Conotruncal anomalies are the leading causes of cyanotic congenital heart disease. We attempted to use live xPlane imaging of ductal arch view and in-plane view of IVS to screen the fetal conotruncal anomalies in 200 fetuses. There were 152 normal cases, 25 conotruncal anomalies and 23 other types of fetal CHDs were involved in this study. The visualization rate of the normal ductal arch view and in-plane view of IVS with live xPlane imaging was 100% (152/152), 100% (152/152) in normal cases, 8% (2/25), 12% (3/25) in conotruncal anomalies and 69.7% (16/23), 73.9% (17/23) in non-conotruncal CHDs, respectively. The visualization rate of abnormal ductal arch and in-plane view in conotruncal anomalies was much higher than that in non-conotruncal anomalies (P<0.001). Therefore, it may be a useful tool for the assessment and diagnosis of fetal conotruncal anomalies. / In conclusion, real-time 3DE is a novel and promising technique to perform the prenatal examination, both the fetal heart and other system. It represents the future of 3D ultrasound and will become a useful tool for prenatal screening and diagnosis. / This thesis summarized real-time 3D ultrasound in obstetric application. With the introduction of matrix transducer, 3D scanning the fetus in real time became available. / We attempted to use real-time 3D ultrasound in obstetrics outside the fetal heart. We evaluated the feasibility of using real-time 3D ultrasound to assist in obtaining a true midsagittal view in first trimester. Eight sonographers, including FMF-certified and non FMF-certified operators, were asked to perform ultrasound examinations on five patients and forty patients were examined in total. It showed that the deviation from true midsagittal view was reduced greatly with the guidance of live xPlane imaging. Real-time 3D ultrasound can improve the accuracy of acquisition of a defined sonographic plane, and reduce the difference in performance between operators who are formally certified or not. / We demonstrated a novel method to visualize the aortic and ductal arch with live xPlane imaging. The visualization rate is 100%. Ductal arch view can be visualized by placing the reference line through pulmonary artery and descending aorta and aortic arch view can be acquired by putting the reference line along the transverse view of aortic arch and descending aorta on the 3VT view with live xPlane imaging. Therefore, live xPlane imaging is an easy and feasible method for real-time imaging of the ductal and aortic arch. / We explored the feasibility to perform the fetal heart screening using real-time 3DE with live xPlane imaging. We developed and reported the methodology of acquiring and examining the screening planes of the fetal heart with live xPlane imaging. The procedure was simple and straight. When performing the fetal heart screening with live xPlane imaging, we just need display the apical four-chamber view and mid-sagittal view of fetal upper thorax and other thing could be done by moving the reference line. The overall detection of four cardiac screen planes can reach 100%. / We explored to evaluate the entire fetal IVS with both live xPlane imaging and live 3D imaging. We can successfully assess the entire IVS in most fetuses (153/154). We also compared the images acquired by real-time 3DE and STIC in this thesis. It showed that less motion artifact encounters with real-time 3DE and the image quality of real-time 3DE is similar to STIC volume acquired from the sagittal view (P>0.05) and superior to STIC volume from the four-chamber view (P<0.05). Therefore, real-time 3DE can be used to display the lateral view of the fetal IVS, and potentially may be a useful tool for the assessment and diagnosis of fetal VSDs. / Xiong, Yi. / Adviser: Tzekin Lau. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 116-138). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Another attempt was made to identify CpG-rich paralogues on chromosome 21 for dosage analysis. Methylation profiles of 14 paralogous CpG-rich clusters were screened by bisulfite genomic sequencing and/or combined bisulfite restriction analysis. One of the paralogue pairs showed similar differential methylation patterns, and three other CpG-rich clusters located on chromosome 21 were hypomethylated in the placentas and completely methylated in the maternal blood cells. Detection methods for these novel epigenetic markers were described and discussed, and potential applications were also suggested. / In the second part of this thesis, a technique called digital PCR was used for detecting and quantifying cell-free fetal DNA in maternal plasma. DNA templates are first diluted to a single molecule level and partitioned to separate compartments before subjecting to polymerase chain reaction amplification. Quantification is then made by counting the number of positive reactions directly. Such a technique has allowed the reliable detection of fetal DNA from a high background of maternal plasma DNA, and allows absolute quantification of fetal DNA without using a calibration curve. As a proof-of-principle project, a non-polymorphism-based approach called digital relative chromosome dosage (RCD) method was developed to detect chromosomal imbalance in trisomic cases. The implementation of digital PCR was further facilitated with the technology of integrated fluidics circuits (IFCs), by which nanolitre volumes of reaction mixtures could be manipulated in a high-throughput manner. Such a microfluidics digital PCR system was evaluated systematically and shown to be highly accurate, precise and sensitive compared to other existing detection platforms. The technology has been applied with the RCD approach for rapid detection of trisomy 21 from amniotic fluid samples and 100% accuracy was attained. With the development of new universal markers and robust detection platforms, it is envisioned that circulating fetal DNA in maternal plasma can be applied to an expanding range of clinical applications in the near future. / The first part of my thesis focused on the discovery of new epigenetic markers for fetal DNA detection. Methylation profiles of 7 selected CpG islands on chromosome 21 were revealed by bisulfite sequencing, in the hope of identifying regions with differential methylation patterns between placentas and maternal blood cells. Out of the 14 sub-regions of these CpG islands, five displayed significant difference between the two tissue type and were promising marker candidates. / The presence of circulating fetal DNA in maternal plasma provides a non-invasive source of fetal genetic materials for prenatal diagnosis. Reliance on Y-chromosomal sequences for detecting fetal-specific signals from the background of maternal plasma DNA, however, has restricted the applications to 50% of pregnancies. For a wider extent of diagnostic applications, sex- and polymorphism-independent fetal markers would be necessary. Recently, an epigenetic approach has been adopted to discriminate between the fetal and maternal DNA circulating in maternal plasma. Based on the differential DNA methylation status between the fetus and mother, universal fetal DNA markers have been developed and applied to detect fetal signals in maternal plasma. Identification of more of such markers is important for the development of the field. / Lun, Miu Fan. / Adviser: Yuk Ming Dennis Lo. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3292. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 233-256). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

This thesis explores the political and ethical response to the development of new medical technology in the 1980s through the governmental commission Utredningen om det ofödda barnet [the commission regarding the unborn child] and its final report Den gravida kvinnan och fostret – två individer: om fosterdiagnostik, om sena aborter: slutbetänkande av Utredningen om det ofödda barnet [The Pregnant Woman and the Foetus – two individuals. On prenatal diagnosis. On late abortions: final report on the commission on the unborn child]. This governmental commission, alongside the late 1980s more broadly, have been described as a conservative backlash and reaction to the feminist movement and the fight for women’s right to their bodies. However, a close reading of the report shows that though it draws controversial connections between abortion, prenatal diagnosis and ability variations, the governmental commission advocated an extension of the law, not a limitation of rights. Through a biopolitical perspective this thesis shows how power was distributed between the state, the society and the individual. Unlike previous research’s polarisation, this thesis’s take on medicalisation shows that medicalisation is not something that necessarily opposes moralisation, but that they can be used to legitimate each other. Finally it discusses what this means for our understanding of the political climate in Sweden during the 1980s and how this changes our perception of what makes a human being.

published_or_final_version / Obstetrics and Gynaecology / Master / Master of Philosophy

Foetal anomalies found on ultrasound increase the probability of occurrence of chromosomal abnormalities. They cause about one quarter of all abortions and stillbirths and many of inborn defects in newborns. Karyotype analysis is number one method in prenatal diagnosis whereas array CGH is often used as a verification and supplemental method. The aim of this work was to prove that array CGH gives additional chromosomal findings to karyotypes and could substitute conventional karyotyping as a primary examination method in foetuses with ultrasound findings. We examined 45 prenatal samples using both methods. These samples were referred for invasive examination because of abnormal ultrasound findings. Karyotype analyses found two abnormalities in two (4,4 %) patients and array CGH identified aberrations in five (11,1 %) foetuses whereas both anomalies detected by karyotypes were discovered by array CGH too. This means that array CGH identified about 6,7 % more aberrations than karyotype. Our results correspond with scientific articles which refer that array CGH should replace karyotype not only in postnatal examinations but even in prenatal diagnosis. Keywords: chromosomal aberrations, array CGH, karyotype, prenatal diagnosis, ultrasound

A thesis completed by published work, Submitted to the School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, in fulfillment of the requirements for the degree of Doctor of Philosophy Johannesburg, South Africa 24 May 2017. / Introduction: Prevention of mother-to-child transmission (PMTCT) has potential to eliminate new HIV infections among infants. Yet, in many settings in sub-Saharan Africa, women are unable to adhere to PMTCT recommendations due to social constraints. One such factor may be intimate partner violence (IPV), or any actions taken by a relationship partner that cause physical, sexual, or psychological harm. Despite theoretical and empirical rationale for understanding the links between IPV and PMTCT adherence, few studies in the extant literature have explored this association. Methods: This thesis draws upon four distinct studies that interface using an overall mixed method study design. The first study is a systematic review of the literature around women’s experience of lifetime IPV and adherence to anti-retroviral treatment (ART). The second study is formative qualitative research with pregnant women, health workers, and other local stakeholders that explores how IPV may be related to PMTCT in the urban Johannesburg setting. The third study is a deeper qualitative examination of women living with both IPV and HIV, aiming to understand the mechanisms that link partner violence to PMTCT behaviors using a social constructionist lens. The final study is a quantitative cohort study nested within a randomized control trial testing an intervention for IPV in pregnancy. Using regression techniques and structural equation modeling, I aim to determine the association between IPV and ART adherence in pregnancy and postpartum and identify pathways that mediate the relationship between partner violence and PMTCT. Results: This doctoral research contributes several new findings to the extant literature around PMTCT. I find that IPV is related to ART adherence among HIV-positive women in extant literature, with meta-analysis showing significantly worse odds of ART uptake, self-reported adherence, and viral suppression among women reporting lifetime IPV. In one of first of studies among women in sub-Saharan Africa, I learn that impact of IPV on ART adherence in pregnancy and postpartum is marked. I identify several mechanisms through which IPV influences PMTCT adherence. Mental health emerges as a robust pathway linking IPV to worse adherence in both qualitative and quantitative papers. Partner non-disclosure due to IPV can impede adherence, or women can navigate this challenge through hiding their HIV status or medication. Women experiencing IPV may attend fewer antenatal clinic visits, leading to worsened adherence. An unexpected finding was that women in our qualitative and quantitative studies were resilient and used strategies to adhere despite IPV. Motherhood seems to be a central feature of women who are resilient to the effects of IPV on adherence. Conclusion: The findings of this research have implications for research, policy, and practice. Research should incorporate social factors, such as IPV, into future studies testing PMTCT adherence interventions. Clinical practice and HIV programs should recognize that partner-level dynamics such as IPV may drive persistent gaps in PMTCT coverage. HIV policy urgently needs to incorporate ethical and safety considerations for women who experience IPV around the time of pregnancy. Women living with recent or past IPV are highly resilient and often want to protect their own health and that of their children. Only by recognizing and addressing their experience within the context of HIV care can future PMTCT programs and studies ensure maternal and infant health. / MT2017

A aplicação dos métodos de biologia molecular tem acrescentado benefícios aos métodos convencionais de diagnóstico do grupo sangüíneo Rhesus (Rh). Alguns estudos evidenciaram a superioridade prática da genotipagem RhD por reação em cadeia da polimerase (PCR) em relação às técnicas de identificação do fenótipo dos antígenos do grupo Rh obtidas pela hemaglutinação. Esta análise molecular tem sido realizada utilizando-se várias seqüências cromossômicas e diferentes tipos de técnicas. O grupo Rh contém dois genes homólogos, um codificando o antígeno D e o outro os antígenos C/c e E/e. Os objetivos deste projeto foram: (1) Detectar a presença de seqüência RhD específica dos indivíduos Rh positivo; (2) Comparar a presença/ausência destas seqüências com o grupo sanguíneo detectado pela hemaglutinação e calcular a sensibilidade e a especificidade da PCR. Para cumprir estes objetivos, foram analisadas amostras de DNA extraídas de sangue periférico de 23 indivíduos (4 homens e 19 mulheres) Rh positivo (11) e negativo (12) para amplificação de seqüências dos genes RhD e RhCE utilizando a técnica de PCR convencional. Nestas amostras, a comparação dos resultados da PCR com os da hemaglutinação demonstrou total concordância entre os testes. A sensibilidade do método foi avaliada pela realização da PCR em amostras de sangue Rh positivo diluídas em água e em sangue Rh negativo, amplificando o DNA na concentração de até 4 pg/l. Estes resultados indicaram que a técnica de PCR mostrou-se efetiva no diagnóstico da genotipagem do fator Rh, vislumbrando-se a possibilidade de sua utilização em outros tecidos de origem êmbrio-fetal para orientação de diagnóstico fetal invasivo e do uso profilático da imunoglobulina anti-D apenas nos casos de incompatibilidade Rh materno-fetal. Adicionalmente, indicaram que havendo melhora da sensibilidade desta técnica será possível detectar quantidades objetivamente menores de DNA fetal na circulação materna, fundamentando um importante passo rumo ao diagnóstico do fator Rh fetal por técnica não invasiva. / Molecular biology techniques have added some advantages to conventional diagnosis of the Rhesus (Rh) blood group. Many researches have demonstrated the practical superiority of RhD genotyping using polymerase chain reaction (PCR) over phenotypic identification tests obtained by hemagglutination. The use of different kinds of molecular analysis techniques and genetic sequences has been described. The Rh blood group contains two homologous genes, one encoding the D antigen and the other one coding C/c and E/e antigens. This study objectives were: (1) Detect the RhD sequence specific for the Rh positive individuals; (2) Compare the presence/absence of these sequences with the blood group identified by hemagglutination to calculate PCRs sensitivity and specificity rates. To accomplish these objectives, DNA extracted from venous blood of 23 individuals (4 men and 19 women), Rh positive (11) and negative (12), were analyzed using conventional PCR to amplify RhD and RhCE gene sequences. The comparison of PCR with hemagglutination results has shown total agreement. The sensitivity of this PCR method was evaluated using progressive dilutions of Rh positive samples on water and also on Rh negative samples, which demonstrated successful amplification of until 4 pg/l DNA concentration. These results have indicated that PCR was effective for the RhD genotyping, foreseeing the possibility of its utilization with other embryofetal tissues for invasive diagnosis orientation and anti-D immunoglobulin use only in cases of maternal-fetal incompatibility. Also, with an increase of this techniques sensitivity, fewer DNA amounts could be detected, which will certainly be an important step towards noninvasive fetal RhD diagnosis.

Com o objetivo de caracterizar, do ponto de vista sócio-demográfico, e obter a evolução pós-natal, das gestantes com diagnóstico ultra-sonográfico pré-natal de malformação fetal maior, atendidas no Setor de Medicina Fetal do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de 15/12/2005 a 15/12/2006, foram entrevistadas 335 gestantes. Foram excluídas aquelas que não concordaram em conceder a entrevista e aquelas que não tiveram confirmação da malformação fetal em exame realizado pela equipe de Medicina Fetal. A idade materna média das gestantes foi de 27,1 anos; a cor da pele predominante, parda (48,1%), seguida de branca (35,5%) e negra (16,4%). Em relação à escolaridade, 57,8% das gestantes apresentavam grau de escolaridade igual ou inferior ao ensino médio completo. A renda salarial média foi de 3,1 salários-mínimos. Possuíam planos de saúde privado 19,4% das envolvidas no estudo. Em relação ao uso de medicamentos na gestação, 26,6% referem ter feito uso, sendo que em 5,7% tratava-se de substância abortiva, e 1,2% admitiram ser usuárias de drogas ilícitas durante o 1º trimestre da gestação. Quanto aos antecedentes de malformação fetal, 10,4% das gestantes o referiram, sendo as malformações cardíacas e as síndromes / seqüência as mais comuns (28,6% cada). Dentre os casos de malformação atual, as do sistema nervoso central foram as mais prevalentes (28%), seguidas das malformações renais (9,2%) e cardíacas (8,9%). Foram submetidas a cariótipo fetal 36,7% (123/335) das gestações, sendo 23,6% dos resultados anormais. Em 311 casos (92,8%), o resultado da gestação foi obtido. Destes, 76,8% nasceram vivos; 25,7% evoluíram com óbito neonatal; 16,4% foram natimortos e em 6,3% houve interrupção da gestação. O presente estudo permitiu conhecer as características sócio demográficas e os resultados gestacionais de mulheres com diagnóstico de malformação fetal, o que poderá ser útil para o planejamento periconcepcional deste grupo de pacientes / The purpose of this study is to describe the socio demographic profile and perinatal outcome of pregnant women with prenatal ultrasound diagnosis of major fetal malformation at the Hospital das Clínicas, São Paulo University Medical School. The study was performed from 15th December 2005 to 15th December 2006. Cases that were not confirmed and did not consent to participate in the study were excluded. Mean maternal age was 27.1 years and skin color was brown in 48.1% of the cases (white: 35.5% and black: 16.4%). According to the educational level and salary, 57.8% did not finish college and the mean monthly income was 3.1 minimal wages. 19.4% of the cases had private health insurance coverage. The proportion of women who were taking medications during pregnancy was 26.6%, and from these, 5.7% intended for an abortion. Drug addiction during the first trimester was admitted by 1.2%. A previous history of a fetal malformation was reported by 10.4% of women, most cases were related to cardiac, genetic or environmental syndromes. The central nervous system was the most frequent site of malformation (28.1%), followed by renal (9.3%) and cardiac (9%) defects. Fetal karyotype was determined in 36.7% (123/335) of the fetuses and 23.6% of the results were abnormal. Pregnancy outcome was ascertained in 311 cases (92.8%): 76.8% were alive, 25.7% were neonatal deaths, 16.4% were stillborn and 6.3% miscarried. This study describes social demographic features and perinatal outcome in pregnancies with major fetal malformation diagnosed antenatally. This information is useful for parents preconception counseling

The molecular mechanisms by which pregnancy malaria affects the outcome of fetal development are unknown. Megalin, which has been well studied in kidney, has high expression in the placenta from early stages to term, and is proposed to be an important factor in extensive maternofetal exchange during development of the fetus. Pregnancy malaria (PM) is characterized by inflammation in placenta and is associated with low birthweight (LBW), stillborn birth, and other pathologies. It is hypothesized that PM disturbs megalin function/expression/distribution in the brush boarder of syncytiotrophoblast which, in turn, may contribute significantly to pathology of LBW. Our studies show that the presence of infected erythrocytes in placenta at the time of delivery negatively affects protein abundance for megalin and Dab2. This is the first report associating the abundance of placental megalin system proteins with the birth weight of newborn babies, and associating PM with changes in megalin system protein abundance. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

Com o objetivo de caracterizar, do ponto de vista sócio-demográfico, e obter a evolução pós-natal, das gestantes com diagnóstico ultra-sonográfico pré-natal de malformação fetal maior, atendidas no Setor de Medicina Fetal do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de 15/12/2005 a 15/12/2006, foram entrevistadas 335 gestantes. Foram excluídas aquelas que não concordaram em conceder a entrevista e aquelas que não tiveram confirmação da malformação fetal em exame realizado pela equipe de Medicina Fetal. A idade materna média das gestantes foi de 27,1 anos; a cor da pele predominante, parda (48,1%), seguida de branca (35,5%) e negra (16,4%). Em relação à escolaridade, 57,8% das gestantes apresentavam grau de escolaridade igual ou inferior ao ensino médio completo. A renda salarial média foi de 3,1 salários-mínimos. Possuíam planos de saúde privado 19,4% das envolvidas no estudo. Em relação ao uso de medicamentos na gestação, 26,6% referem ter feito uso, sendo que em 5,7% tratava-se de substância abortiva, e 1,2% admitiram ser usuárias de drogas ilícitas durante o 1º trimestre da gestação. Quanto aos antecedentes de malformação fetal, 10,4% das gestantes o referiram, sendo as malformações cardíacas e as síndromes / seqüência as mais comuns (28,6% cada). Dentre os casos de malformação atual, as do sistema nervoso central foram as mais prevalentes (28%), seguidas das malformações renais (9,2%) e cardíacas (8,9%). Foram submetidas a cariótipo fetal 36,7% (123/335) das gestações, sendo 23,6% dos resultados anormais. Em 311 casos (92,8%), o resultado da gestação foi obtido. Destes, 76,8% nasceram vivos; 25,7% evoluíram com óbito neonatal; 16,4% foram natimortos e em 6,3% houve interrupção da gestação. O presente estudo permitiu conhecer as características sócio demográficas e os resultados gestacionais de mulheres com diagnóstico de malformação fetal, o que poderá ser útil para o planejamento periconcepcional deste grupo de pacientes / The purpose of this study is to describe the socio demographic profile and perinatal outcome of pregnant women with prenatal ultrasound diagnosis of major fetal malformation at the Hospital das Clínicas, São Paulo University Medical School. The study was performed from 15th December 2005 to 15th December 2006. Cases that were not confirmed and did not consent to participate in the study were excluded. Mean maternal age was 27.1 years and skin color was brown in 48.1% of the cases (white: 35.5% and black: 16.4%). According to the educational level and salary, 57.8% did not finish college and the mean monthly income was 3.1 minimal wages. 19.4% of the cases had private health insurance coverage. The proportion of women who were taking medications during pregnancy was 26.6%, and from these, 5.7% intended for an abortion. Drug addiction during the first trimester was admitted by 1.2%. A previous history of a fetal malformation was reported by 10.4% of women, most cases were related to cardiac, genetic or environmental syndromes. The central nervous system was the most frequent site of malformation (28.1%), followed by renal (9.3%) and cardiac (9%) defects. Fetal karyotype was determined in 36.7% (123/335) of the fetuses and 23.6% of the results were abnormal. Pregnancy outcome was ascertained in 311 cases (92.8%): 76.8% were alive, 25.7% were neonatal deaths, 16.4% were stillborn and 6.3% miscarried. This study describes social demographic features and perinatal outcome in pregnancies with major fetal malformation diagnosed antenatally. This information is useful for parents preconception counseling