, with the onset of exercise-induced dyspnea. A comprehensive workup was conducted, with a diagnosis of scimitar syndrome., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tomás Alvarado et al.)

Background: 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., Methods: 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., Results: 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)., Conclusions: 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 of Evidence: LEVEL Ⅲ Retrospective Comparative Study., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Some congenital diaphragmatic hernias are diagnosed beyond 1 month. A late-presenting congenital diaphragmatic hernia shows a variety of clinical manifestations, and the preoperative clinical course is variable. We herein report a pediatric case of late-presenting congenital diaphragmatic hernia diagnosed as acute abdomen., Case Presentation: A 5-year-old boy was brought to our hospital because of herniation of the intestine into the left thoracic cavity, which was observed on radiography performed for abdominal pain. Enhanced computed tomography showed herniation of the small intestine and colon into the left thoracic cavity. Emergency laparoscopic surgery was performed based on the diagnosis of left diaphragmatic hernia. The entire small intestine and part of the colon herniated from the posterolateral defect of the diaphragm. We were able to retract the herniated intestine back into the abdomen but confirmed that the diaphragmatic defect and closure of the defect seemed to be technically challenging via laparoscopy; therefore, we converted the procedure to open laparotomy. The diaphragmatic defect was directly closed with interrupted sutures, and the thoracic cavity was degassed. Postoperatively, the left lung was found to be poorly expanded, but pulmonary hypoplasia was not evident in this case., Conclusions: We herein report a pediatric case of late-presenting congenital diaphragmatic hernia diagnosed as abdominal pain. Late-presenting congenital diaphragmatic hernias present with a wide variety of symptoms; therefore, it is important to be reminded of these conditions and check chest radiographs in children presenting with acute or chronic respiratory or gastrointestinal symptoms of unknown etiology., (© 2024. The Author(s).)

Congenital diaphragmatic hernia (CDH) is a rare surgical cause of respiratory distress in neonates. CDH is caused by the protrusion of the abdominal contents into the thoracic cavity due to the failure of the pleuroperitoneal canal to close by eight weeks of gestation. We present the case of a full-term, female child, weighing 2.85 kg at birth, born by normal vaginal delivery to a 21-year-old primigravida admitted at our level III neonatal intensive care unit (NICU). Antenatal obstetric ultrasonography suggested duodenal atresia. After birth, the child was found to have right-sided CDH with gut malrotation. Intraoperative laparotomy revealed a right Bochdalek posterolateral defect with herniation of small bowel loops and a portion of the right lobe of the liver into the chest cavity and minimally malrotated cecum in the right iliac fossa (RIF). This case highlights the critical need for early detection and multidisciplinary management of congenital anomalies. Effective management requires a multidisciplinary approach, including prenatal counseling, careful surgical intervention, and intensive neonatal care to optimize respiratory and cardiovascular outcomes for affected infants., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Thorbole et al.)

In neonates, pulmonary diseases such as bronchopulmonary dysplasia and other chronic lung diseases (CLDs) pose significant challenges due to their complexity and high degree of morbidity and mortality. This review discusses the etiology, pathophysiology, clinical presentation, and diagnostic criteria for these conditions, as well as current management strategies. The review also highlights recent advancements in understanding the pathophysiology of these diseases and evolving strategies for their management, including gene therapy and stem cell treatments. We emphasize how supportive care is useful in managing these diseases and underscore the importance of a multidisciplinary approach. Notably, we discuss the emerging role of personalized medicine, enabled by advances in genomics and precision therapeutics, in tailoring therapy according to an individual's genetic, biochemical, and lifestyle factors. We conclude with a discussion on future directions in research and treatment, emphasizing the importance of furthering our understanding of these conditions, improving diagnostic criteria, and exploring targeted treatment modalities. The review underscores the need for multicentric and longitudinal studies to improve preventative strategies and better understand long-term outcomes. Ultimately, a comprehensive, innovative, and patient-centered approach can enhance the quality of care and outcomes for neonates with CLDs., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, El-Atawi et al.)

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., (© 2024. The Author(s).)