Congenital heart defects due to the aberrant development of the atrioventricular (AV) valves and septum are among the most common developmental abnormality in newborns and cause significant neonatal morbidity and mortality. A key point in cardiac morphogenesis occurs when cells within the endocardial cushions (ECCs), the precursors for the AV valvoseptal complex, delaminate and undergo an epithelial-to-mesenchymal transformation (EMT). The mesenchymal cells then proliferate and the cushion area elongates to form the AV valves and portions of the AV septae. The signals that initiate region-specific EMT during heart development are unknown. Cilia, known for their role in establishing left-right (LR) asymmetry, function to receive and integrate extracellular signals, including fluid flow, in a range of other organ systems. We hypothesize that cilia could also have a direct role in heart development outside of their role in LR development. Using immunohistochemistry, we demonstrated the presence of cilia on the myocardium, epicardium, and ECCs of wild-type mouse hearts at embryonic day (e) 9.5 and e12.5. To characterize the potential role of these cilia, we compared mice with mutations affecting ciliary biogenesis, motility, and mechanosensation. Using bright field microscopy and in situ hybridization, we analyzed the embryonic heart structure and the expression pattern of Gata4, an EMT transcription factor. We showed that compared to mice with immotile but structurally normal cilia, the mice without cilia had hypocellular ECCs, a thinned compact myocardium (CM), and an up-regulated expression of Gata4. These observations suggest that a subset of cilia called cardiac cilia have a role in cardiogenesis outside of their role in LR development and affect Gata4 expression. One possible function of cardiac cilia is as mechanosensors, integrating fluid flow and influencing cardiac morphogenesis including EMT and development of the CM.

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.

Thesis (M.S.)--University of Wisconsin--Madison, 1983. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 109-115).

Theses (M.S.)--University of Wisconsin-Madison, 1992. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 83-91).

INTRODUCTION: Currently, patients diagnosed with Congenital Heart Disease (CHD) are living longer lifespans, leading to an increased number of these patients presenting for non-cardiac procedures/surgeries. Little research has been recently done analyzing intraoperative complications/risks for CHD patients undergoing non-cardiac surgeries. This study aims to identify common intraoperative events experienced by CHD patients undergoing non-cardiac surgeries using more recent data, while at the same time analyzing to see if there is any difference in frequency of intraoperative events experienced between different types of CHD diagnoses. METHODS: After receiving IRB approval, patients with CHD presenting for non-cardiac procedures/surgeries between the years 2008 and 2012 were pulled from Boston Children’s Hospital’s Electronic Medical records. 1,024 non-cardiac surgical encounters from 362 patients were analyzed to determine average age, average weight, patient gender, average ASA class, frequency of CHD diagnoses, ventricular function, type of non-cardiac procedure, premedication administration, type of induction and type and frequency of intraoperative events experienced. The 1,024 encounters were divided into two groups: those done in patients diagnosed with single ventricle physiology (n=79) and those done in patients diagnosed with non-single ventricle physiology (n=945). Unpaired Mann-Whitney tests were performed to determine if there was a significant difference in overall and specific intraoperative event occurrence between the single ventricle and non-single ventricle groups. RESULTS: Average age and weight at the time of these surgical encounters was 4.86 years and 20.57 Kg. A majority of the surgical encounters were done in males (59.2%). Atrial septal defect was the most common type of CHD, and most of the patients in these surgical encounters received an ASA class of 3. Intraoperative events occurred in 24.4% of the surgical encounters with cardiovascular events being the most common (44.82% of total events). Other events made up 30.49% of events experienced intraoperatively, with respiratory events making up the remaining 24.70%. There was a significant difference in the occurrence of overall events between the single ventricle and non-single ventricle group (P<0.0001). Additionally, there was a significant difference in the occurrence of cardiovascular events (P<0.0001) and Other events (P=0.0001) between the single ventricle and non-single ventricle groups. There was no significant difference in the occurrence of respiratory events between the two groups (P=0.648). DISCUSSION: The most common type of intraoperative event experienced by CHD patients during a non-cardiac surgery was cardiovascular events. Significantly more overall intraoperative events, including cardiovascular and other events, occurred in surgical encounters performed on CHD patients exhibiting single ventricle physiology than those encounters done on CHD patients with a non-single ventricle physiology. Results of this study suggest that it would be likely for CHD patients to have a cardiovascular event occur during non-cardiac surgery and that this may be more likely in patients with a single ventricle physiology. This study was subjected to the limitations of retrospective chart review, as well as missing and infrequent documentation. Future analysis will look to find correlations between the occurrence of intraoperative events, and demographic and procedure variables analyzed in this study. / 2017-06-16T00:00:00Z

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A assistÃncia de enfermagem à crianÃa portadora de cardiopatia congÃnita com Ãnfase na investigaÃÃo de dados antropomÃtricos à recomendada precocemente, pois significantes atrasos no peso e comprimento devido ao comprometimento hemodinÃmico relacionam-se intimamente aos problemas nutricionais. Buscou-se avaliar o estado nutricional de crianÃas menores de 2 anos de idade, portadoras de cardiopatias congÃnitas, mediante estudo antropomÃtrico, caracterizar os dados sociodemogrÃficos, histÃria alimentar e antecedentes perinatais, analisar os percentis e escore Z de peso/comprimento, peso/idade, comprimento/idade, circunferÃncia braquial, Ãndice de massa corporal/idade e verificar os preditores de alteraÃÃo dos parÃmetros antropomÃtricos, dos percentis e escore Z nessas crianÃas. Estudo transversal e observacional desenvolvido em duas instituiÃÃes de saÃde ambulatorial e hospitalar, referÃncias em doenÃas cardÃacas. A coleta de dados ocorreu de janeiro a junho de 2009, utilizando formulÃrio estruturado em dados: identificaÃÃo da crianÃa, sociodemogrÃficos, antecedentes perinatais, diagnÃstico patolÃgico, registro alimentar atual e medidas antropomÃtricas. Respeitaram-se todos os aspectos Ãticos e avaliaram-se 132 crianÃas predominantemente de Fortaleza-CE, do sexo masculino, com mediana de idade atà 8,5 meses e portadoras de cardiopatias congÃnitas acianÃticas, tipo comunicaÃÃo interatrial, em acompanhamento ambulatorial, no perÃodo prÃ-operatÃrio. Conforme os achados, a maioria de crianÃas era desprovida financeiramente; as mÃes haviam cursado atà nove anos de estudo, restritas Ãs atividades do lar, e dividiam com os companheiros os cuidados do filho. A maior parte das crianÃas consumia fÃrmulas lÃcteas infantis acrescentadas de complementos alimentares. Segundo os antecedentes perinatais, evidenciaram-se mÃes com atà dois filhos e aproximadamente 27 anos de idade no nascimento do filho cardiopata, alimentaÃÃo adequada durante o perÃodo gestacional, assinalado por intercorrÃncias: infecÃÃes do trato urinÃrio, sangramentos transvaginais, dores, ameaÃa de aborto, hiperÃmese gravÃdica, hipertensÃo arterial, rubÃola, anemia ferropriva, diabetes gestacional, anorexia e edema. Metade das mÃes realizou atà seis consultas de prÃ-natal. Grande parcela das crianÃas nasceu de parto cesÃreo e foi classificada como RN a termo, com elevados escores de Apgar. Com referÃncia à antropometria, tiveram valores de peso e comprimento adequados ao nascer e outras medidas obtidas no momento do estudo consideradas dentro do padrÃo de normalidade. Os percentis e escores Z predominantes no estudo concentraram-se dentro da faixa de normalidade nutricional. No entanto, os valores de escores Z apresentaram variaÃÃes negativas com desvio para a esquerda, portanto, mesmo incluÃdas na faixa nutricional adequada, as crianÃas estÃo em risco iminente de desenvolver alteraÃÃes nutricionais e seus valores de escores Z ainda sÃo discrepantes em relaÃÃo Ãs crianÃas sadias. Na anÃlise de fatores preditores, a ocorrÃncia de desnutriÃÃo imediata e desnutriÃÃo aguda està relacionada à diminuiÃÃo do valor da prega cutÃnea subescapular e a ocorrÃncia de desnutriÃÃo imediata refere-se ao elevado escore de Apgar no primeiro minuto. AlÃm disso, a desnutriÃÃo crÃnica relacionou-se Ãs crianÃas do sexo feminino com idades maiores. Por fim, em face da magnitude do defeito cardÃaco e sua profunda repercussÃo no estado nutricional da crianÃa, estudos podem aperfeiÃoar o conhecimento do enfermeiro e subsidiar o acompanhamento do crescimento que possibilite melhor prognÃstico dessas crianÃas em diferentes contextos da saÃde.

No description available.

A long standing axiom in the field of teratology states that the teratogenic period, when most birth defects are produced, occurs during the third to eighth weeks of development post-fertilization. Any insults prior to this time are thought to result in a slowing of embryonic growth from which the conceptus recovers or death of the embryo followed by spontaneous abortion. However, new insights into embryonic development during the first two weeks, including formation of the anterior-posterior, dorsal-ventral, and left-right axes, suggests that signaling pathways regulating these processes are prime targets for genetic and toxic insults. Establishment of the left-right (laterality) axis is particularly sensitive to disruption at very early stages of development and these perturbations result in a wide variety of congenital malformations, especially heart defects. Thus, the time for teratogenic insults resulting in birth defects should be reset to include the first two weeks of development.

Disruptions in folate metabolism are known to increase the risk for neural tube defects (NTD) and this is preventable by folic acid supplementation. However, the relationship between folate metabolism and cardiac development remains unclear. The interaction between other folate pathway nutrients, choline and riboflavin, and folate metabolism was studied in a murine model of methylenetetrahydrofolate reductase (MTHFR) deficiency. Maternal choline deficiency, riboflavin deficiency and MTHFR deficiency adversely affected embryonic or heart development. The promoters of MTHFR were also examined for interactions with GATA-4, TBX5, MEF2A and NKX-2.5, known transcription factors of cardiac development. Upstream promoter activity was increased in the presence of GATA-4 and this interaction was further enhanced upon the addition of MEF2A. TBX5 appeared to decrease upstream promoter activity. GATA-4 modestly increased downstream promoter activity. These results highlight the importance of adequate nutrient intake during pregnancy and provide a link between folate metabolism and cardiac development.

No description available.