The Influence of Intrauterine Environment on Cardiovascular Development During Fetal Life

Sammanfattning: Fetal growth restriction has been linked to later cardiovascular disease, possibly through reduced arterial distensibility in response to a suboptimal intrauterine environment. This thesis sought firstly to examine the relationship between fetal growth and haemodynamics and their effect on later cardiovascular function and secondly to examine the effects of differential volume loading on arterial distensibility in genetically identical monochorionic twins with twin-twin transfusion syndrome (TTTS) and to explore the effect that early treatment has on vascular development. Pulse wave velocity, cardiovascular growth and haemodynamics and the response of heart rate and blood pressure to tilt-testing in infancy were examined in two cohorts of normally grown (N) and growth restricted (GR) fetuses examined serially during fetal life and through the first year of life. Fetal growth restriction was associated with altered vascular behaviour, volume blood flow and increased thickness of cardiac walls, possibly in response to documented increased systemic impedance, but by a year of age no differences were observed. Arterial distensibility was higher in GR during the fetal and neonatal periods but not later in infancy. Heart rate was higher in GR during infancy suggesting increased sympathetic drive and blood pressure showed a trend towards higher values. Abnormal responses to tilt testing were documented in GR individuals who had shown abnormal fetal blood flow Doppler waveforms suggesting a possible influence on later baroreceptor function. Monochorionic twins with TTTS showed discordant arterial distensibility that was not present in monochorionic or dichorionic controls. Early definitive treatment with laser photocoagulation reduced, but did not completely abolish intertwin discordance, suggesting that vasoactive substances produced in response to differential volume loading in TTTS may influence later vascular behaviour despite definitive treatment of the disease process in the second trimester.