Caffeine, a mild central nervous system stimulant, is a natural component of common hot and cold beverages like coffee, tea, sodas and cocoa. Animal studies have demonstrated caffeine’s teratogenic effects when administered at high concentrations; however, epidemiologic studies have yielded inconsistent results in humans. Because caffeine containing beverages are commonly consumed by pregnant women, we examined the prevalence of use and explored possible associations of maternal caffeine consumption with cardiovascular malformations in 3,274 cases matched with 3,519 controls enrolled in the 1981-89 “Baltimore-Washington Infant Study,” a population-based case-control investigation. We explored several key aspects of the quality of and distribution of measurements of caffeine consumption among mothers in the study population. We concluded with recommendations for refining data collection to reduce potential bias associated with assessing both caffeine content and changes in caffeine consumption during pregnancy in order to inform future research studies and birth defects/adverse birth outcomes surveillance programs.

No description available.

Transition of the cardiopulmonary circulation at birth requires functional closure of the ductus arteriosus (DA). The DA is an arterial shunt that is vital in the fetus for diverting the pulmonary circulation away from the uninflated lungs. Failure of the vessel to functionally close after birth is known as patent DA, which is the second most common congenital heart disease. Patent DA may seriously compromise neonatal health and current pharmacological treatments are often limited by serious complications or a significant failure rate, thereby increasing the necessity for surgical intervention. Recently, we were the first to show that genetic or pharmacological inactivation of cyclooxygenase (COX) -2 produces postnatal patent DA in mice. We also demonstrated that the DA expresses high levels of COX-2 during normal closure after birth, suggesting novel contractile actions of COX-2-dependent prostanoids in the DA. In humans, patent DA is more common in preterm infants than those born at full-term, however, mechanism(s) responsible for the reduced DA closure have not been identified. In the current studies, we examined COX-1 and COX-2 expression in the DA at multiple stages of gestation to determine whether alterations in the expression of these enzymes contribute to patent DA in preterm mice. Using real-time PCR, analysis of the time-course of COX-2 mRNA in the fetal mouse DA indicated that COX-2 expression significantly increased with advancing gestational age. The preterm (day 17.5) neonatal mouse DA showed attenuated COX-2 expression, as compared to the full-term (day 19.5) neonatal DA at 3 hours after birth. Furthermore, the DA of preterm neonatal mice showed incomplete closure after 3 hours of birth, a time-point when the DA of full-term neonates was completely remodeled. These data indicate a correlation between reduced DA closure and attenuated COX-2 expression. Additionally, COX-2 expression was significantly attenuated in the DA of mice deficient in the prostanoid receptor EP4, which also show a patent DA phenotype, suggesting the importance of this receptor for the induction of COX-2 required for DA closure. Overall, these studies suggest that attenuated expression of COX-2 may contribute to increased patent DA at preterm gestation.

Este trabalho teve como objetivo compreender os efeitos psicológicos da cardiopatia congênita do irmão em crianças saudáveis. A análise da literatura revelou que pouca atenção tem sido dada a esse tema, ainda que se saiba que os irmãos sadios sofrem sentindo-se excluídos e isolados das relações familiares, bem como do tratamento de crianças com doenças crônicas. Foram avaliadas cinco crianças, com idades entre três e onze anos, cujos irmãos, no momento da coleta de dados, estavam internados para tratamento da cardiopatia congênita. A pesquisa foi realizada através de análise qualitativa com referencial psicanalítico de dados colhidos durante entrevista semidirigida com os pais e observação de hora lúdica com as crianças. Foram encontrados temas comuns na vivência desses irmãos saudáveis como alteração na rotina familiar, com acréscimo de responsabilidades e conhecimento e interesse a respeito da doença e tratamento do irmão. Os irmãos saudáveis manifestaram sentimentos preponderantemente de empatia e solidariedade para com a dor e desconforto da criança cardiopata, apresentando comportamentos de cuidado para com o irmão e a família e, de forma encoberta, ciúme e rivalidade. A hora lúdica teve um caráter, além de diagnóstico, interventivo para essas crianças. Atualmente a literatura aponta para a necessidade de intervenções com essa população. A partir dos resultados desta pesquisa, espera-se ter contribuído na produção de conhecimento sobre esses irmãos saudáveis e na criação de propostas para intervenções com o intuito de prevenir ou minimizar possíveis efeitos adversos do convívio com um irmão cardiopata / This study aimed to understand the psychological effects of congenital heart of siblings in healthy children. The literature review revealed that little attention has been paid to this issue, although it is known that the healthy siblings suffer from feeling excluded and isolated from family relationships and the treatment of children with chronic diseases. We evaluated five children, aged between three and eleven, whose siblings, at the time of data collection, were hospitalized for treatment of congenital heart disease. The research was conducted through qualitative analysis with psychoanalysis reference of semistructured interview with parents and observation play therapy hour with children. We found common themes in the experience of healthy siblings as change in family routine, with increased responsibilities and interest in and knowledge about the disease and treatment of their siblings. The healthy siblings predominantly expressed feelings of empathy and solidarity with the pain and discomfort of the child with heart disease, presenting behaviors of care for their siblings and family and, covertly, jealousy and rivalry. The play therapy hour had a interventional character for these children. Currently, the literature points to the need for interventions with this population. From the results of this research is expected to have contributed in knowledge about this healthy siblings and to create proposals for interventions in order to prevent or minimize possible adverse effects of living with a sibling with heart disease

Cardiovascular diseases are the leading cause of death in humans throughout the world and “congenital heart defects” (CHDs) are the major cause of infant mortality and morbidity. GATA4 is one of the most critical and intensely studied cardiac transcription factor. It is important for proliferation of cardiomyocytes as well as their survival and adaptive response. The focus of the following thesis was to identify GATA4 mediators and cofactors in cardiac growth. The first part focused on cyclin D2 (CycD2), a growth inducible cell cycle protein. We identified Ccnd2 (gene encoding CycD2) as a direct transcriptional target of GATA4 in postnatal cardiomyocytes and Ccnd2 cardiomyocyte specific overexpression in Gata4 heterozygote mice was able to rescue their heart size and function. We further uncovered a novel regulatory loop between GATA4 and CycD2. CycD2 enhanced GATA4 activation of its target promoters. GATA4 was able to physically interact with CycD2 and its cyclin dependent kinase CDK4 suggesting that GATA4 recruits CycD2/CDK4 to its target promoters. Together, our data uncover a role of CycD2 in the developing and postnatal heart and provide novel insight for the potential of targeting the cell cycle in cardiac therapy. The second part of the project focused on KLF13, a cell specific cofactor of GATA4. KLF13 is a member of the Krϋppel-like transcription factors that are important regulators of cell proliferation and differentiation. Klf13 is highly enriched in the developing heart where it is found in both myocardial and endocardial cells. To determine its role in the mammalian heart, we deleted the Klf13 gene in transgenic mice. Klf13-/- mice were born at 50% reduced frequency and presented with variable cardiac phenotypes. Epithelial-mesenchymal transformation (EMT) was affected in these mice and reduced cell proliferation was evident in the AV cushion. These data uncover a role for a new class of transcription factors in heart formation and point to KLF13 as a regulator of endocardial cell proliferation and a potential CHD causing gene. Future discovery of more cardiac regulators and understanding the molecular basis of CHDs is essential for preventions of these defects and possible development of therapeutic approaches for myocardial repair.

Cardiovascular diseases are the leading cause of death in humans throughout the world and “congenital heart defects” (CHDs) are the major cause of infant mortality and morbidity. GATA4 is one of the most critical and intensely studied cardiac transcription factor. It is important for proliferation of cardiomyocytes as well as their survival and adaptive response. The focus of the following thesis was to identify GATA4 mediators and cofactors in cardiac growth. The first part focused on cyclin D2 (CycD2), a growth inducible cell cycle protein. We identified Ccnd2 (gene encoding CycD2) as a direct transcriptional target of GATA4 in postnatal cardiomyocytes and Ccnd2 cardiomyocyte specific overexpression in Gata4 heterozygote mice was able to rescue their heart size and function. We further uncovered a novel regulatory loop between GATA4 and CycD2. CycD2 enhanced GATA4 activation of its target promoters. GATA4 was able to physically interact with CycD2 and its cyclin dependent kinase CDK4 suggesting that GATA4 recruits CycD2/CDK4 to its target promoters. Together, our data uncover a role of CycD2 in the developing and postnatal heart and provide novel insight for the potential of targeting the cell cycle in cardiac therapy. The second part of the project focused on KLF13, a cell specific cofactor of GATA4. KLF13 is a member of the Krϋppel-like transcription factors that are important regulators of cell proliferation and differentiation. Klf13 is highly enriched in the developing heart where it is found in both myocardial and endocardial cells. To determine its role in the mammalian heart, we deleted the Klf13 gene in transgenic mice. Klf13-/- mice were born at 50% reduced frequency and presented with variable cardiac phenotypes. Epithelial-mesenchymal transformation (EMT) was affected in these mice and reduced cell proliferation was evident in the AV cushion. These data uncover a role for a new class of transcription factors in heart formation and point to KLF13 as a regulator of endocardial cell proliferation and a potential CHD causing gene. Future discovery of more cardiac regulators and understanding the molecular basis of CHDs is essential for preventions of these defects and possible development of therapeutic approaches for myocardial repair.

Akademisk avhandling--Uppsala. / Extra t.p., with thesis statement, inserted. Bibliography: p. 55-60.

Congenital heart defects are the most frequent congenital malformation being present in eight of every 1000 live births and showing the surgical produces in eighty percent of the cases. The aim of this study was to analyze the factors related to the deficit in the surgical correction of congenital heart disease in Sergipe in the last ten years. Data were collected from records of extracorporeal circulation common to all hospitals in Sergipe from January 1, 2000 to December 31, 2009, composed by the following variables: age, gender, origin, prognosis, postoperative diagnosis, type of surgery, hospital where the procedure was performed, type of medical care, surgical risk category RACHS -1. Data of births and deaths caused by heart disease in the years of study. The study was divided into two periods according to the centralization of resources in a single hospital from 2007. Performed 932 surgeries in ten years. There was reduction in surgery deficit from 69% in the pre-agreement to 55.3% in the post-agreement, 62.8% of the surgery happened between 1-12 years aged. Females had 55% of cases. The SUS system was the most common health care and the VSD was most frequent diagnosis (20.5%), followed by the Patent ductus arteriosus (20,2%) and the Interatrial Communication (19%). The predictors of hospital mortality were age, category RACHS -1 and Hospital where the procedure was performed. Our results indicate that the centralization of human and materials resources is important for the congenital heart surgery, is needed to expand these centers increase their productivity and, thereby, the quality of service. There was difference between the periods in the hospital mortality, pre-agreement 9,8% e post-agreement 5,4%. / As cardiopatias congênitas são a malformação congênita mais freqüente, estando presente em oito de cada 1000 nascidos vivos e apresentando necessidade cirúrgica em 80% dos casos. O objetivo deste estudo foi analisar o tratamento cirúrgico das cardiopatias congênitas de Sergipe em dez anos. Foram coletados dados dos registros de circulação extra-corpórea comum a todos os Hospitais de Sergipe, no período de 1º de janeiro de 2000 a 31 de dezembro de 2009, com as seguintes variáveis: faixa etária, gênero, procedência, destino, diagnóstico pós-operatório, tipo de cirurgia, hospital onde foi realizado o procedimento, tipo de assistência médica, categoria de risco cirúrgico RACHS -1. Foram registrados os dados das declarações de nascidos vivos e óbitos por cardiopatia congênita nos anos do estudo. O estudo foi dividido em dois períodos em função da centralização dos recursos em um único hospital a partir de 2007. Foram realizadas 932 cirurgias nos dez anos. Houve redução do déficit de cirurgias de 69% no período pré-contrato para 55,3% no pós-contrato; quanto à faixa etária, 62,8% dos pacientes tinham entre 1 a 12 anos. Em relação ao gênero, o sexo feminino foi o mais freqüente com 55% dos casos. A assistência médica mais frequente foi o Sistema Único de Saúde e os diagnósticos mais freqüentes foram CIV (20,5%), PCA (20,2%) e CIA (19%). Os fatores preditores de mortalidade hospitalar foram faixa etária, categoria RACHS -1 e Hospital onde foi realizado o procedimento. Os resultados deste estudo indicam que a centralização dos recursos humanos e materiais é importante para cirurgia cardíaca das cardiopatias congênitas. Houve redução na mortalidade hospitalar, no pré-contrato de 9,8% para 5,4% no pós- contrato.

Este trabalho teve como objetivo compreender os efeitos psicológicos da cardiopatia congênita do irmão em crianças saudáveis. A análise da literatura revelou que pouca atenção tem sido dada a esse tema, ainda que se saiba que os irmãos sadios sofrem sentindo-se excluídos e isolados das relações familiares, bem como do tratamento de crianças com doenças crônicas. Foram avaliadas cinco crianças, com idades entre três e onze anos, cujos irmãos, no momento da coleta de dados, estavam internados para tratamento da cardiopatia congênita. A pesquisa foi realizada através de análise qualitativa com referencial psicanalítico de dados colhidos durante entrevista semidirigida com os pais e observação de hora lúdica com as crianças. Foram encontrados temas comuns na vivência desses irmãos saudáveis como alteração na rotina familiar, com acréscimo de responsabilidades e conhecimento e interesse a respeito da doença e tratamento do irmão. Os irmãos saudáveis manifestaram sentimentos preponderantemente de empatia e solidariedade para com a dor e desconforto da criança cardiopata, apresentando comportamentos de cuidado para com o irmão e a família e, de forma encoberta, ciúme e rivalidade. A hora lúdica teve um caráter, além de diagnóstico, interventivo para essas crianças. Atualmente a literatura aponta para a necessidade de intervenções com essa população. A partir dos resultados desta pesquisa, espera-se ter contribuído na produção de conhecimento sobre esses irmãos saudáveis e na criação de propostas para intervenções com o intuito de prevenir ou minimizar possíveis efeitos adversos do convívio com um irmão cardiopata / This study aimed to understand the psychological effects of congenital heart of siblings in healthy children. The literature review revealed that little attention has been paid to this issue, although it is known that the healthy siblings suffer from feeling excluded and isolated from family relationships and the treatment of children with chronic diseases. We evaluated five children, aged between three and eleven, whose siblings, at the time of data collection, were hospitalized for treatment of congenital heart disease. The research was conducted through qualitative analysis with psychoanalysis reference of semistructured interview with parents and observation play therapy hour with children. We found common themes in the experience of healthy siblings as change in family routine, with increased responsibilities and interest in and knowledge about the disease and treatment of their siblings. The healthy siblings predominantly expressed feelings of empathy and solidarity with the pain and discomfort of the child with heart disease, presenting behaviors of care for their siblings and family and, covertly, jealousy and rivalry. The play therapy hour had a interventional character for these children. Currently, the literature points to the need for interventions with this population. From the results of this research is expected to have contributed in knowledge about this healthy siblings and to create proposals for interventions in order to prevent or minimize possible adverse effects of living with a sibling with heart disease

The aim was to explore experiences and needs of information following a prenatal diagnosis of congenital heart defect, and to assess the quality of publicly available information websites about congenital heart defects. Study I was a qualitative interview study that explored experiences among 11 parents to prenatally diagnosed children. Respondents tried to grasp the facts today while reflecting on the future, and personal contact with medical specialists was valued. The analysis showed that the Web contained an overwhelming amount of information. Study II was a qualitative interview study that explored experiences among 26 females and males 5-15 weeks after a prenatal diagnosis. Respondents hunted for information in a confusing reality, with a need for information about various topics and methods for information delivery. Although high satisfaction with the specialist information was described, the information was considered overwhelming and complex. Supplemental information was sought via the Web. Insufficient information about induced abortions was described. Study III was a quantitative study that explored content and quality of 67 English websites about congenital heart defects. Few websites included information about prenatal aspects, such as pregnancy termination. The overall quality was poor, especially reliability and information about treatment choices. Study IV was a mixed methods study that explored the quality of 10 Swedish websites about congenital heart defects, from the perspectives of 9 assessors with personal experience of a prenatal diagnosis. Quantitative Likert scale assessments were followed by written open-ended questions and focus group discussions. Quantitative assessments represented unfulfilled quality criterion for treatment choices, and partially fulfilled quality criteria for appearance, details, relevance, suitability and overall quality. Websites had significantly different scores for all investigated quality criteria. Various issues were highlighted in the responses to the open-ended questions and during the discussions, including inappropriate advertisements, biased information, poor illustrations, complex language and poor trustworthiness. In conclusion, expectant parents faced with a prenatal diagnosis of congenital heart defect in the fetus try to grasp the unexpected, an attempt that involves difficulties in relation to information. These are present during the consultation with health professionals and when searching for web-based information.