Search Results (383)

Objective: The fetal-to-neonatal transition is marked by profound cardio-respiratory changes. Infections emerging within the first 48 h after birth may influence early cardiovascular adaptation. We aimed to evaluate the association between early infection/inflammation markers and vital parameters in neonates during the first 15 min after birth. Methods: This is a secondary outcome parameter post-hoc analysis of data derived from a prospective observation study. Preterm and term neonates with cerebral oxygen saturation (crSO2) monitoring (INVOS 5100C) during the first 15 min after birth and available inflammatory markers (C-reactive protein [CRP], leukocytes, immature-to-total neutrophils ratio [IT ratio]) within 48 h after birth were included. Heart rate (HR) and arterial oxygen saturation (SpO₂) were continuously recorded during the first 15 min. Inflammatory markers obtained at 16–24 and 24–48 h after birth were correlated with crSO₂, SpO₂, and HR at minute 5, 10 and 15. Results: Sixty-eight neonates were included (median (IQR) gestational age 34.0 (32.0; 35.9) weeks, birth weight 1900 (1488; 2542) grams). CRP within the first 24 h correlated negatively with crSO₂ (r = −0.314; p = 0.011) and with SpO₂ (r = −0.393; p = 0.001) at minute 15. IT ratio within 24 h correlated negatively with crSO₂ at minute 5 (r = −0.367; p = 0.005), 10 (r = −0.273; p = 0.035), and 15 (r = −0.306; p = 0.013), and with SpO₂ at minute 5 (r = −0.327; p = 0.008). IT ratio at 24–48 h correlated negatively with crSO₂ at minute 15 (r = −0.384, p = 0.012). No significant correlations were observed with HR. Leukocytes within the first 24 h after birth correlated negatively with crSO2 at minute 5 (r = −0.265; p = 0.046). Conclusions: Early inflammatory markers, particularly CRP and the IT ratio, are associated with cerebral and systemic oxygenation during immediate postnatal transition. These findings suggest a potential association between early inflammatory activation and oxygenation dynamics; however, given the observational design and modest correlation strength, the results should be interpreted cautiously and do not allow conclusions regarding causality or underlying mechanisms. Full article

Background: Chorioamnionitis (CA) is a major pathological cause of preterm labor and is associated with both short- and long-term adverse outcomes in neonates, including early-onset sepsis (EOS) and late-onset sepsis (LOS). Neonatal sepsis remains a significant contributor to morbidity and mortality in neonatal intensive care units (NICUs). Aim: This study aimed to evaluate the association between maternal chorioamnionitis and the incidence of early-onset and late-onset neonatal sepsis in preterm neonates born at <32 weeks’ gestation. Furthermore, the study investigated maternal and neonatal factors affecting the presentation of sepsis. Methods: A retrospective cohort study was conducted on the medical records of preterm neonates born between 2020 and 2022. Inclusion criteria were gestational age < 32 weeks, available microbiological or histological examination for chorioamnionitis, and complete maternal medical records. Infants were categorized into two groups based on the presence (CA group) or absence (non-CA group) of histological and/or microbial chorioamnionitis. Descriptive statistical analyses were performed, including calculation of frequencies and percentages for categorical variables and means with standard deviations and ranges for continuous variables. Results: A total of 189 neonates were included, with a mean birth weight of 1286 ± 405 g and a mean gestational age of 29.2 ± 2.1 weeks. The CA group consisted of 55 neonates (29.1%), while 134 (70.9%) were in the non-CA group. Early-onset sepsis (EOS) occurred in 23 neonates (12.2%), with a significantly higher incidence in the CA group compared to the non-CA group (21% vs. 8%, p = 0.014). Late-onset sepsis (LOS) developed in 66 neonates (34.9%), but no significant difference in incidence was observed between the two groups (p = 0.402). Parsimonious logistic regression analysis identified maternal chorioamnionitis as an independent predictor of EOS (Odds Ratio 2.07, 95% CI 1.85–5.08; p = 0.009). Conclusions: Intrauterine infection and inflammation caused by chorioamnionitis are linked to an increased risk of early-onset sepsis in neonates born before 32 weeks’ gestation. However, chorioamnionitis does not appear to significantly influence the incidence of late-onset sepsis, which appears to be more closely associated with postnatal factors. Full article

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness characterized by disrupted physiologic vascularization followed by pathologic neovascularization, classically organized around the insulin-like growth factor-1 (IGF-1)–vascular endothelial growth factor (VEGF) axis in the retina. Increasing evidence suggests that early-life gut dysbiosis may act as an upstream modifier of this biphasic process. In this review, we synthesize human cohort studies, multi-omics analyses, and experimental animal models examining associations between the neonatal gut microbiome and ROP. Preterm infants who develop severe ROP demonstrate enrichment of facultative anaerobes and reduced acquisition of obligate anaerobes, alongside altered predicted metabolic capacity. Microbiome-derived metabolites, including short-chain fatty acids, bile acid derivatives, and lipid mediators, have been shown in experimental systems to influence systemic IGF-1 production, hypoxia-inducible factor-1α stabilization, and VEGF signaling. Rodent oxygen-induced retinopathy models offer a translation framework to assess the functional link between microbial perturbation and retinal angiogenic responses. Collectively, these findings support a conceptual microbiome–IGF-1–VEGF–retina axis in which early intestinal dysbiosis may modulate inflammatory tone, metabolic signaling, and retinal vascular development. Although current evidence remains largely associative, integrating microbiome profiling with mechanistic and longitudinal studies may clarify potential causal pathways and identify novel biomarkers or preventive strategies for severe ROP. Full article

Objective: Pancreatic stone protein (PSP) is a secretory protein associated with systemic inflammation and β-cell stress. Given its reported association with type 2 diabetes mellitus, this study aimed to evaluate the relationship between serum PSP levels and gestational diabetes mellitus (GDM) and to assess its diagnostic performance. Methods: This single-center, prospective cohort study was conducted between June 2024 and May 2025. Eighty-four pregnant women at 24–28 weeks’ gestation were enrolled: 42 diagnosed with GDM according to Carpenter–Coustan criteria and 42 healthy controls. Serum PSP levels were measured using ELISA at the time of GDM diagnosis, and prior to treatment initiation. Group comparisons were performed using appropriate parametric and non-parametric tests. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analysis. Results: Maternal weight was significantly higher in the GDM group (78.3 ± 10.0 kg vs. 68.4 ± 7.6 kg, p < 0.001). Serum PSP levels were significantly elevated in women with GDM compared to controls (8.89 ± 0.81 ng/mL vs. 7.72 ± 0.64 ng/mL, p < 0.001). Neonatal birth weight was also higher in the GDM group (3606 ± 507 g vs. 3355 ± 308 g, p = 0.008), while Apgar scores did not differ significantly. ROC analysis demonstrated an AUC of 0.883 (95% CI: 0.805–0.946, p < 0.001). At a cut-off value of 8.38 ng/mL, sensitivity was 76.2% and specificity was 85.7%. Conclusions: Serum PSP levels are significantly elevated in GDM and demonstrate good diagnostic performance. PSP may serve as a supportive biomarker reflecting β-cell stress in GDM, warranting further multicenter validation studies. Full article

Primary liver cancer, particularly hepatocellular carcinoma (HCC), remains a major global health burden, ranking as the fifth most common cancer and the third leading cause of cancer-related mortality worldwide. The rising incidence of HCC is closely linked to metabolic comorbidities, including non-alcoholic fatty liver disease (NAFLD), underscoring the need for improved diagnostic and therapeutic strategies. NAFLD can progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by inflammation and fibrosis, which markedly increases HCC risk, especially in individuals with obesity and type 2 diabetes (T2D). NAFLD has recently been redefined as metabolic dysfunction-associated steatotic liver disease (MASLD) to better reflect its metabolic basis. However, robust experimental models to study the progression from MASLD to MASH and ultimately HCC remain limited. This proof-of-concept study investigates sex-specific effects of metabolic dysregulation using the STAM (STelic Animal Model; streptozotocin and high-fat diet) mouse model, which recapitulates key features of human MASH and HCC. Neonatal C57BL/6J mice received streptozotocin to induce T2D-like symptoms followed by a high-fat diet. Streptozotocin (STZ) treated mice showed reduced body fat, lower insulin levels, impaired glucose tolerance, and increased expression of genes linked to inflammation, lipid metabolism, and apoptosis. These findings support the STAM model’s utility for MASLD research and highlight the importance of sex-specific strategies to limit HCC progression. Full article

Pregnancy represents a distinct immunological and physiological state that modifies maternal susceptibility to SARS-CoV-2 and influences the clinical and biological course of COVID-19. Accumulating evidence indicates that the interaction between viral entry determinants, gestation-specific immune modulation, placental endocrine–angiogenic pathways, and systemic inflammatory responses underlies the characteristic manifestations of SARS-CoV-2 infection during pregnancy. This review consolidates current understanding of SARS-CoV-2 viral structure, receptor biology, and the gestational regulation of key entry cofactors, including ACE2, TMPRSS2, NRP1, CTSL and FURIN, within reproductive and placental tissues. The review further integrates documented mechanisms of cytokine-mediated immune dysregulation, endothelial injury, thrombo-inflammation, and steroidogenic alteration observed in affected pregnancies, and examines their contribution to placental malperfusion, preeclampsia-like presentations, fetal growth abnormalities and preterm birth. Published molecular and computational studies characterising trophoblast antiviral defenses, receptor expression patterns, and structural determinants of Spike–ACE2 affinity are synthesised to contextualise the biological basis of placental susceptibility and the rarity of confirmed transplacental transmission. Current evidence on maternal clinical outcomes, fetal and neonatal consequences, vaccination efficacy, therapeutic considerations and contemporary management guidelines is also critically reviewed. By integrating molecular, immunological, pathological and clinical insights, this article provides a comprehensive framework for understanding the interaction between SARS-CoV-2 infection and pregnancy-specific physiology, with implications for risk assessment, preventive strategies and maternal–fetal care. Full article

Background: Gastrointestinal surgery in children and neonates carries high risks of postoperative infections, inflammation, and delayed recovery. Probiotics may help restore gut microbial balance and improve clinical outcomes. This study systematically evaluates the effects of probiotic supplementation on postoperative outcomes in pediatric and neonatal gastrointestinal surgery. Methods: A systematic review and meta-analysis was conducted following Cochrane and PRISMA guidelines. PubMed, Scopus, Cochrane, and Web of Science were searched for randomized controlled trials (RCTs) and observational studies comparing probiotics with placebo, standard care, or surgery alone in children and neonates. Meta-analyses were performed using R programming, with pooled effect estimates reported alongside 95% confidence intervals (CI) and corresponding p-values. Results: Eight studies (6 RCTs and two cohorts) with 437 patients were included. Probiotics significantly reduced postoperative infections (risk ratio = 0.49, 95% CI: 0.26–0.92, p = 0.027) and C-reactive protein elevation (risk ratio = 0.42, 95% CI: 0.26–0.68, p < 0.001) and increased Bifidobacterium abundance (standardized mean difference = 0.84, 95% CI: 0.51–1.17, p < 0.001). No significant effect was seen on hospital length of stay or Lactobacillus concentrations. Qualitative synthesis indicated improvements in bowel function, immune markers, and growth in selected neonatal populations. Conclusions: Probiotics, particularly Bifidobacterium species, may reduce postoperative infections and inflammation in pediatric gastrointestinal surgery; however, the evidence is based on a limited number of studies and small pooled analyses, and larger well-designed trials are needed to confirm these findings. Full article

Background and Objectives: Intrauterine growth restriction (IUGR) affects 5–10% of pregnancies and is associated with increased perinatal morbidity and long-term complications for the neonate. Extracellular vesicles (EVs), and in particular, microparticles (MPs), have emerged as potential biomarkers of pregnancy complications; however, the literature on their role in neonates remains limited. To investigate the functional characteristics, concertation in maternal blood and potential role of MPs in IUGR. Materials and Methods: PubMed, Scopus and preprint servers were systematically searched for studies on MPs in correlation with IUGR from 1 August until 18 September 2025. Data on MP characteristics and concentration in maternal blood samples in the context of IUGR were collected. The systematic review is registered in PROSPERO (CRD420251156939). Results: A total of 12 studies fulfilled the inclusion criteria and were included in the review. In IUGR-complicated pregnancies, circulating MPs exhibited preserved procoagulant activity despite minimal quantitative differences compared to controls. Platelet-, endothelial-, and placenta-derived MPs were most frequently studied. Clinically, elevated AV+ placenta-derived MPs were associated with increased risk of IUGR, whereas MPs from isolated IUGR pregnancies showed limited predictive value. Conclusions: MPs play a crucial role in the pathophysiology of IUGR through their interplay in coagulation, inflammation, and vascular dysfunction. They show potential as predictive biomarkers, particularly in cases of preeclampsia-associated IUGR, reflecting systemic maternal endothelial and inflammatory changes. However, their utility in isolated IUGR appears limited, likely due to the predominantly local placental origin of the pathology. Full article

Objective: To evaluate the diagnostic and prognostic utility of the hemoglobin–albumin–lymphocyte–platelet (HALP) score and several systemic inflammatory indices derived from routine blood parameters—including the systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), pan-immune inflammation value (PIV), and systemic inflammatory response index (SIRI)—for pathogen differentiation and clinical assessment in culture-proven late-onset neonatal sepsis (LOS). Methods: A retrospective analysis was conducted on a cohort of 150 neonates with culture-proven LOS. Systemic inflammatory indices were calculated at baseline (first week of life) and at the time of septic insult. The discriminative power of these indices was assessed via ROC curve analysis, with optimal cut-off points determined by the Youden Index. Risk stratification was performed using Odds Ratio (OR) modeling with 95% Confidence Intervals (CIs) to evaluate the predictive strength of each marker according to its respective threshold. Results: Diagnosis-phase assessments identified SII as the premier discriminator for microbiological etiology (AUC = 0.869; OR = 44.57), outperforming PLR and PIV. Although HALP demonstrated moderate efficacy in distinguishing pathogens, it lacked prognostic value regarding mortality. Conversely, SIRI displayed limited clinical utility, yielding the lowest predictive performance in our cohort. Conclusions: In neonatal sepsis, the HALP score provided additional clinical information when compared with several hematological inflammatory indices. Although HALP was not associated with mortality, prospective multicenter studies are needed to clarify the role of these cost-effective markers in pathogen differentiation and clinical assessment of LOS. Full article

Objectives: Gestational diabetes is linked to increased inflammatory and metabolic stress during the neonatal period. Among the biomarkers elucidating the relationship between diabetes and inflammation, the interleukin-33 (IL-33)/ST2 signaling pathway is of particular interest. Research on the IL-33/sST2 axis in pregnancies complicated by diabetes indicates that these biomarkers are associated with maternal metabolic disorders and inflammation. Therefore, evaluating sST2 levels in infants of diabetic mothers is essential for identifying a biological marker of systemic inflammation resulting from intrauterine hyperglycemia and for clarifying the specific risks associated with this condition. The objective of this study was to examine sST2 levels in infants born to diabetic mothers and to assess their association with perinatal inflammation, metabolic stress, and clinical outcomes. Methods: This prospective observational study included term infants born at Pamukkale University Medical Faculty Hospital. The study group comprised term infants whose mothers had gestational diabetes, while the control group consisted of term infants born to healthy mothers without diabetes. sST2 levels were measured from serum samples obtained from cord blood at birth using the ELISA method. Factors influencing sST2 levels were analyzed using regression analyses. Results: sST2 levels were significantly higher in the diabetic group than in the control group (p < 0.001). The incidences of large for gestational age (LGA), small for gestational age (SGA), hypoglycemia, postnatal respiratory distress, and both the frequency and duration of neonatal intensive care unit admissions were also significantly elevated in the diabetic group. Multivariate analysis identified gestational diabetes as independent predictor. Conclusions: This study is among the first to demonstrate increased sST2 levels at birth in infants of diabetic mothers. The results indicate that intrauterine exposure to hyperglycemia due to gestational diabetes may be associated with heightened inflammation and metabolic stress in the neonatal period, and that sST2 may serve as a potential biomarker reflecting fetal exposure. Full article

Autoantibodies (AAbs) play an important role in the development of autoimmune diseases. While many AAbs induce apoptosis of target cells, a distinct subgroup, termed functional autoantibodies (fAAbs) against G protein–coupled receptors (GPCRs), can modulate physiological receptor signaling without inducing cell death. The functional activity of GPCR-fAAbs may be influenced by various cofactors, including inflammation (e.g., inflammatory cytokine, ciliary neurotrophic factor (CNTF)) and ischemia. As ischemia triggers a substantial release of arachidonic acid (AA) from membrane phospholipids, the present study aimed to examine exploratively the influence of AA, eicosapentaenoic acid (EPA), and CNTF on the responses of spontaneously beating neonatal rat cardiomyocytes to GPCR agonists and GPCR-fAAbs. AA and EPA differentially influenced responses in cardiomyocytes induced by GPCR-fAAbs: AA altered the functional responses associated with adrenergic β₂-fAAb, adrenergic α₁-fAAb, angiotensin II (AT1)-fAAb, endothelin A (ETA)-fAAb and angiotensin 1–7 MAS-fAAbs. However, muscarinergic M₂-fAAb responses remained largely unaffected. In contrast, EPA attenuated the responses to β₂-fAAb, α₁-fAAb, AT1-fAAb, and ETA-fAAb, while MAS-fAAb and M₂-fAAb responses were not markedly altered. CNTF acted as a time-dependent modulator of cardiomyocyte chronotropic responses and influenced the magnitude of GPCR-mediated signaling on a cardiomyocyte bioassay. Together, these findings might suggest that lipid mediators such as AA and EPA or CNTF may modulate functional responses of cardiomyocytes associated with GPCR-fAAbs. Full article

Postnatal corticosteroids are frequently administered to extremely preterm infants to support respiratory management, yet their effects on the immature cardiovascular system are complex and underexplored. As the second installment in a series on physiology-informed steroid use, this narrative review focuses on the cardiovascular consequences of systemic corticosteroid therapy in preterm neonates. We examine how corticosteroids influence key aspects of cardiovascular physiology, including ductal closure, systemic and pulmonary vascular resistance, myocardial remodeling, and autonomic regulation. Attention is given to the hemodynamic transition of early postnatal life and how steroid exposure may interact with patency of the ductus arteriosus and vascular development. The potential for corticosteroids to contribute to reactive myocardial hypertrophy, systemic hypertension, and pulmonary hypertension is also reviewed in the context of both short- and long-term outcomes. Emerging diagnostic and monitoring tools are discussed for their potential to guide individualized therapy. These include targeted neonatal echocardiography (TnECHO) to assess cardiac function and structure, electrocardiography (ECG) for rhythm and conduction abnormalities, heart rate variability analysis for autonomic function, and circulating biomarkers to evaluate myocardial stress and inflammation. Together, these tools may inform tailored steroid timing and dosing, especially in the research context, while monitoring for signs of cardiovascular side effects in real time. By synthesizing mechanistic insights with evolving clinical evidence, this review highlights the need for a more nuanced understanding of how corticosteroids affect the developing cardiovascular system. It underscores the importance of integrating cardiovascular monitoring into routine care to optimize therapeutic benefit while minimizing unintended harm. Alongside companion reviews addressing respiratory and growth impacts, this installment contributes to a broader framework for individualized, physiology-driven steroid use in extremely preterm infants. Full article

Background: Preterm birth is a leading cause of neonatal mortality and long-term disability worldwide. Injury in premature infants is demonstrated by disrupted organ development from inflammation, oxidative stress, hypoxia, and impaired vascular maturation. Current therapies largely provide supportive care and do not directly promote tissue regeneration. Mesenchymal stem cell (MSC)-based therapies have emerged as a potential strategy to enhance endogenous repair across organ systems commonly affected by prematurity. Results: Evidence indicates that MSCs exert therapeutic effects primarily through transient paracrine signaling rather than long-term engraftment. Following administration, MSCs release cytokines, growth factors, and extracellular vesicles that reduce inflammation, promote angiogenesis, and support tissue repair. In preclinical models of neonatal brain injury, MSC therapy has been associated with improved oligodendrocyte maturation and reduced white matter injury. Early clinical trials in neonatal encephalopathy demonstrate feasibility and short-term safety of both autologous and allogeneic cell products. However, studies remain limited by small sample sizes and short follow-up. Cell-free approaches using MSC-derived extracellular vesicles may offer similar biological benefits with potentially lower safety and regulatory concerns. Conclusions: MSC-based therapies represent a promising regenerative approach for complications of prematurity. Rigorous, large-scale trials with standardized protocols and long-term follow-up are necessary to clarify efficacy, optimize delivery strategies, and define safety in this vulnerable population. Full article

Background: C-reactive protein (CRP), a biomarker of systemic inflammation, has been implicated in adverse pregnancy and neonatal outcomes. However, the relationship between maternal CRP and neonatal complications remains unclear. We conducted a systematic review and meta-analysis to synthesize available evidence. Methods: We systematically searched PubMed, Scopus, Web of Science, and Cochrane Library up to July 2025 for observational studies reporting maternal CRP levels in relation to neonatal outcomes. Eligible outcomes included preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), and stillbirth. Random-effects models were used to calculate pooled standardized mean differences (SMD) or odds ratios (OR) with 95% confidence intervals (CI). Statistical heterogeneity was assessed using the I² statistic. Results: The search yielded 6843 records, of which 42 studies (comprising 18,393 pregnant women) met the inclusion criteria. Maternal mean CRP levels were significantly higher in adverse pregnancy outcomes compared with controls (SMD = 0.39; 95% CI 0.08–0.70; p = 0.01; I² = 96.6%). Elevated CRP was strongly associated with PTB (OR = 3.81; 95% CI 2.66–5.47; p < 0.001; I² = 85%; n = 23) and LBW (OR = 2.34; 95% CI 1.35–4.03; p = 0.002; I² = 84.2%; n = 7). No significant associations were observed for SGA (OR = 1.14; 95% CI 0.86–1.49; p = 0.36; I² = 0%; n = 5) or stillbirth (OR = 1.89; 95% CI 0.92–3.90; p = 0.08; I² = 44.9%; n = 4). Conclusion: Maternal CRP is significantly associated with increased risks of preterm birth and low birth weight but not with SGA or stillbirth. These findings support the role of systemic inflammation in adverse neonatal outcomes and highlight the need for prospective studies to clarify causal mechanisms and assess the clinical utility of CRP in pregnancy risk stratification. Full article

Background: Neonates and young infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) are highly vulnerable to pulmonary dysfunction, systemic inflammation, capillary leak, and fluid overload, which may lead to acute kidney injury (AKI) and the need for peritoneal dialysis (PD). Lung ultrasound (LUS) is a bedside, radiation-free tool that allows real-time assessment of lung aeration and pulmonary congestion. However, its role in predicting postoperative renal support remains limited. This study aimed to evaluate whether early postoperative LUS scores could predict the need for PD in neonates after congenital heart surgery with CPB. Methods: In this prospective single-center study, 53 neonates undergoing cardiac surgery with CPB between June 2025 and January 2026 were included. LUS was performed preoperatively and at 0–2 h, 24–48 h, 72 h, 120 h, and 168 h postoperatively using a standardized six-zone scoring system (0–18). The primary outcome was postoperative PD requirement. ROC analysis assessed predictive performance, and multivariable logistic regression identified independent predictors. Results: Total LUS scores significantly increased in the early postoperative period, remained elevated for 24–72 h, and gradually declined by days 5–7. Infants requiring PD (n = 16) had significantly higher LUS scores at 0–2 h, 24–48 h, and 72 h (p < 0.05). The 24–48 h (AUC = 0.784; sensitivity 87%, specificity 62% at cut-off ≥ 11.5) LUS score showed the best predictive value for PD (AUC = 0.831; sensitivity 86%, specificity 74% at cut-off ≥ 13). In multivariable analysis, higher LUS scores at 0–2 h (OR 1.625, p = 0.048) and 24–48 h (OR 1.621, p = 0.048) independently predicted PD. Conclusion: Postoperative LUS is a reliable, noninvasive tool that can aid in predicting the need for PD in neonates undergoing cardiac surgery with CPB, supporting timely fluid and renal management. Full article