Limitations of blood culture, cardiovascular sequelae and the emerging role of metagenomic next generation sequencing in early-onset neonatal sepsis among premature infants

Early-onset neonatal sepsis (EOS) is a leading cause of mortality and long-term morbidity in premature infants. The cornerstone of etiological diagnosis, blood culture, is critically limited in this population by low sensitivity, prolonged turnaround time, and a high rate of culture-negative results, often leading to prolonged empirical antibiotic use. This narrative review synthesizes current evidence on these diagnostic limitations and evaluates the emerging role of metagenomic next-generation sequencing (mNGS) as a transformative, culture-independent alternative. mNGS enables rapid, comprehensive pathogen detection directly from clinical samples, significantly improving diagnostic yield, especially in culture-negative sepsis, and holds promise for guiding targeted antimicrobial therapy. Crucially, this review also examines the established link between the systemic inflammatory insult of severe neonatal sepsis and subsequent cardiovascular dysregulation, including acute hypertensive crises and an elevated risk of chronic hypertension later in life. The integration of advanced diagnostics like mNGS is thus framed within a dual imperative: to optimize acute management through antimicrobial stewardship and to potentially mitigate the long-term programming of cardiovascular disease by enabling faster control of the inflammatory cascade. While challenges in standardization, cost, and interpretation remain, mNGS represents a pivotal step toward precision medicine in neonatology, aiming to improve not only immediate survival but also the lifelong health trajectory of vulnerable premature infants.