Doctoral Degrees (Obstetrics and Gynaecology)

Permanent URI for this collection

https://scholar.sun.ac.za/handle/10019.1/3778

Browse

Browsing Doctoral Degrees (Obstetrics and Gynaecology) by browse.metadata.advisor "Tong, Stephen"

Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    The Preeclampsia intervention with Esomeprazole (PIE) trial: A double blind, randomised, placebo-controlled trial to treat early onset severe preeclampsia
    (Stellenbosch : Stellenbosch University, 2019-04) Cluver, Catherine Anne; Theron, Gerhardus Barnard; Walker, Susan; Tong, Stephen; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Obstetrics and Gynaecology.
    ENGLISH ABSTRACT: This body of work addresses the clinical dilemma posed by preterm preeclampsia. Firstly, we tested a potential therapeutic (esomeprazole) for the treatment of early preterm preeclampsia in a double-blind randomised controlled trial. The primary outcome of interest was prolongation of gestation, with secondary outcomes including maternal and perinatal outcomes. Importantly, this study was underpinned by extensive pharmacokinetic and biomarker studies on both plasma samples and placental tissue. We found that a daily dose of 40mg of esomeprazole did not prolong pregnancy in early preterm preeclampsia and there were no differences in maternal or neonatal outcomes or markers of endothelial dysfunction. The esomeprazole concentrations that were observed in our participants were within the lower range of concentrations used in our preclinical in vitro studies. We therefore concluded that 40 mg may not have been sufficient to have efficacy in treating preterm preeclampsia, and future studies should consider the role of a higher dose or intravenous administration, which has a higher exposure over time and peak concentration. Secondly, we assessed the impact of coexisting fetal growth restriction on pregnancy latency, obstetric, maternal and perinatal outcomes among women undergoing expectant management of early preterm preeclampsia. We found that the latency-to-delivery interval was significantly shorter among pregnancies with coexisting fetal growth restriction. These pregnancies were less likely to reach 34 weeks gestation and more likely to be delivered for suspected fetal compromise. More women with coexisting fetal growth restriction underwent an emergency caesarean section without a trial of labour induction and of those considered eligible for induction of labour, the rate of emergency caesarean section was higher among those with fetal growth restriction. Postnatally, the presence of coexisting fetal growth restriction was associated with a higher rate of postnatal death and necrotising enterocolitis. Interestingly, the rate of maternal complications did not differ between the groups. We concluded that coexisting fetal growth restriction, diagnosed at the same time as preeclampsia, is an important determinant of pregnancy outcome among women being managed expectantly for early preterm preeclampsia Thirdly, we sought to determine the role of expectant management of preeclampsia and the hypertensive disorders of pregnancy after 34 weeks gestation by assimilating the available data in a Cochrane systematic meta-analysis. Based on the limited data available, maternal outcomes appear better with planned early delivery for hypertensive disorders after 34 weeks’ gestation, but it is unclear whether this is associated with increased risks for the baby, especially at earlier gestations. It was not possible to determine whether planned early delivery was beneficial for different hypertensive conditions, particularly preeclampsia. We concluded that further studies are needed, preferably with reliable characterisation of hypertensive disease sub-types, to determine the ideal timing of delivery to optimise maternal and perinatal outcomes for hypertensive disorders of pregnancy occurring after 34 weeks gestation. This research provides new information about a candidate therapeutic for the treatment of preeclampsia. Clinical aspects of the hypertensive disorders of pregnancy that could further improve management are also discussed.