Vulcănescu Anca, Siminel Mirela-Anișoara, Dijmărescu Anda-Lorena, Manolea Maria-Magdalena, Săndulescu Sidonia-Maria, Rădulescu Virginia Maria, Gheorman Valeriu, Dinescu Sorin-Nicolae
"Filantropia" Clinical Municipal Hospital, 200143 Craiova, Romania.
University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
J Clin Med. 2025 Jul 28;14(15):5315. doi: 10.3390/jcm14155315.
: 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. : 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. : 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. : 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.
早发型新生儿败血症（EOS）定义为出生后72小时内发生的感染，仍是全球新生儿发病和死亡的主要原因。尽管围产期护理的进步改善了总体结局，但EOS的诊断仍然具有挑战性。临床表现通常不具有特异性，实验室确诊往往延迟，并且新生儿的免疫反应差异很大。扩大我们对EOS潜在分子机制的理解对于加强早期检测、完善风险分层和指导治疗策略至关重要。本系统综述旨在综合有关EOS所涉及分子途径的现有信息，重点关注病原体诱导的炎症、全身免疫反应、无菌性炎症过程、感染性和非感染性途径之间的相互作用以及新兴的分子诊断方法。：对2015年1月至2025年1月期间发表的原始研究文章和综述进行了全面回顾；纳入的研究基于其对人类新生儿的关注以及对与EOS发病机制、免疫失调或新型诊断策略相关的分子或免疫机制的分析。：病原体驱动的炎症通常涉及Toll样受体（TLR）的激活、中性粒细胞的募集以及促炎细胞因子如IL-6、IL-1β和TNF-α的释放，特别是在应对大肠杆菌和无乳链球菌等病原体的垂直传播时。全身炎症反应以细胞因子失调为特征，导致多器官功能障碍。无菌性炎症通常由缺氧-再灌注损伤或宫内应激引发，会增加败血症的易感性。免疫、代谢和内皮途径之间的相互作用会进一步加剧组织损伤。包括转录组分析、基于微小RNA的生物标志物和免疫检查点研究在内的最新进展为早期诊断和个性化治疗选择提供了有前景的策略。：EOS源于感染性和无菌性炎症机制的复杂相互作用。更深入的分子理解有望推动正确的诊断和靶向治疗，旨在改善新生儿结局。
