Early cardiovascular morphology, function, and health following abnormal foetal growth

The intrauterine milieu affects cardiovascular morbidity in adulthood with both restricted and excessive foetal growth linked to the development of cardiovascular and related disorders in the adult. Adulthood cardiovascular disease seems linked to both being born small or large for gestational age (SGA and LGA), suggesting a U-shaped association between birth weight and the later development of cardiovascular disease. The cardiovascular system has previously been studied in this setting using conventional ultrasound frequencies (<15 MHz), showing an increased carotid intima-media thickness in children following abnormal foetal growth. Similarly, abnormal foetal growth has also been found to associate with changes in the morphology, geometry, and function of the heart. Conflicting findings have, however, been presented, with both SGA and LGA children throughout childhood showing body-size-appropriate cardiovascular dimensions. Recently, very-high resolution ultrasound (VHRU; 22-71 MHz) has been shown to be a more accurate imaging modality for examining the minute structures of the arterial walls during the early newborn and childhood. Similarly, lean body mass (LBM) has been suggested to be a more accurate method for adjusting cardiovascular dimension for body size in children than conventional body surface area (BSA). In this thesis, the objectives were: I) to assess the impact of restricted or excessive foetal growth and body size on arterial morphology and function and their association with body size in preterm and term neonates, II) to assess the impact of restricted or excessive foetal growth on cardiac morphology, shape and function and the association of cardiac morphology with body size factors in preterm and term neonates, III) to assess the impact of restricted or excessive foetal growth on arterial health in early childhood by studying arterial morphology and stiffness in relation to postnatal growth and body composition in 5-year-old children, IV) to assess the impact of restricted or excessive foetal growth on cardiac morphology, shape, and function in relation to postnatal growth and body composition in 5-year-old children. The same children were examined at the neonate phase and followed up to the age of 5-years. This thesis shows, that during the neonatal stage and throughout childhood, both SGA and LGA children exhibit arterial and cardiovascular dimensions appropriate for body size. No clear evidence of adverse arterial or cardiac health, or signs of increased early cardiovascular disease in SGA or LGA neonates and children was found. Minor differences in some cardiac function parameters were observed in both SGA and LGA neonates and children. However, overall cardiac function was unaffected by abnormal foetal growth. Both arterial and cardiac dimensions were mainly predicted body size overall, and LBM in particular, at time of assessment in neonates and young children. Once adjusted for postnatal body size, the association between the abnormal foetal growth and cardiovascular dimensions disappeared. This thesis is the first to include data on the arterial walls in neonates and children born SGA and LGA using VHRU. The results show no abnormalities or changes in cardiovascular health at this stage associated with restrictive or excessive foetal growth, instead suggesting that the epidemiologically observed changes only become visible later in life. Further research should focus on examining the association between foetal programming and cardiovascular disease and examine the root causes of abnormal foetal growth and their association with cardiovascular disease in adulthood. Furthermore, LBM seems to be a promising and strong predictor of cardiovascular dimensions in children, and its role in adjusting arterial and cardiac dimensions for body size, sex and age in paediatric cardiology should be further studied and developed for the clinical setting. Den intrauterina miljön påverkar den kardiovaskulära sjukligheten i vuxen ålder och såväl för liten som för stor fostertillväxt är båda förknippade med utvecklingen av kardiovaskulära och relaterade sjukdomar hos vuxna. Kardiovaskulär sjukdom i vuxen ålder tycks vara förknippat med för liten och för stor födelsevikt för gestationsåldern (SGA respektive LGA, eng. small for gestational age, large for gestational age), vilket skulle tyda på en U-formad association mellan födelsevikt och senare utveckling av kardiovaskulär sjukdom. Det kardiovaskulära systemet har tidigare studerats hos barn med konventionella ultraljudsfrekvenser (