Fetal growth restriction (FGR) is associated with increased risk of mortality and morbidity and impacts 5–10% of pregnancies. The chronic hypoxic environment the FGR fetus is exposed to impacts normal development for multiple organs including the heart, brain and lungs. Investigating alterations in the blood plasma proteome would further our understanding of the pathways, networks and functions involved in these associated adverse outcomes. An established spontaneously occurring piglet model of FGR and ZenoTOF liquid-chromatography mass spectrometry (LCMS) was used to identify alterations in the plasma proteome when compared to normally grown (NG) piglets. Technological advancements, including improvements in sensitivity, allowed for twice the number of proteins to be quantified while halving the sample load required. This study identified 106 dysregulated proteins in FGR compared to NG piglet plasma samples. Alterations to multiple pathways and functions predicted interactions between apolipoproteins, T cell factors, Fetuin A and AKT. These alterations to protein levels were also associated with the protein profile of multiple disease-states such as cardiovascular, neurological, metabolic and gastrointestinal previously identified with long-term adverse outcomes in FGR. Moreover, alterations to immune and inflammatory responses were also observed in FGR plasma. By using LCMS to identify dysregulated proteins associated with disease states, this study provides an important step forward in understanding the underlying mechanisms of injury in FGR. Additionally, the identified pathways have potential for prognostication and therapeutic targeting, offering a foundation for future clinical applications in managing FGR-related diseases.
Musco et al. (2026) studied this question.