OBJETIVOS: Investigar a incidência de prematuridade e de baixo peso ao nascer no município de Bento Gonçalves, Rio Grande do Sul, e identificar fatores associados, sensíveis à Atenção Primária à Saúde MÉTODOS: Amostra consecutiva de 540 puérperas que realizaram pré-natal em Bento Gonçalves, RS, entre agosto de 2009 e fevereiro de 2010. Visitou-se diariamente as puérperas no hospital ou no domicílio para a coleta de dados. Os preditores investigados contemplam variáveis sócio-demográficas e gestacionais. Associações com os desfechos foram estimadas utilizando o modelo de Regressão de Poisson Robusta. RESULTADOS: A incidência de baixo peso ao nascer foi de 11,2% e de prematuridade foi 14,3%. No modelo multivariável para o baixo peso permaneceram associadas as variáveis maternas: idade menor que 17 anos (RR=3,2; IC95%:1,51- 6,75), ter nascimento prévio de baixo peso (RR=4,1; IC95%:1,96-8,48), ter fumado na gestação (RR=2,1; IC95%:1,16-3,77) e ter hipertensão (RR=4,3; IC95%:1,94- 9,47). Como fator de risco de prematuridade permaneceram associadas significativamente após análise multivariada: idade menor de 17 anos (RR=2,7; IC95%:1,12-6,40), ter nascimento prévio de baixo peso (RR=2,8; IC95%:1,52-5,25), pré-natal na rede conveniada/particular (RR=2,2; IC95%:1,35-3,44), pré-eclâmpsia na gestação (RR=3,6; IC95%: 1,76-7,37). CONCLUSÕES: A incidência de prematuridade e de baixo peso ao nascimento aumentou, corroborando com a literatura nacional. Fortalecer os princípios da Atenção Primária em Saúde coloca-se relevante neste contexto, focando-se a atenção na gestante adolescente, medidas antitabaco e monitoramento das doenças hipertensivas, seria possível interferir nas taxas de prematuros e de baixo peso e, por conseguinte, alcançar a redução da mortalidade infantil. Porém, também se faz relevante discutir o papel da saúde suplementar e suas altas taxas de cesarianas. / OBJECTIVE: To investigate the incidence of prematurity and low birth weight in the municipality of Bento Gonçalves, Rio Grande do Sul, and to identify the associated factors that may be sensitive to Primary Health Care. METHODS: Consecutive sample of 540 postpartum women who received prenatal care in Bento Gonçalves, RS, between August 2009 and February 2010. Every day the mothers were visited in the hospital or at home for data collection. The predictors included socio-demographic and pregnancy variables. Associations with outcomes were estimated using robust Poisson regression model. RESULTS: The incidence of low birthweight was 11.2% and of prematurity was 14.3%. The variables associated with low birth weight were being younger than 17 years (RR=3.2; CI95%:1.51-6.75), history of previous low birth weight (RR=4.1; CI95%:1.96-8.48), smoking during pregnancy (RR=2.1; CI95%:1.16-3.77) and having hypertension (RR=4.3; CI95%:1.94-9.47). The variables associated with preterm birth in the multivariable model were being younger than 17 years (RR=2.7; CI95%:1.12- 6.40), history of previous low birth weight (RR=2.8; CI95%:1.52-5.25), prenatal care through the private system (RR=2.2; CI95%:1.35-3.44) and pre-eclampsia during pregnancy (RR=3.6; CI95%:1.76-7.37). CONCLUSIONS: The incidence of prematurity and low birth weight increased, according to national literature. Strengthening the principles of Primary Health Care may be relevant in this context, focusing on teen pregnancy. Tobacco control and monitoring of hypertensive diseases may reduce preterm and low birth weight incidences and therefore achieve the a reduction in infant mortality. However, it is also relevant to discuss the role of supplementary health on the high rates of cesarean.

OBJETIVOS: Investigar a incidência de prematuridade e de baixo peso ao nascer no município de Bento Gonçalves, Rio Grande do Sul, e identificar fatores associados, sensíveis à Atenção Primária à Saúde MÉTODOS: Amostra consecutiva de 540 puérperas que realizaram pré-natal em Bento Gonçalves, RS, entre agosto de 2009 e fevereiro de 2010. Visitou-se diariamente as puérperas no hospital ou no domicílio para a coleta de dados. Os preditores investigados contemplam variáveis sócio-demográficas e gestacionais. Associações com os desfechos foram estimadas utilizando o modelo de Regressão de Poisson Robusta. RESULTADOS: A incidência de baixo peso ao nascer foi de 11,2% e de prematuridade foi 14,3%. No modelo multivariável para o baixo peso permaneceram associadas as variáveis maternas: idade menor que 17 anos (RR=3,2; IC95%:1,51- 6,75), ter nascimento prévio de baixo peso (RR=4,1; IC95%:1,96-8,48), ter fumado na gestação (RR=2,1; IC95%:1,16-3,77) e ter hipertensão (RR=4,3; IC95%:1,94- 9,47). Como fator de risco de prematuridade permaneceram associadas significativamente após análise multivariada: idade menor de 17 anos (RR=2,7; IC95%:1,12-6,40), ter nascimento prévio de baixo peso (RR=2,8; IC95%:1,52-5,25), pré-natal na rede conveniada/particular (RR=2,2; IC95%:1,35-3,44), pré-eclâmpsia na gestação (RR=3,6; IC95%: 1,76-7,37). CONCLUSÕES: A incidência de prematuridade e de baixo peso ao nascimento aumentou, corroborando com a literatura nacional. Fortalecer os princípios da Atenção Primária em Saúde coloca-se relevante neste contexto, focando-se a atenção na gestante adolescente, medidas antitabaco e monitoramento das doenças hipertensivas, seria possível interferir nas taxas de prematuros e de baixo peso e, por conseguinte, alcançar a redução da mortalidade infantil. Porém, também se faz relevante discutir o papel da saúde suplementar e suas altas taxas de cesarianas. / OBJECTIVE: To investigate the incidence of prematurity and low birth weight in the municipality of Bento Gonçalves, Rio Grande do Sul, and to identify the associated factors that may be sensitive to Primary Health Care. METHODS: Consecutive sample of 540 postpartum women who received prenatal care in Bento Gonçalves, RS, between August 2009 and February 2010. Every day the mothers were visited in the hospital or at home for data collection. The predictors included socio-demographic and pregnancy variables. Associations with outcomes were estimated using robust Poisson regression model. RESULTS: The incidence of low birthweight was 11.2% and of prematurity was 14.3%. The variables associated with low birth weight were being younger than 17 years (RR=3.2; CI95%:1.51-6.75), history of previous low birth weight (RR=4.1; CI95%:1.96-8.48), smoking during pregnancy (RR=2.1; CI95%:1.16-3.77) and having hypertension (RR=4.3; CI95%:1.94-9.47). The variables associated with preterm birth in the multivariable model were being younger than 17 years (RR=2.7; CI95%:1.12- 6.40), history of previous low birth weight (RR=2.8; CI95%:1.52-5.25), prenatal care through the private system (RR=2.2; CI95%:1.35-3.44) and pre-eclampsia during pregnancy (RR=3.6; CI95%:1.76-7.37). CONCLUSIONS: The incidence of prematurity and low birth weight increased, according to national literature. Strengthening the principles of Primary Health Care may be relevant in this context, focusing on teen pregnancy. Tobacco control and monitoring of hypertensive diseases may reduce preterm and low birth weight incidences and therefore achieve the a reduction in infant mortality. However, it is also relevant to discuss the role of supplementary health on the high rates of cesarean.

Considera-se prematuridade, o nascimento de uma criança antes das 37 semanas completas de idade gestacional. Estas crianças são denominadas de recém-nascidos pré-termos ou prematuros. Os prematuros tardios são aqueles nascidos com idade gestacional entre 34 e 36 semanas e 6 dias, representando em torno de 70% dos nascimentos na prematuridade. A avaliação da atenção pré-natal torna-se questão central na prevenção desses nascimentos prematuros, e prevenção da morbimortalidade tanto materna como neonatal, e sua qualificação, faz-se necessária. O objetivo do presente estudo foi conhecer o cuidado na gestação de mulheres que tiveram prematuros tardios, e seus atendimentos no âmbito do Sistema Único de Saúde. Trata-se de um estudo qualitativo, do tipo exploratório, cuja coleta de dados realizou-se em três unidades de Estratégia de Saúde da Família, no período de novembro de 2011 a dezembro de 2012, na cidade de Porto Alegre, RS, com 13 informantes, mães desses prematuros tardios. Os dados foram analisados sob o referencial da Análise Temática e de Padrões, compondo dois temas: negligência no cuidado durante a gestação do prematuro tardio e insuficiência do atendimento pré-natal na prematuridade tardia. Observou-se no relato das informantes um distanciamento entre as orientações que deveriam ser seguidas no pré-natal e as que realmente são, caracterizando o modo individual dessas mães vivenciarem esse processo. Constatou-se que as gestantes encontraram estratégias para acessar recursos de saúde por vias próprias, dentro do sistema público ou por intermédio da saúde suplementar, com o objetivo de resolverem demandas percebidas no transcorrer da gestação. Observaram-se diversificadas situações que comprometeram a saúde das gestantes, tais como as doenças por elas desenvolvidas e não adequadamente diagnosticadas, tratadas e acompanhadas (como pré-eclâmpsia, sífilis e infecção do trato urinário); a dificuldade na solicitação, acesso e resultados dos exames em tempo oportuno; a inexistência de articulação entre os serviços que realizam atendimento pré-natal sob a ótica da referência e contrarreferência; a falta de continuidade no atendimento pré-natal; a dificuldade na realização da busca ativa das gestantes (mesmo quando as mesmas têm risco gestacional diagnosticado como maior que o habitual); a não valorização da escuta pelo profissional de saúde no atendimento a essas gestantes; entre tantas outras condições que ocorreram. Neste contexto destaca-se a negligência, que não esteve somente associada ao caráter individual, tampouco ao desejo em relação a estar grávida, mas sim ao contexto social e cultural no qual as gestantes estavam inseridas; e a insuficiência do atendimento pré-natal, que se refere à falta de qualidade, à função inadequada e pouco resolutiva de um atendimento que deveria ser direito garantido às gestantes. Reitera-se a relevância do atendimento pré-natal para diminuição dos fatores de risco que contribuem para a prematuridade. / Prematurity is considered the birth of a child before 37 completed weeks of gestation. The group called late preterm infants refers to gestational age between 34 and 36 weeks and 6 days, representing around 70% of preterm births. Evaluation of prenatal care becomes central issue in the prevention of these premature births, and prevention of morbidity and mortality, both maternal and neonatal, and its qualification is necessary. The aim of this study was to know the pregnancy care of women who delivered late preterm infants and their health care attention in Brazil’s Unique Health System. This is an exploratory-qualitative study, whose data collection held in three units of the Family Health Strategy, from November 2011 to December 2012, in Porto Alegre, RS, with 13 informants, mothers of late preterm infants. The data were analyzed under the Thematic and Patterns Analysis, and composed two themes: negligence of care during pregnancy of late premature infants; and, inadequacy of prenatal care in late prematurity. It was noted a gap between the guidelines that should be followed in the prenatal care and the ones that really are, showing the individual way of these mothers experience this process. It was found that pregnant women create strategies to access health resources by their own way, within the health system or with supplementary care, with the aim of resolving the perceived demands in the course of pregnancy. Diverse situations that compromised the health of pregnant women were observed, such as the diseases they developed and did not properly were diagnosed, treated and monitored (such as preeclampsia, syphilis and urinary infection), difficulties in the request, access and results of laboratorial exams in appropriate time, the lack of coordination between services providing antenatal care from the perspective of the reference and counter-reference, the lack of continuity in prenatal care, the difficulty of active search of pregnant women (even when the pregnant women has risk diagnosed as greater than usual), the devaluation of listening by the part of health professionals in the care of these pregnant women, among many other conditions that occurred. In this context, stands out the neglect, that was not only associated with individual character or in relation to the desire to be pregnant, but associated to the social and cultural context in which pregnant women lived; and the insufficiency of prenatal care, which refers to lack of quality, inadequate function and little resolute of a service that should be right guaranteed to pregnant women. Reiterate the importance of prenatal care to decrease the risk factors that contribute to prematurity. / Se considera prematuridad el nacimiento previo a las 37 semanas de edad gestacional completas. Estos niños son denominados pretérminos o prematuros. El grupo llamado de los prematuros tardíos, que se refiere a la edad gestacional entre 34 y 36 semanas y 6 días, es lo que representa alrededor del 70% de los nacimientos prematuros. Evaluación de la atención prenatal hace convertido en un tema central en la prevención de estos nacimientos prematuros, e de la prevención de la morbimortalidad materna y neonatal, entonces se necesitan intervenciones para la cualificación de la atención en los niveles primarios y secundarios de la atención a la salud apuntando a reducir este tipo de nacimiento. El objetivo de este estudio se fue conocer la atención en el embarazo de mujeres que tuvieron hijos prematuros tardíos, y sus atendimientos dentro del Sistema Único de Salud. Se trata de un estudio cualitativo, exploratorio, cuya colección de datos fue realizada en tres unidades de la Estrategia de Salud de la Familia, de noviembre 2011 hasta diciembre 2012, en Porto Alegre, RS, con 13 informantes, madres de los prematuros tardíos. Los datos fueron analizados en el marco del Análisis Temática de Normas, e compusieron dos temas: negligencia en el cuidado durante el embarazo de lo prematuro tardío; y, insuficiencia de la atención prenatal en la prematuridad tardía. Se observó que existe una brecha entre las directrices que se deben seguir en el prenatal y las que realmente son seguidas, caracterizando una forma individual de las madres experimentaren este proceso. Se encontró que las mujeres embarazadas desarrollan estrategias de acceso a los recursos de salud por sus propios medios, dentro del sistema o por medio de los servicios complementarios, con el objetivo de resolver las demandas percibidas en el curso del embarazo. Se han observado diversas situaciones que comprometieron la salud de las mujeres embarazadas, como las enfermedades que se desarrollan y no fueran correctamente diagnosticadas, tratadas y controladas (como la pre eclampsia, la sífilis y la infección del tracto urinario), las dificultades en la solicitación, acceso y resultados de exámenes de laboratorio en tiempo oportuno, la falta de coordinación entre los servicios que prestan la atención prenatal en la perspectiva de la referencia y contra-referencia, la falta de continuidad en la atención prenatal, las dificultades para llevar a cabo una búsqueda activa de las mujeres (incluso cuando tienen riesgo de embarazo diagnosticado como mayor de lo normal), la disminución de la escucha de los profesionales de la salud en la atención de estas mujeres embarazadas, entre muchas otras condiciones que ocurren. En este contexto, la negligencia, que no sólo hace sido asociada con la conducta individual, o en relación con el deseo de estar embarazada, pero a el contexto social y cultural en que se incluyeron las mujeres embarazadas; y la insuficiencia de la atención prenatal, el cual se refiere a la falta de calidad, inadecuada funcionalidad, e poca resolución de un servicio que debe ser derecho garantizado a las mujeres embarazadas. Entonces se reitera la importancia de la atención prenatal para disminuir los factores de riesgo que contribuyen a la prematuridad.

Submitted by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-10-11T13:39:02Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇAO DANIELLE LATGE.pdf: 794878 bytes, checksum: 5cca76d4644dc8468ea35e9fb8e4dc67 (MD5) / Approved for entry into archive by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-10-11T13:39:16Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇAO DANIELLE LATGE.pdf: 794878 bytes, checksum: 5cca76d4644dc8468ea35e9fb8e4dc67 (MD5) / Made available in DSpace on 2017-10-11T13:39:16Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇAO DANIELLE LATGE.pdf: 794878 bytes, checksum: 5cca76d4644dc8468ea35e9fb8e4dc67 (MD5) Previous issue date: 2015 / Universidade Federal Fluminense. Hospital Universitário Antonio Pedro / Corpo de Bombeiros Militar do Estado do Rio de Janeiro / Atualmente, pode-se perceber um crescente aprimoramento na atenção prestada aos recém-nascidos de maneira geral e, de modo particular, aos recém-nascidos prematuros. É nítido o aumento da sobrevida de recém-nascidos, cada vez mais prematuros, em diversos lugares do mundo, incluindo o Brasil, o qual leva a diminuição dos limites de viabilidade. Diante de um cenário incerto, da possibilidade de graves sequelas e de sofrimento para o recém-nascido e sua família, a reanimação na sala de parto de um recém-nascido no limite de viabilidade envolve inúmeras questões bioéticas. Este estudo consistiu numa pesquisa qualitativa, na qual foram realizadas entrevistas semiestruturadas (em anexo) com os médicos da UTI neonatal de um Hospital de Ensino na Região Metropolitana do Rio de Janeiro que realizam salas de parto. Foram analisados aspectos relacionados à prática da assistência neonatal em sala de parto aos recém-nascidos extremamente prematuros, objetivando compreender os fatores associados à conduta médica diante destes recém-nascidos sob a ótica da bioética. O propósito deste trabalho é o de conhecer e analisar os valores éticos e/ou argumentos morais que embasavam a conduta médica ante ao nascimento de um recém-nascido no limite de viabilidade / Currently, it can be seen a growing improvement in the care provided to newborns in general and, particularly, to premature infants. It is clearly increased newborn survival of increasingly premature, in various parts of the world, including Brazil, which leads to decreased viability limit. Faced of an uncertain scenario, the possibility of serious consequences and suffering for the newborn and his/ her family, resuscitation in the delivery room of a newborn in the limit of viability involves numerous ethical issues. This study was a qualitative research in which semi-structured interviews with the doctors at the neonatal ICU of the University Hospital in a Metropolitan Region of Rio de Janeiro, who perform delivery rooms, were realized. There were analyzed practices related to aspects of neonatal care in the delivery room to extremely premature newborn, aiming at understanding the factors associated to medical management before these newborns from a bioethics perspective. The purpose of this work is to understand and analyze the ethical values and / or moral arguments which were based on a medical management before the birth of a newborn in the limit of viability

Inledning: En prematur födsel framkallar ofta en kris i en familj, syskon blir oftast inte tillräckligt sedda i samband med att ett barn föds mycket för tidigt. Syftet med denna studie var att undersöka syskons och föräldrars upplevelse med ett särskilt fokus på syskonens upplevelse av att få ett extremt för tidigt fött syskon d.v.s. född v 28 och tidigare med en födelsevikt under ett kilo - v < 28 < 1000 g. Frågeställningarna i undersökningen fokuserade på förväntningar på att få ett syskon, vad som präglade tiden på neonatalavdelningen för föräldrar och syskon och hur har familjen föräldrar och syskon påverkats av att få ett extremt för tidigt fött barn. En kvalitativ metod valdes, studien bygger på fyra semistrukturerade intervjuer med syskon i åldrarna tio till femton år och fem kvalitativa föräldraenkäter. Resultatet min studie överensstämmer med vad tidigare forskning kommit fram till inom flera områden. Den neonatala tiden präglades av många känslor alltifrån stark förtvivlan till glädje och lycka. En tid som kom att innefatta mycket av oro för såväl syskon som föräldrar. Starka konfliktkänslor väcktes hos föräldrarna av att inte räcka till för både hemmavarande syskon och för det prematurfödda barnet. Separation och en splittrad familj upplevdes av alla respondenter. Syskonen beskriver en stark avsaknad utav sin mamma. Vardagen för familjerna blev kaotisk, stressig och rörig med lite tid för återhämtning. Diskussion: Flera studier påvisar, sårbarhet av att syskon inte tillräckligt uppmärksammas i samband med en prematur födsel. Vidare forskning inom området utifrån ett familjeperspektiv behövs. Med hänsyn till familjemedlemmars olika behov att hantera och bearbeta, en ofta traumatisk upplevelse som av att få ett mycket förtidigt fött barn. / Introduction A premature birth often provoke a crisis in the family, siblings are often not sufficiently taken in connection with a child is born very prematurely. The purpose of this study was to investigate the siblings and parents 'experience with a particular focus on the siblings' experience of getting an extremely premature siblings, that is, Born rows 28 and earlier with a birth weight under one kilogram - v <28 <1000 g. The questions in the survey focused on expectations about getting a sibling, what marked time in the neonatal unit, and how the family can be affected by getting an extremely prematurely given birth. A qualitative method was chosen, the study is based on four semi-structured interviews with siblings between the ages of ten to fifteen years and five qualitative parental questionnaires. The results my study correspond well with earlier research findings. The neonatal period was characterized by many emotions from strong despair to joy and happiness. A time that was to include a lot of concern for both siblings and parents. Strong conflicting emotions aroused in the parents by not being good enough for both at home and siblings of the prematurely born child. Separation and a broken family experienced by all respondents. Siblings describe a strong absence out of her mother. Everyday life for the families became chaotic, stressful and chaotic with little time for recovery. Discussion several studies demonstrate the vulnerability of the siblings are not sufficiently addressed in the context of a premature birth. Further research in this area from a family perspective is needed. With regard to the family members of the need to manage and process, an often traumatic experience of getting a very premature baby.

Objectif: La prématurité a lieu pendant une période critique de la minéralisation osseuse. Nous avons évalué si la naissance prématurée se traduit par un risque plus élevé de fracture orthopédique chez les enfants. Méthodes: Nous avons mené une étude de cohorte rétrospective sur 788 903 enfants nés entre 2006 et 2016 au Québec, Canada, avec 5 436 400 personnes-années de suivi. Nous avons distingué les enfants nés prématurés (<37 semaines) et nés à terme (≥ 37 semaines). Nous avons identifié les hospitalisations futures pour fractures osseuses nécessitant un traitement chirurgical avant 2018. Nous avons calculé les taux d'incidence et les hazard ratios estimés (HR) avec des intervalles de confiance (IC) à 95% pour mesurer l'association entre la prématurité et les fractures à l'aide de modèles de régression de Cox ajustés pour les caractéristiques de l’enfant et maternelles. Nous avons déterminé si le risque de fracture variait en fonction de l'âge de l'enfant. Résultats: Il y avait 51 212 nouveau-nés prématurés dans cette étude (6,5%). L'incidence de fracture était de 17,9 par 10 000 personnes-années chez les enfants prématurés et de 15,3 par 10 000 personnes-années pour les enfants nés à terme. Comparativement aux enfants nés à terme, les enfants prématurés présentaient un risque de fracture 1,08 fois plus élevé lors du suivi (IC 95% 0,99-1,18). Les associations étaient plus fortes pour le fémur (HR 1,27, IC 95% 1,01-1,60) et les fractures liées à une agression (HR 2,27, IC 95% 1,37-3,76). Les associations variaient également avec l'âge, les enfants prématurés ayant deux fois le risque de fracture du fémur entre 6 et 17 mois (HR 2,20, IC 95% 1,45-3,35), mais aucune association par la suite. Conclusion: La prématurité est associée à un risque accru de certaines fractures osseuses et de fractures liées à des agressions avant l'âge de 18 mois. Les familles d'enfants prématurés pourraient bénéficier de conseils et de soutien pour la prévention des fractures au cours de la petite enfance. / Objective: Preterm birth occurs during a critical period of bone mineralization. We assessed whether preterm birth translates into a higher risk of orthopedic fracture in childhood. Methods: We conducted a retrospective cohort study of 788,903 infants born between 2006 and 2016 in Quebec, Canada, including 5,436,400 person-years of follow-up. We distinguished preterm (<37 weeks) and term (≥37 weeks) infants and identified future hospitalizations for bone fractures that required operative treatment before 2018. We calculated incidence rates and estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association of prematurity with fractures using Cox regression models adjusted for maternal and infant characteristics. We determined if the risk of fracture varied by the child’s age. Results: There were 51,212 preterm infants in this study (6.5%). The incidence of fracture was 17.9 per 10,000 person-years in preterm children and 15.3 per 10,000 person-years in term children. Compared with term, preterm children had 1.08 times the risk of fracture during follow-up (95% CI 0.99-1.18). Associations were stronger for femur (HR 1.27, 95% CI 1.01-1.60) and assault-related fractures (HR 2.27, 95% CI 1.37-3.76). Associations also varied with age, with preterm children having 2 times the risk of femur fracture between 6 and 17 months of age (HR 2.20, 95% CI 1.45-3.35), but no association thereafter. Conclusion: Preterm birth is associated with an increased risk of certain bone fractures and assault-related fractures before 18 months of age. Families of preterm children may benefit from counselling and support for fracture prevention during early childhood.

Hintergrund: Der medizinische Fortschritt der letzten Jahrzehnte verbessert das Überleben insbesondere extrem kleiner Frühgeborener. Bei diesen stellt die adäquate Oxygenierung über die unreife Lunge den kritischsten Prozess in der klinischen Betreuung dar, an dessen Ende häufig eine Beeinträchtigung der postnatalen Lungenentwicklung und -reifung steht. Klinisch als Bronchopulmonale Dysplasie (BPD) imponierend, stellt diese Erkrankung die häufigste Folge der extremen Frühgeburtlichkeit dar und ist im weiteren Verlauf mit einer bedeutenden Langzeitmortalität und gesundheitsökonomischen Belastung verbunden. Außer der Vermeidung der Frühgeburtlichkeit existiert keine Therapie für BPD. Exogene Mesenchymale Stromazellen (MSC) erwiesen sich jedoch in Tiermodellen der BPD als therapeutisch ausgesprochen wirksam und stellen somit einen vielversprechenden Therapieansatz dar. Dennoch ist wenig über die Mechanismen der exogenen MSC-Wirkung in der frühgeborenen Lunge bekannt; ein Verständnis dieser ist jedoch unabdingbar für eine sichere und effektive Translation von MSC-basierten Therapien in die klinische Anwendung. Hypothese: Lungenresidente MSC sind an der normalen Lungenentwicklung beteiligt, werden durch Bedingungen, welche die zu frühe Geburt simulieren, beeinträchtigt, und tragen so zur Pathogenese der BPD bei. Exogene MSC unterstützen die lungenresidenten MSC in ihrer normalen Funktion und/oder schützen sie vor Schaden. Methoden und Resultate: Um mesenchymale Zellen aus human-fetalem Lungengewebe (FLMSC) zu isolieren, wurde eine Methode zur enzymatischen Gewebedissoziation mit anschließender selektiver Dichtegradientenzentrifugation entwickelt. Der überwiegende Mehrheit der isolierten Lungenmesenchymzellen wurde als MSC identifiziert. Damit ist mit der hier vorliegenden Arbeit erstmals die vollständige Beschreibung von humanen, fetalen Lungen-MSC gelungen. Nabelschnur (UC)MSC wurden durch enzymatischen Verdau der Wharton-Sulze gewonnen. Kultur der FLMSC in einer hypoxischen, den intrauterinen Bedingungen ähnlichen Atmosphäre resultierte in einem das Lungenwachstum stimulierenden Cytokin- und Genexpressionsmuster. Zudem produzierten die FLMSC für Lungenwachstum und -reifung unabdingbare Extrazellulärmatrixproteine. Unter Exposition gegenüber hyperoxischen Kulturbedingungen – welche die zu frühe Geburt mit anschließender Behandlung auf einer Neugeborenenintensivstation simulierten – begannen FLMSC einen Transdifferenzierungsprozess und sezernierten proinflammatorische und antiangiogene Signalmoleküle. Zudem wurde eine Reduktion der Produktion von für die Lungenentwicklung unabdingbaren Matrixproteinen beobachtet. FLMSC sendeten zudem “Danger-Signale” an andere Zellen, sobald sie Hyperoxie ausgesetzt wurden. Exogene UCMSC sezernierten in vitro große Mengen an Proteinen, welche Lungenzellen vor Schaden schützen und Lungenwachstum und -differenzierung unterstützen. Diskussion und Schlussfolgerung: Das Mesenchym der humanen fetalen Lunge am Ende der kanalikulären Entwicklungsphase besteht zum Großteil aus MSC, und nicht Fibroblasten. Das impliziert eine mesenchymale Stamm- und Progenitorzellhierarchie in der fetalen Lunge sowie bislang unbeschriebene zelluläre mesenchymale Transdifferenzierungsprozesse im weiteren intrauterinen Entwicklungsverlauf. In vitro wurde Evidenz für eine Beteiligung der endogenen Lungen-MSC an der normalen Lungenentwicklung generiert; eine Beteiligung an der Koordination von epithelialem und endothelialem Lungenwachstum und -reifung durch die endogenen MSC kann auf Grund der vorliegenden Daten angenommen werden. Nach Exposition gegenüber Hyperoxie entwickelten FLMSC einen die BPD unterstützenden Phänotyp. Exogene UCMSC besitzen das Potential, die in diesem Zustand fehlenden Faktoren bereitzustellen. Endogene pulmonale MSC sind daher potentielles Ziel und potentielle Effektorzellpopulation einer MSC-basierten Therapie für BPD. Dennoch sind weitere in vivo Experimente mit Tiermodellen der extremen Frühgeburtlichkeit unabdingbar, um die Rolle der endogenen MSC in der normalen, und insbesondere gestörten Lungenentwicklung zu verstehen und folgend potente, und vor allem sichere zellbasierte Therapeutika für unsere wohl verletzlichste Patientenpopulation – Frühgeborene – bereitzustellen. / Background: Despite great achievements in neonatal and perinatal medicine over the past decades, the immature lung remains the most critical organ to care for after premature birth. As a consequence, impairment of of postnatal lung development – bronchopulmonary dysplasia or BPD – remains the most common complication of extreme prematurity and a major healthcare burden. There is no therapy for BPD, except prevention of premature birth. Recently, exogenous mesenchymal stromal cells (MSC) have been shown to prevent and rescue impaired lung development in animal models. Understanding the mechanisms behind the beneficial action of these cells is crucial for a successful, safe, and effective clinical translation of these promising MSC-based cell therapies in neonates. Hypothesis: Endogenous lung-resident MSC contribute to normal lung development and become impaired in conditions resembling premature birth, thus playing a part in the pathogenesis of BPD. Exogenous MSC act by supporting and/or preserving the endogenous mesenchymal cell’s function. Methods and Results: Using lung tissue from aborted fetuses, a novel enzyme/density gradient technique was employed to obtain endogenous human fetal lung mesenchymal cells (FLMSC). The vast majority of the so-isolated cells fulfilled all criteria of MSC, making the herein presented work the first complete description of MSC from human fetal lung tissue. Human umbilical cord-derived (UC)MSC were isolated by enzymatic digestion of the Wharton’s jelly. When cultured in hypoxic atmospheres resembling intrauterine conditions, resident FLMSC exerted a gene expression- and cytokine profile supporting epithelial and endothelial lung development, and secreted extracellular matrix components crucial for normal lung growth. After exposure to hyperoxia – thus mimicking premature birth and subsequent treatment on a neonatal intensive care unit – FLMSC showed signs of transdifferentiation, acquired a pro-inflammatory / anti-angiogeneitic secretory profile, diminished production of crucial extracellular matrix components and send out danger signals to other cells. Conversely, UCMSC secreted various paracrine factors protecting lung cells, and proteins contributing to lung growth and alveolarization. Discussion and Conclusions: The human fetal lung’s mesenchyme at the late canalicular stage of development mainly consists of MSC rather than fibroblasts, thus implying a complex mesenchymal stem-/progenitor cell hierarchy and previously undescribed cellular transdifferentiation processes of human endogenous lung mesenchymal progenitors during late pregnancy. Evidence for a contribution of FLMSC to normal lung development was generated in vitro, suggesting a co-ordination of endothelial and epithelial cell fate by human endogenous lung MSC. When challenged with hyperoxia, FLMSC cells acquire a phenotype contributing to the pathogenesis of the BPD. Conversely, UCMSC harbor the potential to provide the factors that these damaged resident MSC lack to produce. The endogenous MSC may therefore represent a potential target of cell-based therapies of BPD. However, in vivo data obtained from premature animals is inevitable to gain further insights into the contribution of endogenous lung MSC to normal and disrupted lung development and to clinically translate potent and safe MSC-based therapeutics for our most vulnerable patient population - premature infants.

Many parents experience preterm birth as traumatic and develop high levels of emotional stress, anxiety, and depressive symptoms. This can have a negative impact on the bonding process and the development of their parental identity. The emotional support provided by the staff varies between Swedish neonatal intensive care units (NICUs), and little is known about parents´ needs and preferences for emotional support. Further, there are knowledge gaps regarding parental stress in fathers and their needs for emotional support, differences in stress between mothers and fathers, change of parental stress over time and potential predictors for parental stress. The aim of this thesis was to explore the needs and preferences for emotional support in parents of preterm infants during their infant’s hospitalisation in a NICU, and to describe parental stress in mothers and fathers up until the infant’s age of 12 months and predictors for parental stress.  Study I was a qualitative study using semi-structured interviews with 51 parents of preterm infants, which were analysed using qualitative content analysis. The results showed that parents need a sense of coherence during their infant’s stay in a neonatal intensive care unit, and they want to be offered emotional support according to their preferences. Many parents preferred to attend professionally led parental groups as other NICU parents could really understand their situation and feelings. Parents also emphasised the value of combining parental groups with other means of support. Study II was a longitudinal cohort study in which data on self-reported parental stress during the first year were obtained from 493 mothers and 329 fathers of preterm infants and analysed using descriptive statistics, Student’s independent t-tests, linear regression, and linear mixed-effects modelling. The results showed that mothers perceived more role restriction than fathers, and that fathers experienced more social isolation than mothers. Further, parental stress decreased during the first year for mothers but increased for fathers, especially between 6 months and 12 months postpartum. For both mothers and fathers, having twins and a lower perceived general health were associated to higher levels of parental stress. In addition, mothers with infants of lower gestational age experienced significantly higher levels of parental stress.  In conclusion, individualised emotional support is important for parents of preterm infants for them to manage their situation both during their infant’s hospitalisation and during the first year postpartum. Apart from professional support, peer-support in the form of professionally led parental groups are perceived to be potentially valuable emotional support by parents. This peer-support could, preferably, be combined with other means of support during hospitalisation as ‘one size does not fit all’. In a next step, support interventions need to be designed, tested, and evaluated. Antonovsky’s theory of Sense of Coherence can be used to identify emotional needs in NICU parents and how to provide emotional support consistent with the parents’ preferences. After discharge from the NICU, vulnerable groups of parents, including parents of very preterm infants and twins need additional support. Moreover, there is a need in fathers for additional emotional support programmes offered during the first year of infants’ lives.

La thérapie antirétrovirale (TAR) réduit drastiquement la transmission verticale du VIH. Cependant, des études récentes démontrent une association entre l'utilisation de la TAR pendant la grossesse, particulièrement à base d’inhibiteurs de protéases (IP), et les issues adverses, notamment l’accouchement prématuré. Les objectifs principaux de mon mémoire étaient de caractériser le profil immunitaire/inflammatoire au niveau placentaire et systémique chez les personnes enceintes vivant avec le VIH (PEVVIH) et les comparer en fonction du statut VIH et de la classe de TAR. Au niveau placentaire, l'immunotypage des cellules Hofbauer a révélé que les placentas des PEVVIH contenaient un niveau significativement plus élevé de leucocytes CD45+ attribuable à une augmentation du nombre de cellules Hofbauer que le groupe contrôle. Les analyses multivariables ont révélé que cette augmentation des cellules immunitaires était associée à un profil prédominant CD163+ dans tous les sous-groupes de TAR par rapport au groupe de contrôle. Au niveau systémique, la quantification de 12 médiateurs inflammatoires dans le plasma périphérique a révélé que la TAR à base d'IP est associée à une libération de cytokines pro-inflammatoires et antivirales significativement plus élevée par rapport à la TAR à base d'InSTI aux deux trimestres étudiés, en plus d’être associée à l’accouchement prématuré et une charge virale plus élevée au deuxième trimestre. Ces résultats suggèrent que la classe de TAR n'affecte pas intrinsèquement la sélection des cellules Hofbauer CD163+ et CD68+ au niveau placentaire, mais que la TAR à base d'IP est associée à une réponse immunologique distincte qui augmente le risque d'accouchement prématuré. / Antiretroviral therapy (ART) drastically reduces vertical transmission of HIV. However, recent studies demonstrate an association between the use of ART during pregnancy, particularly protease inhibitor (PI)-based ART, and adverse outcomes, including preterm delivery. The main objectives of my dissertation were to characterize the inflammatory profile at the placental and systemic levels in pregnant people living with HIV (PPLWH) and compare them according to HIV status and ART class. At the placental level, Hofbauer cell immunotyping revealed that placentas of PPLWH contained a significantly higher number of CD45+ leukocytes due to an increase in Hofbauer cells compared to controls. Multivariate analyses revealed that this increase in immune cells was associated with a predominantly CD163+ profile in all ART subgroups compared with the control group. At the systemic level, the quantification of 12 inflammatory mediators in peripheral plasma revealed that PI-based ART was associated with significantly higher pro-inflammatory and antiviral cytokine release compared to InSTI-based ART in both trimesters studied, in addition to being associated with preterm delivery and higher viral load. These results suggest that the class of ART does not intrinsically affect the selection of CD163+ and CD68+ Hofbauer cells in the placenta, but that PI-based ART is associated with a distinct immunological response which may increase the risk of preterm delivery.

<p>Cilj: Svrha ovog istraživanja je da se odredi uticaj promena u funkciji, morfologiji i geometriji leve komore (LK) i odusustva očuvanog dnevno-noćnog profila krvnog pritiska (KP) na intrauterini zastoj u rastu fetusa (IUGR) i preterminsko zavr&scaron;avanje trudnoće kod gestacijske hipertenzije (GH), reverzibilnost tih promena posle porođaja i povezanost GH sa prisustvom arterijske hipertenzije u porodici. Metodologija: U ovu studiju, koja je koncipirana kao prospektivna, uključeno je 90 trudnica, 30 normotenzivnih, 30 sa GH i dipping profilom KP i 30 sa GH i non-dipping profilom KP. Svim ispitanicama urađen je kompletan dvo-dimenzionalni, pulsni i tkivni Doppler ehokardiografski pregled i ambulatorni 24-h monitoring KP u trećem trimestru trudnoće i 6 nedelja posle porođaja. Rezultati i diskusija: U grupi trudnica sa GH značajno vi&scaron;e su bili poremećeni parametri sistolne, dijastolne i globalne funkcije (EF, s&rsquo;, E, A, E/A, E/e&rsquo;, DTE, IVRT, IVCT, ET, Tei indeks, CO, CW, Ees), morfologije (IVSd, PLWd, RWT, masa miokarda, p&lt;0,0005) i geometrije LK (abnormalna geometrija 67,7% vs 3,3% kod normotenzivnih, p&lt;0,0005). Najizraženije promene bile su u podgrupi non-dippera. Posle porođaja registrovano je značajno popravljanje svih promenjenih ehokardiografskih parametara, a 96,7% ispitanica iz non-dipper podgrupe imale su očuvan dnevno-noćni ritam posle porođaja. U grupi sa GH utvrđeno je postojanje arterijske hipertenzije u porodici u 80% slučajeva u odnosu na 26,7% u kontrolnoj grupi (p&lt;0,0005). Analizom rezultata utvrđeno je da su povećanje maksimalne vrednosti noćnog dijastolnog KP, indeksa mase miokarda i totalne vaskularne rezistence nezavisni prediktori IUGR-a, dok su povećanje prosečne vrednosti noćnog sistolnog KP i indeksa mase miokarda i smanjenje EF nezavisni prediktori preterminskog porođaja. Zaključak: Promene u funkciji i morfologiji leve komore i non-dipping profil KP kod GH imaju prognostički uticaj na pojavu IUGR-a i preterminsko zavr&scaron;avanje trudnoće.</p> / <p>Objective: The purpose of this study was to determine the influence of changes in function, morphology, and geometry of the left ventricle (LV) and a non-dipping arterial blood pressure (BP) pattern on the intrauterine growth restriction (IUGR) and preterm delivery in pregnant women with gestational hypertension (GH), reversibility of these changes after delivery and connection between BP in family with GH. Methods: This prospective study included 90 pregnant women, 30 normotensive, 30 with GH and dipping BP pattern and 30 with GH and non-dipping BP pattern. All participants underwent a complete two-dimensional, pulsed and tissue Doppler echocardiography and 24-h ambulatory blood pressure monitoring in the third trimester and 6 weeks after delivery. Results and discussion: Participants with GH had more impaired parameters of the LV systolic, diastolic and global function (EF, s&rsquo;, E, A, E/A, E/e&rsquo;, DTE, IVRT, IVCT, ET, Tei index, CO, CW, Ees), morphology (IVSd, PLWd, RWT, myocardial mass, p&lt;0,0005) and geometry (abnormal geometry 67,7% vs 3,3% in normotensive, p&lt;0,0005). The greatest changes were noticed in non-dippers. All changed echocardiographic parameters became improved, while 96,7 % non-dipper participants became dipper after delivery. Arterial hypertension in family was present in 80% women with GH vs 26,7% in normotensive (p&lt;0,0005). Analyses revealed that maximum night-time diastolic BP, mass index and total vascular resistance were identified as independent predictors of IUGR. Average systolic night-time BP, mass index and EF were identified as independent predictors of preterm delivery. Conclusion: Changes in LV function, morphology and geometry and a non-dipping pattern of BP in GH predicts IUGR and preterm delivery.</p>