In Utero Exposures and Cardiovascular Disease Risk in 8-10 Year Old Children and their Mothers

Abstract

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide and obesity is a risk factor. Globally, the prevalence of obesity is increasing. Research has found that in utero exposures such as pregnancy complications, exposure to maternal smoking or obesity can contribute to childhood CVD risk (CVDr). Microvascular dysfunction is associated with obesity and CVDr in children and adults. Sexual dimorphism in the microvasculature is a growing area of interest. In this thesis, I aimed to determine in utero factors that contribute to obesity and CVDr in children and their mothers in a disadvantaged population. I addressed the effect of obesity on microvascular function, the long term effects of smoking during pregnancy and major pregnancy complications including preeclampsia (PE), gestational hypertension (GH) small for gestational age (SGA) and preterm birth (PTB) on cardiovascular health of the woman and child. Method: I followed up the Adelaide arm of the SCOPE cohort of 1164 women and their children 8-10 years after their pregnancy/birth. 273 mother-child pairs were recruited and data on body composition (TANITA scale), hemodynamic profile (USCOM BP+ and USCOM 1A) and microvascular function (PORH) were assessed between May 2016 and March 2018. Information on socioeconomic index, maternal smoking, BMI, alcohol and drug use during pregnancy, pregnancy complications and child birthweight and gestation were obtained from the initial SCOPE database. I also undertook a systematic review and meta-analysis of studies on obesity and microvascular function. Results: In our systematic review I found that there was a gap in research on the effect of age and sex on child microvascular function. I found that among the SCOPE participants, girls had a lower risk of microvascular impairment than boys. Children whose mothers smoked during pregnancy had increased BMI, cardiac output and impaired microvascular function compared to children whose mothers did not smoke. Early pregnancy maternal alcohol consumption was associated with increased diastolic blood pressure in children aged 8-10 years. Children born preterm had decreased BMI and increased vascular stiffness and microvascular dilation compared to children born of uncomplicated pregnancies. Children born both SGA and preterm had greater microvascular dilation compared to those born preterm alone. Children born of a pregnancy complicated by PE had increased augmentation index and pulse pressure and decreased microvascular function compared to those of uncomplicated pregnancies. Females born to a preeclamptic pregnancy had impaired microvascular function compared to males, whereas males whose mothers had PE had increased augmentation index and suprasystolic pulse pressure. Mothers who had GH had increased diastolic pressure and mean arterial pressure 8-10 years later compared to those who had uncomplicated pregnancies. Conclusions: In this cohort of disadvantaged children, adverse intrauterine conditions increases CVDr factors at 8-10 years. This may have the potential to become a cycle, mediated by the effect of obesity on the microvasculature and in utero exposure to other risk factors which program the child for increased risk. Sexual dimorphism in the vasculature and microvasculature is also seen, which indicates that gender specific interventions in children may be beneficial for preventing CVD.