A Prospective, Case-Control Study of Serum Metabolomics in Neonates with Late-Onset Sepsis and Necrotizing Enterocolitis

Abstract

Late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) are major causes of neonatal morbidity and mortality. In this prospective, case-control study, we evaluated the metabolic profile of neonates with LOS and NEC. Blood samples were collected from 15 septic neonates and 17 neonates with NEC at the clinical suspicion of the specific diseases. Sixteen gestational and postnatal age-matched neonates without sepsis/NEC served as controls. Serum metabolic profiles were assessed using liquid chromatography–quadrupole time-of-flight mass spectrometry. Metabolomic analysis revealed significant differences in the metabolic profile of neonates with LOS or NEC compared to controls. More specifically, a number of molecules possibly identified as phosphatidylcholines or lysophosphatidylcholines were found to be significantly reduced both in neonates with LOS and those with NEC compared to controls. Additionally, L-carnitine could efficiently discriminate NEC cases from controls. The results of the current study suggest that certain phospholipids and their derivatives could possibly be used as biomarkers for the early detection of LOS and NEC.

Advances in Mass Spectrometry-Based Blood Metabolomics Profiling for Non-Cancer Diseases: A Comprehensive Review

“…Notably, the levels of PC and lysophosphatidylcholine (LPC), a derivative of PC, displayed corresponding changes. Conversely, reduced levels of PC and LPC were found in neonates with late-onset sepsis, accompanied by necrotizing enterocolitis [ 76 ]. PCs and LPC may also be considered prognostic markers for evaluating survival risk.…”

“…Scientists explored the blood of preterm infants with both necrotizing enterocolitis and late-onset sepsis and found several distinguishing metabolites and proteins [ 181 ]. Another study showed that molecules identified as PCs or LPCs are both reduced in infants with late-onset sepsis, indicating their potential as biomarkers for early detection [ 76 ]. There is also a comprehensive study on changes in metabolites in neonates during a week of sepsis progression [ 182 ].…”

Metabolomics in NEC: An Updated Review

“…In 2022, Thomaidou et al [ 77 ] performed a case–control prospective study to investigate the blood metabolic profiles of NEC and LOS newborns. Blood samples from 15 septic newborns and 17 newborns with NEC were analyzed upon clinical suspicion of the specific pathology compared to those of 16 control newborns with corresponding gestational and postnatal ages without sepsis or NEC.…”

Biomarkers of necrotizing enterocolitis through the prism of etiopathogenesis

“…Given the fact that the disease can develop in a sufficiently long period, both in the early and late neonatal period, predictive markers allow the identification of children at risk with a high probability of developing NECs, must be determined and have a high sensitivity and specificity in the first days of the child's life, until any traits of NEC are formed [9]. These indicators include markers of systemic immaturity, immaturity of the gastrointestinal tract and immune system, hypoxia, and no factors directly detecting the development of inflammatory reactions and/or damage to the intestine [11,12].…”

“…Functional immaturity of enzyme systems can be determined by direct determination of enzyme activity and/ or quantity [14], by detection of gene expression level [21], and indirectly by the level of metabolites being substrates/products of enzyme response [11,22,23].…”