Early-onset sepsis (EOS) remains a major cause of neonatal morbidity and mortality worldwide, with significant differences in the incidence and outcome of the disease in Europe. Eastern European countries face particular challenges due to differences in access to healthcare, diagnostic facilities, and prevention strategies. This review summarizes the results of recent research to provide insights into maternal risk factors, regional inequalities in access to healthcare, diagnostic biomarkers, pathogen patterns, and treatment protocols for EOS. This review also examines how healthcare infrastructure and socioeconomic factors influence EOS outcomes in Eastern Europe. Introduction: Early-onset sepsis (EOS) presents a significant health challenge for newborns, characterized by sepsis occurring within the first 72 h of life, primarily caused by the vertical transmission of pathogens from mother to child. Despite advancements in medical care, EOS remains particularly burdensome in resource-poor settings, especially in Eastern Europe, where disparities in healthcare access and maternal health are pronounced. This systematic review aims to provide insights into maternal risk factors, regional inequalities in healthcare access, diagnostic biomarkers, pathogen patterns, and treatment protocols for EOS. Background/Objectives: EOS is increasingly recognized as a public health issue, with outcomes significantly influenced by maternal health, socioeconomic status, and healthcare infrastructure. The review seeks to summarize the existing literature on EOS, particularly focusing on differences between high-income Western and low-resource Eastern European countries. The influence of maternal access to antenatal care, pathogen prevalence, and antibiotic resistance on EOS outcomes across regions will also be examined. Methods: To achieve the review’s objectives, a comprehensive search was conducted across multiple databases including PubMed, Google Scholar, ScienceDirect, and Scopus, adhering to PRISMA guidelines for systematic reviews. The inclusion criteria encompassed studies published within the last 20 years (January 2004–August 2024) that addressed EOS in late preterm or term infants, emphasizing maternal health, risk factors, diagnostic approaches, and treatment protocols pertinent to European populations. Exclusion criteria included non-English publications and studies lacking a focus on maternal and neonatal health. A total of 29 peer-reviewed articles meeting the specified criteria were ultimately included in the analysis. Results: The findings highlight significant regional disparities in EOS management between Western and Eastern Europe. Key issues include maternal risk factors, socioeconomic barriers to healthcare, diagnostic biomarkers, and pathogen resistance trends. Limited access to prenatal screenings and healthcare infrastructure in Eastern European countries, especially in rural regions in Romania, exacerbate the challenges faced by expectant mothers. Financial burdens, such as high out-of-pocket expenses, were shown to further restrict access to necessary maternal care. Conclusions: This systematic review emphasizes the urgent need for targeted investments in maternal healthcare infrastructure in Eastern Europe to mitigate the impacts of EOS. Enhanced screening programs, standardized surveillance systems, and ensuring equitable health policies are essential to improving neonatal outcomes. Additionally, tailored education and awareness campaigns for disadvantaged groups and comprehensive health policy reforms, including universal antenatal care and Group B Streptococcus (GBS), are essential to bridging healthcare gaps.

Neonatal mortality, particularly due to early-onset sepsis (EOS), remains a pressing issue in Eastern Europe, with Romania experiencing one of the highest neonatal mortality rates in the European Union. EOS, caused by bacterial infections within the first 72 h of life, significantly contributes to neonatal deaths, particularly in rural and underserved areas where healthcare resources are limited. Disparities in prenatal care access, maternal demographics, and systemic healthcare gaps worsen this issue, highlighting the need for comprehensive interventions. Objectives: This review aims to examine the prevalence of neonatal mortality due to EOS in Romania and the broader Eastern European context, focusing on current prenatal care monitoring protocols and maternal demographics, and comparing the available literature with new data. By evaluating disparities in healthcare access, costs, and outcomes, this study identifies systemic barriers to maternal and neonatal care. Methods: A systematic review of 100 articles was conducted using PRISMA guidelines. Key sources included PubMed, Google Scholar, and open-access journals, with 25 articles meeting the inclusion criteria. The analysis encompassed maternal age, parity, literacy levels, marital status, and their impact on neonatal outcomes, alongside the financial burden of prenatal care. Results: The findings underscore stark inequalities in healthcare delivery between rural and urban regions, where limited prenatal visits, out-of-pocket costs, and cultural barriers hinder prompt EOS prevention and management. Advanced maternal age, low literacy, and socioeconomic disparities were identified as critical risk factors. Conclusions: To reduce neonatal mortality due to EOS, targeted efforts must address healthcare accessibility, improve prenatal care protocols, and integrate culturally sensitive practices. These interventions can bridge systemic gaps and promote equitable health outcomes for mothers and newborns across Eastern Europe.

Background/Objectives: Heterotopic cesarean scar pregnancy (HCSP) is an exceptionally rare and potentially life-threatening form of ectopic pregnancy, characterized by the coexistence of a viable intrauterine pregnancy and an ectopic implantation within a previous cesarean section scar. Its incidence has risen in recent years, primarily due to the increased rate of cesarean deliveries and the widespread use of assisted reproductive technologies (ART). This systematic review aims to provide a comprehensive synthesis of published evidence on HCSP, with a focus on epidemiology, diagnostic challenges, therapeutic strategies, complications, and maternal-fetal outcomes. Methods: A systematic literature search was conducted in PubMed, Scopus, and Web of Science up to May 2025, in accordance with PRISMA guidelines. Included studies comprised case reports, case series and retrospective reviews documenting confirmed HCSP cases. Data were extracted on clinical presentation, imaging, treatment approaches, outcomes, and complications. Results: Thirty studies reporting 40 confirmed HCSP cases were included. Transvaginal ultrasonography was the primary diagnostic tool, although diagnosis was often delayed by the presence of a viable intrauterine pregnancy. Management strategies included surgical intervention, local medical therapy and conservative approaches or expectant management. Maternal complications included hemorrhage and uterine rupture, while fetal outcomes were variable. In selected cases, intrauterine pregnancy continued to term. Conclusions: HCSP is a rare but high-risk obstetric entity requiring early recognition and multidisciplinary management. Prompt ultrasound-based diagnosis and individualized treatment can significantly reduce maternal morbidity and improve fetal outcomes. Further multicenter studies are warranted to establish standardized diagnostic and management protocols.

Background/Objective: Early-onset neonatal sepsis (EOS), defined as infection occurring within the first 72 h after birth, remains a major contributor to neonatal morbidity and mortality worldwide. Although advances in perinatal care have improved overall outcomes, the diagnosis of EOS continues to be challenging. Clinical presentations are often nonspecific, laboratory confirmation is often delayed, and immune responses vary considerably among neonates. Expanding our understanding of the molecular mechanisms underlying EOS is essential in enhancing early detection, refining risk stratification, and guiding therapeutic strategies. This systematic review aims to synthesize the available information on the molecular pathways involved in EOS, focusing on pathogen-induced inflammation, systemic immune responses, sterile inflammatory processes, interactions between infectious and non-infectious pathways, as well as emerging molecular diagnostic approaches. Methods: A comprehensive review of original research articles and reviews published between January 2015 and January 2025 was conducted; studies were included based on their focus on human neonates and their analysis of molecular or immunological mechanisms relevant to EOS pathogenesis, immune dysregulation, or novel diagnostic strategies. Results: Pathogen-driven inflammation typically involves the activation of Toll-like receptors (TLRs), the recruitment of neutrophils, and the release of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α, particularly in response to vertical transmission of organisms like Escherichia coli and Streptococcus agalactiae. Systemic inflammatory responses are marked by cytokine dysregulation, contributing to multi-organ dysfunction. Sterile inflammation, often initiated by hypoxia–reperfusion injury or intrauterine stress, amplifies susceptibility to sepsis. Interactions between immune, metabolic, and endothelial pathways further exacerbate tissue injury. Recent advances, including transcriptomic profiling, microRNA-based biomarkers, and immune checkpoint studies, offer promising strategies for earlier diagnosis and individualized therapeutic options. Conclusions: EOS arises from a complex interplay of infectious and sterile inflammatory mechanisms. A deeper molecular understanding holds promise for advancing correct diagnostics and targeted therapies, aiming to improve neonatal outcomes.

Background: Microbiological confirmation of early-onset neonatal infection is inconsistently available in many secondary-care maternity units, and early management often relies on maternal risk profiles and inflammatory markers. Objectives: This study aimed to describe maternal infectious risk factors, neonatal biomarkers, and early antibiotic treatment patterns among late preterm and term newborns evaluated for suspected maternal–fetal infection (MFI) in a Romanian secondary-care maternity, and to explore whether a simplified bedside indicator (NeoSIR) corresponded with antibiotic initiation and treatment-related outcomes. Methods: Observational cohort study (April–September 2024) including newborns with gestational age ≥ 35 weeks evaluated within 24 h for suspected MFI based on maternal risk factors and/or neonatal clinical findings. We recorded maternal infections and screening results, neonatal complete blood count and C-reactive protein (CRP) at 24 h, cultures obtained as part of routine care, antibiotic initiation, treatment duration, and neonatal intensive care unit (NICU) admission. Results: Among 443 newborns, empirical antibiotics were initiated in 414 (93.5%) and 62 (14.0%) required NICU admission. Maternal urinary tract infection (UTI) documented during pregnancy (recorded diagnosis and/or positive urine culture and/or treatment) was associated with antibiotic initiation (p = 0.005). Elevated CRP (>0.5 mg/dL) was associated with antibiotic selection (p = 0.032) and longer therapy (mean 8.33 vs. 6.98 days, p < 0.001); courses were also longer in NICU-admitted infants (mean 10.39 vs. 6.81 days, p < 0.001). The exploratory two-item NeoSIR indicator (maternal UTI and CRP > 0.5 mg/dL) was feasible to compute but showed limited discrimination for antibiotic initiation in this high-treatment cohort. Conclusions: In this selected high-risk cohort, antibiotic exposure was highly prevalent and closely associated with maternal urinary tract infection history and neonatal CRP evolution. These findings primarily describe early management patterns in a secondary-care maternity with limited microbiological confirmation and should be interpreted as hypothesis-generating. The exploratory NeoSIR indicator is not intended as a diagnostic or decision-support tool and requires validation against culture-confirmed outcomes in more heterogeneous populations.