Search Results (189)

Neutrophil extracellular traps (NETs) play a key role in the development of bronchopulmonary dysplasia (BPD), yet their molecular mechanisms in contributing to BPD remain unexplored. Using the GSE32472 dataset, which includes 100 blood samples from postnatal day 28, we conducted comprehensive bioinformatics analyses to identify differentially expressed genes (DEGs) and construct gene modules. We identified 86 DEGs, which were enriched in immune and inflammatory pathways, including NET formation. Weighted gene co-expression network analysis (WGCNA) revealed a key gene module associated with BPD. By intersecting 69 NET-related genes (NRGs), 149 module genes, and 86 DEGs, we identified 12 differentially expressed NET-related genes (DENRGs). Immune infiltration analysis revealed an increase in neutrophils, dendritic cells, and macrophages in BPD patients. Machine learning models (LASSO, SVM-RFE, and RF) identified 5 upregulated biomarkers—MMP9, Siglec-5, DYSF, MGAM, and S100A12—showing potential as diagnostic biomarkers for BPD. Validation using nomogram, ROC curves, and qRT-PCR confirmed the diagnostic accuracy of these biomarkers. Clinical data analysis showed that Siglec-5 was most strongly correlated with BPD severity, while DYSF correlated with the grade of retinopathy of prematurity (ROP) and its laser treatment. Clustering analysis revealed two distinct BPD subtypes with different immune microenvironment profiles. Drug–gene interaction analysis identified potential inhibitors targeting MGAM and MMP9. In conclusion, the study identifies five NET-related biomarkers as reliable diagnostic tools for BPD, with their upregulation and association with disease severity and complications, such as ROP, highlighting their clinical relevance and potential for advancing BPD diagnostics and treatment. Full article

Microtubule-actin cross-linking factor 1 (MACF1), also known as actin cross-linking family protein 7 (ACF7), is a giant cytolinker protein with multiple conserved domains that can orchestrate cytoskeletal networks of actin and microtubules. MACF1 is involved in various biological processes, including cell polarity, cell–cell connection, cell proliferation, migration, vesicle transport, signal transduction, and neuronal development. In this review, we updated the physiological and pathological roles of MACF1, highlighting the components and signaling pathways involved. Novel evidence showed that MACF1 is involved in diverse human diseases, including multiple neuronal diseases, congenital myasthenic syndrome, premature ovarian insufficiency, spectraplakinopathy, osteoporosis, proliferative diabetic retinopathy, and various types of cancer. We also reviewed the physiological roles of MACF1, including its involvement in adhesome formation, bone formation, neuronal aging, and tooth development. In addition, MACF1 plays other roles, functioning as a biomarker for the prediction of infections in patients with burns and as a marker for genome selection breeding. These studies reinforce the idea that MACF1 is a bona fide versatile, multifaceted giant protein. Identifying additional MACF1 functions would finally help with the treatment of diseases caused by MACF1 defects. Full article

Premature infants with retinopathy of prematurity (ROP) have neovascularization of the retina, potentially resulting in low vision and even blindness. Some of these infants still have visual impairment, even if ROP resolves as they age. However, the mechanisms underlying the visual problems post–ROP are poorly understood. Because the pathological neovascularization in ROP infants can be mimicked in a mouse model with oxygen–induced retinopathy (OIR), we recapitulated post–ROP with post–OIR mice a few months after spontaneous regression of retinal neovascularization. Our pattern electroretinogram test demonstrates that post–OIR mice exhibit reduced P1–N2 responses, suggesting the impairment of retinal ganglion cells, the retina’s output neurons. However, immunohistochemistry reveals that the density of retinal ganglion cells remains unchanged in post–OIR mice, indicating that the aforementioned pattern electroretinogram changes are functional. Our data further demonstrate that both light–adapted ex vivo electroretinogram a–waves (cone responses) and in vivo electroretinogram b–waves (ON cone bipolar cell responses) were significantly impaired in post–OIR mice. These results suggest that post–OIR impairment of the retinal cone pathway appears to result in the dysfunction of retinal ganglion cells, contributing to visual problems. A similar cellular mechanism could occur in post–ROP children, which is responsible for their visual impairment. 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

Background/Objectives: Preterm infants represent a population group at increased risk for vitamin D deficiency (VDD) and for its negative impact on various outcomes like metabolic bone disease or rickets, respiratory complications like respiratory distress syndrome and the development of bronchopulmonary dysplasia, necrotizing enterocolitis, or retinopathy of prematurity. Methods: Despite the growing interest in vitamin D research, there is still uncertainty regarding clear recommendations for each high-risk category of premature infants concerning the optimal dosage, optimal product, and timing for initiating vitamin D supplementation to prevent VDD. Results: An analysis of the literature suggests that early intervention for the optimal enteral supplementation of vitamin D is not only successful in achieving higher 25-hydroxi-vitamin D (25(OH)D) at one month but is also linked with improved outcomes. Conclusions: The traditional concepts and current recommendations for assessing vitamin D status and optimal supplementation need to be revised. Since parenteral nutrition, fortified mothers’ own milk, and special formula for preterm infants cannot provide adequate vitamin D levels, initiating oral supplementation soon after birth is essential to correct VDD in preterm infants. 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

Background/Objectives: Premature neonates are at risk for retinopathy of prematurity (ROP) and routinely undergo screening exams that involve substantial physical manipulation, often causing significant signs of pain, despite pain-relieving interventions. It remains unclear whether these exams affect energy utilization, cellular hypoxia, and clinically significant events, and whether receiving supplemental oxygen affects these relationships. This work examines the effects of ROP screening on (1) urinary uric acid-to-creatinine concentration ratios ([UA]/[Cr]), a known marker of ATP degradation, hypoxia, and oxidative stress; and (2) clinically significant events (apnea, bradycardia, gastric residuals, and oxygen desaturations) in premature neonates on room air or oxygen support. Methods: This prospective pilot study included premature neonates requiring ROP screening examinations at Loma Linda University’s NICU. Urinary [UA]/[Cr], measured by high-performance liquid chromatography, and clinical events, documented by prospective medical chart review, were analyzed pre- and post-exam in subjects on room air (n = 18) or on oxygen support (n = 20). Statistical analyses included a generalized linear mixed model for urinary [UA]/[Cr] and Wilcoxon signed rank tests for clinical events. Results: A significant time effect (p = 0.010) was observed for urinary [UA]/[Cr], with higher levels at 0–12 (p = 0.023) and 12–24 (p = 0.023) hours post-exam. Subjects receiving oxygen support had more total (p = 0.028) and more severe (p = 0.026) oxygen desaturations. Conclusions: ROP examinations may increase energy utilization in premature neonates, with those receiving oxygen support being particularly susceptible to oxygen desaturations post-exam. Further research is needed to clarify the full impact of the procedure and to identify strategies to minimize stress associated with these screening examinations. Full article

The premature aging disease Hutchinson–Gilford Syndrome (HGPS) is caused by defined mutations in the LMNA gene, resulting in the activation of a cryptic splice donor site, which leads to a defective truncated prelamin A protein called progerin. Notably, progerin expression has also been detected in non-mutated healthy individuals, and therefore, its involvement in the physiological aging process has been widely discussed. Since diabetes mellitus is associated with premature aging and increased cardiovascular mortality, we aimed to investigate the role of progerin expression in patients with diabetic retinopathy (DR). mRNA expression of progerin was analyzed in blood samples from 140 patients with DR who received anti-vascular endothelial growth factor (VEGF) therapy. Progerin mRNA levels were significantly lower in female compared to male patients (n = 42 vs. n = 98; 0.67 ± 0.19 vs. 0.89 ± 0.51, p = 0.006) and higher in patients with non-proliferative (NP)DR (n = 87 vs. n = 53; 0.9 ± 0.51 vs. 0.71 ± 0.29, p = 0.013) compared to those with proliferative (P)DR. Additionally, a positive correlation was found between progerin mRNA expression and the number of intravitreal anti-VEGF applications (n = 139, r = 0.21, p = 0.015), central macula thickness (CMT), (n = 137, r = 0.18, p = 0.036) and nicotine consumption (n = 105, r = 0.235, p = 0.002). The nuclear localization and significant upregulation of progerin mRNA and protein levels in dermal fibroblasts from HGPS donors emphasize its role in cellular aging mechanisms. Progerin mRNA levels were higher in patients with NPDR. CMT, number of intravitreal anti-VEGF therapy treatments, and cigarette consumption were positively related to progerin mRNA, suggesting an association with disease progression and premature aging. Full article

Background: Retinopathy of prematurity (ROP) is a serious disease causing blindness in childhood. Gestational age (GA) and birth weight are major factors associated with the development and progression of ROP, but postnatal systemic inflammation is also an important well-known risk factor. Methods: This study retrospectively analyzed the relationship between systemic inflammation and ROP severity using the corrected GA (CGA), which reflects the intrinsic immaturity of the infant, rather than days of life. Three acute phase reactants (APRs) were analyzed using discriminant probability and compared with conventional ROP prediction models: C-reactive protein, α1AG, and haptoglobin. Results: Alpha 1AG was the best predictor of ROP onset and progression, and could be predicted with blood samples up to 30 weeks (30 W) CGA (p = 0.006). Incorporation of APR into the conventional GA + body weight (BW), ROP score, and Children’s Hospital of Philadelphia (CHOP) predictive models improved the decision to treat (4–5% increase in discrimination probability) and helped determine whether treatment of ROP was necessary by CGA 30 W. Conclusions: Therefore, simply adding α1AG protein to the assessment is useful for predicting the need to treat ROP. Full article

Background: Retinopathy of prematurity (ROP) is the major cause of blindness in children. It is a biphasic disease with retinal vessel growth cessation and loss (Phase I) followed by uncontrolled retinal vessel growth (Phase II). Folate is an essential nutrient for fetal development and growth. Premature infants have a high risk for folate deficiency. However, the contribution of folate to ROP risk remains unknown. Methods: In mouse oxygen-induced retinopathy (OIR), the nursing dams were fed with a folic acid-deficient or control diet after delivery until the end of hyperoxia. Alternatively, pups received direct injection of either folic acid or vehicle during Phase I hyperoxia. Genes involved in the folate cycle and angiogenic responses were examined using real-time PCR. Total retinal folate levels were measured with the Lactobacillus casei assay. Results: Maternal folic acid deficiency in early life exacerbated pathological retinal vessel growth, while supplementation with folic acid suppressed it. Genes involved in the folate cycle were downregulated in Phase I OIR retinas and were highly expressed in Müller glia. Folic acid reduced pro-angiogenic signaling in cultured rat retinal Müller glia in vitro. Conclusions: Appropriate supplementation of folic acid might be a new and safe treatment for ROP at an early stage. Full article

Background/Objectives: Sodium glycerophosphate improves the adverse side effects of parenteral nutrition. Therefore, this study aimed to evaluate different outcomes, including metabolic bone disease and electrolyte imbalance, associated with the use of sodium glycerophosphate or inorganic phosphate in parenteral nutrition for preterm neonates. Methods: This retrospective cohort study enrolled 402 newborns admitted to the neonatal intensive care unit of one medical center between January 2019 and September 2021. Of them, 205 received sodium glycerophosphate as parenteral nutrition, while the other 197 received inorganic phosphate. Baseline characteristics and growth parameters, including body weight, body length, and head circumference in the first year of life; calcium and phosphate content of parenteral nutrition in the first 4 weeks; calcium, phosphorus, alkaline phosphatase (ALP), and creatinine levels; and morbidities were compared. Results: During the first 4 weeks, the calcium and phosphate contents of parenteral nutrition were significantly higher in the sodium glycerophosphate vs. inorganic phosphate group. Growth parameters did not differ significantly between groups. The sodium glycerophosphate group showed a higher mean serum phosphate level (4.0 ± 1.2 mg/dL vs. 3.5 ± 1.3 mg/dL, p = 0.001), lower serum ALP level (402.8 ± 202.8 U/L vs. 466.4 ± 228.6 U/L, p = 0.004), lower seizure incidence (4.9% vs. 13.2%, p = 0.003), and higher hypocalcemia incidence (41.5% vs. 31.5%, p = 0.038). However, there were no significant intergroup differences in other common morbidities such as metabolic bone diseases of prematurity, bronchopulmonary dysplasia, electrolyte imbalance, hypoglycemia, retinopathy of prematurity, or intraventricular hemorrhage. Conclusions: Compared to inorganic phosphate, sodium glycerophosphate is associated with higher serum phosphate levels, lower ALP levels, and reduced seizure incidence in premature infants. However, as the study was retrospective and single-center, further randomized controlled trials are needed to confirm these findings. Full article

Retinopathy of Prematurity (ROP), a leading cause of blindness in preterm infants, arises from dysregulated angiogenesis and inflammation. Without timely intervention, ROP can progress to severe outcomes, including dense fibrovascular plaques and retinal detachment. MicroRNAs (miRNAs) regulate key pathways such as hypoxia response, VEGF signaling, and vascular remodeling. Studies have identified miRNAs (e.g., miR-210, miR-146a, and miR-21) as potential biomarkers and therapeutic targets. Preclinical evidence supports miRNA-based therapies (e.g., miR-18a-5p and miR-181a), targeting HIF-1α and VEGFA to mitigate neovascularization, with nanoparticle delivery systems enhancing stability and specificity. These strategies, combined with anti-VEGF agents, show significant potential for improving ROP management. While promising, miRNA therapies require validation in clinical trials to ensure safety and efficacy. This review discusses the role of miRNAs in ROP, highlighting their relevance as diagnostic and therapeutic tools. Full article

Background/Objectives: The aim of this study was to examine the incidence and severity of refractive errors that occur following the treatment of retinopathy of prematurity (ROP) with anti-vascular growth factor (anti-VEGF) agents and laser photocoagulation. Methods: A review of the literature using three databases (PubMed, Embase, Medline) was performed using appropriate search terms, and the results of the relevant studies were compiled and extracted for descriptive analysis. Results: Sixty articles were identified. The cohorts in the studies were treated with either anti-VEGF monotherapy, laser photocoagulation, or a combination, with a high prevalence of myopia, ranging from 0 to 47.7%. Refractive errors of myopia, hypermetropia, astigmatism, and anisometropia were considered in infants who received ocular interventions for ROP. Conclusions: In comparison to laser photocoagulation, anti-VEGF monotherapy appears to yield lower levels of myopia and anisometropia; however, the incidence of hypermetropia and astigmatism is variable among cohort groups treated with different anti-VEGF agents. Full article

Background: Feeding intolerance (FI) following surgery for neonatal necrotizing enterocolitis (NEC) can impact recovery and prognosis, making the early identification of FI risk essential for optimizing management and improving outcomes. Methods: We retrospectively collected data from patients who underwent surgery for NEC between January 2013 and December 2023. Multivariate binary logistic regression was performed to identify independent factors influencing postoperative feeding intolerance. Results: Of the 519 infants enrolled in this retrospective study, 155 (29.9%) were diagnosed with feeding intolerance, while 364 (70.1%) were identified as having feeding tolerance. Compared to infants with feeding tolerance, those with feeding intolerance had lower birth weight, smaller gestational age, and lower Apgar scores (all p < 0.01). A 5 min Apgar < 7 (OR 4.794; 95%CI 1.339–17.156), the interval between diagnosis and surgery (OR 0.973; 95%CI 0.947–1.000), and primary anastomosis resection (OR 0.278, 95%CI 0.139–0.555) were identified as significant factors influencing postoperative feeding intolerance. The results remained consistent after performing propensity score matching analysis. Feeding intolerance may result in prolonged hospital stays, and more complications such as retinopathy of prematurity, intestinal failure-associated liver disease, and intraventricular hemorrhage. Conclusions: A lower 5 min Apgar score, shorter interval from diagnosis to surgery and intestine resection with ostomy are associated with a higher incidence of FI after surgery. FI after NEC surgery can prolong recovery and increase family burden. Full article

Background/Objectives: Postnatal growth faltering (PGF) is a risk factor for adverse neurodevelopment in very preterm neonates. The aim of this retrospective study was to determine which infants’ baseline characteristics, prenatal risk factors and neonatal morbidities are associated with two definitions of PGF: defined as loss of >2 weight z-scores (severe PGF) or as loss of >1 weight, length, and head circumference z-scores between birth and discharge (complex PGF); Methods: 146 premature newborns (<32 weeks of gestational age, <1500 g) were included in the study. Anonymized data including anthropometric measurements (weight, length, and head circumference), perinatal and neonatal data (demographics, maternal morbidities and previous pregnancies, and neonatal and perinatal morbidities) were extracted from the clinical electronic database. Changes in anthropometric age- and sex-specific z-scores using the Fenton 2013 preterm growth charts were calculated to diagnose severe PGF and complex PGF; Results: The incidence of severe PGF was 11% and complex PGF was 24%. Both PGF definitions were associated with bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP), longer respiratory support, and longer hospital stay. Severe PGF was associated with surgical necrotizing enterocolitis at 25% vs. 1.5%, p = 0.001. Complex PGF was associated with severe brain injury at 51% versus 27%, p = 0.007. Complex PGF was more common in newborns born most prematurely, while severe PGF was more common in newborns born small for gestational age (SGA); Conclusions: Both severe and complex PGF are associated with several important neonatal morbidities, which might explain why growth faltering is associated with suboptimal neurodevelopment. Appropriate early identification of faltered growth may influence medical and nutrition interventions which in turn could improve the outcome of very preterm newborns. Full article