LAUSR

Background Premature birth entails an adverse cardiovascular risk profile, but the underlying mechanisms are insufficiently understood. Here, we employed an unbiased cardiovascular proteomics approach to profile former very preterm-born preschoolers. Methods This observational study investigated differences in plasma concentrations of 79 proteins, including putative cardiovascular biomarkers between very preterm- and term-born children on average 5.5 years old (53.1% male) using multiple-reaction monitoring mass spectrometry. Results Very preterm-born ( n  = 38; median gestational age 29.6 weeks) compared to term-born ( n  = 26; 40.2 weeks) children featured lower plasma concentrations of platelet factor 4 (PLF4; −61.6%, P  < 0.0001), platelet basic protein (CXCL7; −57.8%, P  < 0.0001), and hemoglobin subunit beta (−48.3%, P  < 0.0001). Results remained virtually unchanged when adjusting for complete blood count parameters, including platelet count. Conversely, whole blood hemoglobin was higher (+7.62%, P  < 0.0001) in preterm-born children. Conclusions Very preterm birth was associated with decreased markers of platelet activation among preschoolers. These findings are consistent with reduced platelet reactivity persisting from very preterm birth to a preschool age. Impact Former very preterm-born preschoolers featured reduced levels of platelet activation markers. While lower platelet reactivity in very preterm-born compared to term-born infants in the first days of life was established, it was unknown when, if at all, reactivity normalizes. The current study suggests that platelet hyporeactivity due to very preterm birth persists at least up to a preschool age. “Immaturity of the hemostatic system” may be a persistent sequel of preterm birth, but larger studies are needed to investigate its potential clinical implications.