Search

This study retrospectively aims to evaluate nine cases of congenital pulmonary ai rway malformation (CPAM) diagnosed during the prenatal period. Prenatal diagnosis of CPAMs is critical in the diagnosis of fetal thoracic malformations. Case studies provide a better understanding of the clinical course, treatment options, and outcomes of CPAMs. Cases with prenatally diagnosed lung lesions screened in the high-risk pregnancy category between October 2021 and February 2024 were analyzed retrospectively. The characteristics, location, and accompanying findings of the lesions were evaluated by perinatology specialists. The diagnosis of CPAM was categorized based on prenatal ultrasound images. This study show the demographic characteristics and clinical findings of the patients with CPAM. In our study, the mean age was 33 years, and the median week at diagnosis was 21 weeks and 2 days. The median birth weight was 2970 gm. The rate of vaginal delivery was 55.6%, while additional anomalies were detected at a rate of 66.7%. Most lesions were located in the right lung and had a cystic or solid-cystic nature. The distribution according to CPAM type was 22.2% type 1, 33.3% type 2, and 44.4% type 3. According to the results obtained by analyzing nine cases, two cases resulted in termination, regression was observed in two cases, and postnatal surgery was performed in one case. One case was followed up postnatally. This study examined the clinical course, treatment options, and outcomes of rare cases diagnosed with CPAM. The results highlight the importance of prenatal and postnatal processes of diffeternt types of CPAM. [ABSTRACT FROM AUTHOR]

Background: We aimed to conduct a systematic review and meta-analysis to evaluate the fetoscopic tracheal occlusion in patients with isolated severe and left-sided diaphragmatic hernia. Methods: Cochrane Library, Embase, and PubMed (Medline) databases were searched from inception to February 2024 with no filters or language restrictions. We included studies evaluating the outcomes of fetoscopic intervention compared to expectant management among patients with severe congenital diaphragmatic hernia exclusively on the left side. A random-effects pairwise meta-analysis was performed using RStudio version 4.3.1. Results: In this study, we included 540 patients from three randomized trials and five cohorts. We found an increased likelihood of neonatal survival associated with fetoscopic tracheal occlusion (Odds Ratio, 5.07; 95% Confidence Intervals, 1.91 to 13.44; p < 0.01) across general and subgroup analyses. Nevertheless, there were higher rates of preterm birth (OR, 5.62; 95% CI, 3.47–9.11; p < 0.01) and preterm premature rupture of membranes (OR, 7.13; 95% CI, 3.76–13.54; p < 0.01) in fetal endoscopic tracheal occlusion group compared to the expectant management. Conclusions: Our systematic review and meta-analysis demonstrated the benefit of fetoscopic tracheal occlusion in improving neonatal and six-month postnatal survival in fetuses with severe left-sided CDH. Further studies are still necessary to evaluate the efficacy of tracheal occlusion for isolated right-sided CDH, as well as the optimal timing to perform the intervention. [ABSTRACT FROM AUTHOR]

Background: Arginase 1 (Arg1) encodes a key enzyme that catalyzes the metabolism of arginine to ornithine and urea. In our recent study, we found that knockdown of Arg1 in the lungs of fetal mice induces apoptosis of epithelial cells and dramatically delays initiation of labor. As the most abundant internal mRNA modification, N6‐methyladenosine (m6A) has been found to play important roles in lung development and cellular differentiation. However, if the knockdown of Arg1 affects the RNA m6A modification in fetal lungs remains unknown. Methods: In the current study, the RNA m6A levels and the expression of RNA m6A related enzymes were validated in 13.0 dpc fetal lungs that Arg1 was knocked down by adeno‐associated virus carrying Arg1‐shRNA, using western blot, immunofluorescence, and RT‐qPCR. Results: No statistical differences were found in the expression of methyltransferase, demethylases, and binding proteins in the fetal lungs between AAV‐shArg1‐injected mice and AAV‐2/9‐injected mice. Besides, there is no significant change of overall RNA m6A level in fetal lungs from AAV‐shArg1‐injected mice, compared with that from AAV‐2/9‐injected mice. Conclusions: These results indicate that arginase 1 does not affect RNA m6A methylation in mouse fetal lung, and the mechanisms other than RNA m6A modification underlying the effects of Arg1 knockdown on the fetal lung development and their interaction with labor initiation need to be further explored. [ABSTRACT FROM AUTHOR]

Abstract Background Neonatal respiratory distress syndrome (RDS) is a leading cause of neonatal respiratory failure and neonatal mortality. It is frequent in preterm infants, because deficient surfactant needed to keep the airways (alveoli) open to assist infants breathe after birth. Nonetheless, it was also seen in full-term pregnancies. Noninvasive approaches for predicting the development of neonatal respiratory distress (RD) in preterm newborns include comparing the prenatal clinical outcome with the pulmonary artery resistance index (PA-RI) and fetal lung capacity as assessed by the virtual organ computer-aided analysis (VOCAL). Our study aimed to estimate optimal cutoff values and compare measurements of fetal pulmonary artery resistance index (PA-RI) and fetal lung volume (LV) assessed by VOCAL as noninvasive measures to predict neonatal RD development in preterm pregnancies to show which is more accurate. Results Out of the examined 147 women who delivered 147 living newborns, 59 of newborn (40.1%) developed neonatal RD. PA-RI has a higher value in 45 (76.27%), while fetal lung volume (FLV) was significantly lower in 43 (72.88%) of neonates who developed RD. Combining both measurements of PA-RI and FLV could predict all cases of RDS 59 (100%). Thirty of RDS neonates had mechanical ventilation and died (50.85%). Cutoff values of PA-RI ≥ 0.75 with 76.27% sensitivity, 82.95% specificity and 81.5% accuracy, whereas a cutoff of FLV ≤ 28 cm3 with sensitivity of 72.88%, specificity of 65.91% and accuracy of 74.8%, for prediction of RDS. Combining both cutoffs generated a more accurate detection 100%, specificity of 65.91% and 66.3% positive predictive value (PPV) and 100% negative predictive value (NPV) and 83% accuracy. Conclusions Both PA-RI and FLV are promising noninvasive tools which help in predicting RD fetuses with high sensitivity and specificity. PA-RI is more accurate than FLV cm3 in prediction of neonatal RDS. Combining these parameters increases the predictive value.

No previous studies have quantitatively assessed the effect of color tones on ultrasound texture analysis techniques. Our objective was to compare heterogeneity index (HI) between fetal lung images captured in grayscale and those same images after conversion to Ice and Sepia. Fetal lung images were obtained during medically indicated ultrasound examinations. We observed that HI is affected by the application of color tones to ultrasound images of the fetal lung. Therefore, for each type of biological tissue and color tone, determination of distinct HI nomograms and cut off points is recommended. [ABSTRACT FROM AUTHOR]

Background: Neonatal respiratory distress syndrome (RDS) is a leading cause of neonatal respiratory failure and neonatal mortality. It is frequent in preterm infants, because deficient surfactant needed to keep the airways (alveoli) open to assist infants breathe after birth. Nonetheless, it was also seen in full-term pregnancies. Noninvasive approaches for predicting the development of neonatal respiratory distress (RD) in preterm newborns include comparing the prenatal clinical outcome with the pulmonary artery resistance index (PA-RI) and fetal lung capacity as assessed by the virtual organ computer-aided analysis (VOCAL). Our study aimed to estimate optimal cutoff values and compare measurements of fetal pulmonary artery resistance index (PA-RI) and fetal lung volume (LV) assessed by VOCAL as noninvasive measures to predict neonatal RD development in preterm pregnancies to show which is more accurate. Results: Out of the examined 147 women who delivered 147 living newborns, 59 of newborn (40.1%) developed neonatal RD. PA-RI has a higher value in 45 (76.27%), while fetal lung volume (FLV) was significantly lower in 43 (72.88%) of neonates who developed RD. Combining both measurements of PA-RI and FLV could predict all cases of RDS 59 (100%). Thirty of RDS neonates had mechanical ventilation and died (50.85%). Cutoff values of PA-RI ≥ 0.75 with 76.27% sensitivity, 82.95% specificity and 81.5% accuracy, whereas a cutoff of FLV ≤ 28 cm3 with sensitivity of 72.88%, specificity of 65.91% and accuracy of 74.8%, for prediction of RDS. Combining both cutoffs generated a more accurate detection 100%, specificity of 65.91% and 66.3% positive predictive value (PPV) and 100% negative predictive value (NPV) and 83% accuracy. Conclusions: Both PA-RI and FLV are promising noninvasive tools which help in predicting RD fetuses with high sensitivity and specificity. PA-RI is more accurate than FLV cm3 in prediction of neonatal RDS. Combining these parameters increases the predictive value. [ABSTRACT FROM AUTHOR]

The associations between bronchopulmonary dysplasia (BPD) and the gestational pathologies of chorioamnionitis (CA) and hypertensive disorders of pregnancy (HDP) have become increasingly well recognized. However, the mechanisms through which these antenatal conditions cause increased risk of BPD remain less well characterized. The objective of this review is to discuss the role of the placenta in BPD predisposition as a primary driver of intrauterine alterations adversely impacting fetal lung development. We hypothesize that due to similarities in structure and function, placental disorders during pregnancy can uniquely impact the developing fetal lung, creating a unique placental-pulmonary connection. In the current review, we explore this hypothesis through analysis of clinical literature and preclinical model systems evaluating BPD predisposition, discussion of BPD phenotypes, and an overview on strategies to incorporate placental investigation into research on fetal lung development. We also discuss important concepts learned from research on antenatal steroids as a modulator fetal lung development. Finally, we propose that the appropriate selection of animal models and establishment of in vitro lung developmental model systems incorporating primary human placental components are key in continuing to understand and address antenatal predisposition to BPD. [ABSTRACT FROM AUTHOR]

Congenital lung anomalies vary in origin with numerous theories about overall formation. While many of these lesions may be asymptomatic or incidentally detected, on occasion these can have potentially life-threatening effects such as mass effect on adjacent structures and pulmonary hypoplasia. Prenatal diagnosis is advantageous to help direct prenatal counseling and perinatal care. Ultrasound and magnetic resonance imaging (MRI) are the most widely used modalities for fetal imaging and provide complementary information. This review describes congenital fetal chest lesions with a focus on differentiating imaging features. • Congenital lung lesions can range from asymptomatic to life threatening. • Pre and postnatal imaging with ultrasound and magnetic resonance imaging can assist in counseling and care. • Recognition of salient imaging findings can facilitate diagnosis. [ABSTRACT FROM AUTHOR]

Many preterm infants require mechanical ventilation as life-saving therapy. However, ventilation-induced overpressure can result in lung diseases. Considering the lung as a viscoelastic material, positive pressure inside the lung results in increased hydrostatic pressure and tissue compression. To elucidate the effect of positive pressure on lung tissue mechanics and cell behavior, we mimic the effect of overpressure by employing an uniaxial load onto fetal and adult rat lungs with different deformation rates. Additionally, tissue expansion during tidal breathing due to a negative intrathoracic pressure was addressed by uniaxial tension. We found a hyperelastic deformation behavior of fetal tissues under compression and tension with a remarkable strain stiffening. In contrast, adult lungs exhibited a similar response only during compression. Young’s moduli were always larger during tension compared to compression, while only during compression a strong deformation-rate dependency was found. In fact, fetal lung tissue under compression showed clear viscoelastic features even for small strains. Thus, we propose that the fetal lung is much more vulnerable during inflation by mechanical ventilation compared to normal inspiration. Electrophysiological experiments with different hydrostatic pressure gradients acting on primary fetal distal lung epithelial cells revealed that the activity of the epithelial sodium channel (ENaC) and the sodium-potassium pump (Na,K-ATPase) dropped during pressures of 30 cmH2O. Thus, pressures used during mechanical ventilation might impair alveolar fluid clearance important for normal lung function.

The mechanism of parturition is still unclear. Evidence has shown that delivery is associated with cellular senescence of the amniotic membrane. We isolated fetal lung-associated exosomes from the amniotic fluid from term labor (TL-exos) and verified that the exosomes can cause primary human amniotic epithelial cell (hAEC) senescence and apoptosis and can release higher levels of senescence-associated secretory phenotype (SASP)-related molecules and proinflammatory damage-associated molecular patterns (DAMPs) than exosomes isolated from the amniotic fluid from term not in labor (TNIL-exos). The human lung carcinoma cell lines (A549) can be used as an alternative to alveolar type 2 epithelial cells producing pulmonary surfactant. Therefore, we isolated A549 cell-derived exosomes (A549-exos) and found that they can trigger hAEC to undergo the same aging process. Finally, the animal experiments suggested that A549-exos induced vaginal bleeding and preterm labor in pregnant mice. Therefore, we conclude that exosomes derived from fetal lungs in term labor amniotic fluid induce amniotic membrane senescence, which may provide new insight into the mechanism of delivery.

Abstract Background In this study, we combined ultrasound and Doppler parameters to conclude the most accurate and applicable method for fetal lung maturity assessment. The purpose is to reduce risk of neonatal respiratory distress by assessment of fetal lung maturity through ultrasound and Doppler instead of amniocentesis. Results A total of 120 women were included. The ultrasound examination was performed at a gestational age ranging between 30 and 37 weeks and delivery occurred within 72 h from ultrasound. After birth, 19 fetuses were diagnosed with RDS. The ultrasound parameters assessed for fetal lung maturity showed varying sensitivity and specificity but presence of proximal tibial epiphyses showed the highest sensitivity (91%) and specificity (95%) followed by the presence of distal femoral epiphyses with 90% sensitivity and 84% specificity. The placental grade III maturity showed a sensitivity of 81% and 74% specificity followed by the presence of the amniotic fluid free-floating particles with an 83% sensitivity and 63% specificity, while echogenic fetal thalamus showed 77% and 79% for sensitivity and specificity, respectively, for prediction of fetal lung maturity. By using the fetal biometry, we could report that a BPD between 82.8 and 93.5 mm, AC between 295 and 322 mm, and FL (62.7-72.1 mm) correlated with mature fetal lungs. Regarding Doppler indices, increased resistive index of umbilical artery > 0.69 and of pulmonary artery > 0.78 correlated with neonatal RDS while fetuses with UtA RI values between 0.43 and 0.66 noticed in RDS vs (0.42-0.57) in the non-RDS. MCA RI values are also higher in RDS 0.77–0.88 vs 0.74–0.79 in non-RDS. On the other hand, analysis of colon grading and fetal lung echogenicity in relation to liver showed no significant value in the assessment of fetal lung maturity. Conclusion Ultrasound and Doppler showed good predictive value and accuracy and is considered a valuable non-invasive procedure in assessment of fetal lung maturity. However, no single parameter alone could show a definitive sign

Large scale early scanning of fetuses via ultrasound imaging is widely used to alleviate the morbidity or mortality caused by congenital anomalies in fetal hearts and lungs. To reduce the intensive cost during manual recognition of organ regions, many automatic segmentation methods have been proposed. However, the existing methods still encounter multi-scale problem at a larger range of receptive fields of organs in images, resolution problem of segmentation mask, and interference problem of task-irrelevant features, obscuring the attainment of accurate segmentations. To achieve semantic segmentation with functions of (1) extracting multi-scale features from images, (2) compensating information of high resolution, and (3) eliminating the task-irrelevant features, we propose a multi-scale model with skip connection framework and attention mechanism integrated. The multi-scale feature extraction modules are incorporated with additive attention gate units for irrelevant feature elimination, through a U-Net framework with skip connections for information compensation. The performance of fetal heart and lung segmentation indicates the superiority of our method over the existing deep learning based approaches. Our method also shows competitive performance stability during the task of semantic segmentations, showing a promising contribution on ultrasound based prognosis of congenital anomaly in the early intervention, and alleviating the negative effects caused by congenital anomaly. [ABSTRACT FROM AUTHOR]

Objectives: To analyze and compare, using ultrasound-based radiomics technology, fetal-lung texture in pregnancies affected by gestational diabetes mellitus (GDM) and/or pre-eclampsia (PE) and in normal pregnancies, overall and at different gestational ages.Methods: In this retrospective study, 430 high-throughput features per fetal-lung image were extracted from 548 fetal-lung ultrasound images (obtained at the level of the four-chamber view of the heart) in 548 pregnant women who delivered between July 2018 and August 2019 at the Obstetrics and Gynecology Hospital of Fudan University. Images had been obtained during ultrasound examinations between 28 and 41 weeks of gestation. The data were divided randomly into training set (80% of fetal-lung images) and independent test set (20% of images), and 20% of the images in the training set were then selected as the validation set. A standard machine-learning model based on ultrasound-based radiomics technology was created using features of fetal-lung texture extracted from the images, and a regression model was used to evaluate the relationship between lung-texture features, GDM and/or PE and gestational age.Results: Of the 548 pregnancies included, 108 were affected by GDM alone, 71 by PE alone and 25 by both GDM and PE, and 344 were normal. The overall performance of the GDM and PE prediction model was superior to that of the gestational-age prediction model, with an area under the receiver-operating-characteristics curve of 0.95-0.99, sensitivity of 78.8-97.1% in the validation set and 74.5-91.3% in the independent test set, specificity of 79.8-94.3% in the validation set and 75.7-88.4% in the independent test set and accuracy of 81.0-95.3% in the validation set and 80.6-86.4% in the independent test set.Conclusions: Using ultrasound-based radiomics technology, fetal lungs from pregnancies grouped according to whether they were affected by GDM and/or PE could be distinguished from each other and from fetal lungs of normal pregnancies, and lungs from pregnancies at different gestational ages could be distinguished. These findings support further research to explore the use of this non-invasive technology to predict neonatal respiratory complications in women with PE, GDM or their combination. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Pulmonary hypoplasia is associated with severe respiratory distress immediately after birth and frequently leads to neonatal death. In this study, we compared the fetal lung echo texture in pregnancies at high and low risk for pulmonary hypoplasia. Ultrasonic tissue heterogeneity was determined by a dynamic range calculation. This quantification uses a dithering technique based on the Floyd‐Steinberg algorithm, in which the pixels are transformed into a binary map. Pregnancies at high risk for pulmonary hypoplasia showed decreased fetal lung heterogeneity on ultrasound imaging. This image‐processing technique may allow improved risk stratification, patient counseling, and treatment approaches for pulmonary hypoplasia. [ABSTRACT FROM AUTHOR]

Background: In this study, we combined ultrasound and Doppler parameters to conclude the most accurate and applicable method for fetal lung maturity assessment. Thepurpose is to reduce risk of neonatal respiratory distress by assessment of fetal lung maturity through ultrasound and Doppler instead of amniocentesis. Results: A total of 120 women were included. The ultrasound examination was performed at a gestational age ranging between 30 and 37 weeks and delivery occurred within 72 h from ultrasound. After birth, 19 fetuses were diagnosed with RDS. The ultrasound parameters assessed for fetal lung maturity showed varying sensitivity and specificity but presence of proximal tibial epiphyses showed the highest sensitivity (91%) and specificity (95%) followed by the presence of distal femoral epiphyses with 90% sensitivity and 84% specificity. The placental grade III maturity showed a sensitivity of 81% and 74% specificity followed by the presence of the amniotic fluid free-floating particles with an 83% sensitivity and 63% specificity, while echogenic fetal thalamus showed 77% and 79% for sensitivity and specificity, respectively, for prediction of fetal lung maturity. By using the fetal biometry, we could report that a BPD between 82.8 and 93.5 mm, AC between 295 and 322 mm, and FL (62.7-72.1 mm) correlated with mature fetal lungs. Regarding Doppler indices, increased resistive index of umbilical artery > 0.69 and of pulmonary artery > 0.78 correlated with neonatal RDS while fetuses with UtA RI values between 0.43 and 0.66 noticed in RDS vs (0.42-0.57) in the non-RDS. MCA RI values are also higher in RDS 0.77–0.88 vs 0.74–0.79 in non-RDS. On the other hand, analysis of colon grading and fetal lung echogenicity in relation to liver showed no significant value in the assessment of fetal lung maturity. Conclusion: Ultrasound and Doppler showed good predictive value and accuracy and is considered a valuable non-invasive procedure in assessment of fetal lung maturity. However, no single parameter alone could show a definitive sign [ABSTRACT FROM AUTHOR]

Chorioamnionitis, a potentially serious inflammatory complication of pregnancy, is associated with the development of an inflammatory milieu within the amniotic fluid surrounding the developing fetus. When chorioamnionitis occurs, the fetal lung finds itself in the unique position of being constantly exposed to the consequent inflammatory meditators and/or microbial products found in the amniotic fluid. This exposure results in significant changes to the fetal lung, such as increased leukocyte infiltration, altered cytokine, and surfactant production, and diminished alveolarization. These alterations can have potentially lasting impacts on lung development and function. However, studies to date have only begun to elucidate the association between such inflammatory exposures and lifelong consequences such as lung dysfunction. In this review, we discuss the pathogenesis of and fetal immune response to chorioamnionitis, detail the consequences of chorioamnionitis exposure on the developing fetal lung, highlighting the various animal models that have contributed to our current understanding and discuss the importance of fetal exposures in regard to the development of chronic respiratory disease. Finally, we focus on the clinical, basic, and therapeutic challenges in fetal inflammatory injury to the lung, and propose next steps and future directions to improve our therapeutic understanding of this important perinatal stress.

Surfactant protein B (SP-B) is a key component of pulmonary surfactant. SP-B is processed to a mature, surface-active protein from a pro-peptide by two distinct cleavage events in its N-terminal and C-terminal regions. Napsin A, a protease expressed in type II pneumocytes, is responsible for the N-terminal cleavage event. Here, for the first time, we have evaluated the expression of Napsin A in normal fetal lungs at different gestational ages and in lungs from fetuses and neonates with congenital and acquired pathological pulmonary conditions. Lung samples were collected from fetal and neonatal autopsies at the Department of Medicine and Surgery's Pathology Unit of Parma University (Italy). Immunohistochemical analysis was performed using a primary anti-Napsin A (clone IP64 clone) monoclonal antibody. A section of lung adenocarcinoma was used as an external positive control. Napsin A was expressed early in normal fetal lungs throughout the epithelium of the distal pseudoglandular tracts. In fetuses at 30 weeks of gestation and term newborns, Napsin A was already expressed only in isolated cells within the alveolar epithelium, similar to adult subjects. Furthermore, increased expression of Napsin A compared with a control group was observed in lung tissue from fetuses and a newborn with pathological conditions (inflammatory diseases and pulmonary hypoplasia). In conclusion, this study demonstrates that Napsin A is produced early in fetal life, and that its production is increased in many diseases, presumably in an effort to remedy functional pulmonary failure. [ABSTRACT FROM AUTHOR]

Purpose: The evaluation of fetal lung maturity is critical for clinical practice since the lung immaturity is an important cause of neonatal morbidity and mortality. For the evaluation of the development of fetal lung maturation degree, our study established a deep model from ultrasound images of four-cardiac-chamber view plane. Methods: A two-stage transfer learning approach is proposed for the purpose of the study. A specific U-net structure is designed for the applied deep model. In the first stage, the model is to first learn the recognition of fetal lung region in the ultrasound images. It is hypothesized in our study that the development of fetal lung maturation degree is generally proportional to the gestational age. Then, in the second stage, the pretrained deep model is trained to accurately estimate the gestational age from the fetal lung region of ultrasound images. Results: Totally 332 patients were included in our study, while the first 206 patients were used for training and the subsequent 126 patients were used for the independent testing. The testing results of the established deep model have the imprecision as 1.56 ± 2.17 weeks on the gestational age estimation. Its correlation coefficient with the ground truth of gestational age achieves 0.7624 (95% CI 0.6779 to 0.8270, P value < 0.00001). Conclusion: The hypothesis that the development of fetal lung maturation degree can be represented by the texture information from ultrasound images has been preliminarily validated. The fetal lung maturation degree can be considered as being represented by the deep model's output denoted by the estimated gestational age. [ABSTRACT FROM AUTHOR]

Chorioamnionitis, a potentially serious inflammatory complication of pregnancy, is associated with the development of an inflammatory milieu within the amniotic fluid surrounding the developing fetus. When chorioamnionitis occurs, the fetal lung finds itself in the unique position of being constantly exposed to the consequent inflammatory meditators and/or microbial products found in the amniotic fluid. This exposure results in significant changes to the fetal lung, such as increased leukocyte infiltration, altered cytokine, and surfactant production, and diminished alveolarization. These alterations can have potentially lasting impacts on lung development and function. However, studies to date have only begun to elucidate the association between such inflammatory exposures and lifelong consequences such as lung dysfunction. In this review, we discuss the pathogenesis of and fetal immune response to chorioamnionitis, detail the consequences of chorioamnionitis exposure on the developing fetal lung, highlighting the various animal models that have contributed to our current understanding and discuss the importance of fetal exposures in regard to the development of chronic respiratory disease. Finally, we focus on the clinical, basic, and therapeutic challenges in fetal inflammatory injury to the lung, and propose next steps and future directions to improve our therapeutic understanding of this important perinatal stress. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the toxic effects of cigarette smoke exposure on lung and the protective role of Omega 3 and Vitamin D against these toxic effects biochemically and histologically. 28 pregnant Wistar Albino rats were divided into four groups. The first group was control group; the second group was exposed to smoke of 10 cigarette by puff device 2 hours/day after pregnancy; the third group was exposed to cigarette smoke together with Omega 3 (0.5 mg/kg/day) and the fourth group was exposed to cigarette smoke together with vitamin D (42 microgram/kg/day). Finally, lung tissue sections of the newborn rats were stained with Hemotoxilen eosine and Masson tricromite. Malondialdehyde (MDA) and Fluorescent Oxidation Products (FOU) levels were measured. Fetal weights and the number of fetuses were significantly lower in the group received only cigarette smoke (both p<0.001). Histopathologically, pulmonary volume, number of developed alveols and parenchyma elasticity decreased significantly, meanwhile interstitial tissue increased, elastin and collagen did not develop adequately. Histopathologic changes significantly decreased in the group given Omega 3 and Vitamin D. Statistically, MDA and FOU levels were found to be higher in the group exposed to cigarette smoke compared to the control group, and MDA and FOU levels were lower in the group given Omega 3 along with cigarette smoke (p<0.001). Cigarette smoke caused histologically significant damage to fetal lung tissue, oxidative stress and increased MDA and FOU levels. This damage was significantly reduced with Omega 3 and Vitamine D supplementation. Omega 3 is an important antioxidant; vitamin D has no significant antioxidant effect. [ABSTRACT FROM AUTHOR]

Bovine alphaherpesvirus type 1 (BoAHV-1) is associated with respiratory and reproductive syndromes. Until present the immunologic mechanisms involved in BoAHV-1 abortion are partially known. We studied key elements of the innate immune response in the placentas and fetal lungs from cattle experimentally-inoculated with BoAHV-1. These tissues were analyzed by histopathology. Furthermore, virus identification was performed by qPCR and the expression of the inflammatory cytokines such as tumor necrosis factor-alpha, interleukin 1-alpha and inflammatory mediators like inducible nitric oxide synthase and cyclooxeganse-2 was evaluated by immunohistochemistry. The viral transplacental infection was confirmed by the detection of BoAHV-1 by qPCR in the placenta and fetal organs, which revealed mild inflammatory lesions. Inducible nitric oxide synthase immunolabelling was high in the lungs of infected fetuses and placentas, as well as for tumor necrosis factor-alpha in the pulmonary parenchyma and cyclooxeganse-2 in fetal annexes. However, the expression of interleukin 1-alpha was weak in these organs. To our knowledge, this is the first study that provides strong evidence of an early immune response to BoAHV-1 infection in the conceptus. Advances in the knowledge of the complex immunological interactions at the feto-maternal unit during BoAHV-1 infection are needed to clarify the pathogenesis of abortion. • BoAHV-1 transplacental infection causes an early immune response at the feto-maternal unit. • BoAHV-1 induces protein expression of iNOS in fetal lung and placenta. • BoAHV-1 induces protein expression of TNFα in fetal lungs and COX-2 in the placenta. • The expression of pro-inflammatory mediators in the placenta by BoAHV-1 might trigger the abortion or control the infection. [ABSTRACT FROM AUTHOR]

The major surfactant protein, SP-A (a product of the SFTPA gene), serves as a marker of type II pneumocyte differentiation and surfactant synthesis. SFTPA expression in cultured human fetal lung (HFL) epithelial cells is upregulated by hormones that increase cyclic AMP (cAMP) and activate TTF-1/NKX2.1 and NF-κB. To further define mechanisms for type II cell differentiation and induction of SP-A, we investigated roles of microRNAs (miRNAs). Using microarray to identify differentially expressed miRNAs in HFL epithelial cells during type II cell differentiation in culture, we observed that members of the miRNA 199a (miR-199a)/miR-214 cluster were significantly downregulated during differentiation. Validated and predicted targets of miR-199a-3p/miR-199a-5p and miR-214, which serve roles in type II cell differentiation (COX-2, NF-κB p50/p65, and CREB1), and the CREB1 target, C/EBPβ, were coordinately upregulated. Accordingly, overexpression of miR-199a-5p, miR-199a-3p, or miR-214 mimics in cultured HFL epithelial cells decreased COX-2, NF-κB p50/p65, CREB1, and C/EBPβ proteins, with an associated inhibition of SP-A expression. Interestingly, overexpression of the EMT factor, ZEB1, which declines during cAMPinduced type II cell differentiation, increased pri-miR-199a and reduced the expression of the targets NF-κB/p50 and COX-2. Collectively, these findings suggest that the developmental decline in miR-199a/miR-214 in HFL causes increased expression of critical targets that enhance type II cell differentiation and SP-A expression. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) has a higher incidence of neonatal respiratory distress syndrome, and lipogenesis is required for the synthesis of pulmonary surfactants. The aim of this study was to determine the effect of insulin treatment in GDM on the production of lipids in the lungs of fetal rats. GDM was induced by streptozotocin, and insulin was used to manage diabetes. Type II alveolar epithelial cells (AEC II), bronchoalveolar lavage fluid (BALF), and lung tissues of the neonatal rats were sampled for analyses. Insulin treatment could not decrease plasma glucose to normal level at a later gestational stage. Lipids/phospholipids in AEC II, BALF, and lung tissues decreased in GDM, and insulin treatment could not increase the levels; quantitative PCR and western blotting demonstrated a lower level of sterol regulator element-binding protein 1 (SREBP-1), SREBP cleavage-activating protein (SCAP), and insulin-induced gene 1 (INSIG-1) in GDM, but insulin treatment upregulated only SREBP-1. Nuclear translocation of the SREBP-1 protein in AEC II was impaired in GDM, which could not be ameliorated by insulin treatment. These findings indicated that insulin treatment in GDM cannot promote lipogenesis in the fetal lung because of failure to redress the imbalance among SREBP-1, SCAP, and INSIG-1. [ABSTRACT FROM AUTHOR]

• Ultrasonography has been explored to quantitatively examine the fetal lung as a non-invasive means. • We proposed a deep learning model for automated fetal lung segmentation and measurement. • Our model was constructed combined U-Net with Graph model and pre-trained Vgg-16 network. • The correlation between the size of fetal lung/heart as delineated by the model with gestational age was analyzed. • Our research will alleviate the labor of the clinicians in routine measurement of the fetal lung/cardiac. The neonatal respiratory morbidity that was primarily caused by the immaturity of the fetal lung is an important clinical issue in close relation to the morbidity and mortality of the fetus. In clinics, the amniocentesis has been used to evaluate the fetal lung maturity, which is time-consuming, costly and invasive. As a non-invasive means, ultrasonography has been explored to quantitatively examine the fetal lung in the past decades. However, existing studies required the contour of the fetal lung which was delineated manually. This may lead to significant inter- and intra-observer variations. We proposed a deep learning model for automated fetal lung segmentation and measurement, which was constructed combined U-Net with Graph model and pre-trained Vgg-16 network. The graph connection would extract stable feature for final segmentation and pre-trained method could speed up convergence. The model was trained with 3500 datasets augmented from 250 ultrasound images with both the fetal lung and heart delineated manually, and tested on 50 ultrasound images. In addition, the correlation between the size of fetal lung/heart as delineated by the model with gestational age was analyzed. The fetal lung and cardiac area were segmented automatically with the accuracy, average Intersection over Union (IoU), sensitivity and precision being 0.991, 0.818, 0.909 and 0.888, respectively. In addition, the size of fetal lung/heart was well correlated with the gestational age, demonstrating good potentials for assessing the fetal development. This study proposed a new robust method for automatic fetal lung segmentation in ultrasound images using Vgg16-GCN-UNet. Our proposed method could be utilized potentially not only to improve existing research in quantitative analyzing the fetal lung using ultrasound imaging technology, but also to alleviate the labor of the clinicians in routine measurement of the fetal lung/cardiac. [ABSTRACT FROM AUTHOR]

Resumen (español) El objetivo de la investigación fue determinar las modificaciones del Doppler de las arterias pulmonares fetales posterior al uso de betametasona para la maduración pulmonar. Se realizó una investigación de tipo explicativa, prospectiva y longitudinal con un diseño cuasi-experimental y una muestra no probabilística intencional de 106 pacientes que acudieron a la consulta Pre-natal de Alto Riesgo del Hospital Central “Dr. Urquinaona". Una vez seleccionadas las pacientes se les administró inyecciones intramusculares de betametasona (12 mg/día) por dos días consecutivos. Se realizaron las mediciones de índice de pulsatilidad, índice de resistencia y relación sistólico / diastólica de las arterias pulmonares fetales. Se observó disminución significativa de los valores promedio del índice de pulsatilidad en la segunda medición comparado con la medición inicial (p < 0,05). Sin embargo, el promedio de la tercera medición no mostró diferencia significativas con los valores iniciales (p = ns). El índice de resistencia disminuyó en la segunda medición para luego aumentar en la tercera medición comparado con el valor inicial (p < 0,05 para las dos mediciones). El valor promedio de la relación sistólico / diastólica presentó disminución significativa durante la segunda medición para luego presentar un aumento significativo al momento de la tercera medición comparado con el valor inicial (p < 0,05 para las dos mediciones). Se concluye que el uso de betametasona para la inducción de la maduración pulmonar produce modificaciones en las mediciones Doppler de las arterias pulmonares fetales. Abstract (english) The objective of research was to determine Doppler modifications of fetal pulmonary arteries after use of betamethasone for lung maturation. An explicative, prospective and longitudinal research was done with a quasi-experimental design and an intentional non-probabilistic sample of 106 patients who assisted to High Risk Antenatal Consult at Hospital Central “Dr. Urquinaona". Once patients were selected, two intramuscular injections of betamethasone (12 mg/day) were administered for two consecutive days. Measurements of pulsatility index, resistance index and systolic / diastolic ratio of fetal pulmonary arteries were done. There was observed a significant reduction of mean values of pulsatility index after second measurement compared with initial measurement (p < 0.05). However, mean value of third measurement did not show significant difference with initial value (p = ns). Resistance index decreased in second measurement and later increased in third measurement compared with initial measurements (p < 0.05 for both measurements). Mean value of systolic / diastolic ratio showed a significant reduction during second measurements and then presented a significant increase at the moment of third measurements (p < 0.05 for both measurements). It is concluded that the use of betamethasone for induction of lung maturation produces modifications in Doppler measurements of fetal pulmonary arteries.

The article compares the haemodynamics of DCC against ICC, using a non-asphyxial ~40 s interval between clamping and ventilation in preterm lambs (Smolich & Kenna, 2022). The findings from Smolich and Kenna suggest that the haemodynamic benefits of DCC, compared with this current ventilation time delay following ICC, may be minor in uncomplicated preterm deliveries. Keywords: birth transition; delayed cord clamping; fetal heart; fetal lung; neonatal resuscitation; neonate; ventilation EN birth transition delayed cord clamping fetal heart fetal lung neonatal resuscitation neonate ventilation 3641 3642 2 08/17/22 20220815 NES 220815 The transition of the fetus to newborn life involves a number of physiological changes, specifically to the respiratory and cardiovascular systems. [Extracted from the article]

Key points Chronic fetal hypoxaemia is a common pregnancy complication associated with intrauterine growth restriction that may influence respiratory outcome at birth., We investigated the effect of maternal chronic hypoxia for a month in late gestation on signalling pathways regulating fetal lung maturation and the transition to air-breathing at birth using isobaric hypoxic chambers without alterations to maternal food intake., Maternal chronic hypoxia in late gestation increases fetal lung expression of genes regulating hypoxia signalling, lung liquid reabsorption and surfactant maturation, which may be an adaptive response in preparation for the successful transition to air-breathing at birth., In contrast to other models of chronic fetal hypoxaemia, late gestation onset fetal hypoxaemia promotes molecular regulation of fetal lung maturation. This suggests a differential effect of timing and duration of fetal chronic hypoxaemia on fetal lung maturation, which supports the heterogeneity observed in respiratory outcomes in newborns following exposure to chronic hypoxaemia in utero., Abstract Chronic fetal hypoxaemia is a common pregnancy complication that may arise from maternal, placental and/or fetal factors. Respiratory outcome of the infant at birth likely depends on the duration, timing and severity of the hypoxaemic insult. We have isolated the effect of maternal chronic hypoxia (MCH) for a month in late gestation on fetal lung development. Pregnant ewes were exposed to normoxia (21% O2) or hypoxia (10% O2) from 105 to 138 days of gestation (term ∼145 days). At 138 days, gene expression in fetal lung tissue was determined by quantitative RT-PCR. Cortisol concentrations were determined in fetal plasma and lung tissue. Numerical density of surfactant protein positive cells was determined by immunohistochemistry. MCH reduced maternal [ABSTRACT FROM AUTHOR]

Preterm birth remains the major cause of neonatal morbidity and mortality throughout the world. This is due, in part, to our incomplete understanding of the mechanisms that underlie the maintenance of pregnancy and the initiation of parturition at term. In this article, we review our current knowledge of the complex, interrelated and concerted mechanisms whereby progesterone maintains myometrial quiescence throughout most of pregnancy, as well as those that mediate the upregulation of the inflammatory response and decline in progesterone receptor function leading to parturition. Herein, we review findings that demonstrate a role of the fetus in the timing of birth. Specifically, we focus on our own studies indicating that maturation of the fetal lung and enhanced secretion of the surfactant components, surfactant protein A (SP-A) and the potent inflammatory glycerophospholipid, platelet-activating factor (PAF), initiate a signaling cascade culminating in parturition. Our studies suggest an essential role of steroid receptor coactivators, SRC-1 and SRC-2, which activate expression of genes encoding SP-A and LPCAT1. LPCAT1 is a key enzyme in the synthesis of PAF, as well as DPPC, a highly surface-active glycerophospholipid component of surfactant. Thus, we describe a novel pathway through which the fetus contributes to the initiation of labor by signaling the mother when its lungs have achieved sufficient maturity for survival in an aerobic environment. [ABSTRACT FROM AUTHOR]

Exposure to altered intrauterine conditions during pregnancy influences both fetal growth and organ development. Chronic fetal hypoxaemia is a common pregnancy complication associated with intrauterine growth restriction (IUGR) that may influence the risk of infants experiencing respiratory complications at birth. There are a variety of signalling pathways that contribute to normal fetal lung development at the molecular level. The specific molecular effects of chronic hypoxaemia associated with IUGR on lung development are likely to be dependent on the specific aetiology (maternal, placental and/or fetal factors) that can alter hormone concentrations, oxygen and nutrient transport to the fetus. This review discusses molecular pathways that may contribute to altered fetal lung maturation following exposure to chronic hypoxaemia. Importantly, these studies highlight that the heterogeneity in respiratory outcomes at birth in this obstetric subpopulation are likely determined by the timing, severity and duration of chronic hypoxaemia encountered by the fetus during pregnancy. [ABSTRACT FROM AUTHOR]

More women than not are entering pregnancy either overweight or obese. This presents a significant health care burden with respect to maternal morbidities and offspring complications at birth and in later life. In recent years it has also become clear that maternal obesity is an even greater global health problem than anticipated, because the effects are not limited to the mother but are also programmed in the fetus, known as the 'intergenerational cycle of obestiy'. Despite a large body of epidemiological evidence reporting outcomes of obese pregnancies, including offspring respiratory complications, much less is known about the molecular effects of maternal obesity on fetal lung development. This review focuses on the influence of altered substrate supply associated with the obesogenic intrauterine environment on fetal lung development. Understanding the molecular mechanisms contributing to altered fetal lung development will lead to improved respiratory outcomes for offspring at birth and in later life. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the feasibility of using diffusion-weighted magnetic resonance imaging (DW-MRI) to assess the fetal lung apparent diffusion coefficient (ADC) at 3 Tesla (T).Materials and Methods: Seventy-one pregnant women (32 second trimester, 39 third trimester) were scanned with a twice-refocused Echo-planar diffusion-weighted imaging sequence with 6 different b-values in 3 orthogonal diffusion orientations at 3T. After each scan, a region-of-interest (ROI) mask was drawn to select a region in the fetal lung and an automated robust maximum likelihood estimation algorithm was used to compute the ADC parameter. The amount of motion in each scan was visually rated.Results: When scans with unacceptable levels of motion were eliminated, the lung ADC values showed a strong association with gestational age (P < 0.01), increasing dramatically between 16 and 27 weeks and then achieving a plateau around 27 weeks.Conclusion: We show that to get reliable estimates of ADC values of fetal lungs, a multiple b-value acquisition, where motion is either corrected or considered, can be performed. J. Magn. Reson. Imaging 2016;44:1650-1655. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the independent association of fetal pulmonary response and prematurity to postnatal outcomes after fetal tracheal occlusion for congenital diaphragmatic hernia.Methods: Fetal pulmonary response, prematurity (<37 weeks at delivery) and extreme prematurity (<32 weeks at delivery) were evaluated and compared between survivors and non-survivors at 6 months of life. Multivariable analysis was conducted with generalized linear mixed models for variables significantly associated with survival in univariate analysis.Results: Eighty-four infants were included, of whom 40 survived (47.6%) and 44 died (52.4%). Univariate analysis demonstrated that survival was associated with greater lung response (p=0.006), and the absence of extreme preterm delivery (p=0.044). In multivariable analysis, greater pulmonary response after FETO was an independent predictor of survival (aOR 1.87, 95% CI 1.08-3.33, p=0.023), whereas the presence of extreme prematurity was not statistically associated with mortality after controlling for fetal pulmonary response (aOR 0.52, 95% CI 0.12-2.30, p=0.367).Conclusion: Fetal pulmonary response after FETO is the most important factor associated with survival, independently from the gestational age at delivery. [ABSTRACT FROM AUTHOR]

Congenital cystic adenomatoid malformation accounts for the vast majority of congenital cystic lung pathologies. The clinical spectrum of congenital cystic adenomatoid malformation is wide and ranges from silent incidental lesions to severe congenital respiratory distress or stillbirths. Management of clinically silent lesions is still a matter of debate, with conservative follow-up being a popular approach during the last decade. However, an optimal methodology of follow-up is yet to be determined. In this study, ultrasound is proposed as a follow-up tool for clinically silent lesions based on the findings in a case with known congenital cystic adenomatoid malformation from the antenatal period, which has been followed up for four years. [ABSTRACT FROM AUTHOR]

Intrauterine growth restriction induced by placental restriction (PR) in sheep leads to chronic hypoxemia and reduced surfactant maturation. The underlying molecular mechanism involves altered regulation of hypoxia signaling by increased prolyl hydroxylase domain (PHD) expression. Here, we evaluated the effect of intratracheal administration of the PHD inhibitor dimethyloxalylglycine (DMOG) on functional, molecular, and structural determinants of lung maturation in the control and PR sheep fetus. There was no effect of DMOG on fetal blood pressure or fetal breathing movements. DMOG reduced lung expression of genes regulating hypoxia signaling (HIF-3α, ACE1), antioxidant defense (CAT), lung liquid reabsorption (SCNN1-A, ATP1-A1, AQP-1, AQP-5), and surfactant maturation (SFTP-A, SFTP-B, SFTP-C, PCYT1A, LPCAT, ABCA3, LAMP3) in control fetuses. There were very few effects of DMOG on gene expression in the PR fetal lung (reduced lung expression of angiogenic factor ADM, water channel AQP-5, and increased expression of glucose transporter SLC2A1). DMOG administration in controls reduced total lung lavage phosphatidylcholine to the same degree as in PR fetuses. These changes appear to be regulated at the molecular level as there was no effect of DMOG on the percent tissue, air space, or numerical density of SFTP-B positive cells in the control and PR lung. Hence, DMOG administration mimics the effects of PR in reducing surfactant maturation in the lung of control fetuses. The limited responsiveness of the PR fetal lung suggests a potential biochemical limit or reduced plasticity to respond to changes in regulation of hypoxia signaling following exposure to chronic hypoxemia in utero. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate fetal lung growth using 3‐dimensional sonography in healthy fetuses and those with congenital diaphragmatic hernia (CDH). Methods: Right and total lung volumes were serially evaluated by 3‐dimensional sonography in 66 healthy fetuses and 52 fetuses with left‐sided CDH between 20 and 37 weeks' menstrual age. Functions fitted to these parameters were compared for 2 groups: (1) healthy versus those with CDH; and (2) fetuses with CHD who survived versus those who died. Results: Fetal right and total lung volumes as well as fetal observed‐to‐expected right and total lung volume ratios were significantly lower in fetuses with CDH than healthy fetuses (P<.001) and in those fetuses with CDH who died (P<.001). The observed‐to‐expected right and total lung volume ratios did not vary with menstrual age in healthy fetuses or in those with CDH (independent of outcome). Conclusions: Lung volume rates were lower in fetuses with left‐sided CDH compared to healthy fetuses, as well as in fetuses with CDH who died compared to those who survived. The observed‐to‐expected right and total lung volume ratios were relatively constant throughout menstrual age in fetuses with left‐sided CDH, suggesting that the origin of their lung growth abnormalities occurred before 20 weeks and did not progress. The observed‐to‐expected ratios may be useful in predicting the outcome in fetuses with CDH independent of menstrual age. [ABSTRACT FROM AUTHOR]

An increase in oxygen tension at birth is one of the key signals that initiate pulmonary vasodilation in the fetal lung. We investigated the hypothesis that targeting endothelial nitric oxide synthase (eNOS) to the mitochondrial outer membrane regulates reactive oxygen species (ROS) formation in the fetal pulmonary artery endothelial cells (PAEC) during this transition. We isolated PAEC and pulmonary arteries from 137-day gestation fetal lambs (term = 144 days). We exposed PAEC to a simulated transition from fetal to (3% O2) to normoxic (21%) or hyperoxic (95% O2) postnatal PO2 or to the nitric oxide synthase (NOS) agonist ATP. We assessed the effect of O2 and ATP on eNOS interactions with the mitochondrial outer membrane protein porin and with the chaperone hsp90. We also investigated the effect of decoy peptides that blocked eNOS interactions with porin or hsp90 on PAEC angiogenesis and vasodilator function of pulmonary arteries. Transition of fetal PAEC from 3 to 21% O2 but not to 95% O2 or exposure to ATP increased eNOS association with hsp90 and porin. Decoy peptides that blocked eNOS interactions decreased NO release, increased O2 consumption and mitochondrial ROS levels, and impaired PAEC angiogenesis. Decoy peptides also inhibited the relaxation responses of pulmonary artery rings and dilation of resistance size pulmonary arteries to ATP. The mitochondrial-antioxidant mito-ubiquinone restored the response to ATP in decoy peptide-treated pulmonary arteries. These data indicate that targeting eNOS to mitochondria decreases endothelial oxidative stress and facilitates vasodilation in fetal pulmonary circulation at birth. [ABSTRACT FROM AUTHOR]

The expression pattern of thyroid transcription factor 1 (TTF-1) and neuroendocrine markers, neuron cell adhesion molecule (NCAM; CD56), chromogranin A (CgA) and synaptophysin (Syp), of different lung cell lineages was histologically analyzed in 15 normal human fetal lungs and 12 neuroendocrine tumors (NETs) using immunohistochemical methods. During pseudoglandular phase strong nuclear TTF-1 staining was detected in the columnar nonciliated epithelial cells, while NCAM, CgA and Syp had a moderate expression in the proximal airways and mild expression in the distal airways. Neuroendocrine cells (NECs) in proximal lung airway were co-localizing TTF-1 and other neuroendocrine markers while neuroendocrine bodies (NEBs) exhibit only staining with NCAM and Syp. In the canalicular phase TTF-1 nuclear staining was expressed only in several epithelial cells in proximal airways, while budding airways epithelium showed strong TTF-1 expression. Expression of NCAM, CgA and Syp in this phase equals the one in pseudoglandular phase. NEBs cells were co-localizing TTF-1 and NCAM in proximal airways and few NECs in distal airway were co-localizing TTF-1 and Syp. TTF-1 staining in the saccular phase was limited to subsets of epithelial cells in the proximal airways with stronger positivity in the distal airways. NCAM expression is moderate only in proximal airways, while Syp and CgA show mild expression in proximal and distal airways. NECs were co-localizing TTF-1 and NCAM in proximal lung airway. With regard to NECs, all small cell lung cancer (SCLC) cells had strong TTF-1, NCAM, Syp and CgA positivity and TTF-1 co-localized with other neuroendocrine markers. All pulmonary typical carcinoids were TTF-1 negative, while pulmonary atypical carcinoids were focal positive for TTF-1 and some neoplastic cells co-localized TTF-1 with neuroendocrine markers. Our results indicate that TTF-1 expression in NECs suggests a possible role in their normal development and differentiation. Our results also indicate that possible cell of origin for poorly differentiated SCLC and some atypical carcinoid could be a progenitor cell in neuroendocrine lineage while in typical carcinoids possible cell of origin is localized in terminally differentiated NECs. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To evaluate lung growth in healthy fetuses and those with congenital diaphragmatic hernia ( CDH) using two-dimensional ( 2D) ultrasound. Methods Fetal right lung measurements obtained by 2D ultrasound between 19 and 37 weeks' gestation were evaluated longitudinally in 66 healthy fetuses and 52 fetuses with isolated left-sided CDH. Right lung areas were determined by the 'tracing' and 'longest-diameters' methods and, subsequently, lung area-to-head circumference ratios ( LHRs) were calculated. Functions fitted to these size parameters with respect to gestational age were evaluated for three sets of group-wise comparisons: (1) healthy vs CDH fetuses; (2) different degrees of severity of CDH; and (3) CDH fetuses that survived vs those that died by 6 months postpartum. Results There was a significantly slower increase in right lung areas and LHRs with advancing gestational age in CDH fetuses than in healthy individuals ( P < 0.05). Compared to those with milder forms of CDH, lung areas and LHRs of fetuses with more severe forms displayed a smaller increase ( P < 0.05) and LHRs of fetuses with severe CDH did not increase during pregnancy ( P > 0.05). Individuals who died postpartum did not show any increase in LHR ( P > 0.05) throughout gestation. Conclusions The right lung area and LHR, calculated using either the longest-diameters or tracing method, display reduced growth rates during gestation in cases of isolated left-sided CDH as compared with healthy fetuses. The growth curve characteristics of fetal lung areas and LHRs may be useful for predicting neonatal mortality. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Copyright of African Journal of Cancer / Journal Africain du Cancer is the property of Lavoisier 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.)

Purpose: The lung structures are formed in parallel following several successive stages of development: embryonic phase, pseudoglandular phase, canalicular phase, saccular phase, alveolar phase. Finally the following structures are finalized: bronchi, bronchioles, blood vessels lung parenchyma, that can be functional only after the secretion of surfactant. Starting from these data we have tried to objectify the lung development during fetal life. Material and Method: In order to highlight the fetal lungs we used parasagittal sections on mice fetuses with the cephalic-caudal dimensions of 30 mm, which corresponds to the ontogenetic time of the 3rd trimester of gestation. Results: For each lung we can describe a base a diaphragmatic surface, a tip and tow surfaces: costal and mediastinal. Discussions: The respiratory segment is formed from bronchi of different structures and caliber. We have observed large bronchi and than bronchi in diferent stages of dicotomization. The small bronchi have in their wall structure peripheral myoblasts, with elongated shape acidophil cytoplasm and central nucleus. The covering epithelium is cylindrical simple. The bronchioles are coated with simple cubic epithelium. The middle tunica can poorly identified by the presents of a few myoblasts and the adventitia is missing. Conclusions: Microscopic aspect of the lungs is pseudoglandular. The bronchi's wall is undergoing differentiation. Vessels have similar structure to the one of the adult. [ABSTRACT FROM AUTHOR]

Fetal lung interstitial tumor, a newly recognized lung lesion in infants, was first reported in 2010. Here, we report the first Japanese case of fetal lung interstitial tumor which was originally diagnosed as atypical congenital cystic adenomatoid malformation/congenital pulmonary airway malformation type 3. A 7-day-old girl was referred to our hospital with respiratory distress and a left lung mass and she subsequently underwent left lower lobectomy. The specimen showed a 5 cm solid mass with a fibrous capsule. Histological examination revealed immature airspaces and interstitium, containing bronchioles and cartilage. The epithelial and interstitial cells contained abundant glycogen granules. Immunohistochemistry showed nuclear/cytoplasmic expression of β-catenin in the epithelial and interstitial cells. β-catenin gene mutations and trisomy 8 were not detected, so a neoplastic origin could not be confirmed. The histological findings were partly consistent with normal fetal lung at the canalicular stage, pulmonary interstitial glycogenosis, and congenital cystic adenomatoid malformation/congenital pulmonary airway malformation type 3. In this report, we compare the above conditions and discuss the pathogenesis of fetal lung interstitial tumor. [ABSTRACT FROM AUTHOR]

Background: Numerous studies in cultured cells indicate that damage to mitochondrial DNA (mtDNA) dictates cellular responses to oxidant stress, yet the consequences of mtDNA damage have not been studied directly in the preterm lung. Objective: We sought to determine whether hyperoxia-induced fetal lung dysmorphogenesis is linked to mtDNA damage and establish mtDNA repair as a potential therapeutic approach for treating lung dysplasia in the preterm neonate. Methods: Hyperoxia-induced mtDNA damage was assessed by quantitative alkaline gel electrophoresis in normoxic (3% O2) and hyperoxic (21% O2) fetal rat lung explants. A fusion protein construct targeting the DNA repair enzyme endonuclease III (Endo III) to the mitochondria was used to augment mtDNA repair. Fetal lung branching and surfactant protein C (SFPTC) were assessed in these tissues. Results: Hyperoxia induced mtDNA damage in lung explants and was accompanied by impaired branching morphogenesis and decreased SFPTC mRNA expression. Treatment of lung explants with Endo III fusion protein prevented hyperoxia-induced mtDNA damage and restored normal branching morphogenesis and SFPTC mRNA expression. Conclusion: These findings support the concept that mtDNA governs cellular responses to oxidant stress in the fetal lung and suggest that modulation of mtDNA repair is a potential pharmacologic strategy in the prevention of hyperoxic lung injury. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The D2-40 antigen is a glycosylated sialomucin that is strongly expressed by lymphatic endothelial cells. Recently we observed the expression of D2-40 on the luminal surface of pulmonary airspaces in lung sections. The aim of the study was to assess the expression of D2-40 antigen in normal lung development and in various pathologic conditions in which abnormal alveolar infiltrates were present. Formalin-fixed lung tissue was selected from 42 fetal/neonatal autopsy cases ranging in gestational age from 12 to 41 weeks and from 10 adult lungs. In the fetal/neonatal group, 22 cases were histologically normal, whereas 20 were abnormal (including cases of pneumonia, alveolar hemorrhage, meconium aspiration, pulmonary hypoplasia, and pulmonary interstitial emphysema). In the adult group, 5 cases were histologically normal and 5 had pneumonia. Immunohistochemical staining was performed on all cases using antibody to D2-40. All cases of normal fetal/neonatal lung and normal adult lung showed diffuse strong expression of D2-40 on the luminal surface of the alveolar lining cells. D2-40 expression was also noted on the bronchiolar lining cells of normal fetal/neonatal lung. In all cases in which there was an abnormal infiltrate or foreign material within the airspaces, expression of D2-40 was lost in the alveolar lining. The production of the D2-40 antigen in the alveolar lining occurs as early as 12 weeks gestation and continues to be present throughout all other stages of lung development, as well as in adult lung. These results suggest that D2-40 may have a cell membrane protective function. [ABSTRACT FROM AUTHOR]

Prenatal identification of lung abnormalities has increased with prenatal surveillance. With the advent of improved antenatal imaging over the past ten years, the diagnosis, assessment and management of congenital cystic lung abnormalities have changed. These were once considered the exclusive domain of the surgeon, who had the authority to operate on all congenital cystic lung abnormalities regardless of size or clinical signs in order to avoid the risk of cancer and improve lung growth in even asymptomatic infants. Clinicians are reconsidering this approach in the light of the spontaneous improvement and possible resolution that occurs over months to years with many of these lesions, thinking about the opportunity to take a more conservative approach in many minimally symptomatic or asymptomatic infants in the early months of life. The risks of subsequent cancer are poorly understood and probably overstated. Many centers advocate surgery only in cases of symptomatic or significant lesions, although there is little consensus as to what constitutes a significant lesion. This article will review current knowledge (classification, pathogenesis, genetics, prenatal evaluation, clinical implications) on congenital cystic adenomatoid malformations (CCAM) and discuss management options for young children with these lung abnormalities. [ABSTRACT FROM AUTHOR]

Abstract: Maturation of pulmonary fetal type II cells to initiate adequate surfactant production is crucial for postnatal respiratory function. Little is known about specific mechanisms of signal transduction controlling type II cell maturation. The ErbB4 receptor and its ligand neuregulin (NRG) are critical for lung development. ErbB4 is cleaved at the cell membrane by the γ-secretase enzyme complex whose active component is either presenilin-1 (PSEN-1) or presenilin-2. ErbB4 cleavage releases the 80kDa intracellular domain (4ICD), which associates with chaperone proteins such as YAP (Yes-associated protein) and translocates to the nucleus to regulate gene expression. We hypothesized that PSEN-1 and YAP have a development-specific expression in fetal type II cells and are important for ErbB4 signaling in surfactant production. In primary fetal mouse E16, E17, and E18 type II cells, PSEN-1 and YAP expression increased at E17 and E18 over E16. Subcellular fractionation showed a strong cytosolic and a weaker membrane location of both PSEN-1 and YAP. This was enhanced by NRG stimulation. Co-immunoprecipitations showed ErbB4 associated separately with PSEN-1 and with YAP. Their association, phosphorylation, and co-localization were induced by NRG. Confocal immunofluorescence and nuclear fractionation confirmed these associations in a time-dependent manner after NRG stimulation. Primary ErbB4-deleted E17 type II cells were transfected with a mutant ErbB4 lacking the γ-secretase binding site. When compared to transfection with wild-type ErbB4, the stimulatory effect of NRG on surfactant protein mRNA expression was lost. We conclude that PSEN-1 and YAP have crucial roles in ErbB4 signal transduction during type II cell maturation. [Copyright &y& Elsevier]

Aim: To evaluate the potential of different lung measurements using three-dimensional ultrasonography (3D-US) to predict perinatal outcome in isolated congenital diaphragmatic hernia (CDH). Methods: Twenty-one fetuses presenting isolated CDH were prospectively evaluated by 3D-US between January 2002 and November 2003. Observed/expected total, contralateral and ipsilateral fetal lung volume ratios (o/e-TotFLV, o/e-ContFLV and o/e-IpsiFLV, respectively) were calculated using the rotational technique and ultrasonographic fetal total lung volume to bodyweight ratio (USFLW). These lung measurements were compared to each other and to perinatal outcomes: perinatal deaths, severe pulmonary hypoplasia (PH) and pulmonary arterial hypertension (PAH). Results: Perinatal death occurred in 11 of the 21 infants (52.4%), severe PH in 14 of 21 infants (66.7%) and PAH in 14 of 20 neonates (70%). Severe PH and PAH occurred simultaneously in 12 of 20 (60%) infants. Good correlations between lung ratios were observed. O/e-TotFLV, o/e-IpsiFLV and USFLW correlated statistically with postnatal diagnosis of severe PH, while only o/e-TotFLH correlated statistically with postnatal diagnosis of PAH. The accuracies of o/e-TotFLV, o/e-ContFLV, o/e-IpsiFLV and USFLW in predicting perinatal deaths were 85.7, 76.2, 66.7 and 76.2%, respectively. Conclusion: O/e-TotFLV using 3D-US appears to be the most accurate predictor of perinatal mortality because it can predict both PH and PAH. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the potential application of diffusion-weighted (DW) magnetic resonance imaging (MRI) in fetuses with congenital diaphragmatic hernia (CDH). The mothers of 93 fetuses with normal lungs and 14 fetuses with left-sided CDH were scanned using the magnetic resonance imaging (MRI) system. The study found that the DW MRI is a useful predictor of postnatal outcome.

The authors assess causal, cellular and inflammatory links between intraamniotic infection with Ureaplasma parvum or Mycoplasma hominis and preterm labor in a nonhuman primate model. Long-term catheterized rhesus monkeys received intraamniotic inoculations of clinical isolates of Ureaplasma parvum serovar 1, M hominis, media control or physiological saline. Genital mycoplasmas were quantified in amniotic fluid (AF) and documented in fetal tissues by culture and PCR. In association with elevated AF colony counts for U parvumor M hominis, there was a sequential upregulation of AF leukocytes, proinflammatory cytokines, prostaglandin E2 and F2α, metalloproteinase-9 and uterine activity (P< .05). Fetal membranes and lung were uniformly positive for both microorganisms; fetal blood and cerebrospinal fluid cultures and PCR were more often positive for M hominis than U parvum. Histopathologic findings of chorioamnionitis, a systemic fetal inflammatory response and pneumonitis worsen with duration of in utero infection. U parvum or M hominis, as sole pathogens, elicit a robust proinflammatory response which contributes to preterm labor and fetal lung injury. [ABSTRACT FROM AUTHOR]