Introduction : Les enfants prématurés ont la particularité de naître alors que leur développement est souvent incomplet et nécessite la mise en œuvre de soins intensifs visant à poursuivre leur croissance en dehors de l’environnement utérin. Souvent cependant, le stade développemental de l’enfant ne lui permet pas d’assimiler une alimentation entérale du fait de l’immaturité de son système digestif. Le recours à une voie centrale délivrant les nutriments assurant le développement devient alors une nécessité. Ce type de nutrition, appelée nutrition parentérale (NP, ou total parenteral nutrition TPN), permet l’administration de molécules simples, directement dans le sang du prématuré. Il n’est toutefois pas exempt de risques puisqu’exposée à la lumière, la NP peut s’oxyder et générer des molécules oxydantes telles que des hydroperoxydes lipidiques susceptibles de se fragmenter par la suite en hydroxy-alkénals. Ceci devient problématique au vu de l’immaturité des systèmes de défenses antioxydants du nouveau-né prématuré. L’utilisation prolongée de la NP est d’ailleurs à l’origine de maladie hépatiques dans lesquelles le stress oxydant et la nécro-inflammation sont des composantes majeures. Nous avons émis l’hypothèse que l’infusion chez les enfants prématurés, d’aldéhydes d’origine lipidique est en relation avec le développement du stress oxydant et de l’inflammation hépatique. Objectif : Notre étude a consisté à évaluer la relation entre les quantités d’hydroxy-alkénals dans la NP et les effets hépatiques engendrés sur les marqueurs de stress oxydant et les voies de signalisation responsables d’une induction de processus inflammatoire. Dans ce but, nous avons cherché à mesurer la peroxydation lipidique dans l’émulsion lipidique de la NP et la conséquence de l’infusion en continue d’hydroxy-alkénals sur les marqueurs de stress oxydant, sur la voie de signalisation médiée par le Nuclear Factor κB et sur le déclenchement du processus inflammatoire hépatique. A la suite de ce travail, nous avons également travaillé sur des alternatives à la photoprotection, qui est la seule méthode réellement optimale pour réduire la peroxydation des lipides de la NP, mais cliniquement difficilement praticable. Résultats : Nos résultats ont mis en évidence la génération de 4-hydroxynonenal in vitro dans la NP, ce phénomène est augmenté par une exposition lumineuse. Dans ce cadre, nous avons montré l’inefficacité de l’ajout de multivitamines dans l’émulsion lipidique comme alternative à la photoprotection. Dans la validation biologique qui a suivi sur un modèle animal, nos résultats ont permis de démontrer que l’augmentation des adduits glutathion-hydroxynonenal était imputable à l’augmentation de 4-hydroxynonenal (4-HNE) dans la NP, et non à une peroxydation endogène. Nos données indiquent que la probable augmentation hépatique des niveaux de 4-HNE a conduit à une activation du NFκB responsable de l’activation de la transcription des gènes pro-inflammatoires du Tumour Necrosis Factor-α (TNF-α) et de l’interleukine-1 (IL-1). Nous avons alors évalué la capacité d’une émulsion lipidique enrichie en acides gras polyinsaturés (AGPI) n-3 à baisser les concentrations de 4-HNE dans la NP, mais également à moduler le stress oxydant et les marqueurs pro-inflammatoires. Enfin, nous avons démontré, en collaboration avec l’équipe du Dr Friel, que certains peptides isolés du lait humain (par un processus mimant la digestion) permettent également une modulation du stress oxydant et du processus inflammatoire. Conclusion : Le stress oxydant exogène issu de la NP a conduit par activation de facteurs de transcription intra-hépatiques au déclenchement d’un processus inflammatoire potentiellement responsable du développement de maladies hépatiques reliées à la NP telle que la cholestase. Dans ce sens, les AGPI n-3 et les peptides antioxydants peuvent se poser en tant qu’alternatives crédibles à la photoprotection. / Introduction: Premature infants usually born before full term require intensive care to continue to grow up outside the uterine environment. Premature newborns are born with gastrointestinal systems that are too immature to absorb nutrients safely. Therefore they receive their initial nutrients through intravenous feeding, called total parenteral nutrition which delivers simple nutrients directly into bloodstream. However, light exposed-TPN can generate oxidant molecules such as lipid hydroperoxides, which can potently break up into hydroxy-alkenals. Prolonged use of TPN is also a cause of liver disease in which oxidative stress and necro-inflammation are major components. Thus, we hypothesize that lipid aldehydes contained in TPN are associated with oxidative stress and hepatic inflammation developments. Objectives: The aim of our study is to assess the relationship between quantities of hydroxyl-alkenals generated in TPN and effects on oxidative stress biomarkers and cell-signalling pathways molecules implicated in hepatic inflammation induction. To this end, we measure lipid peroxidation in the TPN lipid emulsion in and the consequence of continuous infusion of hydroxy-alkenals on markers of oxidative stress, on cell-signaling pathway mediated by the NFkB, and on liver inflammation induction. Following these data, we also worked on alternatives of photoprotection, which is the only optimal method for preventing lipid peroxidation, but unfortunately clinically impractical. Results: In vitro studies have highlighted the generation of 4-HNE in the TPN, increased under light exposure. In this context, we have demonstrated that the addition of multivitamins in the lipid emulsion cannot be a valuable alternative to photoprotection. Concerning the biological validation in our guinea pig animal model, our results demonstrated that the increase of GS-HNE adducts was due to increased 4-HNE in the TPN, and does not provide from endogenous peroxidation. Our data also indicate that the increase of hepatic 4-HNE led to an activation of NFkB, responsible for the activation of the transcription of proinflammatory genes TNF-α, IL-1. In the next study, we have evaluated the ability of a lipid emulsion enriched with n-3 polyunsaturated fatty acids (PUFA) to reduce 4-HNE concentrations generated in TPN, and to modulate oxidative stress markers and pro-inflammatory process on the same animal model. We also have demonstrated, in collaboration with Dr Friel’s team, that two antioxidant peptides (derived from a process mimicking digestion process of human milk) allow also a modulation of oxidative stress and inflammatory process in the liver. Conclusion: This form of exogenous oxidative stress from the TPN led to an inflammatory process resulting from the activation of intrahepatic transcription, which is potentially responsible of liver disease development such as cholestasis. In this sense, the n-3 PUFA and antioxidant peptides may arise as a valuable alternative of photoprotection.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Made available in DSpace on 2016-06-02T20:44:15Z (GMT). No. of bitstreams: 1 5849.pdf: 1061693 bytes, checksum: 88926ff22d4e1191409542e3b320cf8c (MD5) Previous issue date: 2014-02-25 / Financiadora de Estudos e Projetos / The Neonatal ICUs are designed for newborns at high risk, as in the case of premature infants.The environment in the NICU is a protective factor for life, but may prove to be inappropriate for the neurological development of preterm, specifically in relation to visual aspects. The aim of this study was to develop and propose a protocol for evaluating the context of the NICU, as a checklist to identify the risk and protective factors visual development of premature infants. Moreover , had the following specific objectives : Map and describe the national and international scientific literature on the Neonatal Intensive Care Units in respect of related visual development of premature variables ; Identify the risk factors and protection to the visual development of premature newborns present in neonatal intensive care units , expressed in the literature. The methodology was based on bibliometric analysis of papers retrieved on the basis of national and international data: VHL, ScienceDirect and Scopus. Bibliometric indicators analyzed under the classification into two categories were produced: Category 1 - Primary Issue (TP) and Category 2 - Issue Secondary (TS). Since the focus of this study lies in the studies classified into Primary Issue , were analyzed and categorized into the following themes : " Retinopathy of Prematurity Risk Factors , Incidence, Prevalence , Screening and Prevention " , " Retinopathy of Prematurity Treatment " , " Normal Development " , " Retinopathy of Prematurity Instrument " , " Environment and Retinopathy of Prematurity " Retinopathy of Prematurity Theory " . These studies the risk factors and protection to the visual development of preterm infants were identified. These factors allowed the construction of check list (initially with partial version and then the final version ). As most of the studies ( 97.7 % ) address on the Retinopathy of Prematurity (ROP) , the instrument will help identify risk and protective for the development of ROP in premature infants in the NICU context factors . It is intended in the future instruments available to professionals in neonatal ICUs, thereby preventing ROP in premature and thereby reduce the incidence and progression of disease. / As UTIs Neonatais são destinadas aos recém-nascidos de alto risco, como no caso dos prematuros. O ambiente na UTI Neonatal é um fator de proteção à vida, mas pode vir a ser inapropriado para o desenvolvimento neuropsicomotor do prematuro, especificamente em relação aos aspectos visuais. O objetivo geral deste trabalho foi elaborar e propor um protocolo de avaliação do contexto da UTI Neonatal, na forma de um check list, para identificação de fatores de risco e proteção ao desenvolvimento visual dos prematuros. Além disso, teve como objetivos específicos: Mapear e descrever a produção científica nacional e internacional sobre as Unidades de Terapia Intensivas Neonatais em relação às variáveis relacionadas ao desenvolvimento visual dos prematuros; Identificar os fatores de risco e proteção ao desenvolvimento visual de recém-nascidos prematuros presentes em unidades de terapia intensivas neonatais, expressos na literatura. A metodologia utilizada foi a análise bibliométrica dos trabalhos recuperados nas bases de dados nacionais e internacionais: BVS, ScienceDirect e Scopus. Foram produzidos indicadores bibliométricos analisados sob a classificação em duas categorias: Categoria 1- Temáticas Primárias (TP) e Categoria 2- Temáticas Secundárias (TS). Como o foco deste estudo recai nos estudos classificados em Temáticas Primárias, foram analisados e categorizados nos seguintes temas: Retinopatia da Prematuridade Fatores de Risco, Incidência, Prevalência, Triagem e Prevenção , Retinopatia da Prematuridade Tratamento , Desenvolvimento Normal , Retinopatia da Prematuridade Instrumento , Retinopatia da Prematuridade Ambiente e Retinopatia da Prematuridade Teoria . Foram identificados nestes estudos os fatores de risco e proteção ao desenvolvimento visual dos prematuros. Estes fatores permitiram a construção do check list (inicialmente com a versão parcial e depois a versão final). Como a maioria dos estudos (97,7%) abordam sobre a Retinopatia da Prematuridade (ROP), o instrumento irá auxiliar na identificação dos fatores de risco e proteção ao desenvolvimento da ROP nos prematuros no contexto da UTI Neonatal. Pretende-se no futuro disponibilizar o instrumento aos profissionais que atuam em UTIs Neonatais, para assim prevenir a ROP em prematuros e com isso diminuir a incidência e progressão da doença.

No description available.

No description available.

La première partie de ce travail vise à étudier les effets de la présence vocale maternelle, chant et la parole, sur l'état clinique de l'enfant prématuré, évalué en termes de paramètres physiologiques (fréquence cardiaque, oxygénation du sang et événements critiques) et sur son état comportemental. Dans cette partie on observe donc la mère comme sujet actif et stimulant, par rapport à un bébé prématuré qui, à travers des indices comportementaux et physiologiques, montre bénéficier de la stimulation directe de la voix de la mère. La comparaison des périodes avec et sans stimulation vocale maternelle révèle un plus haut niveau de saturation en oxygène et la fréquence cardiaque et significativement moins d'événements critiques négatives (p <0,0001) lorsque la mère parle et chante. Une connexion renouvelé à la voix de la mère peut être une expérience importante et significative pour les enfants prématurés. L'exposition à la parole et au chant de la mère montre des effets bénéfiques précoces importantes sur l'état physiologique du bébé, tels que les niveaux de saturation en oxygène, le nombre d'événements critiques et la prévalence de l'état d'alerte calme. Ces résultats ont des implications pour les interventions en USIN, encourageant l'interaction maternelle avec leurs nouveau-nés prématurés médicalement stables.La deuxième partie inverse le point de vue, visant à évaluer les effets du comportement de l'enfant sur la mère qui chante et parle: on évalue la capacité de l'enfant à être un partenaire actif dans ces première proto-interactions en vis à vis. On analyse en termes acoustiques les effets du comportement du nouveau-né sur la voix maternelle directe. La voix de la mère présente des caractéristiques spécifiques en termes de minimum de fréquence fondamentale (F0min) pendant les 5 secondes qui précèdent les réactions positives des nouveau-nés. Les mères ont élevé la hauteur de leur voix en présence d'un comportement positif de l'enfant, en particulier dans la communication parlée. En outre, la variance de la F0 (F0sd), augmente en particulier dans la langue maternelle, lorsque l'enfant ouvre les yeux. Ces résultats suggèrent que les comportements positifs des prématurés nés hospitalisés, dans le contexte des interactions, peuvent évoquer, dans les mères des formes précoces de attachement, mesurée par l'augmentation des caractéristiques du parler-bébé. En particulier, le F0min a un rôle crucial pour détecter la réactivité émotionnelle de la mère au cours des interactions vocales. Dans la dernière partie, enfin, on analyse dans le détail quelques épisodes de régulation réciproque dans la dyade mère-enfant: une hypothèse hasardeuse. Il s’agit de trouver, dans une relation dyadique profondément compromise, les traces de syntonisations affectives, des imitations amodales, des épisodes d’ajustement mutuel, de désengagements suite aux stimulations excessives. Nous avons analysé trois situations différentes dans lesquelles les mères et les nouveau-nés prématurés interagissent. Les trois séquences présentent (a) un cas de imitation intermodale, où la mère accompagne par la voix et du visage imitation changement postural du nouveau-né; (b) une séquence interactive dans laquelle on peut identifier un moment d’échange du regard entre les deux partenaires, qui est interrompue et réglementé par le bébé prématuré. La troisième microanalyse (c) vise à montrer les caractéristiques acoustiques d'une interaction vocale entre l’adulte (père et mère) et le nouveau-né prématuré. / This thesis investigated the effects, the responsiveness, the characteristics of maternal voice speaking and singing to preterm infants in NICU.In Study 1 we investigated the effects of live maternal speaking and singing on physiological parameters of preterm infants in the NICU and to test the hypothesis that vocal stimulation can have differential effects on preterm infants at a behavioural level.Methods: Eighteen mothers spoke and sang to their medically stable preterm infants in their incubators over 6 days, between 1 and 2 pm. Heart rate (HR), oxygen saturation (OxSat), number of critical events (hypoxemia, bradycardia and apnoea) and change in behavioural state were measured.Results: Comparisons of periods with and without maternal vocal stimulation revealed significantly greater oxygen saturation level and heart rate and significantly fewer negative critical events (p < 0.0001) when the mother was speaking and singing. Unexpected findings were the comparable effects of maternal talk and singing on infant physiological parameters and the differential ones on infant behavioural state.Conclusion: A renewed connection to the mother’s voice can be an important and significant experience for preterm infants. Exposure to maternal speech and singing shows significant early beneficial effects on physiological state, such as oxygen saturation levels, number of critical events and prevalence of calm alert state. These findings have implications for NICU interventions, encouraging maternal interaction with their medically stable preterm infants. In Study 2 we aimed (1) to examine qualitative change in maternal infant-directed singing and speaking, prior to a positive behaviour display by the preterm infants (i.e. eye opening and lip-corner raising), (2) to analyse the effects of the two behaviours on concomitant acoustic characteristics of maternal infant-directed vocal communication (IDVC), (3) to determine whether changes in maternal voice quality persist after the infant’s positive behavioural display.Methods: Participants included 10 mothers who were asked, on different occasions, to speak and sing to their medically stable infants in incubators, 128 vocalization extracts were examined. Results: The maternal voice shows specific characteristics in terms of fundamental frequency minimum (F0min) during the 5 seconds before the positive reactions of newborns. Mothers raised their pitch in presence of infant’s positive behaviour, especially during the speaking stimulation, reinforcing the higher pitched ID speech. Moreover, the variance of the F0 (F0sd), increases in particular in the maternal speaking, when the infant opens the eyes. Conclusions: These findings suggest that the preterm hospitalized infants’ positive displays, in the context of interactions, can evoke in mothers early forms of attachment, measured by the increase of the characteristics of Infant Directed Speech. In particular the F0min has a crucial role for detecting maternal emotional responsiveness in contingent vocal interactions. In the third part we aimed to analyse, with qualitative methods, the interaction between mothers and preterm infants. We will analyse three different situations in which mothers and preterm infants interact. The three sequences will present (a) a case of intermodal imitation, where the mother accompanies through voice and facial imitation postural change of the newborn; (b) an interactive sequence in which we can identify a moment of eye contact between the two partners, which is interrupted and regulated by the premature baby. The third microanalysis (c) aims to show the acoustical features of a vocal interaction bertween adults (mother and father) and their preterm infants.

A prematuridade está associada com uma alta incidência de complicações no período neonatal sendo uma das mais importantes a retinopatia da prematuridade (ROP) e suas seqüelas: ambliopia, estrabismo, cegueira. Estudos indicam que alterações no fluxo sanguíneo retiniano estão envolvidas na patogênese da ROP causando um crescimento vascular anormal dos vasos da retina. A análise por ultrassonografia Doppler (USD) dos vasos da órbita permite uma estimativa do fluxo sanguíneo local. Objetivo: estabelecer valores de velocidade do fluxo sanguíneo e de seus índices na artéria oftálmica em recém-nascidos pré-termos de muito baixo peso (RNPTMBP) "saudáveis" do nascimento até a alta. Metodologia: Coorte de recémnascidos pré-termos de muito baixo peso, nascidos na UTI Neonatal do Hospital de Clínicas de Porto Alegre (HCPA) no período de agosto de 2006 a abril de 2008. Foram obtidas as medidas de velocidade sistólica (VS), velocidade diastólica (VD), índice de pulsatilidade (IP) e índice de resistência (IR) da artéria oftálmica por USD nas primeiras 24 horas de vida, com sete dias, com 28 dias e no momento da alta hospitalar. Incluímos RN com peso de nascimento abaixo de 1500 gramas e idade gestacional <= 32 semanas, sem ROP graus 2 e 3, e sem hemorragia peri-intraventricular (HPIV) graus 3 e 4. A análise estatística foi realizada utilizando teste t pareado e análise de variância (ANOVA). Resultados: Foram estudados 46 RNPTMBP (92 olhos examinados). No primeiro exame os valores em média do fluxo sanguíneo e índices da artéria oftálmica foram: VS 18,42 cm/s; VD 6,22 cm/s; IP 1,40; IR 0,70 e com 28 dias de vida: VS 22,38 cm/s; VD 6,97 cm/s; IP 1,51; IR 0,75 (p<0.001). Não houve diferença significativa entre as medidas obtidas no olho direito e no esquerdo, e entre primeiro e segundo exames. Da mesma forma, as medidas obtidas com 28 dias de vida foram similares aquelas no momento da alta hospitalar. Conclusão: Ocorre uma elevação nas velocidades de fluxo sanguíneo da artéria oftálmica do período pós-natal até a alta em recémnascidos pré-termo de muito baixo peso de nascimento "saudáveis". Os índices calculados não mostraram diferença estatisticamente significativa. O conhecimento deste padrão normal poderá auxiliar na prevenção e no screening para detecção de doença ocular. / Retinopathy of prematurity (ROP) is a multifactorial disease of very low birth weight infants (VLBWI), and the vascular component has an important role. Evaluation of retinal blood flow is essential to understand its physiopathology. Objective: To establish normal blood flow velocity and Doppler indices of the ophthalmic arteries from birth to discharge of "healthy" VLBWI.Methods: Cohort study of newborns with birth weight < 1500 grams and gestational age <= 32 weeks born at our Hospital from August 2006 to April 2008. Doppler ultrasound exam was done in both eyes in the first 24 hours after birth, at 7 and 28 days old, and at hospital discharge for systolic velocity (SV), diastolic velocity (DV), pulsatility index (PI) and resistance index (RI). We excluded those with ROP stage 2 and higher, periintraventricular hemorrhage grades 3 and 4, and death. Statistical analysis was performed using paired t test and repeated measures ANOVA. The study was approved by our Ethic Committee.Results: 46 VLBWI (92 eyes) were studied. First exam: SV 18.40 cm/s; DV 6.23 cm/s; PI 1.41; RI 0.70 and 28 days after birth: SV 22.30 cm/s; DV 6.77 cm/s; PI 1,50; RI 0.75 ( p<0.001). Both eyes had similar Doppler findings at all examined moments. SV and DV increased significantly from the first 24 hours to hospital discharge. There were no significant changes during the study period in PI and RI. Conclusions: There was a increase of SV and DV retinal blood flow from birth to hospital discharge in "healthy" VLBWI; other Doppler measurements were stable. Knowing this normal pattern will provide prevention and screening for ROP.

Objetivo: Avaliar o impacto do nascimento pré-termo sobre a mortalidade neonatal numa série temporal de 2000 a 2014 no município de Porto Alegre. Métodos: Estudo de coorte retrospectivo de base populacional com a utilização dos registros oficiais de nascimento e de morte ligados de 2000 a 2014 de recém-nascidos com menos de 32 semanas de idade gestacional de Porto Alegre. Foram utilizadas como variáveis independentes idade e escolaridade maternas, número de consultas pré-natal, tipo de hospital, via de parto, idade gestacional (IG), sexo e peso do recém-nascido e ano de nascimento. O desfecho primário foi morte neonatal (morte ocorrida de 0 a 27 dias de vida). Foram excluídos recém-nascidos duplicados, com menos de 500 gramas ou com peso inconsistente, com IG menor de 22 semanas, com anomalias congênitas, gemelares e de partos extra hospitalares. Foi calculado razão de risco (hazard ratio-HR) ajustado para o risco de morte neonatal para todas as variáveis independentes através de análise de sobrevivência pela regressão de Cox para riscos proporcionais com nível de significância p<0,05. Posteriormente, foi realizado análise por quintil de peso de nascimento. Resultados: Foram analisados os registros de 3282 recém-nascidos com IG menor que 32 semanas de 2000 a 2014 dos quais, 643 foram ao óbito neonatal e 2639 sobreviveram. O risco de morte neonatal absoluto diminuiu de 25% no triênio 2000 a 2002 para 17% no período de 2012 a 2014. O mesmo risco ajustado foi significativamente menor para os recém-nascidos de menor peso (média de 673 ± 86 gramas) de parto cesáreo [HR 0,57 (IC95% 0,45-0,73)] enquanto que, para os de maior peso (média 1.834 ± 212 gramas) este risco inverteu-se e foi significativamente maior para esta via de parto [HR 8,44 (IC95% 1,86-38,22)]. Conclusão: Houve diminuição do risco absoluto de morte neonatal entre os recém-nascidos com IG menor de 32 semanas nos últimos anos em Porto Alegre e o aprimoramento do uso racional do parto cesáreo nos hospitais do município pode contribuir para uma redução ainda maior desse indicador. / Objective: Assess impact of prematurity on neonatal mortality from 2000 to 2014 in Porto Alegre through official information systems. Methods: Populational base retrospective cohort study with record linkage of birth and death database certificates. There were included records of birth and death from 2000 to 2014 of infants with less than 32 weeks of gestational age of Porto Alegre. There were used mother age and schooling, number of antenatal visits, delivery type, hospital type, gestational age, sex and birth weight and birth year of infant as independent variables. The primary outcome examined was neonatal death (death at 0-27 days of age). There were excluded infant records duplicate, with less than 500g or inconsistent birthweight, with gestational age less than 22 weeks, with congenital anomalies, twins and out-of-hospital births. Adjusted Hazard Ratio (HR) were calculated for the risk of neonatal death for all independent variables through Cox regression for survival analysis with p-value<0,05 for statistical significance. The analysis also was performed at quintiles of birthweight. Results: There were 3282 infant records of infants with less than 32 weeks of gestational age from 2000 to 2014 who progress to 643 neonatal deaths or 2639 survival. The neonatal death absolut risk decline from 25% at 2000-2002 period to 17% at 2012-2014 period. The adjusted neonatal death risk was significantly reduced for lightest preterm (mean birthweight 673g ± 86) born by C-section [HR 0.57 (CI95% 0.45-0.73)], while, for the heaviest ones (mean birthweight 1.834g ± 212) the risk was significantly increased for that delivery route [HR 8.44 (CI95% 1.86-38.22)]. Conclusion: The absolut risk of neonatal death in infants with less than 32 weeks of gestational age has been declining over the years and more rational use of C-section can contribute to further improving the neonatal survival.

Introdução: Sabe-se que os fatores angiogênicos e antiangiogênicos encontram-se alterados nas gestações com pré-eclâmpsia (PE), mas se desconhece seu comportamento nestes recém-nascidos (RNs). Objetivo: Dosagem do vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFtl-1) e heterodímero vascular endothelial growth factor/placental growth factor (VEGF/PlGF) em pré-termos filhos de mães com PE. Métodos: Incluídos: RNs com peso de nascimento < 2.000 g e idade gestacional (IG) ≤ 34 semanas, divididos em dois grupos: filhos de mães com e sem PE. Excluídos: RNs transferidos de outra instituição com mais de 72 horas de vida, óbito antes da coleta dos exames, malformação congênita maior, erros inatos de metabolismo, gestações múltiplas, mães com infecção do grupo sífilis, toxoplasmose, rubéola, citomegalovírus, herpes (STORCH) ou vírus da imunodeficiência humana (HIV) e doença autoimune. Coletado sangue nas primeiras 72 horas de vida, e nos RNs que permaneceram internados, foi realizada uma segunda coleta com 28 dias. Foi utilizado método ELISA para a dosagem do VEGF, sFlt-1 e VEGF/PlGF. Resultados: Incluídos: 88 pacientes (37 filhos de mães com PE, 51 sem PE) com IG de 29,12 ± 2,96 semanas e peso de nascimento de 1223,80 ± 417,48 g. O VEGF foi menor no grupo com PE [32,45 (6,36-85,75) x 82,38 (35-130,03) pg/mL], p = 0,001 e o sFlt-1 foi maior no grupo com PE [1338,57 (418,8-3472,24) x 318,13 (182,03-453,66) pg/mL], p < 0,001. Na análise multivariada, o VEGF foi 80% menor e sFlt-1 13,48 vezes maior no grupo com PE. O sFlt-1 foi maior nos RNs pequenos para idade gestacional (PIG) do que nos adequados para idade gestacional (AIG) [1044,94 (290,64-3472,24) x 372,67 (236,75-860,14) pg/mL], p = 0,013. No grupo com PE, houve um aumento [≠ 151,71 (76,55-226,86); p < 0,001] entre as dosagens do VEGF entre a primeira e a segunda coleta com 28 dias, já o sFlt-1 diminuiu [≠ 1941,44 (2757,01-1125,87); p < 0,001] entre as duas dosagens. O VEGF/PlGF foi maior nos filhos de mães com PE [20,69 pg/mL (12,79-52,86) x 12,19 pg/mL (0,03 -21,58)], p = 0,003. Esses achados mantiveram-se na análise multivariada, com o VEGF/PlGF 1,05 vezes maior nos filhos de mães com PE. Os níveis de VEGF/PlGF foram inversamente proporcionais ao peso de nascimento, com p < 0,001 e r = - 0,418. Na segunda coleta com 28 dias de vida não houve diferença entre os dois grupos. Conclusão: Os maiores níveis de sFlt-1 e VEGF/PlGF e menores níveis de VEGF no grupo com PE, assim como maiores concentrações de sFlt-1 nos PIG refletem uma predominância dos mecanismos antiangiogênicos na PE e na restrição de crescimento. Os níveis de VEGF/PlGF também foram relacionados ao peso de nascimento, sendo inversamente proporcionais. O estado antiangiogênico da PE tende à normalização com 28 dias de vida. / Background: It is known that angiogenic and antiangiogenic factors are altered in pregnant women with preeclampsia (PE), but the pattern of expression of these factors in their newborn infants remains unknown. Objective: To measure vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and vascular endothelial growth factor/placental growth factor (VEGF/PlGF) heterodimer levels in preterm neonates born to mothers with PE. Methods: Neonates with birth weight < 2,000 g and gestational age ≤ 34 weeks were included and divided into two groups: born to mothers with and without PE. Exclusion criteria were as follows: the neonate was transferred from another institution after 72 hours of life; the neonate died before blood collection; major congenital anomalies; inborn errors of metabolism; congenital infections (STORCH screen); HIV-positive mothers; multiple pregnancies; and mothers with autoimmune disease. Blood was collected from neonates within the first 72 hours of life, and a second sample was collected at 28 days of life from those who remained hospitalized. VEGF, sFlt-1 and VEGF/PlGF levels were measured using the ELISA method. Results: A total of 88 neonates were included (37 born to mothers with and 51 without PE), with mean gestational age of 29.12 ± 2.96 weeks and birth weight of 1223.80 ± 417.48 g. VEGF was lower in the group with PE [32.45 (6.36-85.75) vs. 82.38 (35-130.03) pg/mL] (p = 0.001), and sFlt-1 was higher in the group with PE [1338.57 (418.8-3472.24) vs. 318.13 (182.03-453.66) pg/mL] (p < 0.001). In the multivariate analysis, VEGF was 80% lower and sFlt-1 was 13.48 times higher in the group with PE. sFlt-1 concentration was higher in neonates small for gestational age (SGA) than in those appropriate for gestational age (AGA) [1044.94 (290.64-3472.24) vs. 372.67 (236.75-860.14) pg/mL] (p = 0.013). In the group with PE, VEGF levels increased [≠151.71 (76.55-226.86); p < 0.001) between the first and second collection (at 28 days), while sFlt-1 levels decreased [≠1941.44 (2757.01-1125.87); p < 0.001] between the two measurements. Median VEGF/PlGF levels were significantly higher among infants born to mothers with PE (20.69 pg/mL [12.79-52.86] vs. 12.19 pg/mL [0.03-21.58], p = 0.003). These findings held on multivariate analysis, with VEGF/PlGF levels 1.05-fold higher in the PE group. VEGF/PlGF levels were inversely proportional to birth weight (p < 0.001, r = - 0.418). There were no between-group differences in blood samples collected at age 28 days. Conclusion: Higher sFlt-1 and VEGF/PlGF and lower VEGF levels in the group with PE, as well as higher sFlt-1 levels in SGA neonates, reflect a predominance of antiangiogenic mechanisms in PE and growth restriction. The VEGF/PlGF levels also affected the weight at birth, with VEGF/PlGF levels inversely proportional to birth weight. This antiangiogenic state of PE shows a trend toward normalization within 28 days of life.

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No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) tese_6422_2011_Milena Batista Santos.pdf: 4504155 bytes, checksum: 2e5a0bc2576eeeb83dab522c8a5772df (MD5) / Há evidências de que fatores de risco para ocorrência de Doenças Crônicas não Transmissíveis têm início silencioso em etapas precoces do desenvolvimento. Essa questão foi suscitada a partir de estudos que relacionaram o peso ao nascer com o desenvolvimento de doenças na vida adulta, cuja hipótese se baseia na ideia de que o feto seria programado intra-útero, principalmente por fatores nutricionais que influenciariam no metabolismo e na fisiologia do indivíduo por toda a vida. O objetivo deste estudo foi investigar a saúde cardiovascular de crianças de 9 a 10 anos e sua relação com as condições de nascimento (baixo peso ao nascer e prematuridade) e de amamentação. Foram avaliadas 231 crianças, de ambos os sexos, matriculadas em escolas públicas e privadas do município de Vitória/ES. As crianças compareceram em jejum, acompanhadas de seus responsáveis, no Centro de Investigação Cardiovascular da UFES para realização de exames antropométricos, laboratoriais e hemodinâmicos (pressão arterial e velocidade de onda de pulso carótida-femoral - VOP). No dia da visita, as crianças e seus responsáveis responderam a um questionário sobre questões de saúde atuais e pregressas. O teste Kolmogorov-Smirnov foi utilizado para testar a normalidade das variáveis contínuas e depois realizados os testes t de Student para amostras independentes ou Mann Whitney. O teste do qui-quadrado (X2) foi utilizado para avaliar a distribuição das variáveis categóricas. Variáveis hemodinâmicas, categorizadas em tercis, foram analisadas utilizando ANOVA a uma via, seguida do teste de Tukey para avaliação entre grupos. Variáveis contínuas foram correlacionadas utilizando teste de Pearson ou de Spearman. Aplicou-se a análise de regressão linear múltipla para identificar a contribuição parcial e total dos fatores na determinação dos valores de VOP e de pressão arterial. O nível de significância estabelecido para todos os testes foi de =0,05. Observou-se maior frequência de meninos nas classes socioeconômicas A+B (61%) e na condição de sobrepeso (meninas= 38%, meninos= 51%, p=0,05). O baixo peso ao nascer foi mais frequente entre meninas (meninas=18%, meninos=7%, p=0,01). Crianças do sexo masculino apresentaram maiores médias de PAS (p=0,05), VOP (p=0,03) e peso ao nascer (p<0,01), quando comparados às meninas. A PAS foi maior entre as crianças nascidas com peso igual ou superior a 2500g. Não foi encontrada diferença estatística das médias de PAD e VOP e peso ao nascer. A prematuridade e amamentação também não foram associadas aos níveis pressóricos e à rigidez arterial. O IMC apresentou associação positiva e significativa com PAS, PAD e VOP. A análise de regressão linear indicou que 44% do aumento da PAS nas crianças avaliadas são explicados pelo IMC. Para a PAD as variáveis que se mantiveram no modelo foram o IMC e VOP, explicando 38% nas alterações de PAD. Os fatores que explicaram as alterações na VOP foram IMC e PAD (r=0,29; p<0,01). Conclui-se que a hipótese de programação fetal e infantil não foi comprovada neste estudo e que apenas o IMC foi associado ao aumento da PAS, da PAD e da VOP, após ajuste por sexo. / There are evidences that risk factors for the occurrence of Chronic Non-Communicable diseases begin silently in early stages of development. This question was raised from studies related to birth weight in the development of diseases in adulthood, whose hypothesis is based on the idea that the fetus would be programmed in utero, mainly nutritional factors that influence the metabolism and physiology the individual throughout life. The objective of this research was investigate the cardiovascular health of children 9-10 years and their relation to perinatal conditions (low birth weight and prematurity) and breastfeeding. We evaluated 231 children of both sexes enrolled in public and private schools of the city of Vitória / ES. The children attended fasting, were accompanied by their guardians to the Cardiovascular Research Center of UFES for exams anthropometric, laboratory and hemodynamic (blood pressure and pulse wave velocity carotid-femoral). On the day of the visit, children and their parents completed a questionnaire on health issues, and were instructed to collect the urine of 12 hours night. The Kolmogorov-Smirnov test was used to test the normality of continuous variables and then performed the Student t test for independent samples or Mann Whitney. The chi-square (X2) was used to assess the distribution of categorical variables. Hemodynamic variables, categorized into tertiles were analyzed using ANOVA to a route followed by the Tukey test to evaluate between groups. Continuous variables were correlated using Pearson or Spearman. We applied the multiple linear regression analysis to identify the contribution partial and total factor in determining values of PWV and blood pressure. The significance level for all tests was set at α = 0.05. There was a higher frequency in boys socioeconomic classes A + B (61%) and overweight status (girls = 38%, boys = 51%, p = 0.05). The low birth weight was more common among girls (girls = 18%, boys = 7%, p = 0.01). Male children had higher mean SBP (p = 0.05), PWV (p = 0.03) and birth weight (p <0.01) when compared to girls. SBP was higher among infants born weighing less than 2500g. There was no statistical difference of mean DBP and PWV and birth weight. Preterm birth and breastfeeding were not associated with blood pressure and arterial stiffness. BMI showed significant positive association with increased SBP, DBP and PWV. Linear regression analysis indicated that 44% of the increase of SBP in children evaluated are explained by BMI. For DBP the variables that remained in the model were BMI and PWV changes in explaining 38% of PAD. Factors that explained the changes in PWV were BMI and DBP (0.29, p <0.01). We conclude that the hypothesis of fetal programming and child was not proven in this study and that only BMI was associated with increased SBP, DBP and PWV after adjustment for sex.