Pulmonary Hypoplasia Research Articles

Proximal Interruption of Pulmonary Artery: Spectrum of Radiological Findings With Emphasis on Chest Radiograph and Contrast-Enhanced Computed Tomography (CECT).

Introduction Proximal interruption of pulmonary artery (PIPA) is a congenital anomaly presenting withaberrant termination of the pulmonary artery at the hilum. It results in a variety of radiological andclinical manifestations. Clinically, isolated PIPA can be asymptomatic till late adulthood or can present with dyspnoea, chest discomfort, hemoptysis and recurrent infections. PIPA can be associated with multiple cardiovascular anomalies such as tetralogy of Fallot (TOF), ventricular septal defects (VSD), and scimitar syndrome. We present a spectrum of cases with both isolated proximal interruption of the pulmonary arteryand cases associated with other cardiovascular abnormalities.Typical chest radiographs and chest contrast-enhanced computed tomography (CECT) findings are discussed and demonstrated in detail.Proper and early diagnosis is a crucial step as it can significantly modify the treatment choice, thereby reducing morbidity. Objective To document the different presentations of the proximal arrest of pulmonary arteries, to document associations with cardiovascular and pulmonary manifestations, and to elaborate on and demonstrate the various radiological imaging findings. Material and methods All the cases that were reported with proximal interruption of pulmonary artery on the CECT studies conducted between 2019 and 2022 at a tertiary care hospital in Telangana, India. The demographic data, clinical presentation, chest radiographs, and chest CECT were collected retrospectively. Data analysis was done using Microsoft Excel 2019 to calculate descriptive statistics.A total of 22 cases were identified of which three cases were excluded of as they were previously operated and 19 cases were taken as the study population. Results Nineteen patients were included in the study. Demographic details, clinical history, CECT, and chest radiographs were collected wherever available. The majority of the cases belonged to the ≤ 10 yrs age group with the most common clinical presentation being a previous diagnosis of tuberculosis or recurrent upper respiratory tract infections. The predominant findings on chest radiographs were deviation of the trachea to the affected side, volume loss in the ipsilateral lung field, and compensatory hyperinflation of the contralateral lung field. On the CECT chest, the main findings were interrupted pulmonary artery, hypoplastic lung fields with bronchiectasis, or ground glassing. Associated cardiovascular and pulmonary malformations were identified with notable cases: TOF, right-sided aortic archand scimitar syndrome. Their typical imaging findings have been elucidated and discussed in detail. Conclusions Patients with recurrent respiratory infections or hemoptysis having hypoplastic lung field with hyperinflation of the contralateral lung on chest radiographs should be evaluated for pulmonary artery interruptions. Chest CECT allows evaluation of the bronchial tree and lung parenchyma at the same time which helps distinguish pulmonary interruption from conditions such as Swyer-James-Macleod syndrome, pulmonary hypoplasia, thromboembolismand arteritis. Cases with PIPA can also be associated with cardiovascular and pulmonary anomalies such as TOF, partial anomalous pulmonary venous connection (PAPVC), and VSD. The knowledge of these associations is essential as they can influence the mode of treatment and can help reduce the long-term morbidity and mortality associated with the condition.

The effect of tracheal occlusion in congenital diaphragmatic hernia in the nitrofen rat lung explant model

Here, we establish a tracheal occlusion (TO) model with rat lung explants in nitrofen-induced pulmonary hypoplasia in the congenital diaphragmatic hernia (CDH). We extracted lungs from rats on an embryonic day 18. We mimicked TO in the lung explants by tying the trachea. We assessed lung weight, morphometry, and abundance of Ki-67, Active caspase-3, and Prosurfactant Protein C (proSP-C) with immunofluorescence. Lung weight was higher in TO + than TO - on day 1. Abundance of Ki-67 was higher in TO + than TO - (0.15 vs. 0.32, p = 0.009 for day 1, 0.07 vs. 0.17, p = 0.004 for day 2, 0.07 vs. 0.12, p = 0.044 for day 3), and Active caspase-3 was higher in TO + than TO - on day 2 and day 3 (0.04 vs. 0.03 p = 0.669 for day 1, 0.03 vs. 0.13 p < 0.001 for day 2, 0.04 vs. 0.17 p = 0.008 for day3). However, proSP-C protein abundance was lower in TO + than TO - (67.9 vs. 59.1 p = 0.033 for day 1, 73.5 vs. 51.6 p = 0.038 for day 2, 83.1 vs. 56.4 p = 0.009 for day 3). The TO model in lung explants mimics the outcomes of current surgical models of TO and further studies can reveal the cellular and molecular effects of TO in CDH lungs.

Targeting the lung endothelial niche to promote angiogenesis and regeneration: A review of applications.

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

Termination of pregnancy after a prenatal diagnosis of congenital diaphragmatic hernia: Factors influencing the parental decision process.

To evaluate the incidence of termination of pregnancies (TOP) and factors associated with the decision for TOP in prenatally detected congenital diaphragmatic hernia (CDH). Single-centre retrospective cohort includes all prenatally detected CDH cases born between January 2009 and December 2021. Parental factors, such as parity, and fetal characteristics, such as disease severity, were collected. Descriptive statistics were used to present the data. Differences between terminated and continued pregnancies were analysed. The study population consisted of 278 prenatally detected CDH cases of which 80% detected <24weeks of gestation. The TOP rate was 28% in cases that were detected <24weeks of gestation. Twenty continued pregnancies resulted in either intrauterine fetal demise (n=6), preterm birth <24weeks (n=2), or comfort care after birth (n=12). The survival rate was 70% in the remaining 195 live born cases. Factors associated with the decision for TOP were additional fetal genetic or anatomical abnormalities (p<0.0001) and expected severity of pulmonary hypoplasia in left-sided CDH (p=0.0456). The decision to terminate a pregnancy complicated by fetal CDH depends on the severity of pulmonary hypoplasia and the presence of additional abnormalities. This emphasises the importance of early referral to expertise centres for detailed evaluation and multidisciplinary counselling.

Buccal carcinoma associated with adult congenital pulmonary hypoplasia: A case report and literature review

Congenital pulmonary hypoplasia is a relatively rare lung malformation. The disease is usually identified in the neonatal period or early childhood. Most affected patients die of respiratory insufficiency after birth. Mild congenital dysplasia is asymptomatic, while moderate congenital dysplasia manifests as respiratory distress or does not become evident until adulthood. Cases of congenital pulmonary hypoplasia in adults are rare, especially in combination with malignant tumors. We report the case of a 64-year-old man with buccal carcinoma who was accidentally found to have hypoplasia of the left lung during treatment. After chest computed tomography and chest radiograph, the diagnosis of adult congenital pulmonary hypoplasia was confirmed. Since the patient had a history of bronchiectasis for more than 30 years and only had 1 healthy lung, the cardiopulmonary compensatory function was poor and the patient could not tolerate surgery, he was given radiotherapy and chemotherapy. Radiotherapy and chemotherapy were successfully completed, and within the patient's tolerance, there was no serious adverse reaction of respiratory system. Congenital pulmonary hypoplasia's diagnosis is challenging in adults because the condition can easily be mistaken for a more common disease. However, early diagnosis is very important to enable prompt therapy and ensure proper follow-up to detect and treat complications such as pulmonary infection and pulmonary hypertension in a timely manner.

Transcervical Amnioinfusion in Meconium Stained Amniotic Fluid in the Pregnant Women at Labour and Foetomaternal Outcome Attending Labour Ward of Rajshahi Medical College Hospital

Background: Amniotic fluid is the fluid present in amniotic sac which surrounds the foetus, provides nutrition and maintains temperature of the foetus. Physically it allows the foetus to move and prevents it from injury. Functionally it enables foetal breathing mobility that prevents pulmonary hypoplasia and exercises digestive tract by swallowing amniotic fluid. Objective: The objective of the study was to explore the role of amnioinfusion in intrapartum management of meconium stained amniotic fluid in the pregnant women at labor and foetomaternal outcome of the patients attending labor ward of Rajshahi Medical College Hospital. Methods: This experimental randomized control trial study carried out in the Department of Obstetrics and Gynecology of Rajshahi Medical College Hospital, Rajshahi from July, 2012 to June, 2014. Sample size was 100 and randomly allocated into equally two halves as study group and control group. Purposive sampling technique was followed. Results: In this study the age of the study group up to 30 years was 38(47.5%), control group 42(52.5%) and total 80(80.0%). On the other hand, in &gt;30 year’s study group was 12(60.0%), control group 8(40.0%) and total 20(20.0%) respectively. and that of control group was 26.24 (±4.75) years. The mean age of the study group was 27.44 ± 5.59, control group was 26.24 ± 4.75 and total was 26.84 ±5.18 years. The mean weight of the study group was 66.84 (±3.25) kg and in the control group 62.64(±2.84) kg. In this study, 96.0% of the respondents had normal vaginal delivery and among them, 52.1% were in the study group and 47.9% in the control group. On the other hand, only 4% of the respondents had lower segment caesarean section and all of them were in the control group. The mean gestational age at delivery of the respondents in the study group was 39.88 ± 0.78 weeks and in the control group 39.84 ± 0.75 weeks. Conclusion: In this study Tran’s cervical amnioinfusion gave positive result by providing reducing picture of operative delivery in study group. There was significant difference in respiratory distress in the baby having lower percentage in the study group. A large scale study should be carried out to make the result of this study a reliable one.

Outcomes of patients with exomphalos and associated congenital heart diseases

Exomphalos is an anterior abdominal wall defect resulting in herniation of contents into the umbilical cord. Severe associated chromosomal anomalies and congenital heart disease (CHD) are known to influence mortality, but it is not clear which cardiac anomalies have the greatest impact on survival. We performed a retrospective review of the treatment and outcome of patients with exomphalos over a 30-year period (1990-2020), with a focus on those with the combination of exomphalos major and major CHD (EMCHD). There were 123 patients with exomphalos identified, 59 (48%) had exomphalos major (ExoMaj) (defect > 5cm or containing liver), and 64 (52%) exomphalos minor (ExoMin). In the ExoMaj group; 17% had major CHD (10/59), M:F 28:31, 29% premature (< 37weeks, 17/59) and 14% had low birth-weight (< 2.5kg, 8/59). In the ExoMin group; 9% had major CHD (6/64), M:F 42:22, 18% premature and 10% had low birth-weight. The 5-year survival was 20% in the EMCHD group versus 90% in the ExoMaj with minor or no CHD [p < 0.0001].Deaths in the EMCHD had mainly right heart anomalies and all of them required mechanical ventilation (MV) for pulmonary hypoplasia prior to cardiac intervention. In contrast, survivors did not require mechanical ventilation prior to cardiac intervention. EMCHD is associated with high mortality. The most significant finding was high mortality in those with right heart anomalies in combination with pulmonary hypoplasia, especially if pre-intervention mechanical ventilation is required.

Congenital diaphragmatic hernia: phosphodiesterase-5 and Arginase inhibitors prevent pulmonary vascular hypoplasia in rat lungs.

Severe pulmonary hypoplasia related to congenital diaphragmatic hernia (CDH) continues to be a potentially fatal condition despite advanced postnatal management strategies. To evaluate the effect of the antenatal sildenafil and 2(S)-amino-6-boronohexanoic acid (ABH-Arginase inhibitor) on lung volume, pulmonary vascular development, and nitric oxide (NO) synthesis in a Nitrofen-induced CDH rat model. Nitrofen-induced CDH rat model was used. Nitrofen was administrated on embryonic day(E) 9,5. At E14, five intervention groups were treated separately: Nitrofen, Nitrofen+Sildenafil, Nitrofen+ABH, Nitrofen+Sildenafil+ABH and Control. At term, offspring's lungs were weighed, some paraffin-embedded for histology, others snap-frozen to analyze eNOS, Arginase I-II expression, and activity. In CDH-bearing offsprings, ABH or Sildenafil+ABH preserved the total lung/body-weight index (p < 0.001), preventing pulmonary vascular smooth muscle cell hyperproliferation and improving lung morphometry. Sildenafil+ABH increased 1.7-fold the lung nitrite levels (p < 0.01) without changes in eNOS expression. Sildenafil and ABH improved the number of pulmonary vessels. These results suggest that in this CDH rat model, the basal activity of Arginase participates in the lung volume and, together with phosphodiesterase-5, regulates NOS activity in the term fetal lung. The combined treatment (Sildenafil+ABH) could revert some of the pulmonary features in CDH by improving the local NO synthesis and preventing smooth muscle cell hyperproliferation. This study presents Arginase inhibition as a new therapeutic target and the importance of the combined antenatal treatment to improve pulmonary vascular development in a congenital diaphragmatic hernia (CDH) rat model. This study shows that the action of an Arginase inhibitor (ABH) enhances the effects already described for sildenafil in this model. These results reinforce the importance of prenatal treatments' synergy in recovering the hypoplastic lung in the Nitrofen-induced CDH rat model.

Embryology and anatomy of congenital diaphragmatic hernia

Prenatal and postnatal treatment modalities for congenital diaphragmatic hernia (CDH) continue to improve, however patients still face high rates of morbidity and mortality caused by severe underlying persistent pulmonary hypertension and pulmonary hypoplasia. Though the majority of CDH cases are idiopathic, it is believed that CDH is a polygenic developmental defect caused by interactions between candidate genes, as well as environmental and epigenetic factors. However, the origin and pathogenesis of these developmental insults are poorly understood. Further, connections between disrupted lung development and the failure of diaphragmatic closure during embryogenesis have not been fully elucidated. Though several animal models have been useful in identifying candidate genes and disrupted signalling pathways, more studies are required to understand the pathogenesis and to develop effective preventative care. In this article, we summarize the most recent litterature on disrupted embryological lung and diaphragmatic development associated with CDH.

A study on obstetric and perinatal outcome in a pregnancy complicated with oligohydramnios

Oligohydramnios, defined as when the AFI is less than 5. Definition of increased or decreased amniotic fluid volume are based on sonographic criteria. Oligohydramnios complicates approximately 1 to 2% of pregnancies Amniotic fluid provides the cushion effect against the constricting confines of the gravid uterus. It creates space and helps in musculoskeletal development of foetus, helps in normal fetal lung development and prevents compression of umbilical cord, placenta and hence protects the foetus from vascular and nutritional compromises. Oligohydramnios is associated with high risk adverse perinatal outcome like fetal distress, meconium aspiration, low APGAR, joint contracture, pulmonary hypoplasia etc., and associated with maternal morbidity in the form of increased rates of induction and/or operative interference. This study is conducted to find out the effects of oligohydramnios in determining the obstetric and perinatal outcome.To study, 1) Primary outcome- Obstetric outcome in terms of mode of delivery, indication for operative interference. 2) Secondary outcome- Neonatal outcome in terms of birth weight, Apgar score, colour of liquor, admissions to NICU. This is a prospective observational study conducted on 80 patients presenting to Department of Obstetrics and Gynecology at KIMS hospital, Bengaluru from January 2019 to June 2020 who were diagnosed with oligohydramnios with intact membranes with AFI&amp;#60;5cms using sonographic criteria. A total of 80 cases of Isolated Oligohydramnios were assessed. 38.7% cases delivered vaginally, 61.2% of cases underwent Cesarean section, 15% had meconium stained liquor, 15% had APGAR score of &amp;#60;7 at 1 minute, 42.5% had birth weight &amp;#60;2.5kgs and 37.5% of babies required NICU admissions. The present study was conducted to know the fetomaternal outcome in pregnancies with oligohydramnios. The study showed oligohydramnios was associated with higher rates of induction and Cesarean section and associated with Low birth weight babies.

A successful management of left-sided posterior congenital diaphragmatic hernia of the jejunum, ileum, colon and left kidney: a case report

Congenital diaphragmatic hernia (CDH) is a rare developmental anomaly in which abdominal contents herniate into the thoracic cavity due to underdevelopment of the diaphragm, possibly leading to pulmonary hypoplasia. Whereas surgery is not the first priority in treatment, it must be performed within a window of 2 weeks and after hemodynamic stability has been achieved. The patient described in this case report had a CDH of the jejunum, ileum, colon and left kidney diagnosed in a boy of South Asian origin who presented with tachypnea in the third hour of life. Imaging studies conducted included chest X-ray, chest ultrasound including echocardiogram, and abdominal and pelvic ultrasound. Treatment and management were successful despite complications. Future research on CDH is warranted in the populations in the Middle East, and local guidelines must be generated in order to improve diagnosis, treatment and prognosis.

Perinatal outcomes of prenatal diagnosis of congenital pulmonary airway malformation: an experience.

This study aimed to assess the perinatal outcomes of pregnancies with a prenatal diagnosis of congenital cystic adenomatoid malformation. We conducted a retrospective cohort study based on information contained in the medical records of pregnant women whose fetuses had been prenatally diagnosed with congenital cystic adenomatoid malformation by ultrasonography. Sample analysis was based on 21 singleton pregnancies with confirmed isolated fetal congenital cystic adenomatoid malformations. The mean maternal±standard deviation age was 28±7.7 years. Types I, II, and III congenital cystic adenomatoid malformation were detected in 19% (4/21), 52.4% (11/21), and 28.6% (6/21), respectively. All fetuses presented with unilateral congenital cystic adenomatoid malformation (21/21) without associated anomalies, and 52.3% (11/21) were in the right lung. In total, 33.3% (7/21) of fetuses presented a "congenital cystic adenomatoid malformation volume ratio" >1.6 and were managed with maternal betamethasone administration. The mean gestational age at the time of steroid administration was 28.5±0.9 weeks, with a reduction in the lesion dimensions of 9.5% (2/21) (Types I and III of congenital cystic adenomatoid malformation). The mean gestational age at delivery was 38.7±2.4 weeks, and a cesarean section was performed in 76.2% (16/21) cases. Postsurgical resection was necessary for 23.8% (5/21) of the patients, and 4.7% (1/21) of them died because of respiratory complications after surgery. Pulmonary hypoplasia occurred in 9.5% (2/21) of the patients, and 4.7% (1/21) of them died because of respiratory insufficiency. The survival rate was 90.5% (19/21), and 57.2% (12/21) remained asymptomatic. Despite the isolated prenatal diagnosis of congenital cystic adenomatoid malformation, which showed good survival, congenital cystic adenomatoid malformation is associated with significant perinatal morbidity. Maternal betamethasone administration did not significantly reduce fetal lung lesion dimensions.

Proximal interruption of the pulmonary artery: A review of radiological findings.

Proximal interruption of the pulmonary artery (PIPA) has various clinical manifestations. This review focused on and summarized the clinical and radiological features of PIPA, based on relevant literature studies. The study included a total of 25 PIPA cases in the Guangzhou Women and Children's Medical Center between January 2015 and December 2021. Conventional chest photographs and chest computed tomography angiography (CCTA) of patients with PIPA were analyzed and summarized. The radiological results showed that 17 cases were right-sided and 8 cases were left-sided PIPA. Additionally, the percentage of pulmonary hypoplasia on the affected side was 44%, 36% for pulmonary hypertension, 28% for the mosaic sign, 20% for subpleural cystic lucency shadow, 20% for subpleural serrated shadow, 20% for collateral vessel thickening, 16% for subpleural band-like parenchyma, 12% for pneumonia, and 56% for patent ductus arteriosus. The clinical manifestations of PIPA are non-specific. Awareness of this anomaly, based on radiological manifestations, particularly those observed on CCTA images, is important for ruling out alternative diagnoses and implementing appropriate management.

Risk Stratification by Percent Liver Herniation in Congenital Diaphragmatic Hernia

IntroductionCongenital diaphragmatic hernia is associated with pulmonary hypoplasia, pulmonary hypertension, and significant neonatal morbidity. Although intrathoracic liver herniation (LH) >20% is associated with adverse outcomes, the relationship between LH <20% and outcomes is poorly characterized. MethodsA single-center retrospective cohort study was performed from 2011 to 2020 of 80 fetuses with left-sided congenital diaphragmatic hernia that were delivered and repaired at our institution. Perinatal, perioperative, and postoperative data were collected. We evaluated the association of %LH with outcomes as a stratified ordinal variable (0%-10% LH, 10%-19% LH, and >20% LH) and as a continuous variable. Data were analyzed by analysis of variance with Bonferroni post hoc analysis, chi-square analyses, and univariate logistic regression. ResultsExtracorporeal membrane oxygenation (ECMO) (P < 0.001), repair on ECMO (P = 0.002), repair with patch (P < 0.001), length of stay (P = 0.002), inhaled nitric oxide use (P < 0.001), and sildenafil use at discharge (P < 0.001), showed significant differences among LH groups. There were no differences among the groups concerning survival (at discharge, 6 mo, and 1 y) and tracheostomy. On further analysis there was no difference between 10% and 19% LH and ≥20% LH patients concerning ECMO (P = 0.55), repair on ECMO (P = 0.54), repair with patch (P = 1.00), length of stay (P = 1.00), and inhaled nitric oxide use (P = 0.33). Logistic regression analysis displayed a significant association with LH and ECMO, repair on ECMO, repair with patch, inhaled nitric oxide use, and sildenafil use. ConclusionsOur analysis displays no significant difference in perinatal management between patients with 10%-19% and ≥20% LH. These findings suggest that the historical cutoff of ≥20% LH may not be sufficient alone to guide perinatal counseling and decision-making.

The long-term outcome following thoraco-amniotic shunting for congenital lung malformations

Aim of the StudyInsertion of a thoraco amniotic shunt (TAS) during fetal life is a therapeutic option where there is a high risk of death secondary to large congenital lung malformations (CLM). The aim of this study is to present our center's long-term experience. MethodsRetrospective single center review of the period (Jan 2000–Dec 2020). We included all fetuses that underwent TAS insertion for CLM with detailed analysis of those live newborns managed in our center. Data are quoted as median (range). Main resultsThirty one fetuses underwent 37 TAS insertions at a 25 (20–30) weeks gestational age. This was successful on 1st attempt in 30 (97%) fetuses. In 6 cases a 2nd shunt was required at 6.5 (2–10) weeks following the 1st insertion. Twenty-eight survived to be born.Sixteen (9 male) infants were delivered in our center at 39 (36–41) weeks gestational age and birth weight of 3.1 (2.6–4.2) kg. All infants underwent surgery at 2 (0–535) days (emergency surgery, n = 9; expedited n = 4; elective surgery, n = 3). Final histopathology findings were CPAM Type 1 (n = 14, n.b. associated with mucinous adenocarcinoma, n = 1), CPAM Type 2 (n = 1) and an extralobar sequestration (n = 1). Postoperative stay was 16 (1–70) days with survival in 15/16 (94%). One infant died at 1 day of life secondary to a combination of pulmonary hypoplasia and hypertension. Median follow up period was 10.7 (0.4–20.4) years. Nine (60%) children developed a degree of chest wall deformity though none have required surgical intervention. Clinically, 14/15 (93%) have otherwise normal lung function without limitations of activity, sporting or otherwise. One child has a modest exercise limitation (FVC – 70% predicted). ConclusionsTAS insertion is associated with high perinatal survival and should be considered in fetuses at risk of hydrops secondary to large cystic lung malformation. Their long term outcome is excellent although most have a mild degree of chest wall deformity.

Effects of systemic anticoagulation in a murine model of compensatory lung growth.

Neonates with congenital diaphragmatic hernia (CDH) suffer from pulmonary hypoplasia (PH) and may require extracorporeal membrane oxygenation (ECMO) and anticoagulation, often with unfractionated heparin (UFH). UFH interacts with vascular endothelial growth factor (VEGF), a factor important in lung development. We investigated the effects of UFH, low molecular weight heparin (LMWH), and bivalirudin (BV) on a murine model of compensatory lung growth (CLG). Proliferation and apoptosis were assessed in microvascular lung endothelial cells (HMVEC-L) treated with anticoagulants. Eight-week-old C57Bl/6J mice underwent left pneumonectomy and anticoagulation with low- or high-dose UFH, LMWH, BV, or saline control. Lung volume, pulmonary function tests, morphometrics, treadmill exercise tolerance, and pulmonary protein expression were examined. UFH and LMWH inhibited HMVEC-L proliferation. BV promoted proliferation and decreased apoptosis. UFH and LMWH-treated mice had reduced lung volume, total lung capacity, alveolar volume, and septal surface area compared to controls, while BV did not affect these measures. UFH and LMWH-treated mice had lower exercise tolerance compared to controls. UFH and LMWH impair pulmonary growth, alveolarization, and exercise tolerance, while BV does not. Alternative anticoagulants to heparin may be considered to improve functional outcomes for neonates with CDH and pulmonary hypoplasia. Unfractionated heparin and low molecular weight heparin may modify compensatory lung growth by reducing microvascular lung endothelial cell proliferation and affecting pulmonary angiogenic signaling. Functional effects of unfractionated heparin and low molecular weight heparin on murine compensatory lung growth include reduction in exercise tolerance. Bivalirudin, a direct thrombin inhibitor, may increase microvascular lung endothelial cell proliferation and preserves lung volume, alveolarization, and exercise tolerance in a murine compensatory lung growth model. Anticoagulants alternative to heparin should be further investigated for use in neonates with pulmonary hypoplastic diseases to optimize lung growth and development and improve outcomes.

A Special Case of Prune Belly Syndrome

Prune Belly syndrome (SPB) is an extremely rare and complex anatomo-radiological entity with a clear male predominance, characterized by the triad made up of aplasia or hypoplasia of the muscles of the anterior wall of the abdomen, dilatations of the urinary tract and bilateral cryptorchidism. This condition is associated in 75% of cases with pulmonary, skeletal, cardiac and gastrointestinal malformations. There are also so-called incomplete or partial forms that are more common in females and are known as Pseudo-Prune Belly Syndrome. The evolution of this entity is characterized by several complications and the prognosis depends mainly on the severity of the renal damage as well as the presence of pulmonary hypoplasia. Imaging confirms the observed abnormalities. We report the case of a 4-year-old male child presenting with sudden onset abdominal distension evolving for 7 days prior to admission in which the clinical examination found a crumpled and loose wrinkle of the abdominal wall more marked on the right. Abdominal wall muscle hypoplasia was confirmed by abdominal ultrasound and computed tomography.

Pre-viable preterm premature rupture of membranes under 20 weeks of pregnancy: A retrospective cohort analysis for potential outcome predictors

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

The interplay between prenatal liver growth and lung development in congenital diaphragmatic hernia.

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

Treatment with Amniotic Fluid Stem Cell Extracellular Vesicles Promotes Fetal Lung Branching and Cell Differentiation at Canalicular and Saccular Stages in Experimental Pulmonary Hypoplasia Secondary to Congenital Diaphragmatic Hernia

Pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by impaired branching morphogenesis and differentiation. We have previously demonstrated that administration of extracellular vesicles derived from rat amniotic fluid stem cells (AFSC-EVs) rescues development of hypoplastic lungs at the pseudoglandular and alveolar stages in rodent models of CDH. Herein, we tested whether AFSC-EVs exert their regenerative effects at the canalicular and saccular stages, as these are translationally relevant for clinical intervention. To induce fetal pulmonary hypoplasia, we gavaged rat dams with nitrofen at embryonic day 9.5 and demonstrated that nitrofen-exposed lungs had impaired branching morphogenesis, dysregulated signaling pathways relevant to lung development (FGF10/FGFR2, ROBO/SLIT, Ephrin, Neuropilin 1, β-catenin) and impaired epithelial and mesenchymal cell marker expression at both stages. AFSC-EVs administered to nitrofen-exposed lung explants rescued airspace density and increased the expression levels of key factors responsible for branching morphogenesis. Moreover, AFSC-EVs rescued the expression of alveolar type 1 and 2 cell markers at both canalicular and saccular stages and restored markers of club, ciliated epithelial, and pulmonary neuroendocrine cells at the saccular stage. AFSC-EV-treated lungs also had restored markers of lipofibroblasts and PDGFRA+ cells to control levels at both stages. EV tracking showed uptake of AFSC-EV RNA cargo throughout the fetal lung and an mRNA-miRNA network analysis identified that several miRNAs responsible for regulating lung development processes were contained in the AFSC-EV cargo. These findings suggest that AFSC-EV-based therapies hold potential for restoring fetal lung growth and maturation in babies with pulmonary hypoplasia secondary to CDH.