Premature Lung Research Articles

Comparison of Clinical Diagnosis and Autopsy Findings of Early Neonatal Deaths: Diagnostic Challenges and the Value of Autopsy in Identifying Rare Pathologies.

In a non-forensic hospital setting, neonatal death within the first week of life is often related to premature birth and/or lung diseases. Without post-mortem examination, the identification of the cause of death may be challenging. Autopsy can confirm the clinical diagnosis, uncover additional information or change the diagnosis. Our study aimed to assess the correlation between the clinical diagnosis and post-mortem findings in early neonatal deaths. The retrospective study included autopsy cases with neonatal deaths within the first 7 days of life (arbitrary time interval 2006-2021). Discrepancies between clinical and histopathological findings were classified into 3 groups: (i) full agreement, (ii) additional findings discovered by autopsy, or (iii) autopsy changed the diagnosis. A cohort of 27 cases could be identified and lung pathologies were the most common finding (56%). Additional findings could be discovered in 48% of cases. Major discrepancies which changed the clinical diagnosis could be found in 11% (n = 3/27) of cases. Frequently, post-mortem examinations validate the clinical diagnosis while revealing crucial information in a few cases. In these discrepant cases, autopsy findings can provide information for genetic counselling and quality control of clinical management.

Cost-effectiveness of lung cancer screening with volume computed tomography in Portugal.

Aim: Lung cancer is the most common cause of cancer death in Portugal. The Dutch-Belgian lung cancer screening (LCS) study (NELSON), the biggest European LCS study, showed a lung cancer mortality reduction in a high-risk population when being screened. In this study, the cost-effectiveness of LCS, based on the NELSON study protocol and outcomes, was evaluated compared with no screening in Portugal. Methods: The present study modified an established decision tree by incorporating a state-transition Markov model to evaluate the health-related advantages and economic implications of low-dose computed tomography (LDCT) LCS from the healthcare standpoint in Portugal. The analysis compared screening versus no screening for a high-risk population aged 50-75 with a smoking history. Various metrics, including clinical outcomes, costs, quality-adjusted life years (QALYs), life-years (LYs) and the incremental cost-effectiveness ratio (ICER), were calculated to measure the impact of LDCT LCS. Furthermore, scenario and sensitivity analyses were executed to assess the robustness of the obtained results. Results: Annual LCS with volume-based LDCT resulted in €558million additional costs and 86,678 additional QALYs resulting in an ICER of €6440 per QALY for one screening group and a lifetime horizon. In total, 13,217 premature lung cancer deaths could be averted, leading to 1.41 additional QALYs gained per individual diagnosed with lung cancer. Results are robust based on the sensitivity analyses. Conclusion: This study showed that annual LDCT LCS for a high-risk population could be cost-effective in Portugal based on a willingness to pay a threshold of one-time the GDP (€19,290 per QALY gained).

Cost-effectiveness analysis of a lung cancer screening program in the Netherlands: a simulation based on NELSON and NLST study outcomes

Background In the Netherlands, lung cancer is the leading cause of cancer-related death, accounting for more than 10,000 annual deaths. Lung cancer screening (LCS) studies using low-dose computed tomography (LDCT) have demonstrated that early detection reduces lung cancer mortality. However, no LCS program has been implemented yet in the Netherlands. A national LCS program has the potential to enhance the health outcomes for lung cancer patients in the Netherlands. Objective and Methods This study evaluates the cost-effectiveness of LCS compared to no-screening in the Netherlands, by simulating the screening outcomes based on data from NEderlands–Leuvens Longkanker Screenings ONderzoek (NELSON) and National Lung Screening Trial (NLST). We simulated annual screening up to 74 years of age, using inclusion criteria from the respective studies. A decision tree and Markov model was used to predict the incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICERs) for the screening population. The analysis used a lifetime horizon and a societal perspective. Results Compared to no-screening, LCS resulted in an ICER of €5,169 per QALY for the NELSON simulation, and an ICER of €17,119 per QALY for the NLST simulation. The screening costs were highly impactful for the cost-effectiveness. The most influential parameter was the CT scan cost. Cost reduction for CT from €201 to €101 per scan would reduce the ICER to €2,335 using NELSON criteria. Additionally, LCS could prevent 15,115 and 12,611 premature lung cancer deaths, accompanied by 1.66 and 1.31 QALYs gained per lung cancer case for the NELSON and NLST simulations, respectively. Conclusion LCS was estimated to be cost-effective in the Netherlands for both simulations at a willingness-to-pay threshold of €20,000 per QALY. Using the NELSON criteria, less than €5,500 per QALY had to be spent. Lowering the cost per CT exam would lead to a further reduction of this amount.

Shall We Screen Lung Cancer with Volume Computed Tomography in Austria? A Cost-Effectiveness Modelling Study.

This study assessed the cost-effectiveness of a lung cancer screening (LCS) program using low-dose computed tomography (LDCT) in Austria. An existing decision tree with an integrated Markov model was used to analyze the cost-effectiveness of LCS versus no screening from a healthcare payer perspective over a lifetime horizon. A simulation was conducted to model annual LCS for an asymptomatic high-risk population cohort aged 50-74 with a smoking history using the Dutch-Belgian Lung Cancer Screening Study (NEderlands-Leuvens Longkanker ScreeningsONderzoek, NELSON) screening outcomes. The principal measure utilized to assess cost-effectiveness was the incremental cost-effectiveness ratio (ICER). Sensitivity and scenario analyses were employed to determine uncertainties surrounding the key model inputs. At an uptake rate of 50%, 300,277 eligible individuals would participate in the LCS program, yielding 56,122 incremental quality-adjusted life years (QALYs) and 84,049 life years gained compared to no screening, with an ICER of EUR 24,627 per QALY gained or EUR 16,444 per life-year saved. Additionally, LCS led to the detection of 25,893 additional early-stage lung cancers and averted 11,906 premature lung cancer deaths. It was estimated that LCS would incur EUR 945 million additional screening costs and EUR 386 million additional treatment costs. These estimates were robust in sensitivity analyses. Implementation of annual LCS with LDCT for a high-risk population, using the NELSON screening outcomes, is cost-effective in Austria, at a threshold of EUR 50,000 per QALY.

Relationship between commonly defined metabolic health phenotypes and obesity with lung function in a working population: A cross-sectional study

BackgroundFour phenotypes relate metabolism and obesity: metabolically healthy (MHO) and unhealthy (MUO) people with obesity and metabolically healthy (MHNO) and unhealthy (MUNO) people without obesity. No studies have addressed the association between these categories and lung function in the working population. ObjectivesThe aim was to determine the relationship of phenotypes to lung ageing as measured by lung age and its relationship to lung dysfunction. MethodsA descriptive cross-sectional study was conducted in a working population. The outcome variable was lung function assessed by lung age. The four phenotypes of obesity and metabolic health (MHNO, MHO, MUO and MUNO) were determined using NCEP-ATP III criteria. Lung dysfunctions were classified into restrictive, obstructive, and mixed patterns. ResultsThe mean age of the participants was 43.7 years, ranging from 18 to 67 years. Of the 1860 workers, 51.3 % were women. The prevalences found were 71.4 %, 12 %, 10.6 % and 6 % for MHNO, MUO, MHO, and MUNO, respectively. MHO (β = 0.66; p = 0.591) was not associated with increased lung ageing compared with MHNO, but MUO (β = 7.1; p < 0.001) and MUNO (β = 6.6; p < 0.001) were. Concerning pulmonary dysfunctions, MUNO (OR = 1.93; p < 0.001) and MUO (OR = 2.91; p < 0.001) were found to be related to the presence of a restrictive pattern, and MUNO (OR = 2.40; p = 0.028) to the mixed pattern. ConclusionThe results show that metabolic abnormalities, not obesity, are responsible for premature lung ageing and, therefore, lung function decline. In our study, having obesity without metabolic abnormality was not significantly associated with the presence of dysfunctional respiratory patterns.

Genetic Testing Goes Beyond Imaging and Histological Evaluation in Pleuroparenchymal Fibroelastosis

BackgroundLung biopsy remains the gold standard in the diagnosis of fibrotic interstitial lung disease (F-ILD), but there is a growing appreciation of the role of pathogenic gene variants in telomere and surfactant protein genes, especially in familial pulmonary fibrosis (FPF). Pleuroparenchymal fibroelastosis (PPFE) is a rare disease that can coexist with different patterns of F-ILD, including FPF. It can be progressive and often leads to respiratory failure and death. This study tested the hypothesis that genetic testing goes beyond radiological and histological findings in PPFE and other F-ILD further informing clinical decision-making for patients and affected family members by identifying pathological gene variants in telomere and surfactant protein genes.MethodsThis is a retrospective review of 70 patients with F-ILD in the setting of FPF or premature lung fibrosis. Six out of 70 patients were diagnosed with PPFE based on radiological or histological characteristics. All patients underwent telomere length evaluation in peripheral blood by Flow-FISH or genetic testing using a customized exome-based panel that included telomere and surfactant protein genes associated with lung fibrosis.ResultsHerein, we identified six individuals where radiographic or histopathological analyses of PPFE were linked with telomere biology disorders (TBD) or variants in surfactant protein genes. Each case involved individuals with either personal early-onset lung fibrosis or a family history of the disease. Assessments of telomere length and genetic testing offered insights beyond traditional radiological and histopathological evaluations.ConclusionDetecting anomalies in TBD-related or surfactant protein genes can significantly refine the diagnosis and treatment strategies for individuals with PPFE and other F-ILD.

Research Progress on the Prevention of Premature Infant Lung Injury and Neonatal Respiratory Support

Research Progress on the Prevention of Premature Infant Lung Injury and Neonatal Respiratory Support

Mechanical properties of the premature lung

Mechanical properties of the premature lung

Positive end-expiratory pressure and surfactant administration mode influence function in ex-vivo premature sheep lungs.

Respiratory distress syndrome often necessitates endotracheal surfactant administration in extremely preterm infants. Our study aimed to explore a multi-modal simulation tool for investigating treatment strategies in exvivo sheep lungs during spontaneous breathing. An electromechanical lung simulator (xPULM) mimicking spontaneous breathing was coupled with a non-aerated premature sheep lung, replicating a premature respiratory system. Changes in tidal volume for different positive end-expiratory pressure (PEEP) levels prior to and after either bolus or nebulised surfactant administration were compared. In two preterm sheep lungs, we observed a progressive decline in tidal volume with increasing PEEP levels prior to surfactant delivery from 0.30 ± 0.01 mL at zero PEEP to 0.04 ± 0.01 mL at 15 cmH2O PEEP. Our measurements showed that both bolus (p < 0.05) and nebulised (p < 0.05) surfactant administration resulted in a significant increase in tidal volume, with no significant difference (p = 0.71) between the two methods. The experimental setup demonstrated the feasibility of xPULM for investigating the effectiveness of different PEEP levels and modes of surfactant administration with respect to tidal volume in premature sheep lungs. The lack of adequate lung water resorption in our model warrants further investigations.

Cost-effectiveness of volume computed tomography in lung cancer screening: a cohort simulation based on Nelson study outcomes

Objectives This study aimed to evaluate the cost-effectiveness of lung cancer screening (LCS) with volume-based low-dose computed tomography (CT) versus no screening for an asymptomatic high-risk population in the United Kingdom (UK), utilising the long-term insights provided by the NELSON study, the largest European randomized control trial investigating LCS. Methods A cost-effectiveness analysis was conducted using a decision tree and a state-transition Markov model to simulate the identification, diagnosis, and treatments for a lung cancer high-risk population, from a UK National Health Service (NHS) perspective. Eligible participants underwent annual volume CT screening and were compared to a cohort without the option of screening. Screen-detected lung cancers, costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were predicted. Results Annual volume CT screening of 1.3 million eligible participants resulted in 96,474 more lung cancer cases detected in early stage, and 73,825 fewer cases in late stage, leading to 53,732 premature lung cancer deaths averted and 421,647 QALYs gained, compared to no screening. The ICER was £5,455 per QALY. These estimates were robust in sensitivity analyses. Limitations Lack of long-term survival data for lung cancer patients; deficiency in rigorous micro-costing studies to establish detailed treatment costs inputs for lung cancer patients. Conclusions Annual LCS with volume-based low-dose CT for a high-risk asymptomatic population is cost-effective in the UK, at a threshold of £20,000 per QALY, representing an efficient use of NHS resources with substantially improved outcomes for lung cancer patients, as well as additional societal and economic benefits for society as a whole. These findings advocate evidence-based decisions for the potential implementation of a nationwide LCS in the UK.

PM2.5 pollution in Texas: a geospatial analysis of health impact functions.

Air pollution is the greatest environmental threat to human health in the world today and is responsible for an estimated 7-9 million deaths annually. One of the most damaging air pollutants is PM2.5 pollution, fine airborne particulate matter under 2.5 microns in diameter. Exposure to PM2.5 pollution can cause premature death, heart disease, lung cancer, stroke, diabetes, asthma, low birthweight, and IQ loss. To avoid these adverse health effects, the WHO recommends that PM2.5 levels not exceed 5 μg/m3. This study estimates the negative health impacts of PM2.5 pollution in Texas in 2016. Local exposure estimates were calculated at the census tract level using the EPA's BenMAP-CE software. In BenMAP, a variety of exposure-response functions combine air pollution exposure data with population data and county-level disease and death data to estimate the number of health effects attributable to PM2.5 pollution for each census tract. The health effects investigated were mortality, low birthweight, stroke, new onset asthma, new onset Alzheimer's, and non-fatal lung cancer. This study found that approximately 26.7 million (98.9%) of the 27.0 million people living in Texas in 2016 resided in areas where PM2.5 concentrations were above the WHO recommendation of 5 μg/m3, and that 2.6 million people (9.8%) lived in areas where the average PM2.5 concentration exceeded 10 μg/m3. This study estimates that there were 8,405 (confidence interval [CI], 5,674-11,033) premature deaths due to PM2.5 pollution in Texas in 2016, comprising 4.3% of all deaths. Statewide increases in air-pollution-related morbidity and mortality were seen for stroke (2,209 - CI: [576, 3,776]), low birthweight (2,841 - CI: [1,696, 3,925]), non-fatal lung cancers (636 - CI: [219, 980]), new onset Alzheimer's disease (24,575 - CI: [20,800, 27,540]), and new onset asthma (7,823 - CI: [7,557, 8,079]). This study found that air pollution poses significant risks to the health of Texans, despite the fact that pollution levels across most of the state comply with the EPA standard for PM2.5 pollution of 12 μg/m3. Improving air quality in Texas could save thousands of lives from disease, disability, and premature death.

Exogenous hydrogen sulfide attenuates hyperoxia effects on neonatal mouse airways.

Supplemental O2 remains a necessary intervention for many premature infants (<34 wk gestation). Even moderate hyperoxia (<60% O2) poses a risk for subsequent airway disease, thereby predisposing premature infants to pediatric asthma involving chronic inflammation, airway hyperresponsiveness (AHR), airway remodeling, and airflow obstruction. Moderate hyperoxia promotes AHR via effects on airway smooth muscle (ASM), a cell type that also contributes to impaired bronchodilation and remodeling (proliferation, altered extracellular matrix). Understanding mechanisms by which O2 initiates long-term airway changes in prematurity is critical for therapeutic advancements for wheezing disorders and asthma in babies and children. Immature or dysfunctional antioxidant systems in the underdeveloped lungs of premature infants thereby heightens susceptibility to oxidative stress from O2. The novel gasotransmitter hydrogen sulfide (H2S) is involved in antioxidant defense and has vasodilatory effects with oxidative stress. We previously showed that exogenous H2S exhibits bronchodilatory effects in human developing airway in the context of hyperoxia exposure. Here, we proposed that exogenous H2S would attenuate effects of O2 on airway contractility, thickness, and remodeling in mice exposed to hyperoxia during the neonatal period. Using functional [flexiVent; precision-cut lung slices (PCLS)] and structural (histology; immunofluorescence) analyses, we show that H2S donors mitigate the effects of O2 on developing airway structure and function, with moderate O2 and H2S effects on developing mouse airways showing a sex difference. Our study demonstrates the potential applicability of low-dose H2S toward alleviating the detrimental effects of hyperoxia on the premature lung.NEW & NOTEWORTHY Chronic airway disease is a short- and long-term consequence of premature birth. Understanding effects of O2 exposure during the perinatal period is key to identify targetable mechanisms that initiate and sustain adverse airway changes. Our findings show a beneficial effect of exogenous H2S on developing mouse airway structure and function with notable sex differences. H2S donors alleviate effects of O2 on airway hyperreactivity, contractility, airway smooth muscle thickness, and extracellular matrix deposition.

Effect of Nasal Continuous Airway Pressure With and Without Surfactant Administration for the Treatment of Respiratory Distress Syndrome in Preterm Neonates.

Background Neonatal respiratory distress syndrome is a common cause of respiratory distress in newborns, often resulting from a lack of surfactant production or premature lung breakdown. The objective of this study was to compare the effect of nasal continuous airway pressure with and without surfactant administration for the treatment of respiratory distress syndrome in preterm neonates. Methodology A comparative analytical study was conducted on 100 neonates (group A continuous positive airway pressure (CPAP) with surfactant = 50 vs. group B CPAP only= 50 ). The group was allocated to the patient according to sequence. In group A, the neonates were given surfactant by the INSURE (intubation, surfactant, extubation) technique via an endotracheal tube with a single dose of 100 mg/kg/dose within the first hours of life followed by CPAP. In group B, the neonates were given only CPAP after birth. At follow-up after 24 hours, pH, pCO2, pO2, positive end-expiratory pressure (PEEP), and FiO2 were documented. All information was recorded on a predesigned questionnaire and results were subjected to statistical analysis to determine the significance of observed differences. Collected data were entered and analyzed using SPSS version 22 (IBM Corp., Armonk, NY, USA). Both groups were compared for mean pH, pCO2, pO2, PEEP, and FiO2 using an independent-sample t-test and effectiveness using a chi-square test. A significant difference was considered when the p-value was ≤0.05. Results Group A had a mean age of 4.84 ± 0.95 hours, while group B had a mean age of 5.5 ± 1.26 hours (p = 0.04). Gender distribution was similar in both groups, with 46.0% males and 54.0% females in group A, and 48.0% males and 52.0% females in group B (p = 0.841). Regarding post-treatment blood gas analysis, group A had a mean pH of 7.30 ± 0.05, and group B had a mean pH of 7.302 ± 0.07. While there was no significant difference in pO2 levels (p = 0.38), there was a substantial difference in pCO2 levels, with group A at 38.26 ± 4.35 and group B at 35.45 ± 4.36 (p = 0.02).CPAP parameters also showed a statistically significant difference in PEEP pCO2, with group A at 4.5 ± 0.73 and group B at 4.16 ± 0.37 (p = 0.004). After treatment, group A exhibited significant improvements in blood gas analysis and CPAP parameters compared to group B. Conclusions The study revealed that both CPAP with and without surfactant treatment effectively treat respiratory distress syndrome in preterm infants, with both being safe, effective, secure, and reducing side effects. However, CPAP treatment without surfactant is a non-invasive and cost-effective option.

Differential Oxidative Stress Responses in Type II Airway Epithelial Cells Impact Premature Senescence and Lung Fibrosis Susceptibility

Radiation-Induced Pulmonary Fibrosis (RIPF) is a late toxicity characterized by premature senescence in Type II airway epithelial cells (AECII) and accumulation of alternatively activated (M2) macrophages. Differential susceptibility to RIPF is observed across mouse strains. Based on our prior study of the effects of macrophage variation on RIPF, we hypothesized that intrinsic differences in AECII oxidative stress response across mouse strains also impact susceptibility to RIPF. Ten-week-old female mice from C57L, C57BL6 and C3H/HeN strains were exposed to thoracic irradiation (5x6 Gy, n>5 per group). Fifteen weeks after radiation, lung tissue was collected and examined with Masson-Trichrome staining (histologic changes) and β-galactosidase activity assay (senescence). AECII prepared from mice of each strain were exposed to irradiation. To assess differential gene expression, total RNA was extracted and assessed with a multiplex analysis platform and quantitative PCR. Senescence was assessed by β-galactosidase activity assay in primary AECII after irradiation or after co-culture with M2 macrophages polarized with IL13. Susceptibility to radiation-induced lung injury, survival, and premature AECII senescence vary by mouse strain: C57L (fibrosis-prone), C57BL6J (-intermediate) and C3H/HeN (-resistant). Enriched AECII from each strain exhibited differential expression of genes related to inflammatory responses including SASP production after irradiation. Minimal increased expression of Il1r1 was observed in irradiated and unirradiated AECII from C3H/HeN, however Il1rn levels were markedly elevated in response to irradiation. The expression of Thioredoxin (Txn) and Thioredoxin reductase 1 (Txnrd1) in AECII from C3H/HeN was significantly higher than those observed in other strains. In Vivo, C3H/HeN mouse lungs exhibited the least premature senescence in AECII after irradiation. Premature senescence in AECII irradiated In Vitro or co-cultured with superoxide anion-producing M2 macrophages was substantially less in AECII from C3H/HeN compared to other strains. A comparison of primary AECII from three different mouse strains identified intrinsic differences in expression of major inflammatory signaling (IL1R and IL1RN) and redox homeostasis status (TXN and TXNDR1) molecules. This study is the first to demonstrate that intrinsic differences in AECII impacts susceptibility to premature senescence and lung fibrosis after irradiation.

Endothelial to mesenchymal transition in neonatal hyperoxic lung injury: role of sex as a biological variable.

Bronchopulmonary dysplasia (BPD) is characterized by an arrest in alveolarization, abnormal vascular development, and variable interstitial fibroproliferation in the premature lung. Endothelial to mesenchymal transition (EndoMT) may be a source of pathological fibrosis in many organ systems. Whether EndoMT contributes to the pathogenesis of BPD is not known. We tested the hypothesis that pulmonary endothelial cells will show increased expression of EndoMT markers upon exposure to hyperoxia and that sex as a biological variable will modulate differences in expression. Wild-type (WT) and Cdh5-PAC CreERT2 (endothelial reporter) neonatal male and female mice (C57BL6) were exposed to hyperoxia (0.95 [Formula: see text]) either during the saccular stage of lung development (95% [Formula: see text]; postnatal day 1-5 [PND1-5]) or through the saccular and early alveolar stages of lung development (75% [Formula: see text]; PND1-14). Expression of EndoMT markers was measured in whole lung and endothelial cell mRNA. Sorted lung endothelial cells (from room air- and hyperoxia-exposed lungs) were subjected to bulk RNA-Seq. We show that exposure of the neonatal lung to hyperoxia leads to upregulation of key markers of EndoMT. Furthermore, using lung sc-RNA-Seq data from neonatal lung we were able to show that all endothelial cell subpopulations including the lung capillary endothelial cells show upregulation of EndoMT-related genes. Markers related to EndoMT are upregulated in the neonatal lung upon exposure to hyperoxia and show sex-specific differences. Mechanisms mediating EndoMT in the injured neonatal lung can modulate the response of the neonatal lung to hyperoxic injury and need further investigation.NEW & NOTEWORTHY We show that neonatal hyperoxia exposure increased EndoMT markers in the lung endothelial cells and this biological process exhibits sex-specific differences.

1044 Spinal Muscular Atrophy and Sleep: Double-Trouble

Abstract Introduction Spinal muscular atrophy (SMA) is a rare neuromuscular disorder which leads to progressive muscular weakness and respiratory impairment. Affected patients experience a variety of sleep problems including obstructive sleep apnea, nocturnal hypoventilation, and increased sleep disturbances. As of 2019, the first gene therapy was approved to treat patients with SMA under the age of 2, onasemnogene abeparvovec-xioi (ZolgensmaTM), with expedited approval due to findings of improved motor function and milestone achievement as well as survivability. We describe an unusual case of twins with SMA whom developed worsening obstructive sleep apnea after gene therapy. Report of case(s) The patients are a set of 3-year-old male twins with past medical history significant for premature lung disease related to extreme prematurity at 24-weeks and SMA type 2. They were initially referred for polysomnography (PSG) at 1 year of age for evaluation of snoring and as a precaution related to their underlying diagnosis. Physical examination findings were significant for tongue atrophy with fasciculations and generalized muscular weakness which spared the face. Neither twin achieved gross motor milestones of standing or walking to that point. Both patients would receive the gene therapy infusion at 1 year, 8 months with subsequent improvement in hypotonia and ability to ambulate independently. For twin A, baseline PSG at age 1 showed mild obstructive sleep apnea (apnea-hypopnea index (AHI)= 3.24 events per hour) without any signs of hypoxemia or hypoventilation. By comparison, the patient’s post-gene therapy PSG (around 1.5 years post-infusion) at age 3, showed progression to moderate obstruction (obstructive AHI of 6.03 events per hour). For twin B, baseline PSG showed moderate obstructive sleep apnea (AHI=9.09 events per hour) which progressed into the severe range (AHI= 11.90 events per hour) over the same time course. Conclusion Sleep-disordered breathing in SMA is a commonly diagnosed entity. While airway obstruction related to hypotonia would be an expected contributor, our case suggests that despite recovery of motor function through use of gene therapy, clinicians should maintain a high level of suspicion for sleep problems with strong consideration for PSG due to the risk of sub-clinical progression of sleep obstruction. Support (if any)

Neonatal Outcomes for Women at Risk of Preterm Delivery Given Half Dose Versus Full Dose of Antenatal Betamethasone: A Randomized, Multicenter, Double-blind, Placebo-controlled, Noninferiority Trial

(Lancet. 2022;400:592–604) Antenatal corticosteroids are recommended worldwide to help premature fetus lung maturity. However, the current recommended dose may be too high, based on some neurological, mental, and behavioral side effects. This study compared a half-dose (12 mg) of antenatal betamethasone to the typical full dose (24 mg) to determine if a half-dose can be as effective as a full dose, as well as to ultimately determine if a half-dose should be recommended in order to lessen side effects.

Artificial womb: opportunities and challenges for public health.

According to the WHO, 15 million babies are born prematurely each year, of which 1 million die due to complications. The need to reduce neonatal mortality has culminated in the development of artificial amnion and placenta technology, commonly known as the ‘Artificial Womb’, which provides an environment for the ectogestation of the foetus. Ever since 1958, when Westin et al. developed the first artificial womb by cannulation of umbilical vessels, this technology has shown remarkable potential for improvement of clinical outcomes in critically preterm children. Currently, working models of the technology include EXTra-uterine Environment for Neonatal Development (EXTEND) by Children’s Hospital of Philadelphia, Ex-Vivo uterine Environment (EVE) by Tohoku University, and University of Western Australia1. The world’s first artificial womb facility – EctoLife – was launched on 9 December 2022 by a filmmaker and science communicator based in Berlin, Germany2. The ‘Womb’ has been designed to simulate all the necessary physiological mechanisms during gestation. Gaseous exchange is performed via extracorporeal membrane oxygenation. A pumpless arteriovenous circuit is deployed that drives blood exclusively from the foetal heart and is combined with a low-resistance oxygenator. Waste disposal is carried out through dialysis. A polyethylene film-based biobag is used, which is responsible for sterility, size adjustment, and fluid and space volume efficiency. It can be modified to mimic the dimensions and shape of the uterus with more accuracy, thus providing an analogous alternative to the real womb3. Considering the incidence and mortality rates of premature deliveries throughout the world, artificial womb technology (AWT) is no less than a boon. AWT provides the innate environment of a human womb, thereby reducing respiratory struggle incompatible with the premature lung of the foetus. The impervious, sealed design mimicking the amniotic cavity also reduces the risk of infection. It can be a suitable alternative in cases of placental insufficiency, which can lead to preterm labour and intrauterine growth retardation. The health benefits also extend to pregnant women, as this technology provides a safe alternative to high-risk pregnancies and will alleviate the risks of concluding a full-term pregnancy. Women frequently experience pregnancy-related concerns including anaemia, hypertension, mental health issues, and viral infections. Some of these may be fatal to both the mother and the child, but could be prevented with AWT. The benefits on the social front are also very uplifting. AWT enables infertile couples to conceive a child and become the real biological parents of their children. Moreover, it raises a good proportion of the responsibility of carrying a baby, which is otherwise entirely instilled upon the female. Allows both parents to share equal responsibilities even before the child is fully born, raising equity amongst both genders4. This will help women both physically and will mentally and be more independent. AWT is a helpful alternative to surrogacy for same-sex couples, females who have undergone hysterectomy or infertile women. However, there are still issues that need to be resolved. Technology currently aids in the development of the foetus only between 13 weeks and before complete gestation, that is, 38 weeks. As it cannot facilitate embryo to foetal development, it is bound to be preceded by a surgical extraction of the foetus, which may be associated with complications4. The models do not possess the natural ability of the placenta to reduce pulsatile flow from the umbilical artery to laminar flow in the umbilical vein5. Furthermore, there is no collective understanding of the long-term psychological and psychological effects of the womb on parents and future offspring, considering the change it will bring to the concept of ‘giving birth’. Given the multitude of possible applications, the AWT is not without ethical concerns. The main considerations for the foetus include the consequentialism of medical interventions and their legal status, while those for parents include the extent of their autonomy in decision-making on behalf of the infant, impact on maternal bonding, cost-effectiveness, and accessibility. Even societal arguments about the acceptability of ectogenesis and regulation of abortion pose a question that should be answered before the release of this technology. A potential, though remotely possible, application of the technology is ‘complete ectogenesis’ – complete gestation outside the human body. This will greatly affect the substantiated human involvement during gestation, making it an extracorporeal event and thus completely transforming the conventional notion of pregnancy. Ethical approval Not applicable. Sources of funding None. Author contribution The authors declare that they have no financial conflict of interest with regard to the content of this report. Conflicts of interest disclosure There are no conflicts of interest. Guarantor A. Neyazi. Data statement We have not collected any primary data for this research. The authors confirm that the data supporting the findings of this study are available within the article and/or its supplementary materials.

Respiratory support strategies in the prevention and treatment of bronchopulmonary dysplasia.

Neonates who are born preterm frequently have inadequate lung development to support independent breathing and will need respiratory support. The underdeveloped lung is also particularly susceptible to lung injury, especially during the first weeks of life. Consequently, respiratory support strategies in the early stages of premature lung disease focus on minimizing alveolar damage. As infants grow and lung disease progresses, it becomes necessary to shift respiratory support to a strategy targeting the often severe pulmonary heterogeneity and obstructive respiratory physiology. With appropriate management, time, and growth, even those children with the most extreme prematurity and severe lung disease can be expected to wean from respiratory support.

Acute Lung Functional and Airway Remodeling Effects of an Inhaled Highly Selective Phosphodiesterase 4 Inhibitor in Ventilated Preterm Lambs Exposed to Chorioamnionitis.

Phosphodiesterase (PDE) inhibition has been identified in animal studies as a new treatment option for neonatal lung injury, and as potentially beneficial for early lung development and function. However, our group could show that the inhaled PDE4 inhibitor GSK256066 could have dose-dependent detrimental effects and promote lung inflammation in the premature lung. In this study, the effects of a high and a low dose of GSK256066 on lung function, structure and alveolar development were investigated. In a triple hit lamb model of Ureaplasma-induced chorioamnionitis, prematurity, and mechanical ventilation, 21 animals were treated as unventilated (NOVENT) or 24 h ventilated controls (Control), or with combined 24 h ventilation and low dose (iPDE1) or high dose (iPDE10) treatment with inhaled GSK 256066. We found that high doses of an inhaled PDE4 inhibitor impaired oxygenation during mechanical ventilation. In this group, the budding of secondary septae appeared to be decreased in the preterm lung, suggesting altered alveologenesis. Ventilation-induced structural and functional changes were only modestly ameliorated by a low dose of PDE4 inhibitor. In conclusion, our findings indicate the narrow therapeutic window of PDE4 inhibitors in the developing lung.