Exercise in prematurely born preadolescents to mitigate cardiovascular risk and improve cognitive impairment (EXCELSIOR)

• Applicant: Holger Burchert, Ph.D.
• Subject Area: Pediatric and Adolescent Medicine
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 528348751

Preterm birth (born earlier than 37 week’s gestation) affects 14 million live births globally each year (10%) with increasing tendency. It has been identified as an independent risk factor for cardiovascular morbidity and mortality. Depending on the degree of prematurity, it increases the risk of heart failure in childhood and young adulthood 4- to 17-fold compared to term-born controls. Moreover, preterm-birth is associated with a distinct cardiovascular- and cognitive phenotype. The left ventricle of prematurely born individuals is on average shorter, has a reduced internal cavity diameter, thicker walls and the apex orientation is shifted away from the right ventricle. While ejection fraction is preserved at rest, it was found to be reduced during exercise and to decline with increasing workload. In addition, increased blood pressure levels were found and are associated with an enhanced antiangiogenic state. Regarding the cognitive phenotype, the preterm people perform 0.5 standardised mean differences below full-term controls in executive function tasks and were found to have a reduced inhibitory control (ability to override a dominant response). For the general population, cardiovascular health and cognitive function are known to be interrelated. Reduced ventricular function may lower brain perfusion leading to impaired development and accelerated neurodegeneration. In contrast, only little is known about this relationship in preterm-born individuals. Since prematurity-related cardiovascular alterations are apparent in childhood already, early identification and initiation of prevention strategies may be warranted. In adults, cardiovascular risk is linked to retinal arteriolar narrowing which has been associated with hypertension, stroke, and coronary heart disease. Likewise, lower birth weight and being born preterm are associated with narrower retinal arterioles in 6-year-old children. This narrowing can be measured by static retinal vessel analysis (e.g., central retinal artery diameter = CRAE), which is a non-invasive, technique allowing the examination of the human microcirculation across all age groups and is well suited for children. While physical exercise is known to improve cardiovascular- and retinal microvascular health, only little is known about exercise interventions in preterm-born individuals. My aim is to fill this research gap by conducting a prospective, single-centre, two-arm, parallel, randomised controlled trial in preterm preadolescent children. The study is called EXerCise in prEmatureLy born preadoleScents to mItigate CardIOvascular Risk and improve cognitive function (EXCELSIOR). Fifty participants will be randomised 1:1 to either a 10-week multimodal exercise intervention or to a control group. The objectives are the beneficial modification of micro- and macrovascular biomarkers. The primary endpoint is CRAE as microvascular-, and pulse wave velocity (PWV) as a macrovascular biomarker.

• DFG Programme: WBP Fellowship
• International Connection: Switzerland
• Host: Professor Dr. Henner Hanssen