Magister Curationis - MCur / The objectives of this study were to determine midwives’ knowledge in performing foetal heart rate monitoring, to assess midwives’ abilities in the interpretation of foetal heart rate patterns according to their years of clinical experience as a registered midwife.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Magister Curationis - MCur / Despite the awareness of the importance of initiating antenatal care in the first trimester of a pregnancy (before 12 weeks gestation), late initiation of antenatal care (on or after 24 weeks of gestation) remains a common trend amongst pregnant women. The late initiation of antenatal care poses such a risk, to both the pregnant women and their unborn babies that it can contribute to maternal and foetal mortality and morbidity. The late initiation of antenatal care, an entirely avoidable occurrence, has an impact on targets set by the United Nations Millennium Development Goals (MDGs), now focusing on the Sustainable Development Goals (SDG‟s) set out by the United Nations. This study aim to investigate the factors which contribute to and cause the late initiation of antenatal care in pregnant women in a region in the Western Cape. Aim: The aim of this study was to investigate the factors that influence pregnant woman and contribute to late initiation of antenatal care (after 24 weeks gestational age) in one health facility/district in Cape Town. The findings of the study identified possible factors that may cause pregnant women to initiate antenatal care late in pregnancy and these findings could facilitate planning and possible interventions targeting the importance of early initiation in the community.

Reproduction de : Thèse d'exercice : Médecine. Médecine générale : Nantes : 2009. / Bibliogr.

This dissertation considers faunal recoveries from a selection of archaeological sites located in the Canadian Northeastern Plains that date between AD 1000 and 1600. These faunal assemblages derive from three different archaeological cultures that are thought to reflect different subsistence orientations. The analysis quantifies this variability by assessing the taxonomic abundance and intensity of bone processing evident in the recoveries. At issue is determination whether variability in the faunal assemblage reflects differences in subsistence economy deriving from the diverse origins of these societies. This requires control over other potential contributors to variability. This includes ecological comparability of the site localities, consistency of excavation, sampling and analytic methods, and similarities in site function. Particularly important is determination that the selected sites reflect comparable seasons of site occupation. This latter consideration is important since the established archaeological and ethnological literature suggests that both available resources and the economic orientation of resident populations varied significantly with season. To this end, a major research component focused on the development of more refined means of determining the season of site occupation by measuring the degree of osteological development of recovered foetal bison bones. The creation of linear regression equations based on these measurements will allow applied archaeologists to establish season of site occupation without the need for a large, difficult to obtain foetal bison comparative collection. The analysis suggests the variability in the faunal assemblages occurs independently of site cultural affiliation, and might reflect economic activities conditioned by more finely divided seasonal divisions than is apparent with the conventional four-season model deriving from agrarian European societies. Aboriginal language markers, specifically moon-names, were used to identify significant biophysical and bison reproductive events. By placing the six sites within Aboriginal concepts of seasonality, animal food subsistence choices are better understood. These results have implications for the classification scheme archaeologists have used to define subsistence strategies.

Abstract Experiments in this thesis were conducted to investigate the possibility of bestowing lambs with increased resistance to gastrointestinal parasites through maternal protein and copper supplementation. Reproductive outcomes such as birth weight, haematological parameters and faecal egg counts were used as indices of possible foetal programming. This thesis involved 5 experiments. The first three experiments were done using rats as a preliminary study animal on account of their short generational intervals and high fecundity. The final two experiments involved Merino sheep. The first experiment in Chapter 4 investigated the most optimum larval dose to use in order to elicit a measurable immune response. Weaned offspring were infected with a rat nematode, Nippostrongylus brasiliensis and their response measured by faecal egg counts, parasite recovery from intestines at sacrifice, spleen weights and leucocyte numbers, especially manifested as eosinophilia. There was no significant difference in parasite rejection for rats infected with 1000 larvae/rat. When rats were infected with variable larval doses to determine the optimum dose rate, eosinophilia and spleen weight were significantly increased as dose rate increased from 500 L3 to 2,000 larvae. Based on these results, it was decided to use 1,000 larvae for each rat in Chapter 6. The experiment in Chapter 5 involved feeding diets with 5 graded concentrations of copper (Cu) ranging from deficient (1 ppm diet) to high (16 ppm diet). Rats were fed for 4 weeks before mating after which half of them were sacrificed to determine liver Cu concentrations and haematological parameters. The rest were mated and maintained on their respective Cu diets into the second trimester of pregnancy. Pregnant females were sacrificed on approximately gestational Day 10 to recover foetuses and determine the incidence of foetal defects, foetal Cu status as well as maternal liver copper status. It was determined that most morphological defects occurred for the 1 ppm foetuses and both 2 ppm and 4 ppm had similar incidences of brain enlargements. The 16 ppm copper diet was excessive evidenced by reduced liver iron status and erythrocyte counts to similar levels as for 2 ppm rats although it had no adverse effect on foetal development. Significant differences were found for liver Cu status, erythrocyte counts and spleen weights due to the copper diets. A deficient copper diet containing 1 ppm Cu (LC) and an adequate diet containing 8 ppm Cu (SC) were used for the last rat experiment in Chapter 6 which was funded by the Science and Innovation Award. The LC diets were fed for 4 weeks prior to mating. Rats were then fed LC throughout pregnancy, for the 1st trimester only or for the 1st and 2nd trimesters. Other pregnant females were fed the SC diet throughout pregnancy. Offspring were challenged with 1000 L3 N. brasiliensis and their immune responses measured. Copper deficiency at variable stages of prenatal development caused significant postnatal mortalities but had no effect on response to parasite resistance. However, significant parasite and sex effects were found for parameters such as spleen weight, eosinophilia and weight loss during infection. The foetal brain enlargement caused by the deficient 1 ppm Cu diet was determined to be reversible in vivo upon exposure to a normal 8 ppm Cu diet during gestation. Chapter 7 involved Merino ewes which were fed either a high protein diet (21%) or adequate protein diet (12%) during the first 2 trimesters of pregnancy. Production parameters measured included pregnancy weight gain, fleece yield, protein content in milk as well as birth weight of lambs but none were significantly different. After weaning, the lambs were experimentally infected with 10,000 Haemonchus contortus larvae. Barber’s pole worm is responsible for millions of dollars in production losses in the sheep industry. Responses measured were eosinophilia, faecal egg count, anaemia (PCV) and weight gain/loss during the infection period. No significant differences were found for any parameter tested except for a parasite effect on erythrocyte numbers and PCV. In Chapter 8 Merino ewes were used which were mildly Cu deficient due to grazing on pasture that was copper deficient. Control ewes were supplemented with copper oxide wire particles at mating and mid-pregnancy. The rest of the experiment was the same as for Chapter 7 in terms of Barber’s pole worm larval dose. There were no significant differences in birth weight, weaning weight or ewe fleece weights due to copper status. There were no differences in parasite resistance in the lambs due to maternal Cu status measured by live weights, eosinophil concentrations or faecal egg counts. In conclusion, foetal programming by maternal nutritional supplements for postnatal parasite resistance appears to be impossible. It may be that if a different organ was targeted, such as the spleen, the results would have been different. The thymus appears to be non-programmable during foetal development in rats and sheep. However, it was a worthwhile attempt at conferring resistance to parasites in lambs due to the urgency in combating the global problem of parasite resistance to anthelmintics and the resultant large economic losses that are experienced by the global sheep industry.

>Magister Scientiae - MSc / The discovery of cell free foetal DNA (cffDNA) in 1997 allows for the combination of accuracy as well as non-invasiveness for prenatal diagnosis. This non-invasive genetic test requires only a maternal blood sample from which the cffDNA can be isolated and analysed. In this work cffDNA was isolated from a maternal blood sample using a micro-fluidic device which was fabricated using hot embossing and laser ablation techniques. The DNA sample was first pre-concentration by electrokinetic trapping (EKT) and then isotachophoresis (ITP). The concentrated sample was then separated by size using capillary electrophoresis (CE), all in a single device. All parameters and processes concerned with the micro-fluidic device were optimised sequentially. These parameters include both the chemical components as well as the physical processes which occur. The DNA used for the optimisation protocol was analysed using fluorescence spectroscopy, agarose gel electrophoresis as well as an Agilent Bioanalyser. The optimised protocol included a 9% acrylamide/pDMA matrix, 3 M N,N-dimethylurea as a denaturing agent, with tris based buffers for pre-concentration steps and 1X TBE (tris/borate/EDTA) buffer for capillary electrophoresis. The applied voltage of ITP was 300 V and CE was carried out at 180 V. The timing at which DNA was extracted from the device was kept at time = 60 s intervals. The optimised protocol was then used for real sample analysis and these samples were obtained from mothers pregnant with male foetuses. The DNA extracted from the micro-fluidic device was then analysed using real time PCR (RT-PCR) in order to distinguish which was maternal and which was foetal. This was carried out by amplification of male and general (present in male and female) genes respectively. RT-PCR results confirmed that only the male specific gene was amplified in initial samples exiting the device and it was thus successful in isolating cffDNA from a maternal plasma sample.

Magister Pharmaceuticae - MPharm / Gestational diabetes mellitus (GDM) is a condition that affects pregnant women and is one of the most common complications related to pregnancy. According to the World health organisation (WHO), the usual window for diagnosing GDM is between 24 and 28 weeks of gestation and the primary aim of diagnosing gestational diabetes is to identify women and infants at risk of short- or longer-term adverse outcomes. Recent results from the hyperglycaemia and adverse pregnancy outcome (HAPO) study have suggested that even mild levels of hyperglycaemia can have adverse effects on foetal outcomes but there are uncertainties about the prevalence of these outcomes in GDM diagnosed according to the latest WHO 2013 guideline and/or IADPSG 2010 criteria in diverse populations. GDM prevalence has been studied by different researchers, but the prevalence of adverse foetal outcomes in GDM diagnosed based on the latest WHO 2013 guideline and/or IADPSG 2010 criteria have not yet been explored except for the data published by the HAPO study. Due to the lack of sufficient knowledge on foetal outcomes in GDM, this study was conducted to review the evidence on the prevalence of adverse foetal outcomes in GDM diagnosed according to WHO 2013 guideline and/or the IADPSG 2010 criteria. Different databases including PubMed, Science Direct, Google Scholar and CINAHL as well as bibliographic citations were searched using a well-formulated search strategy to find the relevant observational studies (prospective/retrospective cohort and case-control) using explicit inclusion and exclusion criteria. The following search terms were used, “gestational diabetes”, “pregnancy”, “adverse fetal outcomes” and “adverse foetal outcomes”. The findings of this study were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the obtained data analysed using MetaXL ® version 5.3. This review was registered online on PROSPERO, the International prospective register of systematic reviews (registration number: CRD42020155061). Fifteen studies with 88,831 pregnant women (range: 83-25,543 participants) from 12 countries around the world were identified, with a wide variation in the prevalence of foetal outcomes in GDM using the stipulated criteria. These studies were unevenly distributed geographically as six of them were conducted in Asia, four in Europe, four in North America, one in Australia and none in Africa, Antarctica and South America. A meta-analysis found that the overall prevalence of foetal outcomes ranged from 1% (perinatal mortality) to 11% ( large for gestational age). The finding is limited due to the paucity of data on the prevalence of foetal outcomes in GDM. However, more studies using these criteria in low- and middle- income countries (LMICs) are needed by health care providers, to inform practice and allocate resources for control of GDM and its adverse foetal outcomes in diverse settings and ethnic groups, especially in LMICs.

In an attempt to determine mechanisms of certain aspects of ethanol- induced fetal damage, I have established a mouse model of the fetal alcohol syndrome based on the work of Chernoff (1977), using inbred C3H mice. Ethanol or its metabolite, acetaldehyde, was administered to female mice prior to and throughout gestation. Ethanol in doses of 6%, 10% and 20% ethanol derived calories and acetaldehyde 3. 9 mg and 11. 8 mg were administered daily in a nutritionally balanced liquid diet. An acute dose study was also undertaken, in which pregnant C3H mice were given. "binge" doses of 1ml of a 7. 35% solution of ethanol, twice daily through an orogastric tube, on days one and eight or four and twelve of gestation. The mice were sacrificed on day eighteen of gestation and the fetuses weighed and examined macroscopically. Some were sectioned using Wilson's method of free-hand razor blade sectioning (Barrow and Taylor, 1969), and the skeletons of the others were examined using a modified Dawson's method of skeletal preparation (Richmond and Bennett, 1938). A separate in vitro model based on the work of New (1967) was established, in which embryos of eight or nine days' gestation were explanted with visceral yolk sac intact from normal C3H mice. They were cultured for twenty-eight hours in rat serum containing various concentrations of ethanol or acetaldehyde (ethanol 1500, 3000 and 6000mg/l and acetaldehyde 7.4, 19. 7 and 39.4mg/l). During the last four hours of the culture period the embryos were labelled with one microcurie of tritiated thymidine (specific activity 5curies/mmol). At the end of the culture period the embryos were assessed morphologically, and then prepared for liquid-scintillation counting to determine DNA synthesis by measuring tritiated thymidine uptake. Small numbers of embryos from each group were used for autoradiographic studies in an attempt to quantitate the uptake of label in the various parts of the embryo. I found that ethanol given in chronic dosage in vivo was embryotoxic in all three doses studied. There was no evidence of ma tern al toxicity other than hyperactivity at the highest dose used and maternal jaundice in a small number of the 10% EDC and 20% EDC mice. Acetaldehyde given in chronic dosage in vivo produced no toxic effects on mothers or fetuses, other than a reduction in placental weights. Acute "binge" ethanol dosage of mothers on days one and eight or four and twelve of gestation did not appear to have any adverse effects on mothers or fetuses, apart from changes in placental weights. These findings should be viewed with caution, as the in vitro studies did not produce a corresponding result. In the latter study there was a marked time-related response, particularly for acetaldehyde. Ethanol given in vitro produced little evidence of toxicity except at dose levels which in the corresponding in vivo situation were extremely toxic to the mothers. Acetaldehyde, given in vitro in minute fractions of the harmless doses given to mothers in vivo, proved to be highly toxic to 8-day embryos and relatively non-toxic to 9-day embryos. This difference in sensitivity indicates that there must be some protective factor intervening between eight and ten days gestation - possibly the developing placenta may have a role here. From these findings I would suggest that acetaldehyde is a true teratogen, and the abnormalities produced in the chronic ethanol in vivo study were probably largely due to the action of acetaldehyde.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24132号 / 医博第4872号 / 新制||医||1059(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 平井 豊博, 教授 湊谷 謙司, 教授 羽賀 博典 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM