Very preterm birth and fetal growth restriction in adolescence - Cardiovascular and renal aspects

Abstract: This thesis applied magnetic resonance imaging (MRI) to investigate to what extent very preterm birth due to early onset fetal growth restriction (FGR) impacts the cardiovascular system and kidneys in adolescence. The thesis further investigated whether FGR exacerbates the organ-specific effects of very preterm birth.Study I validated a widely available non-contrast enhanced MRI method for quantification of renal cortical and medullary parenchymal volumes and showed that kidney volumes can be quantified with high accuracy and precision.Study II validated an MRI method for pulse wave velocity (PWV) acquisition in neonates and adolescents and showed how the acquired PWV was influenced by commonly used MRI methods. The study proposed the use of 3D angiography images and the time-to-foot method for accurate and precise PWV acquisition.Study III implemented the proposed PWV method from Study II and 24-hour ambulatory blood pressure measurements and showed that very preterm birth due to early onset FGR was associated with higher, yet normal, blood pressure in adolescent boys while very preterm birth was associated with higher arterial stiffness in girls.Study IV showed that very preterm birth was associated with smaller ventricular volumes without alterations in left or right longitudinal and radial pumping. Early onset FGR did not exacerbate the effects of very preterm birth.Study V implemented the newly validated non-contrast enhanced MRI method from Study I together with biomarkers of kidney function. Very preterm birth due to FGR was associated with smaller total kidney and medullary kidneyvolumes, but not with markers of kidney dysfunction or renin-angiontensin-aldosterone system activation in adolescence.This thesis concludes that adolescents born very preterm with and without preceding fetal growth restriction show alterations in cardiovascular and renal morphology. Changes were more pronounced in girls. Cardiovascular andkidney function were however normal, possibly indicating a decreased long-term effect of very preterm birth and fetal growth restriction on these organ systems compared to earlier studies, where clear signs of increased risk were observed already in childhood and adolescence. As indicated by increases in blood pressure, male sex and fetal growth restriction might increase cardiovascular risk in those born preterm. Morphological changes in the heart and in the kidneys may still precede functional decline in this population, and the alterations observed could potentially be used as prognostic markers in the future.