Pulmonary Maturity Research Articles

Toll-like receptors ligand immunomodulators for the treatment congenital diaphragmatic hernia

BackgroundCongenital diaphragmatic hernia (CDH) is a rare disease that affects the development of the diaphragm, leading to abnormal lung development. Unfortunately, there is no established therapy for CDH. Retinoic acid pathways are implicated in the ethology of CDH and macrophages are known to play a role in repairing organ damage.MethodsWe have analyzed the effect of several Toll like receptor (TLR) ligands in the nitrofen-induced CDH model in pregnant rats widely used to study this disease and in the G2-GATA4Cre;Wt1fl/fl CDH genetic mice model. Morphometric and histological studies were carried out. Immune cell infiltration was assayed by immunochemistry and immunofluorescence and retinoic pathway gene expression analyzed in vivo and in vitro in macrophages.ResultsWe found that administering a single dose of atypical TLR2/4 ligands (CS1 or CS2), 3 days after nitrofen, cured diaphragmatic hernia in 73% of the fetuses and repaired the lesion with complete diaphragm closure being on the other hand nontoxic for the mothers or pups. Moreover, these immunomodulators also improved pulmonary hypoplasia and alveolar maturation and vessel hypertrophy, enhancing pulmonary maturity of fetuses. We also found that CS1 treatment rescued the CDH phenotype in the G2-GATA4Cre;Wt1fl/fl CDH genetic mice model. Only 1 out of 11 mutant embryos showed CDH after CS1 administration, whereas CDH prevalence was 70% in untreated mutant embryos. Mechanistically, CS1 stimulated the infiltration of repairing M2 macrophages (CD206+ and Arg1+) into the damaged diaphragm and reduced T cell infiltration. Additionally, those TLR ligands induced retinol pathway genes, including RBP1, RALDH2, RARα, and RARβ, in the affected lungs and the diaphragm and in macrophages in vitro.ConclusionsOur research has shown that TLR ligand immunomodulators that influence anti-inflammatory macrophage activation can be effective in treating CDH, being nontoxic for the mothers or pups suggesting that those TLR ligands are a promising solution for CDH leading to orphan drug designation for CS1. The immune system of the fetus would be responsible for repairing the damage and closure of the hernia in the diaphragm and enhanced proper lung development after CS1 treatment.

Lamellar Body Count (LBC) in amniotic fluid for prediction of fetal lung maturity

Background: Neonatal respiratory distress syndrome (RDS) is a disorder due to pulmonary immaturity with a high mortality characterized by low levels of pulmonary surfactant. RDS is one of the important causes of mortality in neonates. Objective: The aim of the study is to determine the lamellar body count (LBC) cutoff value for foetal lung maturity and to evaluate the clinical usefulness of LBC in predicting the neonatal respiratory distress syndrome (RDS) and to find if the Measurement of LBC can replace the conventional Lecithin/Sphingomyelin ratio. Methods: This prospective observational study was performed on total 47 pregnant women divided as 19 patients with premature labor and 28 patients with healthy full-term singleton pregnancy as controls, with gestational age between 28 – 41 weeks at Ain Shams university maternity hospital in period between April 2014 and January 2015 with inclusion and exclusion criteria. Results: RDS was diagnosed in 20 neonates, two neonates in the 1st group (7.1%) While 18 neonates in 2nd (94.7%) showed development of RDS. Mean lamellar body count in newborns with RDS: 39,200 ± 12,438 with median 37,500 and p-value was <0.0001. ROC (receiver operator characteristics) curve showed that by using 51000/µL as a cut-off point for LBC it is a good predictor for fetal lung maturity with sensitivity 95% and specificity 96.3%. There is a direct relationship between the gestational age and the lamellar body count as the lamellar body count increases as long as the gestational age proceeds with a highly significant positive correlation (p value <0.0001). Conclusion: As evident from the current study, LBC count now replacing the conventional Lecithin/Sphingomyelin ratio because the test can be performed with equipment found in most clinical analysis laboratories and is reliable in predicting foetal lung maturity. This study suggests that LBC cutoff value of ≥51,000/µL can predict pulmonary maturity and reduce the risk of neonatal respiratory distress syndrome.

The need for assisted ventilation corroborates the effectiveness of antenatal corticosteroid therapy in preventing premature lamb mortality

In premature births, deficiency and/or inactivation of surfactant and incomplete development of lung occur, leading to pulmonary complications and greater need for ventilatory interventions. Prenatal corticosteroid therapy is used to improve neonatal lung function and, thus, may reduce mortality and lower incidence and severity of lung injury. Therefore, this study aimed to assess the need for ventilatory support in preterm lambs subjected or not to prenatal betamethasone treatment, and to evaluate the effectiveness on neonatal survival. Lambing was induced and 13 premature lambs were assigned to Corticosteroid Group (n = 8; lambs from ewes subjected previously to 0.5 mg/kg betamethasone, IM, at 133 days of pregnancy) and Control Group (n = 5; non-treated lambs). Lambs were evaluated for vitality, neurologic reflexes, vital functions and birth weight. Three ventilatory modalities were preconized for critical lambs, according to specific criteria: mask oxygen therapy, self-inflating bag with tracheal tube and mechanical ventilation. Non-treated lambs had lower vitality score, muscle tonus and respiratory rate compared to Corticosteroid Group. Ventilatory support was needed for 3 Control lambs and only 1 Corticosteroid neonate. Corticosteroid lamb required significant less time-frame between birth and onset of ventilatory assistance and remained under ventilation for a shorter time. Percentage of ventilated non-treated lambs correlated negatively with birth weight, muscle tone, heart and respiratory rate. In conclusion, antenatal betamethasone treatment reduces the need for ventilatory assistance in premature lambs. Additionally, mortality is low when a protocol for inducing pulmonary maturity (maternal corticosteroid therapy) and/or ventilatory interventions are employed, ensuring the survival of premature lambs.

Historical Perspectives and Clinical Updates on Preterm Bottle Feeding With Noninvasive Ventilation.

The controversial topic of oral feeding while on noninvasive ventilation remains at the forefront of preterm intensive care management. The intersection of pulmonary, neurologic, and gastrointestinal maturation coalesces at a postmenstrual age that requires changes in practices compared with those used in older infants. Various animal models in the past decades aimed to gain physiological knowledge of noninvasive ventilation effects on the suck-swallow-breathe coordination sequence. However, the preterm infant poses nuanced anatomic challenges. Although concerns for oral feeding while on noninvasive ventilation include aspiration risks and potential inpatient obstacles, there is evidence to support the feasibility, initiation, and progression of oral feedings while an infant is supported on high-flow nasal cannula and continuous positive airway pressure. There is evidence to support that this may accelerate attainment of oral feeding milestones and, thus, eventual hospital discharge. More recent multidisciplinary institutional protocols may provide cautious guidance on evaluation and algorithms to assess infants who may benefit from initiation and advancement of oral feeding versus awaiting further maturation.

MitoQ as an antenatal antioxidant treatment improves markers of lung maturation in healthy and hypoxic pregnancy.

Chronic fetal hypoxaemia is a common pregnancy complication that increases the risk of infants experiencing respiratory complications at birth. In turn, chronic fetal hypoxaemia promotes oxidative stress, and maternal antioxidant therapy in animal models of hypoxic pregnancy has proven to be protective with regards to fetal growth and cardiovascular development. However, whether antenatal antioxidant therapy confers any benefit on lung development in complicated pregnancies has not yet been investigated. Here, we tested the hypothesis that maternal antenatal treatment with MitoQ will protect the developing lung in hypoxic pregnancy in sheep, a species with similar fetal lung developmental milestones as humans. Maternal treatment with MitoQ during late gestation promoted fetal pulmonary surfactant maturation and an increase in the expression of lung mitochondrial complexes III and V independent of oxygenation. Maternal treatment with MitoQ in hypoxic pregnancy also increased the expression of genes regulating liquid reabsorption in the fetal lung. These data support the hypothesis tested and suggest that MitoQ as an antenatal targeted antioxidant treatment may improve lung maturation in the late gestation fetus. KEY POINTS: Chronic fetal hypoxaemia promotes oxidative stress, and maternal antioxidant therapy in hypoxic pregnancy has proven to be protective with regards to fetal growth and cardiovascular development. MitoQ is a targeted antioxidant that uses the cell and the mitochondrial membrane potential to accumulate within the mitochondria. Treatment of healthy or hypoxic pregnancy with MitoQ, increases the expression of key molecules involved in surfactant maturation, lung liquid reabsorption and in mitochondrial proteins driving ATP synthesis in the fetal sheep lung. There were no detrimental effects of MitoQ treatment alone on the molecular components measured in the present study, suggesting that maternal antioxidant treatment has no effect on other components of normal maturation of the surfactant system.

Combined Fetal Pulmonary Artery Doppler and Proximal Humeral Ossification center for prediction of Neonatal Respiratory Distress Syndrome at term: a Cohort Prospective Study

Background: Fetal lung maturity is one of the huge dilemmas since a long time ago. Timing of the delivery is crucial for safe fetal delivery since verification of pulmonary maturity diminishes the respiratory morbidity possibility. Recently Pulmonary artery indices have been used to predict the possibility of RDS especially in early term. Together with humeral ossification center which has a remarkable value in estimation of term gestation, both of them can help prediction of fetal lung maturity. Aim of the Work: utilizing PHE with pulmonary artery Doppler indices for accurate prediction of fetal respiratory distress syndrome. The use of PHE in prediction of term gestation. Patients and Methods: Our study included 115 uncomplicated singleton pregnant women with gestational age between 37 to 40 weeks patients from Al-Azhar University Ob/Gyn hospitals during the period from November 2019 to October 2020. The ultrasound scans were done inside a 24 hours interval before delivery with Cesarean section. After delivery, the neonatal APGAR score at 1, 5 minutes, fetal diagnosis with RDS, any NICU admission were recorded respectively. Results: Pulmonary artery RI and PHE had statistically significant diagnostic performance in predicting fetal distress. PHE of ≤1.95 had highest diagnostic characteristics in predicting fetal distress. Among Pulmonary Artery Doppler, RI of ≥0.79 had highest diagnostic characteristics. Conclusion: PHE and Pulmonary artery R.I could predict fetal distress. Pulmonary artery indices and PHE combination (sum) predicted fetal distress better than using pulmonary indices alone. Presence of PHE confirms term gestation.

Preventive effects of antenatal CDP-choline in a rat model of neonatal hyperoxia-induced lung injury.

Antenatal steroid administration to pregnant women at risk of prematurity provides pulmonary maturation in infants, while it has limited effects on incidence of bronchopulmonary dysplasia (BPD), the clinical expression of hyperoxia-induced lung injury (HILI). Cytidine-5'-diphosphate choline (CDP-choline) was shown to alleviate HILI when administered to newborn rats. Therefore, we investigated effects of maternal administration of CDP-choline, alone or in combination with betamethasone, on lung maturation in neonatal rats subjected to HILI immediately after birth. Pregnant rats were randomly assigned to one of the four treatments: saline (1 mL/kg), CDP-choline (300 mg/kg), betamethasone (0.4 mg/kg), or CDP-choline plus betamethasone (combination therapy). From postnatal day 1 to 11, pups born to mothers in the same treatment group were pooled and randomly assigned to either normoxia or hyperoxia group. Biochemical an d histopathological effects of CDP-choline on neonatal lung tissue were evaluated. Antenatal CDP-choline treatment increased levels of phosphatidylcholine and total lung phospholipids, decreased apoptosis, and improved alveolarization. The outcomes were further improved with combination therapy compared to the administration of CDP-choline or betamethasone alone. These results demonstrate that antenatal CDP-choline treatment provides benefit in experimental HILI either alone or more intensively when administered along with a steroid, suggesting a possible utility for CDP-choline against BPD.

La stéatose hépatique aiguë gravidique récidivante : à propos d’un cas et une revue de la littérature

Acute fatty liver of pregnancy (AFLP) is a specific but rare hepatopathy that can usually complicate the third trimester of pregnancy. It is potentially fatal for the mother and the fetus. To our knowledge, only eight cases of recurrence have been published, we report a new case. The first episode presented by our 23-year-old patient was suspected in front of a cutaneous-mucosal jaundice with vomiting occurring on pregnancy of 35weeks of gestation (WG). Hyperleucytosis, abnormalities of the hepatic balance, as well as a hypoglycemia were biological elements supporting the diagnostic beam. On the other hand, medical imaging could not bring a clear confirmation. The evolution was favorable after deferred delivery by caesarean section for pulmonary maturation. Three years later, she presented to the obstetrical emergency room at 36weeks and six days of gestation, with a clinical and biological picture almost similar to that of the first episode. A caesarean section was then indicated for suspicion of recurrence. The evolution is favorable for the mother and her children. The interest of the communication on the risk of recurrence, the clinical and biological monitoring in particular in the third trimester of the subsequent pregnancy are imperative, in order to improve the prognosis of this pathology.

Prenatal or postnatal corticosteroids favor clinical, respiratory, metabolic outcomes and oxidative balance of preterm lambs corticotherapy for premature neonatal lambs

Challenges of the extrauterine environment can be life threatening for a premature fetus with inadequate fetal maturity. Maternal corticosteroids therapy is widely employed to induce fetal pulmonary maturation. Nevertheless, whenever therapeutic pregnancy interruption has to be performed in a time manner insufficient to treat the dam, postnatal corticotherapy can be considered an alternative. However, it is not known if antenatal and postnatal corticotherapy can improve similarly neonatal outcomes and pulmonary function. This research aimed to analyze antenatal and postnatal corticotherapy on premature lambs vitality, pulmonary functioning, metabolic and oxidative status. Lambs were evaluated according to the mode of treatment: Prenatal Corticosteroid Group (8 lambs born after maternal betamethasone treatment 48 h prior to birth), Postnatal Corticosteroid Group (9 lambs subjected to betamethasone treatment 10 min after birth) and Control Group (5 lambs remained untreated). Lambs were medically followed-up from birth to 72 h thereafter through a complete physical examination, as well as lactatemia, glycaemia, blood acid-base balance and antioxidant status. Treated lambs had higher vitality score than the Control Group. Heart rate was higher in postnatal therapy compared to prenatal treatment. Respiratory rate and rectal temperature were higher in treated groups. Treated lambs had hyperglycemia, while the Postnatal Group had higher lactatemia than the Control Group. The Prenatal Group had lower and normal pCO2 from 60 min onwards. The Postnatal Group had higher superoxide dismutase activity than untreated lambs. In conclusion, prenatal and postnatal betamethasone treatments favor neonatal clinical outcome, respiratory function, glucose homeostasis and oxidative balance.

Prediction of Lung Maturity in Fetuses with Growth Restriction through Quantitative Ultrasound Analysis.

The present study aimed to evaluate the performance of QuantusFLM software, which performs quantitative analysis of lung tissue texture through ultrasound images, in predicting lung maturity in fetal growth restriction (FGR). We included patients with singleton gestations between 34 and 38 6/7 wk and divided them into two groups: FGR and control (appropriate for gestational age [AGA]). The images were captured by ultrasound according to a specific protocol up to 48 h before delivery and analyzed with QuantusFLM software. The main clinical outcome evaluated was lung maturity (i.e., the absence of neonatal respiratory morbidity). We included 111 patients; one was excluded because of low image quality, leaving 55 patients in each group. The FGR group had a lower birth weight (2207 g vs. 2891 g, p < 0.001) and a longer stay in the neonatal intensive care unit (NICU) (10 d vs. 5 d, p=0.043). QuantusFLM software was able to predict lung maturity in FGR with accuracy, sensitivity, specificity and positive and negative predictive values of 94.5%, 96.2%, 50%, 98.1% and 33.3%, respectively. QuantusFLM had good accuracy in predicting lung maturity in FGR with reliability in identifying pulmonary maturity.

Fetal adrenal cortex function in pregnancy, complicated by maternal insulin-dependent diabetes mellitus

Fetal adrenal cortex glucocorticoid andfetal hypophysial adrenocorticotropic function in normal pregnancy and pregnancy, complicated with maternal insulin dependent diabetes mellitus were examined in the present study. Statistically significant feta l hypercortisolemia was observed in pregnancies, complicated by insulin-dependent diabetes mellitus. Correlations between vascular complications o f maternal insulin-dependent diabetes mellitus and fetal cortisol andACTG levels were revealed during the investigation. Severe vascular lesions o f maternal diabetes have been associated with delayed feta l lung maturity. Fetal pulmonary maturity was significantly associated with fe ta l cortisol levels.

Fetal lung development via quantitative biomarkers from diffusion MRI and histological validation in rhesus macaques.

To demonstrate sensitivity of diffusion-weighted MRI (DW-MRI) to pulmonary cellular-space changes during normal in utero development using fetal rhesus macaques, compared to histological biomarkers. In vivo/ex vivo DW-MRI was acquired in 26 fetal rhesus lungs (early-canalicular through saccular stages). Apparent diffusion coefficients (ADC) from MRI and tissue area density (H&E), alveolar type-II cells (ABCA3), and epithelial cells (TTF1) from histology were compared between gestational stages. In vivo/ex vivo ADC correlated with each other (Spearman ρ = 0.47, P = 0.038; Bland-Altman bias = 0.0835) and with area-density (in vivo ρ = -0.56, P = 0.011; ex vivo ρ = -0.83, P < 0.0001). In vivo/ex vivo ADC increased exponentially toward saturation with gestational stage (R2 = 0.49/0.49), while area-density decreased exponentially (R2 = 0.53). ABCA3 and TTF1 stains demonstrated expected fetal cellular development. Fetal DW-MRI provides a non-invasive biomarker for pulmonary structural maturation, with a strong correlation to histological markers during tissue development in rhesus macaques. This method has strong potential for assessing human fetal development, particularly in patients with pulmonary hypoplasia.

Improvement in fetal pulmonary hypertension and maturity after reversal of ductal constriction: prospective cohort study.

To test the hypotheses that estimated mean pulmonary arterial pressure (MPAP) decreases and pulmonary vascular maturation, assessed by the ratio of pulmonary arterial flow acceleration time to ejection time (AT/ET ratio), increases after reversal of fetal ductus arteriosus constriction by reducing maternal intake of the causal agent (prostaglandin inhibitors, such as polyphenol-rich foods or non-steroidal anti-inflammatory drugs), and that these effects are independent of gestational age, which are inferences not yet demonstrated in the clinical setting. This was a prospective cohort study comparing Doppler echocardiographic ductal flow dynamics, MPAP and pulmonary arterial flow AT/ET ratio in third-trimester fetuses (≥ 28 weeks' gestation) with ductus arteriosus constriction, at the time of diagnosis and after 2 weeks of reduced maternal intake of prostaglandin inhibitors either by suspending the use of pharmacological agents with potential for prostaglandin inhibition or by restricting the consumption of polyphenol-rich foods. MPAP was estimated using the Dabestani equation (MPAP = 90 - (0.62 × AT)), and pulmonary vascular maturity was assessed using the AT/ET ratio, according to reported validation studies. Student's t-test was used for comparison of variables at diagnosis with those after reversal of ductal constriction. Change in MPAP and pulmonary AT/ET ratio between the two assessments was compared with the expected change in the same gestational period in normal fetuses based on reference curves of MPAP and pulmonary AT/ET ratio constructed in normal fetuses from healthy pregnant women at 19-37 weeks' gestation, encompassing the same gestational age range as the study group (28-37 weeks). Seventy pregnancies with fetal ductus arteriosus constriction were included in the study. After 2 weeks of reduced maternal intake of prostaglandin inhibitors, normalization of mean systolic (change from 1.86 ± 0.34 m/s at diagnosis to 1.38 ± 0.41 m/s; P < 0.001) and diastolic (change from 0.41 ± 0.11 m/s to 0.21 ± 0.065 m/s; P < 0.001) ductal velocities and of mean pulsatility index (change from 1.99 ± 0.20 to 2.55 ± 0.42; P < 0.001) was demonstrated. MPAP decreased between the assessments (change from 66.7 ± 6.90 mmHg at diagnosis to 54.5 ± 6.70 mmHg after 2 weeks; P < 0.001) and mean pulmonary AT/ET ratio increased (change from 0.20 ± 0.06 to 0.33 ± 0.07; P < 0.001). Change in MPAP between diagnosis and after 2 weeks of reduced maternal intake of prostaglandin inhibitors was -12.2 ± 0.30 mmHg, which was 5.3-times higher than that in 305 normal fetuses over 2 weeks during the same gestational period (-2.3 ± 0.19 mmHg) (P < 0.001), and change in pulmonary AT/ET ratio between the two assessments was 0.13 ± 0.08, which was 8.7-times higher than that in normal fetuses in the same gestational period (0.015 ± 0.08) (P < 0.001). Resolution of fetal ductal constriction is followed by a fall in MPAP and by an increase in pulmonary vascular maturity, to a significantly greater degree than is observed in normal fetuses in the same gestational-age period. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Influence of Nutrition and Maternal Bonding on Postnatal Lung Development in the Newborn Pig.

BackgroundMicrobial colonization and immune cell maturation coincide at mucosal sites and are decisive for postnatal lung development. How external factors influence neonatal pulmonary immune development is poorly understood.ObjectiveTo elucidate the impact of key determinants in early life, nutrition, and maternal bonding, on postnatal lung maturation in a human-relevant animal model. To investigate the underlying immunological changes of impaired lung maturation and study the mechanisms of conversion.MethodsNewborn piglets were kept with or without isolation from their mothers and fed bovine milk-based infant formula or received milk of sow. Lung growth, histomorphology, respiratory immune responses, and lung microbiota were analyzed. Mother- and sow-milk-deprived piglets received maternal material or were reintroduced to the maternal environment at varying intervals to study options for reversal.ResultsFormula feeding combined with isolation of newborn piglets resulted in disturbed postnatal lung maturation. Reduced lung growth correlated with dampened IL-33 expression, impaired lung myeloid cell activation, and decreased Th1 differentiation, along with diminished richness and diversity of the lung microbiota. Transfer of bacteria-enriched maternal material reversed the negative effects on pulmonary immune maturation. Early (within 3 days) but not late (within 7 days) reintroduction to the mother allowed restoration of normal lung development.ConclusionOur findings reveal that lung growth, respiratory immunity, and microbial lung colonization in newborns depend on postnatal diet and maternal contact, and targeting these key regulators could promote lung development during this critical life stage.SummaryDisturbances in natural diet and reduced maternal contact during the neonatal period impair postnatal lung maturation. In pediatrics, timely breast milk feeding and intensive maternal bonding represent valuable intervention measures to promote early postnatal lung development.

Differences between preterm infants receiving a dose for lung maturation and those receiving an additional rescue dose of corticosteroids

it is unknown if there is a difference between preterm infants with a history of receiving pulmonary corticosteroid maturation or using an additional rescue dose of corticosteroid. This paper aims to determine the difference between infants with pulmonary maturation and infants who received a rescue dose of corticosteroid. We performed an epidemiological, observational, and cross-sectional study. We analyzed time of stay, the requirement of mechanical ventilation, the use of surfactant, and neurological complications in newborns hospitalized in Neonatology of the Isidro Ayora Gyneco-Obstetric Hospital, 2019. We analyzed 204 preterm infants of 28-37 weeks who received a total lung maturation dose versus an added rescue dose. We analyzed the information with the statistical program SPSS v 22.0. With rescue dose the stay time was 28.4±21.6 days (p &lt;0.05), days of invasive mechanical ventilation 3±5.7 days (p &lt;0.05); Surfactant use 33.3% (p&gt;0.05). We found neurological complications in 6.9% of patients (p&gt; 0.05). In group 2 with not rescue dose use, the stay time was 21.5±16.6 days (p&lt;0.05), days of invasive mechanical ventilation 1.8 ± 4.1 days (p &lt;0.05). Surfactant use was 24.5% (p&gt;0.05), and neurological complications 2% (p&gt; 0.05). Preterm males weighing &lt;1000 g from 30 to 32 weeks, who used rescue doses of corticosteroids, showed an increase in intraventricular hemorrhage (13.7%), seizures (6.9%), and leukomalacia (13.7%), associated with the fact that in the group with rescue dose they are younger and had lower weight.

The pulmonary vascular bed in patients with functionally univentricular physiology and a Fontan circulation.

Fontan palliation represents one of the most remarkable surgical advances in the management of individuals born with functionally univentricular physiology. The operation secures adult survival for all but a few with unfavourable anatomy and/or physiology. Inherent to the physiology is passive transpulmonary blood flow, which produces a vulnerability to adequate filling of the systemic ventricle at rest and during exertion. Similarly, the upstream effects of passive flow in the lungs are venous congestion and venous hypertension, especially marked during physical activity. The pulmonary vascular bed has emerged as a defining character on the stage of Fontan circulatory behaviour and clinical outcomes. Its pharmacologic regulation and anatomic rehabilitation therefore seem important strategic therapeutic targets. This review seeks to delineate the important aspects of pulmonary artery development and maturation in functionally univentricular physiology patients, pulmonary artery biology, pulmonary vascular reserve with exercise, and pulmonary artery morphologic and pharmacologic rehabilitation.

IntraVoxel Incoherent Motion (IVIM) MRI of fetal lung and kidney: Can the perfusion fraction be a marker of normal pulmonary and renal maturation?

PurposeTo investigate the use of IntraVoxel Incoherent Motion (IVIM) MRI in the study of microstructural tissue changes occurring in fetal lung and kidney during gestation. Methods34 normal pregnancies were enrolled. Patients were divided into two groups based on gestational age (GA): group A (21−29 weeks) and group B (30−39 weeks). MR examinations were performed at 1.5T, with a standard fetal MR protocol including a Diffusion-Weighted Echo-Planar Imaging sequence with 10 different b-values (0, 10, 30, 50, 75, 100, 200, 400, 700, 1000s/mm2). For each fetus, two bilateral ROIs were manually placed in lung and renal parenchyma. Mean values of perfusion fraction f, pseudo-diffusion coefficient D* and diffusion coefficient D were obtained. The correlation between IVIM parameters and GA was investigated. ResultsIn renal ROIs a positive correlation between fkidney and GA (p < 0.005) was found; similarly flung showed a statistically significant correlation with GA (p < 0.001). F mean values were significantly higher in group B compared to group A in both renal (p = 0.0002) and lung (p = 0.018) ROIs. No correlation was found in D and D* as a function of GA. ConclusionsThe IVIM perfusion fraction f may be considered as a potential marker of pulmonary and renal maturation in relation to hemodynamic changes described in intrauterine life. Our results highlight that IVIM model is useful as an additional prenatal diagnostic tool to study lung and renal development.

Schistosomes in the Lung: Immunobiology and Opportunity.

Schistosome infection is a major cause of global morbidity, particularly in sub-Saharan Africa. However, there is no effective vaccine for this major neglected tropical disease, and re-infection routinely occurs after chemotherapeutic treatment. Following invasion through the skin, larval schistosomula enter the circulatory system and migrate through the lung before maturing to adulthood in the mesenteric or urogenital vasculature. Eggs released from adult worms can become trapped in various tissues, with resultant inflammatory responses leading to hepato-splenic, intestinal, or urogenital disease – processes that have been extensively studied in recent years. In contrast, although lung pathology can occur in both the acute and chronic phases of schistosomiasis, the mechanisms underlying pulmonary disease are particularly poorly understood. In chronic infection, egg-mediated fibrosis and vascular destruction can lead to the formation of portosystemic shunts through which eggs can embolise to the lungs, where they can trigger granulomatous disease. Acute schistosomiasis, or Katayama syndrome, which is primarily evident in non-endemic individuals, occurs during pulmonary larval migration, maturation, and initial egg-production, often involving fever and a cough with an accompanying immune cell infiltrate into the lung. Importantly, lung migrating larvae are not just a cause of inflammation and pathology but are a key target for future vaccine design. However, vaccine efforts are hindered by a limited understanding of what constitutes a protective immune response to larvae. In this review, we explore the current understanding of pulmonary immune responses and inflammatory pathology in schistosomiasis, highlighting important unanswered questions and areas for future research.

The impact of betamethasone on fetal pulmonary, umbilical and middle cerebral artery Doppler velocimetry and its relationship with neonatal respiratory distress syndrome

BackgroundPrenatal corticosteroid administration is known to be an effective strategy in improving fetal pulmonary maturity. This study aimed to evaluate the impact of maternal betamethasone administration on fetal pulmonary and other arteries Doppler velocity and the correlation between RDS development and Doppler indices results.MethodsFifty one singleton pregnancies between 26 and 34 gestational weeks with a diagnosis of preterm labor were included in the exposed group and received betamethasone. Fifty one uncomplicated pregnancies were included in the non-exposed group. Fetal pulmonary, umbilical and middle cerebral arteries Doppler parameters were evaluated before and 24 to 48 h after steroid administration in the exposed group and two times at same intervals in the non-exposed group. Maternal records were matched to neonatal charts if delivery happened, and demographic and outcome data were abstracted.ResultsWhen compared with the nonexposed group, fetuses treated with corticosteroids demonstrated significantly decreased umbilical artery Pulsatility index (PI) and significantly increased the middle cerebral artery PI, pulmonary artery Acceleration time (AT) and pulmonary artery AT/ET (Ejection time), while all other indices remained similar. We found significantly decreased pulmonary artery AT in the fetuses with respiratory distress syndrome (RDS) compared to those that did not.ConclusionsThe results of our study showed that maternal antenatal betamethasone administration caused significant changes in the fetus blood velocity waveforms and also affected the blood flow in the pulmonary artery which led to an increase in the pulmonary artery AT and AT/ET. Among those fetuses with RDS, we found a significant decrease in the pulmonary artery AT, but we did not observe any pulmonary artery AT/ET differences.

A Case of Alveolar Capillary Dysplasia with Misalignment of the Pulmonary Veins (ACD/MPV): The Importance of Early Genetic Testing

Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is a rare, lethal condition caused by irregular pulmonary vascular maturation. Almost all cases present in the newborn period with ensuing respiratory decline within a couple days of life, ultimately leading to nearly 100% neonatal mortality. While the gold standard for diagnosis is lung biopsy, the identification of the Forkhead Box F1 (FOXF1) gene as the main genetic cause of ACD/MPV has allowed for a definitive diagnosis to be made without performing a high-risk procedure in a critically-ill neonate. This case report describes an ACD/MPV patient with hyperinsulinemia and refractory hypoglycemia as well as multiple anomalies who was found to have a novel pathogenic variant in the FOXF1 gene, identified via exome with copy number analysis, which results in premature protein termination (NM 001451.2 c.637 dup, p.Val213Glyfs*82). Our patient showcases the importance of early genetic testing to diagnose ACD/MPV given the substantial risk in obtaining a lung biopsy in a patient with hypoxemic respiratory failure, severe pulmonary hypertension, and vasodilator-induced pulmonary edema.