Introduction: Neonatal sepsis is a severe and life-threatening condition caused by pathogens in the systemic circulation within the first 28 days of life. The classical definition of neonatal sepsis implies positive central cultures, but recent findings discuss culture-negative sepsis (clinical sepsis associated with laboratory findings). Since infected neonates initially express few non-specific clinical signs and there are unreliable biochemical markers to identify sepsis in the early stages, it is essential to improve the accuracy of diagnosis and reduce unnecessary antibiotic exposure. Objective: Our study aims to assess the influence of risk factors and the utility of currently used biomarkers in culture-negative neonatal early-onset sepsis (CN-EOS). Materials and methods: We performed a retrospective study at Bucharest University Hospital, which included 131 preterm and term newborns at risk for EOS admitted in the Neonatal Intensive Care Unit (NICU) over 12 months. The neonates included were classified into two groups: confirmed negative-culture early-onset sepsis (CN-EOS) and suspected early-onset sepsis (S-EOS). Patients from both groups received antibiotic therapy from the first day of life; the type and duration of antibiotic therapy were different in the two groups. For all the patients, we measured C-reactive protein (CRP), procalcitonin (PCT) and white blood count (WBC) at birth and after 72 h, tested blood culture in the first 24 h of life and correlated the results with clinical signs and prenatal risk factors. Categorical variables were presented as frequencies and percentages, while the continuous variables were the mean and the standard deviation. The differences between the continuous variable groups were determined by Student’s t-test or the Mann–Whitney U test, whereas for the categorical variables, the Chi-square test (X²) was employed. The performance of laboratory biomarkers (CRP and PCT) in diagnosing confirmed EOS was calculated. All the tests were statistically significant at a p-value < 0.05. Results: The findings support the significance of low birth weight and gestational age and low Apgar scores as potential indicators for EOS; PROM diagnosed with chorioamnionitis and smoking during the pregnancy were also important predictive risk factors. Respiratory signs, such as apnea and respiratory distress syndrome, were most encountered in the clinical evaluation of infants with CN-EOS. Inflammatory markers were inconsistent in CN-EOS cases, proving that they are not reliable enough for initiating, continuing or stopping antibiotic therapy. Conclusions: Culture-negative neonatal sepsis remains a significant challenge for the neonatologist, since the time elapsed between the moment sepsis is suspected and the initiation of empirical therapy can make the difference between survival and death. Continued efforts are needed to develop more reliable and effective diagnostic tools for timely and appropriate intervention.

Introduction: Fetal Inflammatory Response Syndrome (FIRS) is widely acknowledged for its contribution to neonatal morbidity in premature infants. Being a systemic inflammatory process triggered by intrauterine infections or other stimuli, FIRS has gained significant attention due to its complex implications for neonatal adverse outcomes: preterm birth, early onset neonatal sepsis, death or long-term neurodevelopmental impairments. Fetal plasma Interleukin-6 (IL-6) levels above 11 pg/mL define FIRS and serve as an essential biomarker, providing insights into the complex mechanisms underlying this response. This study aims to evaluate the clinical, laboratory, and therapeutic differences between preterm neonates with and without FIRS. Methods: A prospective cohort study was conducted, involving 125 preterm neonates with gestational ages between 23 and 37 weeks, who were admitted to the Neonatal Intensive Care Unit (NICU) at the Emergency University Hospital Bucharest between April 2023 and April 2025. Infants were stratified into FIRS and non-FIRS groups based on the measurement of cord blood IL-6 levels greater than 11 pg/mL. Demographic, biochemical, and therapeutic parameters were compared across the two groups. Results: Preterm neonates with FIRS had significantly lower birth weight, length, and head circumference, and lower Apgar scores at 1 and 5 min (p = 0.001). FIRS was associated with a higher incidence of vaginal delivery, meconium-stained amniotic fluid, and neonatal metabolic imbalances, requiring more respiratory support, longer antibiotic treatment periods, and more blood transfusions (p < 0.05). Neonatal complications such as early-onset sepsis (EOS) and late-onset sepsis (LOS), respiratory distress, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP) were significantly more frequent in the FIRS group (p ≤ 0.01). Among maternal cervical screening, Chlamydia trachomatis was the only pathogen significantly associated with FIRS. Conclusions: FIRS in preterm neonates is linked to important perinatal inflammation, adverse short and long-term outcomes, and extensive medical intervention. These findings highlight the value of early identification of intrauterine inflammation and targeted neonatal monitoring strategies. Further studies are needed to explore long-term outcomes and improve diagnostic and therapeutic protocols.

(1) Background: The assessment of neonatal health and prognosis is one of the most critical areas in pediatric medicine. Intrauterine inflammation and the fetal inflammatory response syndrome (FIRS) are increasingly recognized as major determinants of neonatal morbidity. Interleukin-6 (IL-6), measured in the umbilical cord (UC) blood, has emerged as a promising biomarker, reflecting both intrauterine conditions and early neonatal risk. This narrative review aims to synthesize current evidence on the predictive value of umbilical cord blood IL-6 for neonatal outcome, including sepsis, respiratory distress, hypoxic–ischemic encephalopathy (HIE) and mortality. (2) Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science. Studies reporting umbilical cord IL-6 levels in relation to neonatal outcomes were analyzed and summarized narratively. (3) Results: Evidence consistently indicates that elevated umbilical cord IL-6 is associated with early-onset neonatal sepsis (EONS) and respiratory complications, and provides prognostic insight into neurological outcomes, even though results are influenced by gestational age (GA), mode of delivery, and the presence of chorioamnionitis. (4) Conclusions: UC IL-6 represents a valuable early biomarker for neonatal risk stratification and supports clinical decision-making. Future research should prioritize assay standardization, reference interval development, and prospective multicenter studies to validate its integration into routine neonatal care.

A neonatal stroke is a cerebrovascular process caused by interruption of cerebral blood flow that occurs with an incidence between 1 per 1600 and 1 per 2660 live births. Relative higher incidence in the neonatal period compared to later childhood is favored by the hypercoagulability state of the mother, mechanical stress during delivery, transient right to left intracardiac shunt, high hematocrit, blood viscosity, and risk of dehydration during the first few days of life. The exact cause of a neonatal stroke remains unclear in many cases. About 80% of neonatal strokes are due to arterial ischemic events involving the middle cerebral artery. Typical clinical manifestations in a neonatal stroke are usually seizures that appear immediately after birth or after several days of life, but many of the cases may remain asymptomatic. We present the case of a late preterm infant diagnosed with a thalamic stroke on the fifth day of life with no clinical signs except for repeated episodes of apnea. The anamnesis and clinical context, in this case, revealed a SARS-CoV-2 infection in late pregnancy and early bacterial neonatal sepsis. Early identification of a perinatal stroke and increasing awareness of physicians about this condition in the neonatal period have paramount importance to reduce developmental postischemic damage.

Intraventricular hemorrhage (IVH) is a common complication encountered in extremely-low-birth-weight (ELBW) and very-low-birth-weight (VLBW) premature babies. The neurologic outcome of these patients is influenced by the magnitude of the hemorrhagic process that damages the involved anatomic structures but also by the impaired circulation of cerebrospinal fluid (CSF) through the ventricular system, leading to posthemorrhagic ventriculomegaly (PHVM). Cranial ultrasound (CUS) performed by neonatologists (point-of-care ultrasound—POCUS) facilitates the early diagnosis of IVH and PHVM and can objectively quantify structural alterations. Our aim was to identify the best sonographic criteria to follow-up with ventricular dilatation and predict the need for neurosurgery and neurologic deterioration. We performed a literature review in search of the most relevant ventricular measurements considered by neurosurgeons, neonatologists, and pediatric neurologists to reflect the risk of white matter injury and high intracranial pressure (HIP), thus anticipating neurologic developmental impairment (NDI). The tridimensional picture of ventricular dilatation is best captured if more than one index (ventricular index and anterior horn width) or ratio (Evans ratio, fronto-occipital horn ratio, and fronto-temporal horn ratio) is used. Conclusions: If performed using the correct protocol, serially and comprehensively, CUS is an indispensable tool for the diagnosis and follow-up of neurologic complications of preterm babies, and it can make a difference in guiding adequate intervention and improving long-term developmental outcomes.

Tetralogy of Fallot (ToF) with pulmonary atresia (PA) and complete right ventricular outflow tract obstruction (RVOTO) represents one of the most critical forms of congenital heart disease in neonates. These cases require complex and timely interventions to ensure survival and optimize long-term outcomes. While surgical correction offers a favorable prognosis, the period from birth to surgery is often marked by significant hemodynamic, respiratory and nutritional challenges, particularly in neonatal intensive care units (NICUs). This study aims to outline a structured, physiology-guided approach to the preoperative management of neonates with ToF and complete RVOTO, emphasizing stabilization strategies, hemodynamic support, ventilatory management and nutritional optimization. We performed a focused literature review of practices in neonatal ToF management and illustrated our experience through two case reports highlighting divergent outcomes in infants with the same anatomical diagnosis. The management strategies covered include delivery room stabilization, the use of prostaglandins, mechanical ventilation techniques, nutritional interventions and the timing of surgical intervention. A phased, physiology-guided management strategy is the key to the successful preoperative treatment of ToF with pulmonary atresia. Optimizing hemodynamics, ensuring adequate pulmonary blood flow and supporting nutritional needs are the main drivers for growth and may reduce the time from diagnosis to surgical correction.