No description available.

Thesis (Ph.D.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Congenital abnormalities of the diaphragm, specifically congenital diaphragmatic hernia (CDH), affect 1 in 3,000 live births and are associated with substantial morbidity and mortality. Evidence in humans and animal models support genetic causation. The etiology of most cases, however, remains unknown, though is likely polygenic in the majority. Another impediment to uncovering CDH etiology is that collection of human specimens at the onset of diaphragm development (4 weeks gestation) is not feasible. Identification of key transcriptional programs involved in normal diaphragm development is needed to gain a more comprehensive understanding of the genetic etiology of CDH. As an initial step, unique transcriptome-wide data sets are generated from laser-captured mouse embryonic diaphragms at three key time-points of diaphragm development. These data sets provide the first unbiased perspective on genes and signaling pathways active during early and late diaphragm morphogenesis. Moreover, using a curated list of known CDR-associated genes as "baits", the normal expression data sets are filtered for identification of biologically relevant CDH candidate genes. By this approach, 27 novel CDH candidate genes are described, among which, pre-B cell leukemia transcription factor 1 (Pbxl) is selected to validate the prioritization approach. Diaphragm defects resembling the human CDH phenotype, never previously appreciated, are observed among Pbxl mutant mice at E15.5. Secondly, a human family containing several affected individuals with CDH is used for gene discovery. A multiplatform analysis approach, coupled with external filtering with the normal diaphragm expression data, provide a mechanism for identification of candidate modifier loci. This integrative strategy, which identifies a FOG2 deletion and several potential modifiers of the CDH phenotype, is described. The design of a customized diagnostic/discovery capture array for next-generation sequencing of a large CDH patient cohort uses the set of CDR-candidate genes identified herein. / 2031-01-02

Background: In recent years, there has been an increase in the use of automated healthcare databases for drug safety in pregnancy evaluation; their suitability for this purpose needs to be evaluated. Aim: To evaluate the utility of the United Kingdom’s General Practice Research Database (GPRD) to act as an alternative to pregnancy registries, using anticonvulsants as a case study. Methods: Pregnancies in women with epilepsy were identified and first trimester anticonvulsant exposure was determined. Major congenital malformations in the offspring were identified and verified. The risk of major congenital malformations following exposure to a range of anticonvulsants was calculated and compared to those reported by the UK Epilepsy and Pregnancy Register. The ability to identify a known teratogenic association using GPRD data was also assessed. An algorithm was created to identify and classify different types of pregnancy loss in an automated manner. Results: The risks of a pregnancy outcome with a major congenital malformation following first trimester anticonvulsant exposures, were found to be similar in the GPRD to those of the UK Register. The number of exposures to individual products in the GPRD was often small and therefore lacked statistical power. It was, however, possible to identify a known teratogenic association using data from the GPRD. Verification of the algorithm developed to classify pregnancy losses demonstrated that, although not perfect, it would be a beneficial tool when using the GPRD for drug safety in pregnancy research. Conclusion: It is unlikely a single data source or study design will be sufficient for monitoring all aspects of the safety of medicine use during pregnancy. The GPRD has the potential to make a valuable contribution to this field of research and could play an important role in complementing the work of other surveillance systems.

Thesis--Copenhagen. / Summary in Danish. Bibliography: p. 219-235.

Thesis--Copenhagen. / Summary in Danish. Bibliography: p. 219-235.

Submitted by Haroudo Xavier Filho (haroudo.xavierfo@ufpe.br) on 2016-10-07T18:07:19Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Carolina Paim Gomes de Freitas - Dissertação.pdf: 2606222 bytes, checksum: c1285c239db0c6bae33863737f8e0bca (MD5) / Made available in DSpace on 2016-10-07T18:07:19Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Carolina Paim Gomes de Freitas - Dissertação.pdf: 2606222 bytes, checksum: c1285c239db0c6bae33863737f8e0bca (MD5) Previous issue date: 2016-02-26 / Fundamentos: A oximetria de pulso arterial foi descrita como um método de triagem para cardiopatias congênitas críticas. O estabelecimento de nomogramas para saturação pré- e pós-ductal no nosso meio pode colaborar para o refinamento de um método de triagem específico para nossa população. Objetivo: descrever e analisar os principais resultados dos nomogramas para saturação de oxigênio em neonatos triados para cardiopatias congênitas críticas na população paraibana. Metodologia: neonatos assintomáticos com idade gestacional a partir de 34 semanas foram triados para cardiopatias congênitas pelo exame físico e oximetria de pulso arterial em 20 centros do estado da Paraíba. Os resultados das saturações pré e pós-ductais foram comparadas entre diversos grupos com a utilização de testes não paramétricos. Resultados: um total de 44647 neonatos foram analisados. A média da saturação pré-ductal foi de 97,37% e a pós-ductal foi de 97,44%. Houve diferença estatística (p<0,001) entre as duas saturações em praticamente todos os grupos. A média da diferença entre as saturações foi de 0,062, com a grande maioria dos neonatos apresentando diferença ≤ 4%. Neonatos pré-termo tiveram saturações menores do que os nascidos a termo (p<0,001). Não houve diferenças entre os sexos. Conclusões: foram descritos os nomogramas das saturações de oxigênio pré e pósductal, assim como a diferença entre ambas, em mais de 44647 neonatos. Tais nomogramas podem ser úteis na elaboração de metodologias de triagem para cardiopatias congênitas críticas no nosso meio. / Fundamentals: the pulse oximetry was described as a method of screening for congenital heart defects. The establishment of nomograms for pre-and pós-ductal saturation among us can collaborate for the refinement of a screening method specific to our population. Objective: to describe and analyze the main results of nomograms for oxygen saturation in neonates screened for congenital heart defects in critical population of Paraiba. Methodology: asymptomatic neonates with gestational age from 34 weeks were screened for congenital heart disease by physical examination and blood pulse oximetry in 20 centers in the State of Paraíba. The results of the pre-and pós-ductais overruns were compared between groups using nonparametric tests. Results: a total of 44647 newborns were evaluated. The average pré-ductal was 97.37% saturation and the pós-ductal was 97.44%. There was statistical difference (p < 0.001) between the two buffer overruns in almost all groups. The average difference between was 0.062 overruns, with the vast majority of newborns showing difference ≤ 4%. Preterm neonates had smaller overruns than those born at term (p < 0.001). There was no difference between the sexes. Conclusions: nomograms were described of the oxygen saturations pre-and pósductal, as well as the difference between the two in more than 44647 newborns. Such nomograms can be useful in the elaboration of methodologies for screening for congenital heart disease in our reviews.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

Lui Yat Chi. / Publication date from spine. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 93-103). / Acknowledgment --- p.1 / Abstract --- p.2 / Chapter Chapter 1 --- Introduction --- p.3 / Chapter 1.1 --- Background --- p.3 / Chapter 1.2 --- Review of previous epidemiological studies of congenital abnormalities --- p.3 / Chapter 1.2.1 --- Limitation in comparing data with different studies --- p.4 / Chapter 1.3 --- Objectives --- p.4 / Chapter Chapter 2 --- Definition --- p.7 / Chapter 2.1 --- Terminology and definition --- p.7 / Chapter 2.1.1 --- The definition of clinical abnormality --- p.9 / Chapter 2.1.2 --- The current concepts in major and minor anomalies --- p.10 / Chapter 2.1.3 --- The definition of major and minor anomalies --- p.10 / Chapter 2.2 --- Major anomalies and minor anomalies --- p.11 / Chapter Chapter 3 --- Subjects and Methodology --- p.16 / Chapter 3.1 --- The introduction of methodology --- p.16 / Chapter 3.1.1 --- Background --- p.16 / Chapter 3.1.2 --- Different Methodologies and their limitations --- p.16 / Chapter 3.2 --- Methods --- p.17 / Chapter 3.2.1 --- Setting --- p.17 / Chapter 3.2.2 --- Design of the research data recording sheet --- p.18 / Chapter 3.2.3 --- Training --- p.18 / Chapter 3.2.3.1 --- "Training in paediatrics, orthopaedic and clinical genetic centre" --- p.18 / Chapter 3.2.3.2 --- End of training period --- p.19 / Chapter 3.2.4 --- Data Collection --- p.19 / Chapter 3.2.4.1 --- Subject selection --- p.19 / Chapter 3.2.4.2 --- Examination Procedures --- p.20 / Chapter 3.2.4.3 --- Cross checking of the examination --- p.25 / Chapter 3.2.4.4 --- Other sources of information --- p.25 / Chapter 3.3 --- Problems in screening --- p.26 / Chapter 3.4 --- Selection of variables --- p.26 / Chapter 3.5 --- Statistical analysis --- p.27 / Chapter Chapter 4 --- Results --- p.28 / Chapter 4.1 --- Sub-Classification of the newborn infants --- p.28 / Chapter 4.2 --- Weights and Measures --- p.29 / Chapter 4.2.1 --- Result --- p.29 / Chapter 4.2.2 --- Supplement (statistical analysis of Table 4， 5 & 6) --- p.30 / Chapter 4.3 --- The incidence of congenital abnormalities in Newborn Chinese --- p.31 / Chapter 4.4 --- Relationship between incidence of abnormalities and sex --- p.47 / Chapter 4.4.1 --- Result --- p.47 / Chapter 4.5 --- Relationship between incidence of abnormalities and maternal age --- p.53 / Chapter 4.5.1 --- Result --- p.53 / Chapter 4.5.2 --- Supplement (statistical analysis of Table 19) --- p.54 / Chapter 4.5.3 --- Supplement (statistical analysis of Table 21 & 22) --- p.56 / Chapter 4.6 --- Relationship between incidence of abnormalities and parity --- p.58 / Chapter 4.6.1 --- Result --- p.58 / Chapter 4.7 --- Relationship between incidence of abnormalities and mode of delivery --- p.59 / Chapter 4.7.1 --- Result --- p.59 / Chapter 4.7.2 --- Supplement (statistical analysis of Table 23 & 24) --- p.59 / Chapter 4.8 --- Other correlations --- p.62 / Chapter 4.8.1 --- Relationship between incidence of abnormalities and mode of delivery --- p.62 / Chapter 4.8.2 --- Supplement (statistical analysis of Table 25 & 26) --- p.63 / Chapter Chapter 5 --- Discussion --- p.65 / Chapter 5.1 --- Comparative prevalence of congenital anomalies among different studies --- p.65 / Chapter 5.2 --- Comparison of incidence of specific major abnormalities in different survey --- p.68 / Chapter 5.3 --- Relationship between abnormalities and different factors --- p.70 / Chapter 5.3.1 --- Maternal age --- p.70 / Chapter 5.3.2 --- Parity --- p.71 / Chapter 5.3.3 --- Mode of delivery --- p.72 / Chapter 5.4 --- Other correlations --- p.72 / Chapter 5.5 --- The prevalence of birth defects among different systems in this survey --- p.72 / Chapter 5.5.1 --- Central nervous system --- p.72 / Chapter 5.5.2 --- Cardiovascular system --- p.76 / Chapter 5.5.3 --- Alimentary system --- p.79 / Chapter 5.5.4 --- Musculoskeletal system --- p.81 / Chapter 5.5.4.1 --- Supplement (statistical analysis of Table Y) --- p.82 / Chapter 5.5.5 --- Multiple syndrome --- p.86 / Chapter Chapter 6 --- Conclusion --- p.89 / Chapter 6.1 --- Limitations and Benefits --- p.90 / Chapter 6.2 --- Future direction --- p.92 / References --- p.93 / Appendix --- p.104

Introdução: Não foram encontrados na literatura dados sobre a prevalência de diabetes mellitus em mães de crianças com fissura labiopalatina. Dada a relevância do tema esse foi o principal objetivo da presente investigação. Método: Após aprovação do comitê de ética e pesquisa e obtenção do consentimento livre e esclarecido, foram entrevistadas 325 mulheres, mães biológicas de crianças com fissuras labiopalatinas com idades de 0 a 3 anos matriculadas no Hospital de Reabilitação de Anomalias Craniofaciais da Universidade de São Paulo, HRAC-USP. Foi aplicado questionário com 24 questões onde obteve-se a identificação das mães, o tipo de diabetes, os principais sinais clínicos, as comorbidades associadas, hipertensão, obesidade, medicamentos e drogas lícitas e ilícitas usadas durante a gravidez. Também foram aferidos a pressão arterial e o perímetro abdominal das mães e anotados os valores da glicemia de jejum na primeira consulta pré-natal. Resultados: Os resultados obtidos mostraram que 88 mulheres apresentavam diabetes mellitus, sendo 78 com diabetes mellitus gestacional, 05 com diabetes mellitus tipo 1 e 05 com diabetes mellitus tipo 2. A prevalência de diabetes mellitus em mães de crianças com fissuras labiopalatinas foi de 27,08%, comparativamente maior (p<0,01) aos valores encontrados na população adulta brasileira (7,6%). Dessas 88 mulheres, foram excluídos os fatores que de alguma forma pudessem influenciar o aparecimento de fissuras labiopalatinas e obteve-se o percentual de 16%, onde a hiperglicemia materna nessas mães foi o único fator provável no aparecimento dessas fissuras. Conclusão: A prevalência de diabetes mellitus em mães de crianças com fissuras labiopalatinas foi de 27,08%. (p<0,01). Extraídos os fatores tidos como confundidores, tais como medicamentos usados na gestação, álcool, tabaco, drogas ilícitas, obesidade e hipertensão arterial, restaram 52 mães que tinham somente a hiperglicemia materna como fator isolado, num total de 16%. / Introduction: there was no data found on the literature regarding the prevalence of diabetes mellitus in mothers of children born with cleft lip and palate. Given the relevance of the subject, that was the main objective of this investigation. Method: after approval by the research and ethics committee, and the free, informed consent firmed by the mothers, interviews were conducted with 325 women biological mothers of children aged between 0 to 3 years, born with cleft lip and palate, registered at Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo, HRAC-USP. A 24-question survey was applied to collect data regarding the mothers identification, type of diabetes, clinical data, associated comorbidities, hypertension, obesity, medication and legal or illegal drugs used during pregnancy. Blood pressure and abdominal circumference were measured, and fasting blood glucose levels measured at the first prenatal visit. Results: It was found that 88 women had diabetes mellitus, 78 of which had gestational diabetes, 05 had type 1 diabetes and 05 had type 2 diabetes the prevalence of diabetes in mothers of children with cleft lip and palate was 27.08%, a number significantly higher (p<0.01) than the rates found among the Brazilian adult population (7.6%). From this group of 88 women we have suppressed the factors that could contribute to the occurrence of cleft lip and palate in some way, obtaining a prevalence of 16% in which maternal hyperglycemia was the only likely cause of cleft lip and palate. Conclusion: The prevalence of diabetes mellitus in mothers of children born with cleft lip and palate was 27.08% (p<0.01). Suppressing other potentially confusing factors like medication used during pregnancy, alcohol, tobacco, illegal drugs, obesity and hypertension, there were 52 mothers who had only maternal hyperglycemia as an isolated factor, representing 16% of the total studied population.

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