Very preterm birth results in later lower platelet activation markers.

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.

Apolipoprotein Profiles in Very Preterm and Term-Born Preschool Children.

Background Little is known about plasma apolipoprotein profiles in very preterm-born and term-born preschool children compared with the adult population. This is of particular interest because apolipoprotein composition might contribute to cardiometabolic outcome in later life. Methods and Results Children aged 5 to 7 years born at term or with <32 weeks of gestation were included. Apolipoprotein concentrations were measured in plasma collected after an overnight fast using multiple-reaction monitoring-based mass spectrometry. Twelve apolipoproteins were measured in 26 former term and 38 former very preterm infants. Key findings were confirmed by assessing apolipoprotein levels using antibody-based assays. Comparing children born term and preterm, apolipoprotein A-I, A- IV , C- II , and C- III were significantly higher in the latter group. Term-born children showed plasma levels of apolipoprotein C- II and C- III quantitatively similar to the adult range (Bruneck study). Hierarchical clustering analyses suggested that a higher proportion of apolipoprotein C- III and C- II reside on high-density lipoprotein particles in children than in adults given the marked correlations of apolipoprotein C- III and C- II with high-density lipoprotein cholesterol and apolipoprotein A-I in children but not adults. High-density lipoprotein cholesterol concentrations were similar in children and adults but the pattern of high-density lipoprotein cholesterol-associated apolipoproteins was different (lower apolipoprotein A-I and C-I but higher A- II , A- IV , and M). Conclusions Our study defines apolipoprotein profiles in preschoolers and reports potential effects of prematurity. Further large-scale studies are required to provide evidence whether this apolipoprotein signature of prematurity, including high apolipoprotein C- II and C- III levels, might translate into adverse cardiometabolic outcome in later life.