Search Results (485)

Background and Objectives: Early recognition of life-threatening organ dysfunction is central to modern sepsis frameworks. We systematically reviewed the prognostic performance and clinical utility of the Neonatal Sequential Organ Failure Assessment (nSOFA) for mortality and major morbidity in NICU populations. The search identified 939 records across databases; after screening and full-text assessment, 16 studies met the inclusion criteria. Methods: Following PRISMA guidance, we searched major databases (2019–2025) for observational or interventional studies reporting discrimination or risk stratification using nSOFA in neonates. Populations included suspected/proven infection and condition-specific cohorts. Heterogeneity in timing, thresholds, and outcomes precluded meta-analysis. Results: A cumulative sample exceeding 25,000 neonates was identified across late- and early-onset infection, all-NICU admissions, necrotizing enterocolitis, respiratory distress, and very preterm screening cohorts. Across settings and timepoints, nSOFA demonstrated consistent, good-to-excellent mortality discrimination, with reported AUROCs ≥ 0.80 and upper ranges near 0.90–0.92; serial scoring within the first 6–12 h generally improved risk classification. Disease-specific applications (NEC, early-onset infection) showed similar discrimination for death or composite adverse outcomes. Conclusions: Evidence from diverse NICU contexts indicates that nSOFA is a pragmatic, EHR-ready organ dysfunction score with robust discrimination for mortality and serious morbidity, supporting routine, serial use for risk stratification and standardized endpoints in neonatal sepsis pathways, aligned with contemporary organ dysfunction–based pediatric criteria. Full article

Background: Postnatal growth failure in very preterm infants remains a major concern in neonatal care and clinical management is complicated by the lack of a standardized definition. This study aims to identify risk factors for growth faltering (GF) and undernutrition (UN) at hospital discharge, defined according to the latest consensus definitions established by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Methods: We conducted a retrospective observational study of 416 preterm infants (gestational age < 32 weeks and/or birth weight < 1500 g). Growth was monitored using the Intergrowth 21st standards. In line with ESPGHAN criteria, GF was defined longitudinally as a weight for age (WFA) z-score decline ≥ 1 SD from birth, while UN was defined cross-sectionally as a WFA or length for age z-score < −2 SD at discharge. Logistic regression models were used to determine independent predictors for both growth phenotypes. Results: At discharge, the prevalence of GF and UN was 45.3% and 33.1%, respectively. In infants born without growth restriction (GR), UN was almost entirely driven by GF (89.7%). In contrast, 85.5% of infants born with GR remained undernourished at discharge. Multivariate analysis identified bronchopulmonary dysplasia and higher maximal postnatal weight loss as major independent risk factors for GF, while female sex and human milk feeding at discharge were associated with a lower risk of GF. For infants born with adequate weight, maternal hypertension, extremely low birth weight, and the co-occurrence of GF were the strongest predictors of UN. Conclusions: Nearly half of very preterm infants experience significant growth impairment before discharge. By assessing the dynamic process of GF and the static endpoint of UN, we identified distinct clinical trajectories. Standardized ESPGHAN criteria allow for the identification of high-risk “phenotypes”—particularly those with GR at birth or severe neonatal morbidity—enabling more targeted and intensive nutritional management during the critical developmental window. Full article

Background/Objectives: Greater than 50% of surviving very preterm infants are affected by postnatal growth failure and are at high risk of associated development of bronchopulmonary dysplasia (BPD). Given the influence of enteral feeding on growth failure, we aimed to determine the impact of type, volume, and time of introduction of enteral feeds on mitigating the risk of postnatal growth failure and BPD risk. Methods: This was a retrospective chart review of mothers’ own milk (MOM), pooled pasteurized donor human milk (PDHM) feeding, postnatal growth, and BPD severity in preterm infants <33 weeks of gestation admitted to the Children’s Hospital of Richmond at VCU neonatal intensive care unit between 2021 and 2024. Statistical analysis included linear regression with moderation analysis using the Hayes Process model, chi-square tests, linear and multinomial logistic regression, with p-value < 0.05 considered significant. Results: After controlling for the percentage of MOM received at 34 weeks corrected gestational age (cGA), greater severity of BPD was associated with lower infant weight and growth failure, p < 0.001. Early introduction of MOM (3 days of life) and greater volume of MOM showed better linear growth and decreased risk of severe BPD, respectively (p < 0.001). Conclusions: Provision of MOM to preterm infants within 3 days of life was associated with a moderation of the relationship between gestational age and growth velocity, with improved growth velocity trajectory. Preterm infants who received a greater volume of MOM through 34 weeks cGA experienced less severe BPD compared to those fed higher volumes of PDHM. As the incidence of growth failure paralleled the incidence of BPD severity, identification of key MOM components becomes important to address and augment the value of PDHM in the management of preterm infants. Full article

Background: Small-for-gestational-age (SGA) preterm infants are at higher risk for oxidative stress-related complications than appropriate-for-gestational-age (AGA) preterm infants. It has been proposed that HbF may be higher in SGA than in AGA infants due to fetal hypoxia. Aim: The aim of this study was to compare postnatal changes in HbF fractions in very preterm SGA and AGA infants and in subgroups of these patients who had been transfused with red blood cells (RBCs) or not. Methods: We studied 30 SGA and 60 AGA very preterm infants with a gestational age of 27.7 ± 1.6 and 27.9 ± 0.7 weeks, respectively. HbF fractions were recorded daily during the first week of life, at 14 ± 2, 21 ± 2, and 28 ± 2 days of life, and 36 weeks (±3 days of life) of postmenstrual age. Results: The HbF fractions measured from the first day of life to the 36th week of postmenstrual age decreased significantly in both the groups, without differences between the groups. Transfused and non-transfused SGA infants had similar values of HbF fraction, while transfused AGA infants had lower values of HbF fraction than non-transfused infants. Conclusions: HbF fraction decreased similarly in the postnatal period in very preterm SGA and AGA infants. RBC transfusions did not affect hemoglobin fraction (HbF) values in SGA infants but were associated with a reduction in HbF in AGA infants. These findings may be due to the effect of fetal preconditioning hypoxia in very preterm SGA infants. Full article

Background: Probiotic supplementation for very preterm infants is a common practice in many neonatal units. Assessing the effects of early postnatal exposure to probiotics on long-term neurodevelopment, growth, and atopy-related outcomes is important. Extremely preterm (EP: <28 weeks) infants enrolled in our previously reported randomized trial (SiMPro) comparing short-term effects of single (SS: B. breve M-16V) versus triple-strain (TS: B. breve M-16V, B. longum subsp. infantis-M63, B. longum subsp. longum-BB536) probiotic provided a unique opportunity to study this issue. Methods: This follow-up study assessed the five-year outcomes of SiMPro trial infants, including neurodevelopment (cognition (Full Scale Intelligence Quotient/ FSIQ using WPPSI-IV), behavior (Strengths and Difficulties Questionnaire), executive function (BRIEF–P)), growth (anthropometry) and blood pressure (BP). Atopy-related outcomes were evaluated at six to seven years using the ISAAC questionnaire. A linear mixed model was used for longitudinal outcomes. Impairment indicators were modeled using logistic regression and adjusted for Socio-Economic Indexes for Areas (SEIFA) centiles. Results: Follow-up rates (SS: 89.2% versus TS: 95%), neurodevelopmental outcomes [severe impairment (FSIQ < 70): SS: 7.4% versus TS: 4.3%; p = 0.68], growth, BMI, and BP were comparable between the SS and TS groups. The total difficulty score or BRIEF–P executive indices, disability rates (none: 66.7% versus 55.4%), and atopy-related outcomes were comparable between groups. Conclusions: Both TS and SS Bifidobacterium probiotic formulations were safe, with comparable neurodevelopmental, growth, and atopy-related outcomes at school age. Full article

Introduction. Patent ductus arteriosus (PDA) is the most common cardiac anomaly in preterm newborns and may aggravate respiratory disease. Invasive closure options after failure of medical treatment include surgical ligation (SL) and transcatheter closure (TCC). Reports on side effects of intravenous contrast media are scarce. Methods. In this retrospective single-center study, we compared 35 preterm infants below 1500 g birth weight undergoing SL with 35 matched infants undergoing TCC. Outcomes were procedural success, complications and postprocedural ventilation. Results. Closure success was high in both groups (97% SL vs. 86% TCC, p = 0.106). One SL patient underwent re-operation after accidental clipping of the left pulmonary artery, and eight patients (24%) had endoscopy-diagnosed vocal cord palsy after SL. Six TCC patients had complications that required further action, including device embolization, device failure and one case of late device migration that resulted in aortic arch obstruction requiring intervention, and 4 TCC patients developed necrotizing enterocolitis (NEC)-like disease within 24 h, requiring surgery in one patient. SL was associated with longer duration of mechanical ventilation (24 h vs. 144 h, p < 0.001), as opposed to TCC, and higher rates of bronchopulmonary dysplasia (86% vs. 53%, p = 0.004). Discussion. Both techniques achieve high success but differ in complication profiles. TCC may reduce respiratory morbidity. NEC-like disease (probably linked to intravenous administration of contrast agents) warrants further investigation. Full article

Background: The appropriate identification of target patients for methylxanthine therapy may optimize resource allocation and improve clinical outcomes, but data on routine care in low-resource settings are limited. Our study assessed methylxanthine use in clinical practice in two Sub-Saharan settings. Methods: This retrospective, registry-based study investigated methylxanthine use in newborns who were admitted to Tosamaganga Hospital (Tanzania) and Wolisso Hospital (Ethiopia) in 2022–2023. The prevalence and type of methylxanthine treatment were investigated. Neonates receiving methylxanthine were compared to those not receiving it in terms of baseline characteristics, clinical data, treatments, and discharge information. All data were retrieved from local registries. Results: Aminophylline was administered to 196/1674 neonates (11.7%), while caffeine was not available in these settings. This treatment was more common in preterm and smaller infants (p < 0.0001), asphyxiated neonates (p < 0.0001), and the sickest patients (p < 0.001). The need for respiratory support (p < 0.0001), intravenous lines (p < 0.0001), and antibiotic therapy (p < 0.0001), as well as the length of hospital stay (p < 0.0001) and mortality rate (p < 0.0001), were higher in neonates receiving aminophylline. Conclusions: In two Sub-Saharan settings, methylxanthine treatment was limited to aminophylline, which was given to around 12% of infants admitted to the special care units. Overall, the treatment was appropriately given to most eligible neonates, although a considerable subgroup of very preterm infants did not receive aminophylline prophylaxis. Further studies may investigate the reasons for protocol incompliance regarding aminophylline treatment and healthcare staff’s opinions on such an aspect. Full article

Background: Postnatal cytomegalovirus (pCMV) infection is a frequent viral condition in early infancy and is primarily acquired through maternal breastfeeding. Although usually asymptomatic in term infants, it can lead to significant morbidity in preterm neonates (gestational age < 32 weeks) and in those with very low birthweight (<1500 g), presenting with sepsis-like syndrome, pneumonia, cytopenia, hepatitis, or colitis. Severe cases may result in long-term sequelae or death. Objectives: To describe a series of cases of pCMV infection and review the current evidence on its epidemiology, clinical manifestations, outcomes, and therapeutic management, aiming to identify gaps in knowledge and propose opportunities for improving the care of preterm infants. Methods: We analyzed clinical presentations of pCMV disease in a case series of preterm infants and reported cases and reviewed the recent literature regarding diagnostic approaches, antiviral therapy, and strategies for breastmilk management. Results: Current data highlight substantial variability in clinical management and outcomes. The lack of consensus on antiviral indications and treatment duration reflects a limited understanding of the disease’s natural history. Approaches to breastmilk handling differ widely among centers and countries, further complicating the standardization of care. Conclusions: pCMV infection remains a relevant yet under-recognized condition in neonatal medicine. Improved diagnostic strategies, clearer therapeutic guidelines, and harmonized recommendations for breastmilk management are needed to optimize the care of preterm infants at risk of or affected by pCMV disease. Full article

Preterm birth has evolved from being an acute neonatal challenge to a lifelong health determinant, as advances in neonatal care have markedly improved the survival of very and extremely preterm infants. This narrative review synthesizes epidemiological and mechanistic evidence linking preterm birth with heightened cardiometabolic risk across the life course. In adulthood, individuals born preterm demonstrate increased rates of heart failure, ischemic heart disease, stroke, atrial fibrillation, and diabetes. Beneath these overt clinical outcomes lies a distinct phenotype characterized by increased adiposity, insulin resistance, dyslipidemia, hypertension, and atypical growth trajectories, with rapid catch-up growth amplifying long-term risk. Mechanistic pathways highlight adipose tissue maldevelopment, predisposing to metabolic syndrome, alongside cardiac maldevelopment with reduced ventricular size, impaired diastolic function, and diminished exercise capacity. Furthermore, vascular growth arrest, impaired elastin synthesis, and nephron deficiency contribute to sustained elevations in blood pressure, establishing an early substrate for hypertension and cardiovascular remodeling. These alterations reflect the developmental origins of health and disease, whereby early-life disruption of growth and maturation exerts lasting effects on organ structure and function. Collectively, the evidence identifies adults born preterm as a growing yet under-recognized patient population with a unique clinical and biochemical profile and accelerated vulnerability to non-communicable diseases. Greater awareness among pediatric and adult physicians, structured transition of care, and targeted prevention strategies are urgently needed to mitigate early cardiometabolic morbidity and optimize long-term health outcomes in this high-risk group. Full article

Background/Objectives: Although morbidity and mortality are more pronounced in extremely and very preterm infants, there is also considerable morbidity in preterm infants of more advanced gestations. Delivery via cesarean section is associated with a higher risk of perinatal complications even when performed electively. Our aim was to examine the possible contribution of prenatal and perinatal factors to the risk for respiratory morbidity in a population of late-preterm and early-term infants delivered with a high rate of elective cesarean section. Methods: In a retrospective cohort study, all late-preterm and early-term infants (34 to 38 completed weeks of gestation) that were admitted with respiratory distress to the Neonatal Intensive Care Unit of the University Hospital of Patras over a recent period of two years were included in the study. Results: In the study period, 489 infants of all gestations were admitted to the neonatal unit, of whom 221 were born between 34 and 38 + 6 gestational weeks. Ventilated infants had a significantly lower incidence of antenatal corticosteroids (41%) compared to non-ventilated infants (51%, p = 0.036) and a higher duration of parenteral nutrition [4 (1–6) days] compared to non-ventilated infants [2 (1–3) days, p < 0.001]. The incidence of late-onset sepsis was higher in the ventilated infants (26%) compared to the non-ventilated ones (8%, p < 0.001). Conclusions: Late preterm and early term infants who were invasively ventilated had less often received antenatal corticosteroids and had a higher incidence of late-onset sepsis compared to those who were not ventilated. Full article

Perinatal asphyxia (PA) remains a common cause of neonatal death and long-term disability, with an incidence of 20 per 1000 live births. Even mild PA, without significant neurological distress at birth, is linked to neurodevelopmental disorders. Premature babies are at high risk for both PA and long-term neurobehavioral deficits. The use of peripherally inserted central venous catheters in neonatal intensive care units has reduced mortality and morbidity in preterms. Given their prevalent use and associated complications, such as thrombosis, the present study aimed to investigate the effects of hypoxia associated with the ligation of the external jugular vein (JH model) in 5-day-old mice, whose central nervous system development shares similarities with that of human preterms. Diffuse white matter (WM) injury is associated with later neurodisabilities following very premature birth before 32 weeks of gestation. The present study aimed to investigate whether the murine JH model replicates a key phenotype of non-cystic WM injury, namely permanent hypomyelination and sensorimotor deficits. The second aim was to determine whether sodium phenylbutyrate (PBA), which is already prescribed in neonates for another indication, could prevent these disabilities. JH induced lasting dysmyelination in males, not prevented by PBA, contrary to the discrete JH-induced neurobehavioral deficits observed in both sexes in the short and long term. Full article

Hypoxic–ischaemic encephalopathy (HIE) is a major cause of neonatal brain injury and is associated with a high rate of death and lifelong disability. Its pathogenesis is still poorly understood, and there is no proven treatment for preterm infants. Therapeutic hypothermia for term and near-term infants partially improves outcomes, highlighting the need to target additional mechanisms. This review evaluates evidence that necrosis and necroptosis contribute materially to evolving brain injury in both term and preterm brains. Serial imaging studies suggest that lesions typically develop over many days after birth for term infants and over many weeks after birth for preterm infants. Growing evidence from animal studies shows that severe white matter injury can be mediated by programmed necroptosis. In particular, lesions that evolve late after acute HI are characterised by necrosis in association with agglomerations of microglia, with little apoptotic cell death. Critically, preclinical studies in large and small animals show that outcomes can be dramatically improved by very delayed intervention after HI including with cell therapy, anti-inflammatory agents, and endogenous neurotrophins. These findings strongly support the hypothesis that there may be a window of therapeutic opportunity for days or even weeks after birth to prevent delayed necrotic lesions. Full article

Background/Objectives: Preterm infants often require increased caloric intake to maintain appropriate growth while in the neonatal intensive care unit (NICU). Emerging evidence suggests that alterations of the gut microbiome may play a role in infant and childhood growth patterns. The fecal microbiome patterns in infants with normal and poor growth patterns were classified in this study. Methods: We conducted a prospective trial of infants of less than 29 weeks’ gestation with an embedded case–control analysis of infants with normal or poor growth patterns. Fecal samples were collected weekly from infants on full enteral feeds and analyzed blindly using 16s rRNA next-generation sequencing. The relationship between gut microbial diversity and composition and growth pattern and trajectory were assessed. Results: A total of 115 infants were enrolled in the trial with 263 fecal samples selected from 87 enrolled infants for analysis. In total, 37 samples were available from the normal growth cohort, 56 samples from the poor growth cohort, and 170 samples were available for analysis from the very poor growth cohort. Analysis of relative abundance revealed increased representation of Veillonella, Bifidobacterium, and Clostridium in very poor growth infants compared to normal growth infants. Variation in specific taxa was also found to vary significantly across post-menstrual age depending on the degree of growth failure. Conclusions: Gut microbiome composition and variance was modified by the degree of growth failure in our cohort of preterm infants. Our study adds to the growing body of evidence that alteration of the microbiome is associated with poor growth in preterm infants. This may ultimately represent a therapeutic target for growth failure in preterm infants. Full article

Background/Objectives: Cervical insufficiency remains a leading cause of second-trimester pregnancy loss and early preterm birth. Although single-level cerclage techniques such as McDonald or Shirodkar are widely accepted, the potential advantages of double or modified double-level cerclage remain controversial. Methods: This systematic review was conducted in accordance with PRISMA guidelines. Comprehensive searches of PubMed, Embase, Web of Science, and the Cochrane Library (to September 2025) were supplemented by Google Scholar and conference proceedings. Eligible studies included randomized controlled trials, comparative cohort studies, and case series directly comparing double versus single transvaginal cerclage. A total of twenty-six sources were included, spanning randomized trials, comparative cohort studies, published protocols, case series, systematic reviews, conference abstracts, and early technical or historical reports. The primary outcome was preterm birth before 34 weeks; secondary outcomes were GA at delivery, latency, neonatal morbidity and mortality, and maternal complications. Results: Across prophylactic (history- or ultrasound-indicated) settings, double sutures produced outcomes comparable to single-level cerclage without consistent superiority. In contrast, in emergency or exam-indicated cases with advanced cervical dilation or bulging membranes, double or double-level cerclage significantly prolonged latency and reduced very preterm birth (<32–34 weeks). Double-level reinforced techniques (including monofilament-based and modified Wurm-type approaches) showed improved mechanical support and lower neonatal intensive-care admission. Case series further demonstrated successful rescue procedures beyond 24 weeks, indicating expanded surgical feasibility in selected patients. Conclusions: While double cerclage yields similar results to single cerclage in prophylactic use, it appears advantageous in high-risk or emergency scenarios. Comparative analyses suggest that combined mechanical and infection-controlled approaches may improve cervical competence and prolong gestation in selected patients. Ongoing multicenter randomized trials are needed to establish its definitive role in modern obstetric practice. Full article

Objectives: Current guidelines for pulmonary surfactant (PS) administration in preterm infants with respiratory distress rely on clinical signs and FiO₂ thresholds. Lung ultrasound offers a promising alternative for accurately diagnosing neonatal respiratory distress syndrome (NRDS) and assessing its severity. This randomized controlled trial aimed to evaluate whether a lung ultrasound-guided strategy for NRDS diagnosis and lung ultrasound scores (LUS)-guided PS administration could improve respiratory outcomes in preterm infants (<32 weeks’ gestation), compared to conventional methods. Methods: In this non-blinded randomized controlled trial, 89 preterm infants (≤32 weeks’ gestation) with respiratory distress after birth were enrolled. Participants were randomly assigned to either the ultrasound group (PS administration based on ultrasound-confirmed NRDS and LUS criteria) or the control group (PS administration according to standard clinical signs and FiO₂ requirements). Results: The ultrasound group demonstrated a significantly lower rate of invasive mechanical ventilation (p = 0.007) and a shorter duration of ventilation (p = 0.005) compared to the control group. Furthermore, the ultrasound group required less PS (p = 0.03), received their first dose at an earlier time (p = 0.017), and experienced fewer radiation exposures both before surfactant treatment and within the first week after birth (p = 0.023 and p = 0.019, respectively). Conclusions: The integration of lung ultrasound for NRDS diagnosis and LUS-guided surfactant therapy facilitates more precise and timely PS use. This strategy reduces the need for and duration of invasive mechanical ventilation and limits early radiation exposure in very preterm infants. Full article