Chronic hypertension in pregnancy

: Evaluating mechanism and treatment in an ethnically diverse group to assess factors contributing to maternal and perinatal outcome

Abstract

This thesis examines maternal and perinatal outcomes in pregnancy complicated by chronic hypertension. National guidance highlights the paucity of data from randomised controlled trials to guide choice of antihypertensive treatment for chronic hypertension in pregnancy. I performed a systematic review/meta-analysis of all randomised controlled trials comparing antihypertensive agents to non-active treatment/other antihypertensive agents for treatment of chronic hypertension in pregnancy. I demonstrated that antihypertensive agent use was associated with substantial reduction in the incidence of severe hypertension, but no significant differences in other maternal/perinatal outcomes were observed. The pathophysiology underpinning the increased risk of adverse maternal/perinatal outcome in women with chronic hypertension is poorly understood and likely to be multifactorial. I undertook a cohort study of 4481 pregnancies in women with chronic hypertension and assessed the impact of maternal characteristics on adverse perinatal outcome. Black ethnicity was strongly associated with adverse perinatal outcome. I conducted a randomised controlled feasibility study to compare labetalol and nifedipine for treatment of chronic hypertension in pregnancy. Feasibility of recruitment was confirmed and effectiveness of labetalol and nifedipine to control mean blood pressure to target examined. Outside pregnancy, Black women are recommended calcium-channel blockers as first-line antihypertensive treatment. I observed differences in treatment effect between ethnic groups and highlighted areas requiring further investigation. A nested mechanistic study within the trial demonstrated differences in placental/renal biomarker concentrations in women who developed superimposed pre-eclampsia, compared to those who did not, and between women of Black ethnicity compared to non-Black. Additional assessment of maternal vascular function across gestation showed no differences by ethnicity, but longitudinal variation in brachial blood pressure, central aortic pressure, pulse wave velocity, and augmentation index were demonstrated in women with chronic hypertension who developed adverse pregnancy outcome (superimposed pre-eclampsia and in those delivering small for gestational age infants) compared to those who did not.

Date of Award	2017
Original language	English
Awarding Institution	King's College London
Supervisor	Lucy Chappell (Supervisor)