Supplementary Material for: Biomarkers in the Newborn with Fetal Growth Retardation and Early Impairment of Heart Function

Background
Children born with lower birth weight face an increased risk of developing cardiovascular disease later in life. We hypothesize that cardiovascular protein biomarkers in cord blood, associated with birth weight SDS and systolic cardiac function, may reveal mechanisms behind early programming of cardiovascular function.

Method
We investigated the association between birth weight SDS and plasma levels of 184 circulating proteins determined by Proximity Extension Assay (PEA) in cord blood from 48 children. The birth weight associated proteins were correlated with Left Ventricular Longitudinal Strain (LVLS) determined by echocardiography at birth and 3 months of age.

Results
We identified seven cardiovascular protein biomarkers associated with birth weight SDS: Stem cell factor (SCF), Leptin (LEP), Elafin (PI3), Insulin-like growth factor-binding protein-1 (IGFBP-1) , Follastatin (FS), Paraoxonase (PON3) and Epithelial cell adhesion molecule (Ep-CAM). Among these, Ep-CAM significantly correlated with LVLS at three months of age.

Conclusion
PEA successfully identified both established and novel proteins associated with fetal growth and birth size, including one novel protein related to LVLS. This indicates that our approach is promising for uncovering biological pathways that may be involved in direct programming of cardiovascular function in children and affect the risk of cardiovascular disease in adulthood.