The use of proteomics for blood biomarker research in premature infants: a scoping review

Abstract

Over the last decade, the use of proteomics in the setting of prematurity has increased and has enabled researchers to successfully identify biomarkers for an array of associated morbidities. The objective of this scoping review was to identify the existing literature, as well as any knowledge gaps related to proteomic biomarker discoveries in the setting of prematurity. A scoping review was conducted using PubMed, Embase and Medline databases following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The study selection process yielded a total of 700 records, of which 13 studies were included in this review. Most studies used a tandem Mass Spectrometry (MS/MS) proteomics approach to identify key biomarkers. The corresponding studies identified proteins associated with retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC), late onset sepsis (LOS) and gestational age. This scoping review demonstrates the limited use of proteomics to identify biomarkers associated with severe complications of prematurity. Further research is warranted to identify biomarkers of other important morbidities associated with prematurity, such as intraventricular haemorrhage (IVH) and cerebral palsy, and to investigate the mechanisms associated with these outcomes.

Evolution of the Umbilical Cord Blood Proteome Across Gestational Development

“…In a 2021 review of proteomic studies that attempted to identify biomarkers for prematurity-related diseases, Letunica et al determined that only 13% of studies investigated cord blood even though cord blood is a readily available specimen at birth. 11 Suski et al investigated the cord blood proteome of preterm infants in three GA groups (<=26 weeks, 27-28 weeks, and 29-30 weeks) and compared them to the proteomes of a full term control group. They reported differences in inflammatory, immunomodulation, coagulation, and complement systems in preterm versus term infants.…”

“…determined that only 13% of studies investigated cord blood even though cord blood is a readily available specimen at birth. 11 Suski et al investigated the cord blood proteome of preterm infants in three GA groups (<=26 weeks, 27-28 weeks, and 29-30 weeks) and compared them to the proteomes of a full term control group. They reported differences in inflammatory, immunomodulation, coagulation, and complement systems in preterm versus term infants.…”

“…“Omics” methodologies have been previously used to profile amniotic fluid and infant blood to predict pre-eclampsia, preterm birth, and late-onset sepsis 11 , 12 . Mass spectrometry (MS)-based proteomics approaches have emerged as a particularly powerful technology for the comprehensive profiling of proteins comprising the plasma microenvironment 13 .…”

Early Biomarkers of Hypoxia and Inflammation and Two-Year Neurodevelopmental Outcomes in the Preterm Erythropoietin Neuroprotection (PENUT) Trial

“…Though the timing of baseline measurements was variable relative to the time from birth and other associated exposures, the ∼8-hour baseline measurement window relative to birth more accurately mimics real-world clinical scenarios, which increases the translatability of the results. With respect to intra-uterine exposures in particular, cord blood sampling for potential biomarkers remains an important area that was not explored in the PENUT trial [ [65] , [66] , [67] , [68] , [69] ]. Our study was also not powered to examine multiple combinations of biomarkers at multiple timepoints and their associations with long-term outcomes, and we were unable to compare the prognostic accuracy of individual biomarkers against other tools such as the Score for Neonatal Acute Physiology (SNAP-II) and SNAP-Perinatal Extension-II (SNAPPE-II) scores as not all the necessary markers were routinely available [ 70 ].…”