Search Results (140)

Preterm infants often require oxygen supplementation, resulting in high risk for bronchopulmonary dysplasia (BPD) and neurodevelopmental deficits. Despite a growing number of studies, there is still little knowledge about brain injury in BPD models. Therefore, we exposed neonatal C57BL/6 mice to 85% oxygen from birth to postnatal day (P) 14. At P28, two weeks after recovery under normoxic conditions, right hemisphere was used for the analysis of mRNA and the left hemisphere for protein expression of neuronal cells, neuroinflammatory and vascularisation markers, analysed by real-time PCR and Western blot, respectively. Hyperoxia led to an altered expression of markers associated with neuronal and oligodendrocyte maturation and neuroinflammation such as Dcx, Nestin, Il-1β, Il-6, NG2, and YM1/2. These changes were accompanied by an increased expression of genes involved in angiogenesis and vascular remodelling, e.g., Vegf-a, Nrp-1, and Icam-1. Together, 14 days of hyperoxia triggered a phenotypic response, resembling signs of encephalopathy of prematurity (EoP). Full article

Background and Objectives: Neonatal respiratory distress syndrome (NRDS), resulting from a deficiency of pulmonary surfactant (PS), can cause alveoli to collapse. Glucocorticoids reduce inflammation and are effective in reducing pulmonary swelling. This study aims to assess the effectiveness of the combination of PS and budesonide in the management of NRDS. Materials and Methods: Publications between 21 May and 24 November were screened through PubMed, Cochrane and Embase. Data analysis was performed on RevMan 5.3 software. Subgroup analysis was performed to evaluate the routes of administrations. Results: The use of budesonide along with pulmonary surfactant for treating NRDS revealed the following results: (1) a reduced duration of invasive mechanical ventilation (standardized mean difference (SMD) = −1.06, 95% confidence interval (CI) = −1.55 to −0.56, p < 0.0001); (2) reduced rate of bronchopulmonary dysplasia (BPD) occurrence (relative risk (RR) = 0.72, 95% CI = 0.60 to 0.86, p = 0.0003); (3) reduced duration for hospital admittance (SMD = −0.38, 95% CI = −0.64 to −0.11, p = 0.005). The occurrence of complications, i.e., sepsis, pneumothorax, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), rate of mortality, hyperglycemia and intraventricular hemorrhage (IVH), was not significantly different among the intervention and comparison group except for patent ductus arteriosus (PDA) and pulmonary hemorrhage, with their incidence being higher in the control group (p = 0.002 and p = 0.05, respectively). Conclusions: The combination of pulmonary surfactant and budesonide decreases the occurrence of BPD, duration of mechanical ventilation, length of hospital stay and risk of pulmonary hemorrhage and PDA. It does not increase the risk of complications and death and is clinically safe. Full article

Intrauterine inflammation (IUI) is involved in the development of bronchopulmonary dysplasia (BPD). Previously, we observed BPD-like pathological changes in a mouse model of IUI. This study aimed to identify the key molecules involved in IUI-induced lung injury, focusing on NR4A1. Pregnant C57BL/6 mice were randomly divided into control and IUI groups. To verify the intervention effects, Nr4a1 siRNA was administered intranasally on postnatal day 3, while an NR4A1 overexpression plasmid was applied in MLE-12 cells to investigate downstream molecules. We found that the lungs of IUI-induced offspring exhibited a simplified structure on postnatal day 1 and excessive collagen fiber deposition by day 90. Postnatal NR4A1 intervention reversed IUI-induced neonatal lung injury. NR4A1 overexpression reduced cell proliferation and AKT and ERK1/2 phosphorylation levels, while also affecting the expression of the key epithelial–mesenchymal transition (EMT)-related gene TGF-β. EREG is a downstream target with potential NR4A1 binding sites in its promoter region. The expression of EMT-related genes can be recovered by blocking the receptor of EREG. Our findings imply that IUI induces BPD-like lung injury in neonates and fibrosis-like lung lesions in adult mice. The NR4A1-EREG-EGFR signaling pathway in pulmonary epithelial cells is crucial in IUI-induced lung injury, highlighting a key therapeutic target for mitigating BPD-like injury. Full article

Bronchopulmonary dysplasia (BPD) remains a significant complication of premature birth and neonatal intensive care. While much is known about the drivers of lung injury, few studies have addressed the interrelationships between oxidative stress, inflammation, and downstream events, such as endoplasmic reticulum (ER) stress. In this review, we explore the concept of a “destructive cycle” in which these drivers self-amplify to push the lung into a state of maladaptive repair. Animal models, primarily the hyperoxic rat pup model, support a sequential progression from the generation of reactive oxygen species (ROS) and inflammation to endoplasmic reticulum (ER) stress and mitochondrial injury. We highlight how these intersecting pathways offer not just therapeutic targets but also opportunities for interventions that reprogram system-wide responses. Accordingly, we explore the potential of systems pharmacology therapeutics (SPTs) to address the multifactorial nature of BPD. As a prototype SPT, we describe the development of N-acetyl-L-lysyl-L-tyrosyl-L-cysteine amide (KYC), a systems chemico-pharmacology drug (SCPD), which is selectively activated in inflamed tissues and modulates key nodal targets such as high-mobility group box-1 (HMGB1) and Kelch-like ECH-associated protein-1 (Keap1). Collectively, the data suggest that future therapies may require a coordinated, network-level approach to break the destructive cycle and enable proper regeneration rather than partial repair. Full article

Background and Clinical Significance: The incidence of persistent ductus arteriosus (PDA) in preterm infants is the highest and depends on their birth weight (BW) and respiratory condition after birth. Previously, after the unsuccessful drug treatment, surgical ligation was the primary treatment option. However, according to clinical studies, the Amplatzer Piccolo Occluder was approved for PDA closure for patients ≥700 g. In our country, percutaneous PDA embolization has not been performed yet. Case Presentation: We present three premature infants with hemodynamically significant patent ductus arteriosus (hsPDA) in whom percutaneous occlusion was performed using the Amplatzer Piccolo Occluder (APO). The average gestational week (GW) was 27 ± 1, while body weight was 1030 ± 60 g. All patients had respiratory deterioration, with dilatation of the left heart chambers, and renal failure. The second developed a severe form of broncho-pulmonary dysplasia. Transthoracic echocardiography (TTE) examinations revealed a hemodynamically significant PDA (LA/Ao 1.8–2.2) and medical closure was unsuccessfully carried out. Due to the hemodynamically significant PDA maintenance in all neonates, transvenous PDA closure was performed using the APO (APO 9-PDAP-04-02-L, 9-PDAP-04-04-L, 9-PDAP-05-054L, respectively). The entire devices, with both retention discs, are implanted within the duct. TTE pointed out adequate device position without descending aorta, left pulmonary artery obstruction, residual shunt, and reverse remodelling of the left ventricle and left atrium. The first newborn was weaned from mechanical ventilation three days after the procedure and discharged three weeks after. The second patient was extubated 2 weeks after the procedure, and even the severe BPD, X-ray showed improvement. The third patient’s renal failure completely resolved, weaned from inotropic drug support and mechanical ventilation. Conclusions: Due to a significantly lower complication rate than surgical ligation, we will strive to make percutaneous PDA occlusion a new standard for treatment in newborns, especially preterm newborns, in our country. Full article

The complications observed in preterm infants are largely attributable to underdeveloped organ systems and inadequate nutritional stores at birth. Insufficient nutritional support can further exacerbate persistent sequelae, such as bronchopulmonary dysplasia (BPD), metabolic bone disease of prematurity (MBDP), and retinopathy of prematurity (ROP). As a result, clinicians have collaborated to develop optimal nutrition strategies for preterm neonates. However, these clinical nutrition plans may be hindered by several factors, including fluid restrictions due to patent ductus arteriosus (PDA) and delayed enteral nutrition following necrotizing enterocolitis (NEC). Modified strategies for specific conditions can help prevent further deterioration, but inadequate nutritional support may limit organ growth and contribute to additional complications. Achieving an optimal balance between nutritional support and managing specific medical conditions varies across institutions. In addition to fluid balance and energy intake, supplementary nutrition—such as vitamins and probiotics—plays a crucial role in disease prevention. Drawing on recent evidence and our clinical experiences with neonatal nutritional strategies, this review article summarizes the specialized nutritional management required for preterm neonates with conditions such as BPD, NEC, MBDP, PDA, and ROP. Full article

Oxygen (O₂) is vital for cellular development, function, proliferation, and repair, underscoring its critical role in organogenesis. Both hypoxia (reduced tissue O₂) and hyperoxia (excess tissue O₂), when prolonged, can trigger inflammation and oxidative stress, contributing to acute and long-term cardiopulmonary and neurodevelopmental morbidity. In sick neonates, immature defense mechanisms and coexisting morbidities demand nuanced and sometimes opposing strategies for O₂ saturation targets and therapeutic titration. Most current neonatal O₂ targeting guidelines are based on animal models or small clinical studies, resulting in recommendations with limited evidence. This narrative review aims to provide an updated overview of the physiological roles of O₂ in development, its delivery and consumption, approaches to O₂ saturation monitoring, and therapeutic targeting in neonates under both normal and pathological conditions. We also highlight key knowledge gaps and propose directions for future research on neonatal O₂ saturation targeting. Full article

Background/Objectives: Preterm neonates with a birth weight (BW) of 500–1250 g who receive prophylactic methylxanthine have a lower rate of bronchopulmonary dysplasia and neurodevelopmental disability than their counterparts. In a meta-analysis of previous studies (published during 1985–1993, with no routine continuous positive airway pressure), extubation failure rates in preterm neonates with BW < 2500 g who received and did not receive methylxanthine were 25.0% and 50.6%, respectively (risk difference, −0.27; 95% confidence interval [CI], −0.39 to −0.15). However, no study to date has assessed the effects of prophylactic methylxanthine use on endotracheal extubation in infants weighing 1250–2499 g until now. Methods: First-time extubation was compared between 1:1 propensity score-matched methylxanthine and non-methylxanthine groups from a retrospective cohort of 541 neonates (born during 2014–2024). Results: The domains from the overall cohort and propensity-matched data included 541 and 192 neonates, respectively. In the propensity score-matched sample, the mean gestational age and BW were 30.9 ± 1.9 weeks and 1584 ± 273 g, respectively. The median 5-min Apgar score was 9 (range of 7–9). Extubation failure within 7 days occurred in 10 (10.4%) and 13 (13.5%) neonates in the methylxanthine (n = 96) and non-methylxanthine (n = 96) groups, respectively, with a risk difference (95% CI) of −0.03 (−0.12 to 0.06), p = 0.50, and hazard ratio (95% CI) of 0.76 (0.33 to 1.72), p = 0.51. Conclusions: In the current era with new non-invasive ventilation approaches, extubation failure in preterm neonates with a BW of 1250–2499 g is not significantly affected by the use of methylxanthine. Full article

Background/Objectives: Optimal feeding regimens for preterm neonates, including the role of multi-nutrient fortification, are unknown, leading to large practice variation in comparing different feeding regimens that include fortification and their impact on outcomes for preterm infants. Methods: Using a network meta-analyses design, two reviewers independently extracted data. A Cochrane CENTRAL, Medline, Embase, and CINAHL search was conducted for all studies published up to 27 June 2023. Randomized clinical trials of feeding regimens for preterm infants that included multi-nutrient fortification were included. Outcomes were mortality, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), sepsis, periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), time to full enteral feeds, and the Bayley II MDI developmental score. Results: Fifty-nine studies were included. For mortality, NEC, and time to reach full enteral feeds, the top-ranked treatment class was the mother’s own milk with donor milk and a human-milk-based fortifier. For ROP and BPD, the top-ranked treatment class was mother’s own milk with a phosphorus fortifier. For sepsis, the top-ranked treatment class was mother’s own milk with formula. For PVL, the top-ranked treatment classes were mother’s own milk and mother’s own milk with donor milk and a bovine fortifier in the two disconnected networks. For the Bayley II MDI score, the top-ranked treatment class was mother’s own milk with formula and bovine fortification. Conclusions: Treatment rankings are consistent with the underlying hypothesis that increased mother’s own milk intake appears to be associated with better clinical outcomes. This review provides the first global view of interventions and highlights insufficient high-quality evidence to support or refute one fortification feeding regimen over another. Full article

Background: Monochorionic diamniotic (MCDA) twin pregnancies are at risk of complications, particularly selective intrauterine growth restriction. The objective of this study was to evaluate the two-year neurologic outcomes of the eutrophic newborns from monochorionic diamniotic twin pregnancies who were complicated by selective intrauterine growth restriction, compared to newborns from uncomplicated MCDA pregnancies. Our hypothesis was to determine whether selective IUGR in these pregnancies was specifically associated with a risk of delayed psychomotor development at two years old. Methods: We conducted a retrospective–prospective observational cohort study of children from pregnancies and deliveries which were monitored at Hospital Nord of Marseille between 2012 and 2021. The primary outcome measure was the comparison of the Ages and Stages Questionnaire (ASQ) scores at the age of two years between the two groups. The secondary outcome measure was a composite score including the following: neonatal death, grade III or IV intraventricular hemorrhage (IVH) at cerebral MRI or cranial ultrasound, periventricular leucomalacia (PVL) at brain MRI, bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC) of stages II or III. Results: A total of 57 eutrophic children were included in the group from monochorionic twin pregnancies complicated by selective IUGR and 270 children in the group from MCDA twin pregnancies with no complications. The composite morbidity and mortality criterion, including neonatal death, grade III or IV IVH, the presence of PVL, BPD, and/or stage II or III NEC, was 11% in eutrophic newborns from the MCDA group with IUGR and 5% in the uncomplicated MCDA group, with no statistically significant difference (p = 0.18). The 2-year follow-up allowed for the comparison of a total of 38 eutrophic children from complicated pregnancies and 134 children from uncomplicated pregnancies. The median ASQ score at 24 months was 255 in the complicated pregnancy group and 240 in the uncomplicated pregnancy group, with no statistically significant difference (p = 0.27) after adjustment. Conclusions: Our study did not show a statistically significant difference in the neurodevelopmental follow-up of eutrophic children from monochorionic diamniotic twin pregnancies with selective intrauterine growth restriction compared to newborns from the same pregnancies without complications. Full article

Bronchopulmonary dysplasia (BPD) is a severe chronic respiratory disease linked to preterm births. A scoping review was performed to identify risk factors for moderate and severe BPD to develop an evidence-based, early prognostic, globally recognized, and etiology/pathophysiology-based classification. The findings were then validated against a Japanese national database, the Neonatal Research Network Japan. After identifying histological chorioamnionitis, bubbly/cystic appearance on chest X-ray, and small-for-gestational-age infants as risk factors for severe BPD, BPD was divided into nine categories based on the presence or absence of these three risk factors. After consensus was reached using the Delphi method, public comments were requested, and the classification of BPD was finalized. This perspective introduces the new etiology/pathophysiology-based BPD classification, which should be used in research to better understand the respiratory prognosis and pathophysiology of BPD. Full article

Background/Objectives: Maternal milk feeding in the NICU (neonatal intensive care unit) for very low birth weight (VLBW) infants mitigates the effects of preterm birth. This single-center retrospective study analyzed data from VLBW infants born between 2005 and 2019 and investigated the impact on morbidity of exposure to Mother’s Own Milk (MOM), donor human milk (DHM), preterm formula (PF), during NICU hospitalization. The assessed outcomes included necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and late-onset sepsis (LOS). The study also examined the impact of a human milk-based feeding protocol on these outcomes, adjusting for confounding factors. Methods: Statistical analysis involved correlation tests and odds ratios to assess associations between feeding types and outcomes. Results: Surgical NEC occurred in 10% of infants fed exclusively with PF, 1.3% of those fed with DHM, and was completely absent in infants fed exclusively or partially with MOM. ROP across all stages was observed in 24.3% of cases, with severe ROP at 4.7%, and PF feeding was associated with a higher risk of severe ROP; the incidence of LOS was lower in infants fed human milk (−22%/−66%) compared to 10% in formula-fed infants. BPD affected 25.5% of infants, with moderate-to-severe BPD in 22.2%. The association between NEC, LOS, and feeding was statistically significant, even after adjusting for covariates. The type of milk had a significant impact on the incidence of severe forms of all outcomes (p < 0.001). The rate of exclusive MOM feeding increased over time, reaching 45% in 2018–2019. Conclusions: These findings highlight the role of human milk in preventing NEC and LOS, in reducing the risk of severe ROP and BPD, and in promoting MOM feeding, with rates increasing significantly when DHM is available. Full article

Bronchopulmonary dysplasia (BPD) is a neonatal lung condition predominantly affecting preterm infants. Researchers have turned to computational tools, such as artificial intelligence (AI) and machine learning (ML), to better understand, diagnose, and manage BPD in patients. This study aims to provide a comprehensive summary of current AI applications in BPD risk stratification, treatment, and management and seeks to guide future research towards developing practical and effective computational tools in neonatal care. This review highlights breakthroughs in predictive modeling using clinical-, genetic-, biomarker-, and imaging-based markers. AI has helped advance BPD management strategies by optimizing treatment pathways and prognostic predictions through computational modeling. While these developments become increasingly clinically applicable, numerous challenges remain in data standardization, external validation, and the equitable integration of AI solutions into clinical practice. Addressing ethical considerations, such as data privacy and demographic representation, as well as other practical considerations will be essential to ensure the proper implementation of AI clinical tools. Future research should focus on prospective, multicenter studies, leveraging multimodal data integration to enhance early diagnosis, personalized interventions, and long-term outcomes for neonates at risk of BPD. Full article

Despite improved neonatal intensive care, the risk of premature-born infants developing bronchopulmonary dysplasia (BPD) and encephalopathy of prematurity (EoP) remains high. With hyperoxia being a major underlying factor, both preterm-birth-related complications are suggested to be closely interrelated. However, experimental models are lacking for the assessment of the potentially close interplay between both organs. To establish a model, suitable for the assessment of both affected organs, Wistar rats were exposed to 80% oxygen from postnatal day 2 (P2) for seven days. Brain and lung tissues were analysed via histomorphometry, immunohistochemistry, real-time PCR, and western blot at term P11. In the brain, hyperoxia induced significant hypomyelination accompanied by a reduction in oligodendrocytes and CD68 expression on microglia cells. These changes correlate with arrested alveolarisation and an increased number of macrophages in the lung. Interestingly, in contrast to the reduced formation of pulmonary microvessels, an increased vascular density was detected in the brain. Seven days of hyperoxia induces typical characteristics of BPD and EoP in neonatal rats, thereby linking impaired alveolarisation with disturbed myelination in the brain and providing an experimental model for understanding pathophysiological mechanisms and identifying organ-spanning novel therapeutic interventions targeting both diseases. Full article

Background/Objectives: There has been an increase in the incidence of comorbidities among very-low-birth-weight infants (VLBWIs), including periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP). Parenteral nutrition is essential for very-low-birth-weight infants (VLBWIs) who are born with a birth weight of less than 1500 g, but a longer duration of parenteral nutrition is known to have a risk of comorbidity, such as ROP. This study aims to investigate the relationship between the duration of parenteral nutrition and the comorbidities of the VLBWIs. Methods: Using the prospective cohort of Korean neonatal network, we analyzed the perinatal and postnatal data before discharge of the total 2490 subjects born in 2021 and 2022. The primary outcomes were the diagnoses of PVL, BPD, and ROP. The secondary outcomes were the severity of BPD and ROP, treatment of ROP, and proposing the predictive model of comorbidities using the duration of parenteral nutrition. Results: This study found that prolonged parenteral nutrition exceeding 28 days was associated with a higher risk of PVL (odds ratio [OR] 1.71, 95% confidence interval [CI] [1.11, 2.64], p = 0.002) and BPD (OR 1.51, 95% CI [1.10, 2.08], p = 0.011). Furthermore, an intermediate duration of parenteral nutrition was found to be significantly associated with an increased risk of ROP in male subjects. Additionally, a prolonged duration of parenteral nutrition was observed to be linked to greater severity of BPD. Predictive models incorporating the duration of parenteral nutrition demonstrated a high degree of explanatory power in relation to both BPD and ROP. Conclusions: Longer duration of parenteral nutrition has a risk of critical comorbidities in VLBWIs. The nutrition strategy for shorter parenteral nutrition should be encouraged for the prevention of comorbidities. Full article