A narrative review of precision medicine in neonatal sepsis: genetic and epigenetic factors associated with disease susceptibility

Background and Objective: Neonatal sepsis is a dysregulated host response to an infectious agent that results in severe morbidity and mortality among neonates worldwide. Given the complex and heterogenous nature of neonatal sepsis, early diagnosis and individualized treatment remain challenges for clinicians despite clinical advance. Epidemiological studies on twins suggest that hereditary factors act in conjunction with environmental factors to affect neonatal sepsis susceptibility. However, little is known about hereditary risks at present. This review aims to elucidate neonatal hereditary predisposition to sepsis and outline thoroughly the genomic landscape underlying neonatal sepsis, which may, to a large extent, facilitate precision medicine in this area. Methods: PubMed was searched for all published literature relating to neonatal sepsis using Medical Subject Headings (MeSH) terms, with a focus on hereditary factors. Without any restriction on article type, articles published in English prior to June 1, 2022, were retrieved. Additionally, pediatric, adult, and animal-and laboratory-based studies were reviewed wherever possible. Key Content and Findings: This review provides a detailed introduction regarding the hereditary risk of neonatal sepsis in terms of genetics and epigenetics. Its findings demonstrate the potential for translation to precision medicine, where risk stratification, early diagnosis, and individualized interventions might be matched to the certain population. Conclusions: This review delineates the comprehensive genomic landscape underpinning inherent susceptibility to neonatal sepsis, allowing future studies to integrate hereditary information into a routine protocol and drive precision medicine from the bench to the bedside.