Obstetrics and Gynaecology - Theses
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ItemImpact of new criteria for the diagnosis of gestational diabetes: a maternal and neonatal health outcome and economic analysis in a large tertiary level maternity centre( 2017)Background: The development of diabetes mellitus during pregnancy, referred to as gestational diabetes (GDM), is associated with adverse maternal and fetal outcomes. Routine screening for this condition is therefore undertaken in all pregnant women. In 2014, gestational diabetes underwent a more liberal diagnostic update, which has been widely adopted in Australia but not universally accepted internationally. Concerns around a rapidly increasing annual incidence and implications for costs and workloads have been raised, but they are assumed to have been offset by improvements in clinical outcomes. As one of the only large Western countries to have adopted universal screening under the new criteria, Australia is uniquely poised to assess the value of such a system change. Hypothesis: That the change in diagnostic criteria for gestational diabetes has resulted in improved clinical outcomes and equitable health economics. Aim: To compare an entire cohort of women and babies diagnosed with gestational diabetes in 2014 (under the original criteria) with those diagnosed in 2016 (under the updated criteria) and, in particular, to assess any improvements in outcomes, to attribute costs to the increased incidence and to assess any overall economic benefit. Methods: All women diagnosed with gestational diabetes in 2014 and in 2016 were included as cases. Control groups in each year were defined as those who underwent screening and had a negative test (pre-existing diabetes was thus an exclusion criteria). Women with multiple pregnancies were excluded from both cases and controls. Demographic data were collected from all groups. Maternal outcomes and fetal outcomes were selected to represent those reported in the studies upon which the new criteria are based. Three broad groups of outcome analyses were undertaken. Firstly, all women in 2014 were compared to all women in 2016 to determine whether the change in policy has caused a hospital-wide improvement in outcomes. Secondly, women with GDM in 2014 were compared to controls in 2014 and women with GDM in 2016 were compared to controls in 2016. Finally, women with GDM in 2014 were compared to women with GDM in 2016. In each analysis, women with GDM were examined as a whole and subdivided into diet-controlled and insulin-controlled. For the economic analysis, models of care for routine pregnancy, GDM diet-controlled and GDM-insulin controlled were costed using average-occasions-of-service for clinical reviews, pharmacy fees for medications and consumables, and Medicare Benefits Schedule item numbers for ultrasound services. Cost-savings were assessed using modelling of adverse outcome avoided based on relative-risk reductions published in the studies upon which the new criteria were based. Results: There was an increase in annual incidence for GDM from 6.0% to 10.4% with gross costs of care increasing by approximately $900 000 and nett costs of care by approximately $560 000. There was a small hospital-wide reduction in very large babies (>95% for birth weight) from4.31% to 3.61% with no other significant differences between 2014 and 2016. Women with GDM remain a higher risk cohort in both demographics and outcomes than those without GDM, but in 2016 women with GDM that is controlled by dietary measures alone represent a cohort with similar outcomes to women without GDM. Modelling for adverse outcomes avoided by the change in criteria did not reveal a cost-saving in the short-term. Conclusions: The new criteria for diagnosing GDM has resulted in a marked increase in annual incidence (73% relative, 4.4% absolute) without a significant improvement in maternal and neonatal outcomes. While small numbers of adverse outcomes are likely avoided, it is unlikely the potential short-term savings would outweigh the increase in costs if applying a high-risk model of care to all women with GDM. The new criteria may lead to long-term improvements in health of the mother and/or baby that are cost-effective but further research is required to substantiate this possibility. Future randomized controlled trials into different systems of diagnosis and less expensive models of care for mothers with GDM and their babies are also warranted.
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ItemMechanisms of insulin action and identification of defects leading to insulin resistance in maternal obesity and gestational diabetes( 2011)Obesity and type two diabetes mellitus (type II DM) significantly impact not only on the health and wellbeing of individuals, but also the healthcare system. Of particular concern is the alarming increase in childhood obesity and the associated increased risk of type II DM. Abnormalities in maternal metabolism, such as maternal obesity and gestational diabetes mellitus (GDM) may cause fetal metabolic re-programming, thus leading to long term consequences such as childhood obesity and the development of type II DM. As a consequence, understanding the changes involved in the intrauterine environment, governed by interactions with hormones, genetics, nutrition, and environmental factors, is essential in order to further our understanding of pregnancy related diseases and how they contribute to fetal growth. Insulin resistance develops during pregnancy as maternal metabolism is directed towards supplying adequate nutrients to the growing fetus. Low grade inflammation is associated with insulin resistance in pregnancy. Similarly, outside of pregnancy cytokines play a central role in the development of insulin resistance. Given that inflammation is said contribute to the insulin resistance in pregnancy, investigations into both inflammation and glucose metabolism were warranted. Studies have suggested the secretion of placental hormones may negatively regulate glucose metabolism and induce low grade inflammation during pregnancy. The placenta has an extraordinary capacity to synthesise hormones such as progesterone and human placental lactogen (hPL). During pregnancy, these hormones exert endocrine, paracrine and/or autocrine actions which may have immediate effects on placental function and peripheral tissues. Through the use of ex situ tissue explant cultures, the effects of progesterone and hPL on glucose metabolism and inflammation were investigated. Progesterone had no affect on the transduction of the insulin signalling pathway nor did it significantly affect glucose uptake in placenta (collected via Caesaren Section), adipose tissue or skeletal muscle. Additionally, progesterone had no effect on low grade inflammation in maternal or fetal tissues. In contrast, hPL inhibited glucose uptake and induced IL-6 and IL-8 release in both placenta and adipose tissue from NGT pregnant women, although it displayed no affect on skeletal muscle. Inhibition of glucose uptake induced by hPL was shown to work via activation of the prolactin receptor, while hPL-induced inflammation was inhibited by NF-kB. Overall, the data presented supports a role for hPL in regulation of glucose metabolism and inflammation in pregnancy, however no relationship exists between the two, but work via independent mechanisms. In summary, the data presented in this thesis demonstrate changes in glucose homeostasis observed in obese NGT and GDM mothers, are regulated by dysregulation of the insulin signalling pathway in both maternal and fetal tissues. Consequently, the intrauterine environment is vulnerable to fluctuations in maternal glucose homeostasis and may be a mechanism which underlies fetal re-programming. Finally this thesis demonstrates a role for hPL in the pathophysiology of insulin-resistance in pregnancy through its ability to interfere with both glucose uptake and induce low grade inflammation, however via independent mechanisms. This data adds insight into the cellular mechanisms which underlie pregnancy associated insulin resistant pathologies; however further expanding our knowledge is essential in the hope that one day, clinicians can ultimately better control glucose metabolism in pregnant women to provide better long term outcomes for mothers and offspring.