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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]

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]

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.

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]

Fetal lungs have fewer and smaller arteries with higher pulmonary vascular resistance (PVR) than a newborn. As gestation advances, the pulmonary circulation becomes more sensitive to changes in pulmonary arterial oxygen tension, which prepares them for the dramatic drop in PVR and increase in pulmonary blood flow (PBF) that occur when the baby takes its first few breaths of air, thus driving the transition from fetal to postnatal circulation. Dynamic and intricate regulatory mechanisms control PBF throughout development and are essential in supporting gas exchange after birth. Understanding these concepts is crucial given the role the pulmonary vasculature plays in the development of complications with transition, such as in the setting of persistent pulmonary hypertension of the newborn and congenital heart disease. An improved understanding of pulmonary vascular regulation may reveal opportunities for better clinical management., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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]

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]

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]

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]