An investigation of the long-term impact of in-utero exposure to mild chronic hypertension and antihypertensive therapy on childhood subclinical cardiovascular risk factors - Abstract Children with in-utero exposure to hypertensive disorders of pregnancy (HDP; gestational hypertension, chronic hypertension, preeclampsia, and superimposed preeclampsia) have an increased risk for hypertension and cardiovascular disease (CVD). Our preliminary data indicate that administering first-line antihypertensives during pregnancy improves neonatal outcomes. However, the long-term impact of in-utero exposure to antihypertensive treatment on childhood subclinical CVD risk factors (i.e., high oxidative stress, inflammation, and arterial stiffness) is unknown. Further, it has not been established whether environmental exposures influence the association of in-utero exposure to HDP on childhood subclinical CVD. Assessing subclinical CVD in childhood is particularly important because longitudinal research shows that poor cardiovascular health in childhood is associated with a higher incidence of hypertension, atherosclerosis, and other cardiovascular events in later life. Thus, the objectives of this study are to 1) Investigate whether in-utero exposure to antihypertensive treatment (compared to no treatment) is associated with improved childhood (ages 5–10 years) subclinical CVD, and 2) Examine whether neighborhood deprivation (i.e., a composite measure of environmental exposures) influences the association between in-utero exposure to HDP and offspring subclinical CVD. The central hypothesis is that in-utero exposure to antihypertensive treatment is associated with improved subclinical CVD among children born to mothers with HDP. We also posit that neighborhood deprivation significantly influences the association between in-utero exposure to HDP and offspring subclinical CVD. Completion of the research aims in this proposal will inform the development of an intervention to improve vascular outcomes among children born to mothers with HDP. This research plan will be augmented by intensive mentoring from a multidisciplinary team of experts, didactic coursework, and formal training at the University of Alabama at Birmingham and the National Heart, Lung, and Blood Institute. The training plan was crafted to ensure that Dr. Martin achieves her specified career development goals, which are to 1) Develop advanced skills to assess subclinical cardiovascular risk factors in children and gain a deep understanding of the intergenerational transmission of CVD, 2) Develop expertise in the assessment of social determinants of health and environmental exposures, 3) Develop a comprehensive knowledge of intervention approaches and statistical analysis for clinical research in maternal-fetal-child health; and 4) Refine grant writing skills for future grant mechanisms. Completion of the training aims in this proposal will transform clinical care by providing new insight regarding the long-term impact of in-utero exposure to antihypertensive treatment and will uniquely position Dr. Martin for a career that allows her to make a significant contribution to slowing the progression of CVD for high-risk children born to mothers with HDP and other exposures.
