- ItemA critical analysis of preterm birth in a largely homogeneous community near Tygerberg Academic Hospital with a high prevalence of preterm birth(Stellenbosch : Stellenbosch University, 2022-11) Brink, Lucy Theresa; Odendaal, Hendrik Johannes; Hall, David Raymond; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Obstetrics and Gynaecology.ENGLISH ABSTRACT: There is a high priority to address the heavy burden of preterm birth (PTB) on a low- to middle- class community in the Western Cape Province of South Africa (SA), where the Safe Passage Study (SPS) by the PASS Network was conducted. The latter study was undertaken to determine the role of alcohol consumption in stillbirths and sudden infant deaths. We documented a high rate (13.8%) of PTB in that community. Preterm birth (birth before 37 weeks) is one of the most common causes of perinatally related deaths at Tygerberg Academic Hospital (TAH), the tertiary referral hospital for the community. Complications of PTB also account for 75% of perinatal mortalities and more than 50% of chronic infant morbidities and therefore remains one of the greatest challenges in obstetrics. Perinatal outcome is particularly susceptible to socioeconomic conditions that have profound effects on the health of individuals and communities. SA has one of the highest levels of alcohol consumption (including binge drinking i.e. drinking four or more standard drinks during one sitting) as well as concomitant smoking in certain communities. Individuals with low socioeconomic status experience greater exposure to stress and are more likely to engage in risk-taking behaviours such as smoking, drinking and drug use during pregnancy, which may contribute to adverse birth outcomes. Despite the attention given to PTB in medical research, the aetiology remains largely unexplained, and placental pathology may illuminate the clinical understanding thereof. Increasing evidence indicates that placental dysfunction is an important risk factor for PTB, but contexts differ and information from low-income-countries is lacking.
- ItemThe impact of HIV status on staging, treatment and outcomes in locally advanced cervical carcinoma(Stellenbosch : Stellenbosch University, 2019-12) Simonds, Hannah; Botha, Matthys Hendrik; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Obstetrics and Gynaecology.ENGLISH ABSTRACT: Cervical carcinoma is one of the most frequently diagnosed malignancies in women in many countries in sub-Saharan Africa, including South Africa. In sub-Saharan Africa, among women without HIV the age-standardised cervical cancer incidence rate is greater than 40 per 100 000. However, women infected with both the human-immunodeficiency virus (HIV) and the human papilloma virus (HPV) have a higher risk of developing cervical carcinoma than women infected with HPV alone. Published studies of the ideal staging methods, treatment algorithms, and outcomes for women with comorbid locally advanced cervical carcinoma and HIV are scarce. The aim of this body of work is to fill some of these gaps. We conducted four cohort studies of patients with locally advanced cervical carcinoma with or without HIV, recording demographic data, staging information and treatment delivered. Additional information gathered for individual studies included treatment response and survival outcomes. We evaluated the statistical significance of differences between HIV-positive and negative patients. Logistic regression models were utilised to evaluate risk for toxicity, treatment response, and survival outcomes. In the first of three retrospective cohort studies, among 383 patients, early response to chemoradiation was found to be related to advanced stage [OR 2.39, 95% CI 1.45-3.96] and completion of brachytherapy [OR 3.14; 95% CI 1.24-7.94] but not HIV status. In the second retrospective study, among 213 patients undergoing radical radiotherapy, acute Grade 3 / 4 toxicity was associated with receiving chemotherapy [OR4.41; 95%CI 1.76- 11.1; p 0.023] and having HIV [OR 2.16; 95% CI0.98-4.8; p 0.05]. In a prospective study of 492 patients, OS at 5 years was 49.5% (95%CI; 44.6% - 54.4%) among HIV-negative patients but only 35.9% (95% CI; 23.9% - 48.0%) among HIV-positive patients (p=0.002). In our Cox models, factors affecting outcome were HIV infection, stage IIIB disease, hydronephrosis, and delivery of concurrent chemotherapy. In the fourth cohort study, among 273 patients with locally advanced cervical carcinoma who underwent a radiotherapy planning PET-CT scan, overall 235 (84.5%) were upstaged. Upstaging was not associated with HIV status (HIV-negative 83.9% vs HIV-positive 87.2%; p=0.47). Following the PET-CT scan, among the 263 patients who attended for radiotherapy treatment, intent changed for 124 patients (46.3%): 53.6% of HIV-positive patients and 42.9% of HIV-negative patients (p=0.11). This body of work demonstrated that in HIV-positive patients, integration of PET-CT into staging algorithms for cervical carcinoma is a viable option. During treatment HIV-positive patients experienced increased toxicity, but most were able to complete treatment, and their 5-year overall survival was nearly 40%. Among women with locally advanced cervical cancer, those with HIV infection should be treated with the best standard of care. Future research should focus on factors that improve outcomes for these women.
- ItemThe 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.
- ItemThe contextual quality of life of women with cervical cancer in the Western Cape, South Africa.(Stellenbosch : Stellenbosch University, 2018-12) Du Toit, George Campbell; Kruger, T. F.; Stellenbosch University. Faculty of Medicine and Health Science. Dept. of Department of Obstetrics and Gynaecology.ENGLISH ABSTRACT: Please refer to full text for abstract
- ItemComparing the diagnosis of gestational diabetes using the oral glucose tolerance test and a designed breakfast in a randomised, cross-over trial(Stellenbosch : Stellenbosch University, 2017-12) Marais, Colin; Hall, David Raymond; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.ENGLISH ABSTRACT: Objective This study compared a standardised, user-friendly designed breakfast (DB) to the 75g OGTT, comparing venous and capillary glucose values for the diagnosis of gestational diabetes. Methods 6 prospective, randomised, cross-over trial comparing the gold standard OGTT to a designed breakfast glucose profile (DBGP) in the diagnosis of gestational diabetes, was performed from March to December 2015. Fifty-one patients, attending the high-risk antenatal clinic at Tygerberg Hospital, were randomised to OGTT or DBGP at baseline. One week later, before intervention, the alternative test was performed. Fasting and 2-hour, venous and capillary values were measured. Patients qualified for screening on risk factors: previous gestational diabetes, previous unexplained intra-uterine death, previous macrosomic baby, booking BMI >40 kg/m2, age >40 years, affected first degree relative, susceptible family origin (Asiatic), acanthosis nigricans and polycystic ovarian syndrome. Results Fasting and 2-hour capillary glucose values measured during the OGTT correlated significantly with laboratory venous samples (Pearson's 0.74; p <0.001 at both time intervals). The 2-hour capillary glucose values obtained for the DB showed satisfactory correlation to the current gold standard OGTT (Pearson's 0.54; p <0.001). Conclusions The designed breakfast glucose profile provides a user-friendly, sufficiently accurate, promising alternative to diagnose GDM that deserves further investigation.