Abstract

Rates of obesity have reached epidemic proportions worldwide. Over half of women in the UK are now entering pregnancy either overweight or obese. This is particularly concerning as exposure of the fetal offspring to maternal obesity during pregnancy increases their risk of developing cardiovascular disease in adulthood. However, it remains unknown whether offspring cardiovascular dysfunction originates early in life, during fetal development, and what mechanisms are responsible.

My PhD research aims to address this gap in the literature using a novel sheep model of maternal obesity in pregnancy. In this study, control and obese pregnant ewes underwent surgery in late gestation. Under general anaesthesia, the fetal carotid arteries, delivering blood to the brain, and femoral arteries, delivering blood to the hindlimb, were instrumented. Arterial catheters and flow probes were inserted, allowing measurement of fetal blood pressure and blood flow. This permits continuous long-term monitoring of fetal cardiovascular function during pregnancy. Fetal offspring of obese pregnancy were found to have altered cardiovascular function, with increased blood flow towards the brain, known as fetal circulatory brain sparing. Cerebral resistance arteries collected from the brains of fetuses of obese pregnancy showed enhanced relaxation and impaired constriction to vasoactive agents. This enhances vascular conductance, as blood flows more easily through relaxed vessels. These fetal cardiovascular alterations indicate that dysfunction is already present at an early stage in offspring of obese pregnancy, due to stressful intrauterine conditions. This provides a window of opportunity for the identification and treatment of cardiovascular disease at its origin.