Thesis (Ph. D.)--West Virginia University, 2008. / Title from document title page. Document formatted into pages; contains viii, 132 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 77-84).

Thesis (doctoral)--Universität Göttingen, 1972. / Includes bibliographical references (p. xiii-xxvii).

Thesis (M.S.)--West Virginia University, 2000. / Title from document title page. Document formatted into pages; contains vi, 57 p. Vita. Includes abstract. Includes bibliographical references (p. 38-42).

Thesis (M.S.)--Brigham Young University. Dept. of Sociology, 2008. / Includes bibliographical references (p. 29-35).

It is well established that exposure to adverse environments in early life including both maternal under and over-nutrition predisposes individuals to similar adverse traditionally adult onset diseases such as the metabolic syndrome. Epidemiological observations and animal models have highlighted that early life exposure to maternal under-nutrition has a detrimental effect on offspring kidney health. The prevalence of chronic kidney disease has increased rapidly in recent years, concurrently with the growing obesity epidemic. Obesity is now prevalent in all age groups within the population including women of child-bearing age. Despite this, the effect of early life exposure to maternal obesity on long-term kidney health has not been investigated in humans. Studies in animals have demonstrated that exposure to early life under-nutrition programs the offspring kidney. Offspring exposed to maternal calorie restriction or a low protein diet typically display a reduced number of nephrons and increased glomerular areas. No studies to date have investigated the effect of maternal obesity on early life kidney and glomerular morphology. To address this, as part of this thesis, kidney morphology was assessed at weaning in male mice exposed to maternal diet-induced obesity throughout gestation and lactation. There was no effect of maternal diet on the number of nephrons counted within a distinct region in the offspring kidneys. However, glomerular density was decreased and glomerular area was increased in offspring exposed to maternal obesity. Alterations in renal morphology in early life have been linked to hypertension and renal disease in adulthood in both epidemiological and animal studies. Therefore, a second aim of this thesis was to assess blood pressure, renal function and markers of renal damage in offspring exposed to maternal obesity throughout the life-course. Post-pubescent male offspring (8 weeks of age) exposed to maternal obesity displayed increased blood pressure but no signs of renal dysfunction or damage. However, by six months of age offspring exposed to maternal obesity had increased glomerulosclerosis and tubulointerstitial fibrosis. The obesity epidemic is attributed to a shift in behaviours towards consumption of energy dense foods and inactivity. In addition, evidence from human and animal studies has highlighted that exposure to maternal obesity primes offspring to prefer sugary and fatty foods and to consume more calories. As such, offspring exposed to maternal obesity are likely to encounter an obesogenic environment in later life. A third aim of this thesis was therefore to determine the effect of maternal obesity in combination with a post-weaning obesogenic diet on offspring kidney health. To address this aim, offspring either exposed to an obesogenic diet or control diet throughout pregnancy and lactation were weaned onto either an obesogenic or control diet themselves. Six month old offspring exposed to a post-weaning obesity alone displayed indices of renal dysfunction and damage including glomerulosclerosis and tubulointerstitial fibrosis. Importantly, exposure to maternal obesity exacerbated the renal fibrosis in offspring exposed to a post-weaning obesogenic diet. With the growing prevalence of maternal obesity globally, there is great interest in determining an effective intervention to prevent adverse health outcomes in exposed individuals. The Ozanne laboratory has shown that maternal exercise in obese dams during pregnancy reduces maternal serum insulin and offspring insulin to control levels, highlighting that maternal exercise may be a promising intervention to limit adult-onset diseases in offspring exposed to early life obesity. The final aim of this thesis was to therefore assess the effect of exercise during an obese pregnancy on markers of offspring renal development during late gestation. Gene markers of ureteric bud branching, an important precursor of nephrogenesis, were increased in fetuses exposed to maternal obesity with exercise as opposed to obesity alone. Additionally one of these gene markers correlated negatively with maternal insulin levels. Protein markers indicative of an active ureteric bud branching pathway were also increased in offspring exposed to maternal obesity with exercise. In conclusion, studies conducted in this thesis demonstrate that offspring exposed to maternal obesity show alterations in renal morphology in early life and are predisposed for renal disease in later life, especially when they are challenged with a post-weaning obesogenic diet. Maternal exercise might be an effective intervention to rescue offspring renal morphology and later life health associated with maternal obesity, however this requires further investigation. These results have important implications for future generations within the setting of an ever increasing obesity epidemic and a growing prevalence of chronic kidney diseases.

Orientador: Iracema Mattos Paranhos Calderon / Coorientador: Maria Rita Garbi Novaes / Banca: Roseli Mieko Yamamoto Nomura / Banca: José Guilherme Cecatti / Resumo: Realizar uma revisão da literatura mundial e nacional sobre mortalidade materna, descrevendo a população vulnerável, os fatores de risco, as causas, as difi culdades para obtenção dos dados e as medidas de prevenção, de forma a subsidiar as ações de saúde. A coleta dos dados foi realizada por meio de pesquisa de artigos nas bases eletrônicas, SCIELLO, PUBMED, LILACS e MEDLINE, além de materiais publicados por organizações mundiais e nacionais. Foram selecionados estudos publicados no periodo de janeiro de 2000 a maio de 2011, utilizando-se os seguintes descritores: "maternal mortality"[MeSH Terms] OR ("maternal"[All Fields] AND "mortality"[All Fields]) OR "maternal mortality"[All Fields], nos idiomas português, inglês e espanhol. Foram selecionados 36 artigos que atendiam aos critérios de inclusão. O óbito materno está diretamente relacionado com as condições de vida da população e apresenta elevada disparidade entre as diversas regiões sócio-econômicas. Embora a mortalidade materna seja o melhor indicador de saúde da população feminina, seus números muitas vezes são apresentados de forma irreal, pela difi culdade da identifi cação dos casos nos registros de óbito. Medidas de prevenção associadas a diagnóstico e tratamento precoces e adequados são fatores benéfi cos na redução desses óbitos maternos. Apesar da tecnologia avançada e do reconhecimento de algumas medidas de prevenção, um grande número de mulheres morre diariamente por complicações no ciclo gravídico-puerperal. É evidente que para a redução desta tragédia é necessário o comprometimento político, social e econômico com a saúde, para promover as reformas necessárias na assistência ao ciclo gravídico-puerperal / Abstract: Accomplishing a review of worldwide and Brazilian literature on maternal mortality, describing the vulnerable population, risk factors, causes, and difficulties in obtaining the data and preventive measures, in order to subsidize health actions. The data collection was accomplished through a search for articles in the electronic data basis SCIELLO, PUBMED, LILACS and MEDLINE, in addition to published materials from worldwide and Brazilian organizations. Studies published between January 2000 and May 2011 have been selected using the following reference: "maternal mortality" [MeSH Terms] OR ("maternal"[All Fields] AND "mortality" [All Fields]) OR "maternal mortality" [All Fields], in Portuguese, English and Spanish languages. 36 articles that fi tted the criteria for inclusion have been selected.. Maternal death is directly related to the quality of life of the population and presents high disparity among the diverse social-economic regions. Even though maternal mortality is the most accurate health indicator for the female population, its numbers many a time are presented in unreal manners, due to the diffi culties in identifying the cases based on obit registries. Preventing measures associated to early diagnosis and proper treatment are benefi cial factors to the decrease of such maternal deaths. In spite of advanced technology and the recognition of some preventive measures, a large number of women decease daily out of complications through the pregnant and puerperal cycle. It is evident that in order to reduce such tragedy, political, social and economical commitment to Health is necessary to promote the needed reforms in the pregnant and puerperal cycle assistance / Mestre

Introdução - O estudo da morbidade materna contribui para um melhor entendimento do quadro da saúde materna, no Brasil, e para o conhecimento dos problemas obstétricos que podem levar (ou não) ao internamento das gestantes. Os dados de morbidade materna são vitais para os gestores de políticas públicas de saúde, os quais precisam saber quantas mulheres necessitam de cuidados obstétricos básicos para tornar a gestação e o parto mais seguros. Objetivos - Estudar a morbidade materna e os conceptos de puérperas numa maternidade da rede pública de João Pessoa, Paraíba, e identificar mulheres com diagnósticos considerados potencialmente graves e sugestivos de morbidade materna near miss. Método - Trata-se de um estudo transversal que fez parte de uma pesquisa maior sobre a morbimortalidade materna. Foi selecionada uma amostra de 414 puérperas por um processo de amostragem aleatória sistemático, cujos dados foram coletados, prospectivamente, de setembro a novembro de 2011, a partir dos prontuários clínicos e entrevistas complementares, numa maternidade pública de referência e acentuada demanda no município. Resultados - Foram estudadas 383 gestações que terminaram em parto e 391 conceptos. Entre as puérperas, predominou a faixa etária dos 20 aos 34 anos, cor parda, baixa escolaridade, baixa renda e sem ocupação formal no mercado de trabalho. Metade delas tiveram parto cesariano e 17 por cento dos recém-nascidos apresentaram problemas de saúde. Foram identificadas as seguintes intercorrências no parto: lacerações do períneo, hematomas, traumatismos, hemorragias e hipertensões. No puerpério, destacaram-se os transtornos hipertensivos, as hemorragias do pós-parto e as infecções. Entre os 64 diagnósticos sugestivos de near miss, estão as síndromes hipertensivas (58 por cento ) e as síndromes hemorrágicas (32,8 por cento ). Na análise comparativa entre os grupos de puérperas com morbidades sugestivas e não sugestivas de near miss, as seguintes variáveis apresentaram diferenças estatisticamente significantes (p<0,001): problemas de saúde na gestação anterior e atual, hipertensão, gestação de risco e uso de anti-hipertensivos. Não foram encontradas diferenças estatísticas entre as características dos neonatos e a morbidade materna, sugestiva ou não de near miss. Conclusão - O estudo permitiu conhecer as características maternas e a prevalência (15,5 por cento ) de morbidades sugestivas de near miss que ocorrem, seja no parto seja no puerpério. Ampliar o conhecimento sobre os aspectos que envolvem a morbidade materna torna-se crucial para o adequado enfrentamento de complicações no ciclo gravídico-puerperal, além de apoiar o Plano de Ação para acelerar a redução da mortalidade materna e morbidade materna grave. / Introduction The study of maternal morbidity contributes to a better understanding of the maternal health scene in Brazil and to the fuller knowledge of obstetric problems that may lead (or not) to the hospitalization of pregnant women. Maternal morbidity data are vital for the administrators of public health policies, who need to know how many women are expected to need basic obstetric care so as to make pregnancy and delivery safer. Objectives To study maternal morbidity and the conceptuses of puerperae in a public maternity hospital in João Pessoa, Paraíba, and identify women with a diagnosis considered potentially threatening and suggestive of being possible near misses. Method - This is a transverse study that is part of a larger project on maternal morbimortality. A sample of 414 puerperae was selected by a process of systematic random sampling, the data on whom were collected, prospectively, from September to November 2011, on the basis of clinical case notes and complementary interviews, at a public maternity hospital of reference in great demand in the municipality. Results - A total of 383 pregnancies which were carried through to delivery and 391 conceptuses were studied. There predominated, among the puerperas: the 20 - 34 year age-group, of brown skin color, low level of schooling, low income and no formal professional occupation. Half of them underwent caesarian section and 17 per cent of the new-born presented health problems. The following incidents were identified during labour: lacerations of the perineum, haematomas, traumatisms, haemorrhages and hypertensions. During the puerperium, hypertensive disorders, post-partum hemorrhage and other puerperal infections were noteworthy. The most frequent mention in the case notes of maternal causes was of hypertensive disturbances of pregnancy. Among the 64 diagnoses suggestive of near-miss, are the hypertensive (58 per cent ) and the haemorrhagic syndromes (32.8 per cent ). In the comparative analysis of the groups of puerperae with morbidities suggestive of near-miss, the following variables presented statistically significant differences (p<0.001): health problems during the previous and present pregnancy, hypertension, risk pregnancy and use of hypertensive medications. No statistical differences between the characteristics of the newborn and those of maternal morbidity (whether suggestive of near miss or not) were found. Conclusion - The study allowed the identification of maternal characteristics and the prevalence (15.5 per cent ) of the morbidities suggestive of maternal near-miss which occur either during labour or puerperium. It is crucial that our knowledge of the aspects of maternal mortality should be expanded so that the complications of the pregnancy-puerperal cycle may be adequately treated and to provide support for the Action Plan to speed up the reduction of maternal mortality and severe maternal morbidity.

Made available in DSpace on 2018-08-01T22:57:56Z (GMT). No. of bitstreams: 1 tese_6914_Laisa Barroso Ribeiro PPGBF Dissertacao de mestrado 21 08 2015 Orientadora Profa Dra Ana Paula Bittencourt.pdf: 1615838 bytes, checksum: 4ec46cda64c8ecf496eb91b48761a25c (MD5) Previous issue date: 2015-08-21 / A relação maternal perinatal tem fundamental importância no desenvolvimento de circuitos neurais saudáveis que permanecerão como herança mental ao longo da vida. Logo, eventos adversos nesse período tem potencial para desencadear psicopatologias na idade adulta, aumentando a vulnerabilidade a transtornos psiquiátricos e abuso de substâncias. Neste trabalho foi realizada a Separação Maternal (SM) em ratos Wistar machos, no intuito de mimetizar um evento estressor sustentado na infância de humanos. Em seguida, os animais foram submetidos ao protocolo de Enriquecimento Ambiental, uma estratégia não farmacológica empregada num período de plasticidade cerebral, como estratégia potencial para reverter os efeitos prejudiciais da SM. Na idade adulta, procederam-se os testes comportamentais, para aferição de depressão, ansiedade e abuso de álcool, e bioquímicos, como a dosagem de corticosterona plasmática, indicativo da reatividade do eixo hipotálamo-hipófise-adrenal (HHA) ao estresse agudo, e dosagem de dopamina e seus metabólitos em estruturas envolvidas em processo de gratificação cerebral via mesocorticolímbica (núcleo accumbens e córtex pré-frontal). A análise estatística foi realizada por meio do teste t de Student, análise de variância de uma via, duas vias, três vias ou medidas repetidas. Observamos que um protocolo de SM mais extenso tem maior impacto no desenvolvimento de comportamento depressivo na idade adulta. Não observamos hiperresponsividade do eixo HHA em animais separados em resposta a estresse agudo. O EA aumentou a preferência pelo consumo de sacarose e SM e EA concomitantemente aumentaram os comportamentos ativos no Teste do Nado Forçado, sugerindo potencial antidepressivo do EA. O EA parece ter potencial ansiolítico, ao reduzir a ansiedade aprendida aversiva no Teste de Odor de Predador, sem efeito significativo da SM nesses comportamentos. A SM aumenta a preferência pelo consumo de etanol e o EA foi capaz de prevenir esse efeito. No córtex pré-frontal a SM aumentou a quantidade de dopamina e o EA aumentou o turnover dopaminérgico, sugerindo recuperação até certo ponto da atividade dopaminérgica cortical. No núcleo accumbens, SM e EA concomitantemente reduziram os níveis de DOPAC, sem alteração no turnover dopaminérgico. SM e EA parecem não interferir nas memórias de curta e longa duração. Dessa forma, observamos por meio de alterações comportamentais e bioquímicas que eventos adversos perinatais aumentam a vulnerabilidade ao desenvolvimento de abuso de álcool e outros transtornos psiquiátricos na idade adulta; e o EA, empregado na fase de plasticidade neural, tem potencial para exercer efeito compensatório sobre os déficits gerados.

Assisted reproductive technologies have become a common method used to treat infertility. These techniques have advanced quickly since the first birth of an in vitro fertilization (IVF) baby in 1978, at the Royal Oldham Hospital in the United Kingdom. Currently, IVF with or without intracytoplasmic sperm injection, is used throughout the world to achieve oocyte retrieval, fertilization, implantation of an embryo, clinical pregnancy, ongoing clinical pregnancy, and a live-born infant. The rationale for selecting one type of fertility treatment over another is multifactorial: the confirmed or unconfirmed cause of infertility, the age of the gamete donor and the recipient, the availability of the type of treatment, and the cost associated with the treatment. The ultimate goal of any fertility treatment is to achieve a successful pregnancy that results in a healthy infant. However, the literature is equivocal on the effects of fertility treatment cycles on the health outcomes of infants and mothers. Presently, there are thirty-six fertility treatment centres across Canada, eighteen of which reside in Ontario. A national, comprehensive database of assisted reproductive technology treatment cycles (Canadian Assisted Reproductive Technologies Register (CARTR) Plus) began collecting data in 2013, and has made the research objectives of this doctoral thesis feasible. Before this data collection system, population-wide studies involving fertility treatments were not possible in Canada. Two understudied issues associated with IVF are the impact of fertility treatments on the maternal serum screening markers used in prenatal screening programs to identify fetal aneuploidies; and the association between fertility treatments and adverse perinatal outcomes, such as preeclampsia and stillbirth. Given the increasing number of women who are using fertility treatments to conceive, it is imperative that studies investigating the association with adverse outcomes are conducted. As the science supporting fertility treatment procedure has advanced, so has prenatal screening. One of the first screening tests that are performed for newly pregnant women, including women who conceived following IVF, is maternal serum screening. The first objective of this doctoral thesis was to systematically review the literature on the association between IVF treatment and maternal serum screening marker levels and nuchal translucency (NT) thickness. After the search and screening of the literature there were 40 studies that were included in this systematic review. A decrease in pregnancy-associated plasma protein A (PAPP-A) and an increase in total human chorionic gonadotropin (hCG) was consistently reported for IVF pregnancies. However, since the levels of the other maternal serum screening markers reported also varied we were unable to generalize about the differences between prenatal screening results in the IVF population. These results led to investigating maternal serum screening marker levels among IVF patients in Ontario, Canada. The second objective of this thesis was three-fold: 1) to investigate the accuracy of IVF identification on the Ontario prenatal screening record, relative to reference standard on the CARTR Plus database; 2) to compare the prenatal screening markers in IVF versus non-IVF pregnancies in the population of Ontario; and 3) to propose updated IVF adjustment factors for prenatal screening in the Ontario population, based on the more accurate coding for IVF status in the CARTR Plus database. Significant differences between IVF and non-IVF groups, based on both the prenatal screening requisition information and CARTR Plus information, were found among the ethnicity adjusted mean multiple of the median (MoM)s for several prenatal screening markers: alpha-fetoprotein (AFP), PAPP-A, unconjugated estriol (µE3), first trimester hCG, total hCG, and dimeric inhibin A (DIA). When we developed the proposed adjustment factors for all CARTR Plus identified pregnancies we found that for PAPP-A, total hCG, and µE3 the mean adjusted marker MoMs were significantly closer to 1.00, as compared to the prenatal screening adjusted or the unadjusted mean marker MoMs. Currently, there is no adjustment made to the other maternal serum screening markers and NT measurement. The third objective was to examine the effect of type of infertility on placental-mediated adverse outcomes (preeclampsia, intrauterine growth restriction, placental abruption, and stillbirth). Type of infertility was classified as male factor (sperm count, poor sperm motility, and abnormal sperm morphology), female factor (ovulation disorders, tubal infertility, and uterine or cervical causes), and unexplained infertility. No significant associations were found between type of conception and the composite outcome, as well as each individual primary outcome. Similarly, the type of infertility was not associated with the composite outcome or any of the individual primary outcomes, except for female factor infertility, which was associated with increased probability of placental abruption. Overall, the results from this doctoral thesis suggest that there are substantial differences seen in maternal serum screening marker MoMs among women who use IVF to conceive, suggesting that appropriate adjustment factors should be employed to ensure accurate results for determining the risk of Down syndrome and trisomy 18. Additionally, although the literature has shown an association between fertility treatment and placental-mediated adverse outcomes no significant associations were found in the population of Ontario. Further studies should be performed to confirm the results of these observational studies.

ude.dravrah.egelloc@gnufynnej / This research was supported by awards from the National Institutes of Health (NIH), the Eunice Kennedy Shriver Institute of Child Health and Human Development (R01-HD-059835) and the National Institute for Minority Health and Health Disparities (T37-MD000149). The NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The authors wish to thank the dedicated staff members of Asociacion Civil Proyectos en Salud (PROESA), Peru and Instituto Especializado Materno Perinatal, Peru for their expert technical assistance with this research. / Revisión por pares