Patients with liver disease have an increased risk for malnutrition because of side effects of the disease. The Nutrition Focused Physical Exam (NFPE) was developed for nutrition professionals to aid physicians in a nutrition-based diagnosis of malnutrition. The purpose of this study was to examine the NFPE for its validity in liver disease patients being evaluated for transplant. In addition, the NFPE was used to assess incidence and severity of malnutrition in end stage liver disease patients and compare these results to already developed malnutrition tools such as the Patient Generated-Subjective Global Assessment (PG-SGA), Triceps Skinfolds (TSF), Mid-Arm Circumference (MAC), Lumbar Index, and Total Psoas Muscle Area (TPA). The NFPE was found to be highly correlated with PG-SGA results. There was a weak correlation between the NFPE and the TSF, MAC, and Lumbar Index/TPA, except when comparing the bottom 25% quartile of the Lumbar Index to severe malnutrition using the NFPE. This resulted in a moderate correlation. The odds-ratio for hospital admission based on malnutrition and severe malnutrition were both extremely high (14.571, 18.857 respectively). These preliminary results reinforce the significance of the NFPE and the need for additional studies using this tool.

<p>These studies were undertaken to investigate risks of maternal and perinatal complications in pregnant women with chronic hypertensive disease, and to investigate future risk of preeclampsia in women born small for gestational age (SGA). Population based cohort studies using the Swedish Medical Birth Register from different years were performed.</p><p>The maternal complications mild and severe preeclampsia, gestational diabetes and abruptio placenta were studied in a population of 681 515 women, with a prevalence of 0,5% for chronic hypertension. Risk estimates were adjusted for differences in maternal characteristics as age, parity, BMI, ethnicity and smoking habits. Chronic hypertensive women wore found to have significantly increased risks of all complications. </p><p>The perinatal complication SGA was studied in a population of 560 188, with a prevalence of 0,5% for chronic hypertension. Risk estimates were adjusted for differences in maternal characteristics and for the secondary complications mild and severe preeclampsia. Chronic hypertensive women were found to suffer a significantly increased risk of giving birth to an offspring that is SGA. </p><p>The perinatal complication fetal/infant mortality was studied in a population of 1 222 952 with a prevalence of 0,6% for chronic hypertension. Risk estimates were adjusted for differences in maternal characteristics and for the complications mild and severe preeclampsia, gestational diabetes, abruptio placenta and offspring being SGA In the analysis an effect modification by gender was included. Chronic hypertensive women were found to have a significantly increased risk for stillbirth and neonatal death in male, but not in female, offspring. Thus a clear gender difference in mortality was revealed. The risk of mortality of offspring was mediated by severe preeclampsia, abruptio placenta and offspring being SGA. Mild preeclampsia and gestational diabetes did not affect the risk. No increased risk of post neonatal mortality was found.</p><p>A generation study was performed in 118 634 girls of which 5.8% were born SGA. Their future risk for mild and severe preeclampsia in first pregnancy was analysed. Risk estimates were adjusted for age, smoking, BMI and for preeclampsia in the mothers while pregnant with the study population. Women who were born SGA were shown to have a significantly increased risk for severe preeclampsia, but not for mild preeclampsia. </p>

These studies were undertaken to investigate risks of maternal and perinatal complications in pregnant women with chronic hypertensive disease, and to investigate future risk of preeclampsia in women born small for gestational age (SGA). Population based cohort studies using the Swedish Medical Birth Register from different years were performed. The maternal complications mild and severe preeclampsia, gestational diabetes and abruptio placenta were studied in a population of 681 515 women, with a prevalence of 0,5% for chronic hypertension. Risk estimates were adjusted for differences in maternal characteristics as age, parity, BMI, ethnicity and smoking habits. Chronic hypertensive women wore found to have significantly increased risks of all complications. The perinatal complication SGA was studied in a population of 560 188, with a prevalence of 0,5% for chronic hypertension. Risk estimates were adjusted for differences in maternal characteristics and for the secondary complications mild and severe preeclampsia. Chronic hypertensive women were found to suffer a significantly increased risk of giving birth to an offspring that is SGA. The perinatal complication fetal/infant mortality was studied in a population of 1 222 952 with a prevalence of 0,6% for chronic hypertension. Risk estimates were adjusted for differences in maternal characteristics and for the complications mild and severe preeclampsia, gestational diabetes, abruptio placenta and offspring being SGA In the analysis an effect modification by gender was included. Chronic hypertensive women were found to have a significantly increased risk for stillbirth and neonatal death in male, but not in female, offspring. Thus a clear gender difference in mortality was revealed. The risk of mortality of offspring was mediated by severe preeclampsia, abruptio placenta and offspring being SGA. Mild preeclampsia and gestational diabetes did not affect the risk. No increased risk of post neonatal mortality was found. A generation study was performed in 118 634 girls of which 5.8% were born SGA. Their future risk for mild and severe preeclampsia in first pregnancy was analysed. Risk estimates were adjusted for age, smoking, BMI and for preeclampsia in the mothers while pregnant with the study population. Women who were born SGA were shown to have a significantly increased risk for severe preeclampsia, but not for mild preeclampsia.

Objetivo: Avaliar a influência de diferentes ambientes intrauterinos na concentração de hormônios no leite materno e sua relação com o peso da criança nos primeiros seis meses de vida. Materiais e Métodos: Trata-se de um de estudo de coorte prospectivo de uma amostra de recém-nascidos a termo da cidade de Porto Alegre. O recrutamento dos pares mãe-bebê ocorria 24 a 48 horas após o parto e os sujeitos incluídos em um dos cinco grupos: Diabetes, Hipertensão, Tabagistas, Pequenos para Idade Gestacional (PIG) e Controle. O colostro foi coletado no pós-parto e o leite maduro no 1º mês. Foram quantificadas as concentrações de Leptina, Adiponectina e Insulina pelo método ELISA. O peso e a estatura das mães e das crianças foram obtidos em todas as entrevistas Resultados: A concentração dos hormônios diminuiu com a maturação do leite materno com diferença estatística do colostro para o leite maduro para leptina no PIG (p=0,05) e Insulina nos grupos PIG (p=0,012) e Controle (p=0,041). O grupo PIG diferiu estatisticamente do Controle na concentração de leptina no 1M (p=0,045). O peso dos recém-nascidos PIG foi inferior aos outros grupos no nascimento e na alta hospitalar, mantendo-se diferente aos 15 dias do diabetes e controle, e, apenas do controle, no 1º mês. A partir dessa entrevista, a média de peso do PIG foi semelhante aos outros grupos indicando um catch up precoce avaliado pela diferença de escore-Z de peso para idade (>0,67). Tanto a leptina (r=-0,295; p=0,03) quanto a insulina (r=0,262; p=0,047) do leite maduro se correlacionaram com o ganho de peso da criança no 1º mês. Conclusões: A concentração dos hormônios no leite materno dos cinco grupos é semelhante ao nascimento, mas diminui do colostro para o leite maduro. A leptina e a insulina tem redução estatisticamente significativa no grupo PIG. O estudo demonstra uma antecipação metabólica do leite materno sobre a condição de PIG, relacionando-se com a possibilidade de um catch up precoce no primeiro mês de vida desses lactentes. / Objective: To evaluate the influence of different intrauterine environments on breast milk hormones concentration and its relationship with infant weight up to 6 months. Material and Methods: This is a thematic, prospective and longitudinal term born cohort from Porto Alegre, Brazil. Mother-infant pairs were recruited 24 to 48 hours after birth and then included in one of five groups: diabetes, hypertension, smoking, mothers of Small for Gestational Age (SGA) and controls. Colostrum was collected at 24h postpartum and mature milk 1 month later. Breast milk leptin, adiponectin and insulin were determined by ELISA. In all interviews mother and infant weight and height were obtained. Results: Adipokines levels decreased according to milk maturation with statistical difference in leptin from colostrum to mature milk in SGA group (p=0.05) and insulin in SGA (p=0.012) and control (p=0.041) groups. SGA differed statistically from control at colostrum in leptin concentration (p=0,045). SGA had low maternal BMI means values in all measurements reflecting in lower leptin and insulin concentration. SGA infant weight was statistically different from all groups at born and at discharge keeping different from diabetes and control at 15 days postpartum and only from control at 1 month. After, the weight mean of SGA was similar from others groups indicating an early catch up. Both, leptin (r=-0.295; p=0.03) and insulin (r=0.262; p=0.047) at 1 month were correlated with infant weight gain at 1 month. Conclusion: Breast milk hormones are similar at birth in all groups but the concentration decreases from colostrum to mature milk. SGA had a significant reduction in leptin and insulin concentration. This study demonstrates breast milk metabolic anticipation on SGA, probably is related to early catch up at 1 month of life.

Chez un individu infecté, le VHC circule sous la forme d’une population de variants viraux appelés quasi-espèce. Lors d’un évènement de transmission, certains variants viraux sont préférentiellement transmis et un effondrement de la diversité virale chez l’individu nouvellement infecté est souvent observé. Les propriétés électives de ces variants ainsi que leur rôle dans l’évolution clinique sont méconnus. L’objectif de cette étude est d’identifier si des déterminants moléculaires situés au niveau des glycoprotéines d’enveloppe du VHC sont associés à une plus grande capacité de transmission. Les propriétés fonctionnelles des variants transmis et non transmis seront étudiées, en particulier la sensibilité à la neutralisation autologue. Les échantillons étudiés proviennent de couples mère-enfant infectés chroniquement par le VHC issus de d’un essai clinique réalisé en Thaïlande. La composition des populations virales au sein de 3 paires a été étudiée à l’aide d’une technique d’amplification après dilution limite (SGA) suivie d’un séquençage profond (Illumina). Le variant majoritaire chez la mère était retrouvé majoritaire chez l’enfant pour les paires 1 et 3. Pour 2 paires (2 et 3), une moindre diversité génétique a été observée chez l’enfant par rapport à la mère témoignant d’un goulot d’étranglement génétique lors de la transmission. Après clonage des gènes E1E2, des tests d’infectivité sur cellules hépatocytaires ainsi que des tests de neutralisation par le sérum maternel sont réalisés avec le modèle de rétrovirus pseudotypés (VHCpp). Pour la 1ère paire, le variant majoritaire chez la mère (variant transmis à l’enfant) est infectieux et résistant au sérum autologue. Pour la deuxième paire, le variant minoritaire (transmis) est légèrement résistant à la neutralisation autologue. Un variant majoritaire non transmis apparait sensible à la neutralisation autologue. Des études complémentaires en système de virus réplicatifs issus de la culture cellulaire (VHCcc) sont en cours. Au final, les résultats de cette étude contribuent à comprendre les étapes précoces de l’infection par le VHC, afin de mieux appréhender de futures approches immunoprophylactiques ou vaccinales. / In infected individuals, HCV circulates as a complex mixture of genetically different, but closely related viral variants named quasispecies. In a transmission event, some viral variants are preferentially transmitted. The genetic and functional properties of these variants are still unknown. The aim of our work was to identify molecular determinants of E1E2 associates with a greater capacity of transmission. We also intend to study the functional properties of transmitted and no transmitted variants, as for example sensibility to autologous neutralization. Studied sera samples were obtained from three women and their child infected by the HCV, who were participating in HIV prevention clinical trial for the prevention of perinatal transmission of HIV in Thailand. Quasispecies were studied with single genome amplification (SGA) followed by deep sequencing (Illumina). A decrease in intra-host diversity (genetic bottleneck) was observed in the viral population of child near birth (week 6) compared with that observed in the mother (just before delivery). For 2 pairs, the major variant observed in the mother was the same as the major one identified in the child. Retroviral pseudotypes (HCVpp), bearing each transmitted and non-transmitted envelope glycoproteins were produced. For each one, the level of infectivity on HuH7 cells was measured as well as the neutralizing activity of the autologous sera. For the first pair, the major variant (transmitted) appears resistant to autologous neutralization. For the second pair, the transmitted minor variant appears slightly resistant to autologous neutralization. A non-transmitted major variant is sensitive to autologous neutralization. Complementary studies with HCV derived from cell culture (HCVcc) are in progress We hope that the results of this study may be helpful to better understand early steps of HCV infection, which is of great interest for the development of immunoprophylaxis and vaccine strategies.

Objetivo: Avaliar a influência de diferentes ambientes intrauterinos na concentração de hormônios no leite materno e sua relação com o peso da criança nos primeiros seis meses de vida. Materiais e Métodos: Trata-se de um de estudo de coorte prospectivo de uma amostra de recém-nascidos a termo da cidade de Porto Alegre. O recrutamento dos pares mãe-bebê ocorria 24 a 48 horas após o parto e os sujeitos incluídos em um dos cinco grupos: Diabetes, Hipertensão, Tabagistas, Pequenos para Idade Gestacional (PIG) e Controle. O colostro foi coletado no pós-parto e o leite maduro no 1º mês. Foram quantificadas as concentrações de Leptina, Adiponectina e Insulina pelo método ELISA. O peso e a estatura das mães e das crianças foram obtidos em todas as entrevistas Resultados: A concentração dos hormônios diminuiu com a maturação do leite materno com diferença estatística do colostro para o leite maduro para leptina no PIG (p=0,05) e Insulina nos grupos PIG (p=0,012) e Controle (p=0,041). O grupo PIG diferiu estatisticamente do Controle na concentração de leptina no 1M (p=0,045). O peso dos recém-nascidos PIG foi inferior aos outros grupos no nascimento e na alta hospitalar, mantendo-se diferente aos 15 dias do diabetes e controle, e, apenas do controle, no 1º mês. A partir dessa entrevista, a média de peso do PIG foi semelhante aos outros grupos indicando um catch up precoce avaliado pela diferença de escore-Z de peso para idade (>0,67). Tanto a leptina (r=-0,295; p=0,03) quanto a insulina (r=0,262; p=0,047) do leite maduro se correlacionaram com o ganho de peso da criança no 1º mês. Conclusões: A concentração dos hormônios no leite materno dos cinco grupos é semelhante ao nascimento, mas diminui do colostro para o leite maduro. A leptina e a insulina tem redução estatisticamente significativa no grupo PIG. O estudo demonstra uma antecipação metabólica do leite materno sobre a condição de PIG, relacionando-se com a possibilidade de um catch up precoce no primeiro mês de vida desses lactentes. / Objective: To evaluate the influence of different intrauterine environments on breast milk hormones concentration and its relationship with infant weight up to 6 months. Material and Methods: This is a thematic, prospective and longitudinal term born cohort from Porto Alegre, Brazil. Mother-infant pairs were recruited 24 to 48 hours after birth and then included in one of five groups: diabetes, hypertension, smoking, mothers of Small for Gestational Age (SGA) and controls. Colostrum was collected at 24h postpartum and mature milk 1 month later. Breast milk leptin, adiponectin and insulin were determined by ELISA. In all interviews mother and infant weight and height were obtained. Results: Adipokines levels decreased according to milk maturation with statistical difference in leptin from colostrum to mature milk in SGA group (p=0.05) and insulin in SGA (p=0.012) and control (p=0.041) groups. SGA differed statistically from control at colostrum in leptin concentration (p=0,045). SGA had low maternal BMI means values in all measurements reflecting in lower leptin and insulin concentration. SGA infant weight was statistically different from all groups at born and at discharge keeping different from diabetes and control at 15 days postpartum and only from control at 1 month. After, the weight mean of SGA was similar from others groups indicating an early catch up. Both, leptin (r=-0.295; p=0.03) and insulin (r=0.262; p=0.047) at 1 month were correlated with infant weight gain at 1 month. Conclusion: Breast milk hormones are similar at birth in all groups but the concentration decreases from colostrum to mature milk. SGA had a significant reduction in leptin and insulin concentration. This study demonstrates breast milk metabolic anticipation on SGA, probably is related to early catch up at 1 month of life.

Objetivo: Avaliar a influência de diferentes ambientes intrauterinos na concentração de hormônios no leite materno e sua relação com o peso da criança nos primeiros seis meses de vida. Materiais e Métodos: Trata-se de um de estudo de coorte prospectivo de uma amostra de recém-nascidos a termo da cidade de Porto Alegre. O recrutamento dos pares mãe-bebê ocorria 24 a 48 horas após o parto e os sujeitos incluídos em um dos cinco grupos: Diabetes, Hipertensão, Tabagistas, Pequenos para Idade Gestacional (PIG) e Controle. O colostro foi coletado no pós-parto e o leite maduro no 1º mês. Foram quantificadas as concentrações de Leptina, Adiponectina e Insulina pelo método ELISA. O peso e a estatura das mães e das crianças foram obtidos em todas as entrevistas Resultados: A concentração dos hormônios diminuiu com a maturação do leite materno com diferença estatística do colostro para o leite maduro para leptina no PIG (p=0,05) e Insulina nos grupos PIG (p=0,012) e Controle (p=0,041). O grupo PIG diferiu estatisticamente do Controle na concentração de leptina no 1M (p=0,045). O peso dos recém-nascidos PIG foi inferior aos outros grupos no nascimento e na alta hospitalar, mantendo-se diferente aos 15 dias do diabetes e controle, e, apenas do controle, no 1º mês. A partir dessa entrevista, a média de peso do PIG foi semelhante aos outros grupos indicando um catch up precoce avaliado pela diferença de escore-Z de peso para idade (>0,67). Tanto a leptina (r=-0,295; p=0,03) quanto a insulina (r=0,262; p=0,047) do leite maduro se correlacionaram com o ganho de peso da criança no 1º mês. Conclusões: A concentração dos hormônios no leite materno dos cinco grupos é semelhante ao nascimento, mas diminui do colostro para o leite maduro. A leptina e a insulina tem redução estatisticamente significativa no grupo PIG. O estudo demonstra uma antecipação metabólica do leite materno sobre a condição de PIG, relacionando-se com a possibilidade de um catch up precoce no primeiro mês de vida desses lactentes. / Objective: To evaluate the influence of different intrauterine environments on breast milk hormones concentration and its relationship with infant weight up to 6 months. Material and Methods: This is a thematic, prospective and longitudinal term born cohort from Porto Alegre, Brazil. Mother-infant pairs were recruited 24 to 48 hours after birth and then included in one of five groups: diabetes, hypertension, smoking, mothers of Small for Gestational Age (SGA) and controls. Colostrum was collected at 24h postpartum and mature milk 1 month later. Breast milk leptin, adiponectin and insulin were determined by ELISA. In all interviews mother and infant weight and height were obtained. Results: Adipokines levels decreased according to milk maturation with statistical difference in leptin from colostrum to mature milk in SGA group (p=0.05) and insulin in SGA (p=0.012) and control (p=0.041) groups. SGA differed statistically from control at colostrum in leptin concentration (p=0,045). SGA had low maternal BMI means values in all measurements reflecting in lower leptin and insulin concentration. SGA infant weight was statistically different from all groups at born and at discharge keeping different from diabetes and control at 15 days postpartum and only from control at 1 month. After, the weight mean of SGA was similar from others groups indicating an early catch up. Both, leptin (r=-0.295; p=0.03) and insulin (r=0.262; p=0.047) at 1 month were correlated with infant weight gain at 1 month. Conclusion: Breast milk hormones are similar at birth in all groups but the concentration decreases from colostrum to mature milk. SGA had a significant reduction in leptin and insulin concentration. This study demonstrates breast milk metabolic anticipation on SGA, probably is related to early catch up at 1 month of life.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study aimed to propose an environmental management system for a Winery within the perspective of ISO 14001, as a situational diagnosis made in the company from November 2008 to May 2009. This is a case study, which used a qualitative approach. The media used were literature and field research. This work was characterized as descriptive and explanatory. The data for the study, were collected through primary sources (unstructured interview, questionnaire for the company s technical director, on-site observation) and secondary (company s legal documents and publications relevant to research). In order to confirm and validate the information provided, the researchers recorded photographic observations in the environment of the organization during the 2009 harvest and construction of flow charts of the processes of wine. The data collected and analized were showed scope for improvement through implementation of an environmental management system. It is based on a set of actions related to production processes of the organization and health management, safety and environmental protection. The study further demonstrates the importance of environmental management it s presented, a survey of environmental aspects and impacts provokated by the activities of the winery and actions that the company has been adopting for the beneficts of the environment. After this diagnosis, it was suggested an environmental policy with goals and targets for the winery. It is understood that the first step to implement a environmental management system in the company s awareness of the Executive Department of the importance of environmental issues. This proposed model is extended to other industries in the wine sector / Este estudo objetivou propor um Sistema de Gestão Ambiental para uma vinícola sob a ótica da ISO 14001, a partir do diagnóstico situacional realizado na empresa no período de novembro de 2008 a maio de 2009. Trata-se de um estudo de caso, que utilizou uma abordagem qualitativa. Os meios de investigação utilizados foram a pesquisa bibliográfica e a pesquisa de campo. Com relação aos fins, este trabalho foi caracterizado como descritivo e explicativo. Quanto aos dados para a realização do estudo, estes foram coletados através de fontes primárias (entrevista não-estruturada; questionário aplicado para o diretor técnico da empresa; observação in loco) e secundárias (documentos legais da empresa e diversas publicações pertinentes à pesquisa). Visando a confirmação e validação das informações fornecidas, foram realizados registros fotográficos, observações no ambiente da organização durante a safra 2009 e construção de fluxogramas dos processos da Vinícola. Os dados coletados e analisados demonstraram possibilidades de melhorias mediante implantação de um sistema de gestão ambiental na organização. O Sistema proposto constitui-se num conjunto de ações relacionadas aos processos de produção da organização e gestão dos assuntos de saúde, segurança e proteção ambiental. O estudo, além de demonstrar a importância da gestão ambiental, apresentou o levantamento dos aspectos e impactos ambientais provocados pelas atividades da Vinícola e ações que a empresa já vem adotando em prol do meio ambiente. Após a realização deste diagnóstico, foi sugerida uma política ambiental, com objetivos e metas ambientais para Vinícola. Entende-se que o passo inicial para implantação de um sistema de gestão ambiental na empresa é a sensibilização do Conselho Administrativo para a importância das questões ambientais. Este modelo proposto é extensivo a outras indústrias do setor vitivinícola.

Etwa 3-5% der Neugeborenen werden kleinwüchsig geboren. Bei einem Teil dieser Kinder bleibt auch nach der Geburt ein Aufholwachstum aus. Eine prä- und postnatale Wachstumsverzögerung kann neben unmittelbaren Folgen wie zum Beispiel psychosozialen Problemen auch mit Langzeitrisiken im Erwachsenenalter, vor allem Diabetes mellitus und kardiovaskulären Erkrankungen einhergehen. In den letzten 10 Jahren konnten verschiedene Mutationen im Gen des IGF1 Rezeptors (IGF1R) bei Patienten mit Kleinwuchs, Mikrozephalie und erhöhten IGF1-Spiegeln identifiziert werden. Aufgrund eines gestörten IGF1 Signales kommt es hauptsächlich zu einem fehlenden Längenwachstum. Aber auch Funktionen des Glukosestoffwechsels sind bei manchen Patienten gestört. In dieser Arbeit wurde eine solche IGF1R Mutation in der Tyrosinkinasedomäne bei zwei Brüdern und deren Vater nachgewiesen. Auffällig waren neben einem Kleinwuchs und Mikrozephalie auch ein zunehmend gestörter Glukosemetabolismus unter Wachstumshormontherapie. Der IGF1R Gendefekt liegt in einer über Speziesgrenzen hinweg hochkonservierten Region und ließ sich mittels dHPLC und Genotypisierungsuntersuchungen bei über 1200 Kontrollen nicht nachweisen. Zusätzlich machen Vererbungsmodus und klinische Manifestationsform die IGF1R Mutation als Ursache der beobachteten prä- und postnatalen Wachstumsverzögerung sehr wahrscheinlich. Eine aufgezeichnete zunehmende Glukoseintoleranz der IGF1R Mutationsträger unter Wachstumshormontherapie spricht für eine komplexe Mitbeteiligung des IGF1R im Glukosestoffwechsel. Bei der Resequenzierung des AKT1 Gens, einem Haupteffektormolekül des IGF1R, wurden bei 70 kleinwüchsigen Kindern fünf neue Genpolymorphismen identifiziert. Eine die Proteinsequenz verändernde Mutation konnte jedoch ausgeschlossen werden. Insgesamt bestätigen diese Ergebnisse die wichtige Funktion des IGF1R im menschlichen Wachstumsprozess und geben Hinweise auf eine mögliche Mitbeteiligung des IGF1R Signalweges bei Störungen des Glukosestoffwechsels.:Inhaltsverzeichnis Bibliographische Beschreibung I. Abkürzungen 1. Einführung 1.1 Epidemiologie und Ätiologie prä- und postnatalen Kleinwuchses 1.2 Das IGF-System im Wachstumsprozess 1.3 Der IGF Typ 1 Rezeptor 1.4 Die Protein Kinase PKBα/AKT1 1.5 Die Rolle des IGF-Systems im Glukosestoffwechsel 2. Das Promotionsprojekt 2.1 Hintergrund und Fragestellung 2.2 Gen-Sequenzierung des AKT1 bei 70 SGA-Kindern 2.2.1 Methoden 2.2.2 Ergebnisse der AKT1 Resequenzierung 2.3 Geno- und phänotypische Charakterisierung der heterozygoten C1248Y IGF Typ 1 Rezeptor Mutation 2.3.1 Patienten und Methoden 2.3.2 Ergebnisse 2.4 Anmerkungen 3. Publikation 4. Zusammenfassung und Interpretation 5. Literaturverzeichnis II. Erklärung über die eigenständige Abfassung der Arbeit III. Lebenslauf IV. Danksagung

INTRODUCTION: Plusieurs études ont été menées sur le risque d’issus indésirables de grossesse associé à la prise de caféine durant la grossesse; cependant aucune étude n'a encore été réalisée sur les facteurs prédictifs de cette exposition. Pourtant, une prise en considération de ces facteurs augmenterait l’efficacité des recommandations nutritionnelles à ce sujet. En outre, peu d'études ont évalué le risque de nouveau-nés petits pour l'âge gestationnel (PAG) comparé aux autres issues indésirables de grossesse. OBJECTIFS: 1) Déterminer la fréquence de la consommation de caféine durant la grossesse et ses facteurs prédictifs ; 2) quantifier l’association de cette exposition au risque de (PAG). MÉTHODE: 3458 participantes ont été sélectionnées aléatoirement dans le Registre Québécois des Grossesses (RQG) créé par l’appariement de trois banques de données administratives : RAMQ, MED–ÉCHO et ISQ. Des analyses statistiques ont permis d’étudier les facteurs prédictifs de cette utilisation et une étude cas-témoins a permis de quantifier le risque de (PAG) qui lui est associé. RÉSULTATS: 87,3% des participantes consommaient de la caféine avant leur grossesse et 71,4% durant. L'âge maternel avancé, le tabagisme, l'hypertension et les hospitalisations avant la grossesse sont des facteurs prédictifs de la consommation de caféine durant la grossesse. Une augmentation de 20% de risque de PAG a été observée [OR = 1,19; 95% IC (1,01–1,40)]. CONCLUSION: La consommation de caféine pendant la grossesse est répandue et la sécurité de cette utilisation doit être questionnée. Nos résultats suggèrent que la consommation de caféine durant la grossesse augmenterait le risque de PAG. / BACKGROUND: Several studies have been conducted on the association between several adverse pregnancy outcomes and caffeine intake during pregnancy; but, no study has yet been conducted on the predictors of such exposure. However, a consideration of these factors would contribute in making nutritional recommendations in this regard more efficient. In addition, few studies had evaluated the risk of small for gestational age infants (SGA) compared to other adverse pregnancy outcomes. OBJECTIVES: 1) To determine the frequency of caffeine consumption during pregnancy and its predictors, 2) Quantify the association between SGA outcome and this exposure. METHODS: 3458 participants were randomly selected from the Quebec Pregnancy Registry (QPR) created by the linking of three administrative databases: RAMQ, MED-ECHO and ISQ. Statistical analyzes were used to examine predictors of the use and case-control study was conducted to quantify the risk of SGA associated with it. RESULTS: 87.3% of participants consumed caffeine prior to pregnancy and 71.4% during. Maternal age, smoking, hypertension and hospitalizations before pregnancy are predictors of caffeine consumption during pregnancy. A 20% increase in SGA risk was observed [OR = 1.19, 95% CI (1.01 - 1.40)]. CONCLUSION: Caffeine consumption during pregnancy is common and safety of this use must be questioned. Our results suggest that caffeine consumption during pregnancy increases the risk of SGA.