Common, complex disorders are polygenic and multifactorial traits representing interactions between environmental, genetic and epigenetic risk factors. More often than not, contributions of these risk factors have been studied individually and this is especially true for complex reproductive traits where application of genomic technologies has been challenging and slow to progress. This thesis explores the potential of genetic and epigenetic components contributing to a better understanding of the biological pathways underlying disease risk in two specific female complex reproductive traits - polycystic ovary syndrome (PCOS) and preterm premature rupture of membranes (PPROM). The PCOS projects focus on characterization of a gene, DENND1A, whose association to PCOS has been established by Genome Wide Association Studies (GWAS) and is known to contribute to PCOS steroidogenic phenotype. In addition, differential microRNAs expression contributing to DENND1A expression regulation in PCOS theca cells was identified. The studies on PPROM utilize a Whole Exome Sequencing approach to identify rare variants in fetal genes contributing to extracellular matrix composition and synthesis contributing to PPROM risk. The results suggest that fetal contribution to PPROM is polygenic and is driven by a significant genetic burden of potentially damaging rare variants in genes contributing to fetal membrane strength and integrity. Tissue and location specific expression patterns of the Chromosome 21 miRNA cluster (miR-99a, miR-125b, let-7c) in fetal membranes from term pregnancies with spontaneous rupture were investigated. The results suggest that these miRNAs play potential roles in fetal membrane rupture and fetal membrane defects associated with T21.

A dissertation submitted to the Faculty of Health Sciences, University of Witwatersrand, Johannesburg in fulfillment of the requirements for the degree of Master of Science in Medicine, Johannesburg , 2013 / South Africa’s Prevention of Mother-to-Child Transmission (PMTCT) programme is critical for eliminating vertical HIV transmission and reducing infant mortality. Early treatment of HIV-infection to curb infant deaths requires earlier diagnostic testing than the currently recommended six-week test. This study describes the continuum of PMTCT care at a Johannesburg hospital to identify interventions for improvement and investigates birth HIV testing for infants. Data from a cohort study at the hospital evaluating diagnostic assays in HIV-exposed infants were collated with routine clinical data, validated and analysed. Among 838 mother-infant pairs, 38% of mothers attended antenatal clinics early enough to receive optimal antenatal prophylaxis. Only 72% of infants accessed six-week testing at the hospital; a further 10% underwent testing elsewhere. Of 38 HIV-infected infants, 29 were infected in-utero and could have been identified at birth (sensitivity of 76.3% for birth testing), compared to only 26 (68%) diagnosed by six-week testing at the hospital. Majority (88%) of these 26 infants accessed antiretroviral therapy, but treatment was only initiated at a median age of 16.0 weeks and 43% of HIV-infected infants who initiated treatment had defaulted or died before the end of the study. Mathematical modelling demonstrated that birth testing would be superior to a six-week test to maximise infants diagnosed and life years saved, with the ideal algorithm being a birth and ten-week test. The PMTCT programme can be enhanced by earlier antenatal care for women and earlier infant diagnosis. Birth testing would diagnose HIV-infection before infants die or default from the PMTCT programme, thereby enabling effective monitoring of MTCT, and would allow earlier treatment initiation to reduce early infant mortality.

Este trabalho trata da interrupção da gestação, em casos de diagnóstico de malformação fetal letal e os processos psíquicos dela decorrentes. São feitas algumas considerações sobre os aspectos históricos e políticos da reprodução e da sexualidade, explorando, em seguida, aspectos relativos ao contexto cultural do aborto; o debate sobre o início da vida humana; questões da bioética e da legislação. O trabalho explora, ainda, questões sobre a legislação brasileira, Medicina Fetal e os processos psíquicos desencadeados a partir do diagnóstico de anomalia fetal letal. Foi desenvolvida uma pesquisa de campo, na Divisão de Clínica Obstétrica do Hospital das Clínicas da FMUSP, para aprofundar as questões teóricas discutidas. No período de agosto de 1998 a dezembro de 2003, foram realizadas entrevistas abertas com 249 mulheres, após terem recebido o diagnóstico de malformação fetal letal e entrevista semidirigida com trinta e cinco destas pacientes após a interrupção da gravidez. Este trabalho tem como objetivos específicos: identificar os processos psíquicos desencadeados nas mulheres, após o diagnóstico de malformação fetal letal; no processo de decisão pela interrupção judicial da gravidez; após a interrupção da gravidez; e identificar, na opinião das mulheres que receberam o diagnóstico de malformação fetal letal e que realizaram a interrupção da gestação, qual o papel da consulta psicológica nesse processo. A análise dos dados se deu de forma quantitativa e qualitativa. Os resultados obtidos versam tanto sobre o momento do diagnóstico como experiência que propicia um caos temporário com perda do raciocínio lógico, não permitindo reflexões imediatas. Demonstra as angústias vivenciadas no processo de decisão pela interrupção ou manutenção da gravidez, apresentando o processo de reflexão como de fundamental importância para decisão consciente e para posterior satisfação com a decisão tomada. O acompanhamento psicológico foi destacado como de fundamental importância para elaborar a situação vivida. Conclui que o diagnóstico de malformação fetal letal ativa mecanismos de defesa para manutenção do equilíbrio psíquico. O processo de decisão pela interrupção da gravidez deve ser acompanhado por um psicólogo para que ocorra revisão dos valores morais e culturais permitindo uma decisão adequada que visa minimizar o sofrimento vivido. / This research is about the termination of pregnancy in situations where lethal fetal malformation has been diagnosed, and the psychic process that the patient goes through in these cases. The study was done with some consideration for the historical and political process of reproduction and sexuality, exploring aspects about the cultural context of abortion, the beginning of human life, issues about bioethics, and specific Brazilian laws on abortion. It discusses the point of view of the Catholic Church on the termination of pregnancy. This research also explores questions about Brazilian laws, fetal medicine, and the psychic processes triggered after the diagnosis of fetal anomaly. This study was performed at the Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo, in the Department of Obstetrics Between august, 1998 and December, 2003 open interviews was performed with 249 women after they have been diagnosed with lethal malformation of the fetus, and semi-direct interviews with 35 women after their pregnancy had been terminated. The objective of this research was not only to identify the psychic process women undergo after the diagnosis of lethal fetal malformation, during the decision-making process for the judicial intervention in the pregnancy, and after the termination itself; but also to know their opinion about the function of the psychological consult in this process. The data analysis was quantitative and qualitative. The results show that the moment of the diagnosis is an experience that creates a temporary chaos that deprives logical reasoning, and this situation does not allow an immediate decision. It shows the distress experienced in the decision-making process, showing that a reflective process is essential to the conscious decision and to being satisfied with the decision once it has been made. The psychological follow-up was determined to be of essential importance to understanding this situation. The study concludes that the diagnosis of lethal malformation of the fetus triggers a defense mechanism to maintain the psychic equilibrium. A psychologist must follow the process of the decision through to the termination of the pregnancy in order to provide a moral and cultural reflection leading to the correct decision and minimizing the emotional distress for the patient.

This dissertation had three primary aims. The first aim was to systematically review evidence documenting incidence of sexually transmitted infections (STI) during pregnancy. Eighteen papers were included in the final review which reported incidence of five STIs: chlamydia, gonorrhea, human papillomavirus (HPV), herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV). The review found that there are very limited data on incidence of STIs during pregnancy and even fewer data comparing risk between pregnant and non-pregnant women. Although data are limited, studies suggest that women continue to acquire STIs during pregnancy, with incidence varying by type of infection, population of interest and geographic setting. Highest incidence was found for HPV and chlamydia although some studies of chlamydia showed low proportions of pregnant women infected. Studies in which partners were known to be infected with HSV-2 and HIV showed higher rates of acquisition in pregnant women compared to studies where partner status was not known. The second aim of this dissertation was to describe the impact of pregnancy on behavioral risk factors and vaginal practices that are associated with increased risk of STI acquisition. Data for this and the following aim came from the Methods for Improving Reproductive Health in Africa (MIRA) study, a randomized clinical trial conducted in South Africa and Zimbabwe 2003-2006. The analysis for the second aim included women in the MIRA trial who had a pregnancy during follow-up. Pregnancy was found to decrease sexual activity, particularly in the third trimester, but women were more likely to report sex without condoms while pregnant. There were lower reports by women during pregnancy of other risk factors for STI acquisition, including anal sex, concurrent sexual relationships and new sex partners. Vaginal wiping and insertion of material into the vagina, potentially important mechanisms for STI acquisition, were also less common during pregnancy. The data from this aim present a complicated picture of risk for STIs during pregnancy as a result of increased unprotected sex but decreased frequency of other known behavioral risk factors. The third and final aim of the dissertation was to measure incidence of four STIs in pregnant and non-pregnant women and to evaluate whether women are at greater risk during pregnancy for acquiring four STIs: chlamydia, gonorrhea, trichomoniasis and HIV. This analysis included 4,549 women 18-50 years of age, 17% (N=766) of whom had a pregnancy during follow-up. In general, women continued to be sexually active but reported less overall sex than non-pregnant women. Report of condom use was lower during pregnancy as were other types of high risk sexual behaviors, such as multiple sexual partners, sex in exchange for drugs or money and anal sex, as well vaginal practices. STI incidence was measured during pregnancy and it was found that women continued to acquire STIs when pregnant. In addition, during periods when women became pregnant, they appeared to be a high risk for acquiring chlamydia, trichomoniasis and HIV. Finally, in examining the association between pregnancy status and STI risk, we found that in multivariable models adjusted for demographic and time-varying self-reported behavioral risk factors and vaginal practices, pregnancy was not associated with increased STI risk. However in visit intervals when women became pregnant, they appeared to be at higher risk for contracting chlamydia compared to non-pregnant periods.

Este trabalho trata da interrupção da gestação, em casos de diagnóstico de malformação fetal letal e os processos psíquicos dela decorrentes. São feitas algumas considerações sobre os aspectos históricos e políticos da reprodução e da sexualidade, explorando, em seguida, aspectos relativos ao contexto cultural do aborto; o debate sobre o início da vida humana; questões da bioética e da legislação. O trabalho explora, ainda, questões sobre a legislação brasileira, Medicina Fetal e os processos psíquicos desencadeados a partir do diagnóstico de anomalia fetal letal. Foi desenvolvida uma pesquisa de campo, na Divisão de Clínica Obstétrica do Hospital das Clínicas da FMUSP, para aprofundar as questões teóricas discutidas. No período de agosto de 1998 a dezembro de 2003, foram realizadas entrevistas abertas com 249 mulheres, após terem recebido o diagnóstico de malformação fetal letal e entrevista semidirigida com trinta e cinco destas pacientes após a interrupção da gravidez. Este trabalho tem como objetivos específicos: identificar os processos psíquicos desencadeados nas mulheres, após o diagnóstico de malformação fetal letal; no processo de decisão pela interrupção judicial da gravidez; após a interrupção da gravidez; e identificar, na opinião das mulheres que receberam o diagnóstico de malformação fetal letal e que realizaram a interrupção da gestação, qual o papel da consulta psicológica nesse processo. A análise dos dados se deu de forma quantitativa e qualitativa. Os resultados obtidos versam tanto sobre o momento do diagnóstico como experiência que propicia um caos temporário com perda do raciocínio lógico, não permitindo reflexões imediatas. Demonstra as angústias vivenciadas no processo de decisão pela interrupção ou manutenção da gravidez, apresentando o processo de reflexão como de fundamental importância para decisão consciente e para posterior satisfação com a decisão tomada. O acompanhamento psicológico foi destacado como de fundamental importância para elaborar a situação vivida. Conclui que o diagnóstico de malformação fetal letal ativa mecanismos de defesa para manutenção do equilíbrio psíquico. O processo de decisão pela interrupção da gravidez deve ser acompanhado por um psicólogo para que ocorra revisão dos valores morais e culturais permitindo uma decisão adequada que visa minimizar o sofrimento vivido. / This research is about the termination of pregnancy in situations where lethal fetal malformation has been diagnosed, and the psychic process that the patient goes through in these cases. The study was done with some consideration for the historical and political process of reproduction and sexuality, exploring aspects about the cultural context of abortion, the beginning of human life, issues about bioethics, and specific Brazilian laws on abortion. It discusses the point of view of the Catholic Church on the termination of pregnancy. This research also explores questions about Brazilian laws, fetal medicine, and the psychic processes triggered after the diagnosis of fetal anomaly. This study was performed at the Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo, in the Department of Obstetrics Between august, 1998 and December, 2003 open interviews was performed with 249 women after they have been diagnosed with lethal malformation of the fetus, and semi-direct interviews with 35 women after their pregnancy had been terminated. The objective of this research was not only to identify the psychic process women undergo after the diagnosis of lethal fetal malformation, during the decision-making process for the judicial intervention in the pregnancy, and after the termination itself; but also to know their opinion about the function of the psychological consult in this process. The data analysis was quantitative and qualitative. The results show that the moment of the diagnosis is an experience that creates a temporary chaos that deprives logical reasoning, and this situation does not allow an immediate decision. It shows the distress experienced in the decision-making process, showing that a reflective process is essential to the conscious decision and to being satisfied with the decision once it has been made. The psychological follow-up was determined to be of essential importance to understanding this situation. The study concludes that the diagnosis of lethal malformation of the fetus triggers a defense mechanism to maintain the psychic equilibrium. A psychologist must follow the process of the decision through to the termination of the pregnancy in order to provide a moral and cultural reflection leading to the correct decision and minimizing the emotional distress for the patient.

Includes examples of information booklets as appendices / Includes bibliographical references: p. 232-251 / xiv, 251 p. : photo. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Community Medicine, 1994

Includes examples of information booklets as appendices Includes bibliographical references: p. 232-251

<p>Antenatal care has been associated with improved maternal and perinatal outcomes but there is no agreement on the most effective model in terms of content as well as the number and timing of visits. A cluster randomised controlled trial was conducted in a rural area of Zimbabwe to assess a 5-visit goal-oriented antenatal care model against standard care. In the same population was also determined the sensitivity of factors used for risk screening to predict pregnancy complications and the effectiveness of the referral system in managing women with identified risk markers or pregnancy complications. </p><p>Pregnancy records of 10 572 out of total 13 517 recruited women were available for analysis. The new model did not change the number of visits but resulted in better use of health care. The classical risk screening system had low predictive value and identified too large a risk group for referral. Nulliparous women had an increased risk for pregnancy complications whereas women with previous uncomplicated pregnancies were at low risk of complications even with high parity. Multiparous women with previous complications had an increased risk of complications but better utilisation of health care services for delivery reduced adverse perinatal outcomes. There was a functional referral system in Gutu and women complied with referral indications but efficiency of the system was reduced by failure of care providers to comply with referral recommendations. </p><p>Antenatal care can be improved in a rural setting through a focussed programme and the unpredictability of many pregnancy complications limits the value of antenatal risk screening. Until universal access to essential obstetric care facilities is attained in low resource settings, a critical re-examination of risk factors could avoid overburdening the referral system.</p>

Antenatal care has been associated with improved maternal and perinatal outcomes but there is no agreement on the most effective model in terms of content as well as the number and timing of visits. A cluster randomised controlled trial was conducted in a rural area of Zimbabwe to assess a 5-visit goal-oriented antenatal care model against standard care. In the same population was also determined the sensitivity of factors used for risk screening to predict pregnancy complications and the effectiveness of the referral system in managing women with identified risk markers or pregnancy complications. Pregnancy records of 10 572 out of total 13 517 recruited women were available for analysis. The new model did not change the number of visits but resulted in better use of health care. The classical risk screening system had low predictive value and identified too large a risk group for referral. Nulliparous women had an increased risk for pregnancy complications whereas women with previous uncomplicated pregnancies were at low risk of complications even with high parity. Multiparous women with previous complications had an increased risk of complications but better utilisation of health care services for delivery reduced adverse perinatal outcomes. There was a functional referral system in Gutu and women complied with referral indications but efficiency of the system was reduced by failure of care providers to comply with referral recommendations. Antenatal care can be improved in a rural setting through a focussed programme and the unpredictability of many pregnancy complications limits the value of antenatal risk screening. Until universal access to essential obstetric care facilities is attained in low resource settings, a critical re-examination of risk factors could avoid overburdening the referral system.

Title from PDF of title page. / Document formatted into pages; contains 62 pages. / Thesis (M.S.P.H.)--University of South Florida, 2003. / Includes bibliographical references. / Text (Electronic thesis) in PDF format. / ABSTRACT: Sudden Infant Death Syndrome (SIDS) is the third leading cause of infant mortality between birth and the first year of life in the United States. Along with the identication of various maternal risk factors, the role of fetal hypoxia has been hypothesized to be one of many causal factors associated with SIDS. The purpose of this study was to develop a profile of the SIDS infant and assess whether six pregnancy complications consistent with fetal hypoxia were associated with the increased outcome of SIDS. The secondary data analysis of Florida linked birth to death certificate data specific to Hillsborough County and Duval County were analyzed retrospectively for the period of time between 1998 and 2000. Of the 86, 342 births, 69 SIDS cases were identified, 34 in Hillsborough County and 35 in Duval County. / A majority of the infants were White males with an average age of death of 80 days. The Chi-Square test for Independence with Cramer's V, odds ratios and 95% confidence intervals were calculated to determine if an association existed between pregnancy complications, specific maternal risk factors and SIDS. Eclampsia was the only statistically significant prenatal complication found in this cohort (OR=4.67: 95% CI 1.49, 14.57). Maternal tobacco use (OR= 3.13: 95% CI 1.83, 5.36) and late initiation into prenatal care were also found to be significant in the SIDS cases, with the greatest risk occuring in women who did not receive prenatal care (OR=4.37: 95% CI 1.38, 13.89). These findings will assist with the development of a profile of infants who are at greater risk of dying of SIDS in Hillsborough County and Duval County as well as contribute to what is currently known about the association between fetal hypoxia and SIDS. / System requirements: World Wide Web browser and PDF reader. / Mode of access: World Wide Web.