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.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-12-15T14:26:56Z No. of bitstreams: 1 hericasilvadutra.pdf: 3223242 bytes, checksum: 250a7a107719f5970fd463ae5025faf6 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-12-15T14:39:16Z (GMT) No. of bitstreams: 1 hericasilvadutra.pdf: 3223242 bytes, checksum: 250a7a107719f5970fd463ae5025faf6 (MD5) / Made available in DSpace on 2016-12-15T14:39:16Z (GMT). No. of bitstreams: 1 hericasilvadutra.pdf: 3223242 bytes, checksum: 250a7a107719f5970fd463ae5025faf6 (MD5) Previous issue date: 2010-03-19 / Um aumento na sobrevida de recém-nascidos cada vez mais imaturos tem sido observado em consequência dos avanços em neonatologia. Crianças de muito baixo peso ao nascer (MBPN) e extremo baixo peso ao nascer (EBPN) podem apresentar como desfechos complicações a curto e longo prazo devido à assistência intensiva no período neonatal, o que pode determinar alterações em sua qualidade de vida (QV). Os objetivos foram avaliar a QV de crianças nascidas MBPN e EBPN a partir da utilização de questionário validado; descrever domínios incluídos no instrumento e estabelecer um perfil de satisfação da criança a partir do autorrelato e da perspectiva de seus responsáveis. Foram avaliadas 40 crianças e 45 responsáveis selecionados a partir dos dados do serviço de follow-up do HU-UFJF. A QV foi avaliada a partir do AUQUEI. Outros dados de interesse foram obtidos a partir de avaliação dos prontuários e inquérito direto ao responsável pela criança. A idade das crianças variou de 3 a 7 anos. O peso médio, ao nascer, foi 1173,13 (± 222,84). A idade gestacional variou de 24 a 33 semanas (29,40 ± 2,08). A QV média na avaliação das crianças foi de 49,75 (± 5,973) e na avaliação dos responsáveis 49,24 (± 6,675). A correlação entre os escores totais de crianças e responsáveis obteve intensidade de nível razoável (Correlação de Pearson = 0,391 / p = 0,013). Entretanto, a classificação final da QV (prejudicada x satisfatória), obteve concordância pobre (índice de Kappa = 0,143 / p = 0,457). A QV de crianças nascidas MBPN e EBPN foi considerada satisfatória na perspectiva delas mesmas e de seus responsáveis. A concordância entre os escores das crianças e seus pais foi alta. Entretanto a classificação em QV satisfatória e prejudicada teve concordância pobre, o que reforça a importância de valorizar o auto-relato de crianças e adicionar a perspectiva dos pais na avaliação da QV. O domínio lazer foi considerado o componente mais importante da QV na infância pelas crianças e responsáveis. / An increase in the number of more immature newborn survivors has been observed due to neonatology advances. Children born very low birth weight (VLBW) and extremity low birth weight (ELBW) can present as outcomes complications at short and long time, due to intensive care assistance in the neonatal period, what can determine alterations in their quality of life (QoL). This study aims: to evaluate the QoL of children born VLBW and ELBW using a validated questionnaire; to describe domains included in the instrument and to establish a satisfaction profile of the child using self-report and parent proxy-report. 40 children and 45 parents were selected from data at the follow-up service of the HU-UFJF. The QoL was evaluated using the AUQUEI. Other interest data had been collected from follow-up records and direct inquiry to the responsible one for the child. The age of the children varied from 3 to 7 years. The average birth weight was 1173,13g (± 222,84). The gestacional age varied from 24 to 33 weeks (29,40 ± 2,08). The QoL score in the self-report was 49,75 (± 5,973) and in the proxy-report was 49,24 (± 6,675). The correlation between the total scores of children and parents has got intensity of reasonable level (Correlation of Pearson = 0,391 / p = 0,013). However, the QoL final classification (damaged x satisfactory), got poor agreement between them (index of Kappa = 0,143 / p = 0,457). The QoL of children born VLBW and ELBW was considered satisfactory in the self-report and proxy-report. The total scores agreement between them were high, however the classification in satisfactory / damged QoL had poor agreement, what strengthens the importance to evaluate the self-report and to add the proxyreport of the QoL. The domain leisure was considered the most important component of the QoL in childhood by self and proxy-report.

INTRODUÇÃO: Baixos níveis séricos de fator de crescimento insulin-like I (IGF- 1) ao nascimento têm sido considerados um fator de risco para o desenvolvimento da retinopatia da prematuridade em recém-nascidos prematuros de extremo baixo peso. Isto se deve ao seu papel como fator permissivo para o fator de crescimento endotelial vascular (VEGF) exercer sua função no desenvolvimento normal e patológico dos vasos da retina. OBJETIVO: Testar a hipótese de que a administração do JB-1 (um análogo do IGF-1 que inibe de forma potente a auto-fosforilação do receptor do IGF-1 pelo IGF-1) durante a hiperóxia previne a retinopatia induzida por oxigênio em nosso modelo experimental em ratos. MATERIAL E METODOS: Ratos recém-nascidos foram expostos a 50% de oxigênio com três episódios consecutivos de hipóxia (12% de oxigênio) do nascimento ao 14º dia de vida. Os ratos foram tratados com injeções subcutâneas de 1) JB-1 (1g/d) nos três primeiros dias de vida (JB-1 x3); 2) JB- 1(1g/d) por dias alternados do 1º ao 13º dias de vida (JB-1x7) 3) ou volume equivalente de solução salina. Grupos controles foram criados em ar ambiente nas mesmas condições, exceto pelo ciclo de hiperóxia/ hipóxia. Os grupos foram analisados após a exposição ao oxigênio no 14º dia de vida ou deixados em ar ambiente por mais sete dias até o sacrifício, no 21º dia de vida. Determinou-se as dosagens sistêmicas e oculares de fator de crescimento endotelial vascular (VEGF), receptor tipo1 solúvel do fator de crescimento endotelial vascular (sVEGFR-1) e fator de crescimento insulin-like I (IGF-1), associados a análise da vascularização retiniana e do perfil dos genes relacionados à angiogênese retiniana. RESULTADOS: O tratamento com JB-1x3 resultou em supressão efetiva da retinopatia induzida por oxigênio, sem efeitos adversos no crescimento somático e foi associado a um aumento do sVEGFR-1 quando comparado com o JB-1x7. Ao contrário, o tratamento com JB-1x7 durante a exposição ao oxigênio levou à diminuição do peso corpóreo e níveis mais altos de IGF-1 e VEGF relacionados à presença de tortuosidades vasculares e neovascularização retiniana, quando comparado com as retinas que receberam apenas solução salina. CONCLUSÃO: O tratamento curto e sistêmico com JB-1 durante a hiperóxia resultou em prevenção da retinopatia induzida por oxigênio sem restrição do crescimento somático. Novos estudos devem ser realizados para determinar se o JB-1 pode ser usado em recém-nascidos de extremo baixo peso na prevenção da retinopatia da prematuridade / INTRODUCTION: Low serum insulin growth factor (IGF-1) levels at birth is a risk factor for the development of retinopathy of prematurity in extremely low birth weight infants. This may be due to its role as a permissive factor for vascular endothelial growth factor (VEGF) function in normal and pathologic vascular development. OBJECTIVE: To test the hypothesis that JB-1 (an IGF-1 analog that potently inhibits the autophosphorylation of the IGF-1 receptor by IGF-1) administration during hyperoxia prevents oxygen induced retinopathy in our rat model. MATERIAL AND METHODS: Neonatal rats were exposed to 50% oxygen with brief, clustered, hypoxic (12% oxygen) episodes from birth to day 14. The pups were treated with subcutaneus injections of 1) JB-1 (1g/d) on the first, second, and third day (JB-1x3) 2) JB1 (1g/d) on alternate days from first to day 13 (JB- 1x7); or equivalent volume of saline. Control littermates were raised in room air with all conditions identical except for inspired oxygen. Groups were analyzed after hyperoxia/hypoxia cycling on day 14 or allowed to recover in room air until the 21st day. Systemic and ocular VEGF, soluble VEGFR-1, and IGF-1; retinal vasculature and gene profile of retinal angiogenesis were assessed. RESULTS: JB-1x3 treatment resulted in successful suppression of oxygeninduced retinopathy with no adverse effect on anthropometric growth, which was associated with increased sVEGFR-1 compared to JB-1x7. In contrast, intermittent and long exposure to JB-1 (JB-1x7) during the hyperoxia/hypoxia cycling period resulted in decreased body weight and higher ocular IGF-1 and VEGF levels as well as vascular tortuosity and retinal neovascularization compared with saline treated retinas. CONCLUSION: Systemic treatment with JB-1 during hyperoxia results in successful prevention of oxygen-induced retinopathy with little adverse effects on anthropometric growth. Further confirmatory studies are needed to determine whether systemic JB-1 should be used in extremely low birth weight infants to prevent retinopathy of prematurity

Submitted by Neusa Fagundes (neusa.fagundes@unioeste.br) on 2018-07-10T19:46:34Z No. of bitstreams: 2 Joziana_Pastro2018.pdf: 1649555 bytes, checksum: 769cd69a9e879a09907152dd2e64987c (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-07-10T19:46:34Z (GMT). No. of bitstreams: 2 Joziana_Pastro2018.pdf: 1649555 bytes, checksum: 769cd69a9e879a09907152dd2e64987c (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-03-13 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Retinopathy of prematurity (ROP) is a vasoproliferative disease, related to blindness, in Premature Newborns (PN) who, within other factors, used oxygen during hospitalization. Early visual follow-up of preterm newborns by ophthalmologists makes it possible to identify the stage and grade of the disease and the indication of treatment or attendance of its evolution. Nursing orientation is essential to the PN relatives, since ROP is not an easily seen disease, so, parents being aware that the ophthalmologic follow-up is of vital importance for the visual recovery of the baby will make a difference in the child future visual health. Therefore, this study aims to evaluate the prevalence and evolution of ROP in PN, hospitalized in a Neonatal Intensive Care Unit (NICU) and attended at a referral ophthalmologic follow-up service. This is a quantitative, descriptive and exploratory study, carried out in the city of Cascavel. Data collection was done in medical records of PN, born between January 2014 and June 2016, hospitalized in the NICU of the West Paraná University hospital, and followed by the outpatient clinic of Cascavel Eyes Hospital, totaling 181 charts. A quantitative analysis was performed through descriptive and inferential statistic. The prevalence of ROP was 11.31% (n = 50). Relating its characteristics to evolution, the diagnoses prevalent in the PN of the study were respiratory diseases (41.99%) and among comorbidities, sepsis prevailed (63.54%). 80 PN required blood transfusion (44,20%) and 152 (83.98%) used oxygen therapy, with a predominance of mask device (n = 141; 77,90%) and orotracheal tube - TOT (n = 100; 55.25%), on average for 15 days. The highest concentration recorded was hood (45.0%). The time of use and the O2 concentration of TOT, time of mask use and time and concentration of O2 of Continuous Positive Airway Pressure (CPAP), were significant to trigger ROP. Among ROP cases, ten (5.5%) children had severe ROP and required laser treatment. All the PN diagnosed with ROP used oxygen. ROP prevailed in moderate preterm newborns (44%), with ROP grade 3 being the most severe, affecting both extreme and moderate PN. Respiratory diseases, sepsis and procedures such as blood transfusion and oxygen therapy influenced the presence of ROP, with prevalence in moderate preterm newborns. The adoption of ophthalmologic screening for ROP detection, with background examinations of the eyes in the NICU contributed to the early treatment and prevention of severe visual impairment and blindness caused by ROP. Thus, nurses are fundamentally important, from the prevention, the diagnosis until the course of the treatment and for discharge counselling. / A Retinopatia da Prematuridade (ROP) é uma enfermidade vasoproliferativa, relacionada à cegueira, em recém-nascidos prematuros (RNPT) que, dentre outros fatores, utilizaram oxigênio durante a hospitalização. O acompanhamento visual precoce de prematuros por oftalmologistas possibilita a identificação do estágio e do grau da doença, assim como a indicação de tratamento ou de acompanhamento da sua evolução. A orientação da enfermagem é primordial aos familiares dos RNPT, visto que a ROP não é uma doença de fácil visualização; portanto, os pais estarem cientes de que o acompanhamento oftalmológico é de vital importância para a recuperação visual do bebê fará diferença na vida futura da criança. Assim, este estudo objetiva avaliar a prevalência e a evolução da ROP em RNPT internados em uma Unidade de Terapia Intensiva Neonatal (UTIN) e acompanhados em serviço de seguimento oftalmológico de referência. Trata-se de uma pesquisa quantitativa, descritiva e exploratória, realizada no município de Cascavel. A coleta de dados ocorreu em prontuários de RNPT, nascidos entre janeiro de 2014 e junho de 2016, hospitalizados na UTIN do Hospital Universitário do Oeste do Paraná – HUOP, e em seguimento pelo ambulatório do Hospital de Olhos de Cascavel, totalizando 181 prontuários. Realizou-se análise quantitativa, por meio de estatística descritiva e inferencial. A prevalência de ROP foi de 11,31% (n=50). Relacionados às suas características e evolução, os diagnósticos prevalentes nos RNPT do estudo foram as doenças respiratórias (41,99%) e, entre as comorbidades, a sepse prevaleceu (63,54%). Necessitaram de transfusão de sangue 80 RNPT (44,20%), e 152 (83,98%) fizeram uso de oxigenioterapia, com predomínio do dispositivo máscara (n=141; 77,90%) e tubo orotraqueal - TOT (n=100; 55,25%), em média por 15 dias. A maior concentração registrada foi por halo (45%). O tempo de uso e a concentração de O2 de TOT, tempo de uso de máscara e tempo e concentração de O2 do Continuous Positive Airway Pressure (CPAP) foram significativos para desencadear a ROP. Dentre os casos de ROP, dez (5,5%) crianças tiveram ROP grave e necessitaram de tratamento com laser. Todos os RNPT diagnosticados com ROP fizeram uso de oxigênio. A ROP prevaleceu nos prematuros moderados (44%), sendo o grau 3 de ROP o mais grave encontrado, acometendo tanto RNPT extremos quanto moderados. Doenças respiratórias, sepse e procedimentos como a transfusão de sangue e a oxigenioterapia influenciaram na presença da ROP, com prevalência em prematuros moderados. A adoção da triagem oftalmológica para a detecção da ROP, com exames de fundo de olho sistematicamente realizados na UTIN, contribuíram para o tratamento precoce e a prevenção de deficiências visuais graves e cegueira causados pela ROP. Nesse sentido, o enfermeiro é de fundamental importância, desde a prevenção, o diagnóstico até o decorrer do tratamento e a alta.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-02-26T11:57:05Z No. of bitstreams: 1 jomaraoliveiradossantosyogui.pdf: 569717 bytes, checksum: be9f77d66f6c940acf5caed0b7a11a98 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-03-03T13:37:39Z (GMT) No. of bitstreams: 1 jomaraoliveiradossantosyogui.pdf: 569717 bytes, checksum: be9f77d66f6c940acf5caed0b7a11a98 (MD5) / Made available in DSpace on 2016-03-03T13:37:39Z (GMT). No. of bitstreams: 1 jomaraoliveiradossantosyogui.pdf: 569717 bytes, checksum: be9f77d66f6c940acf5caed0b7a11a98 (MD5) Previous issue date: 2015-03-11 / A Retinopatia da Prematuridade(ROP) é uma das principais causas de cegueira na infância. A ROP pode ser evitável ou minimizada, desde que diagnosticada em tempo hábil. Objetivos: Determinar a ocorrência de retinopatia da prematuridade e avaliar os principais fatores associados e implicados no seu desenvolvimento. Métodos: Trata-se de um estudo transversal de base hospitalar, realizado no período de 2002 a 2012, no Hospital Universitário, HU/CAES/UFJF, de Juiz de Fora/MG-Brasil. A população de estudo é composta por 392 recém-nascidos, com idade gestacional < 37 semanas e qualquer peso ao nascimento. Resultados:A ocorrência da ROP no HU/CAS/UFJF foi de 29,9%. Os fatores associados à ROP, após a regressão logística, foram: baixo peso ao nascer, oxigenoterapia (cateter nasal e CPAP) e sepse neonatal. Conclusão: O presente estudo demonstrou significantes fatores associados à ROP após realizar a análise multivariada: peso ao nascer (foi demonstrado que quanto mais baixo o peso ao nascer maior é a ocorrência da ROP), oxigenioterapia (cateter nasal e CPAP) e sepse neonatal. / The retinopathy of prematurity(ROP) is one of the main causes of childhood blindness. The ROP can be avoided or minimized as long as it is diagnosed in time. Purposes: To determine the occurrence of retinopathy of prematurity and assess the main associated factors involved in its development. Methods: Seccional study carried out from 2002 at 2012, at the University Hospital HU/CAES/UFJF, Juiz de Fora (MG) – Brazil. The sample was composed of 392 newborns, with less than 37 weeks of gestational age and any birth weight. Results: The occurrence of ROP in HU/CAS/UFJF was of 29, 9%. The associated factors of ROP after the logistic regression were birth weight, oxygen Therapy (nasal catheter, CPAP), neonatal sepsis. Conclusion: The present study showed significant associated factors to ROP: birth weight (It was noticed that the lower the birth weight, the higher is the occurrence of ROP), oxygen Therapy (nasal catheter, CPAP) and neonatal sepsis.

Abstract Respiratory distress syndrome, RDS, is a multifactorial lung disease of premature infants. The main cause of RDS is a deficiency of pulmonary surfactant, a lipoprotein mixture required to reduce surface tension at the air-liquid interface and to prevent generalized atelectasis of the alveolar ducts and alveoli. Prematurity is the most important factor predisposing to RDS. During the past decade the number of multiple pregnancies has increased significantly as a result of diversified infertility treatments and advanced maternal age. Due to the considerably higher rate of preterm births of multiples compared to singletons, RDS is one of the major causes of morbidity among them. The objectives of the present research were to evaluate the incidence and risk factors of RDS in twins compared to singletons, and to assess the role of SP-A and SP-B gene variations and gene-environment interactions in the susceptibility to the disease in a population of preterm twins and higher order multiples. This research showed that during the past fifteen years the gestational age-specific incidence of RDS has declined. Twin infants do not have increased risk of RDS except when born very immaturely at a very early gestational age. The presenting twin is less susceptible to RDS than the non-presenting twin or singleton infant after 28 weeks of gestation until term. Additionally the SP-B Ile131Thr polymorphism was shown to affect the susceptibility specifically in the presenting twin. The role of SP-A polymorphisms in the risk of RDS in twins turned out to be different from that in singletons. The major allele and genotype of SP-A1 were associated with a decreased risk of RDS in near-term twin infants. The threonine allele in SP-B Ile131Thr appeared interactively with SP-A1 to associate with the risk of RDS both in twins and in singletons: associating with a lower risk of RDS in singletons at very early gestation, but surprisingly associating with a protection in twins and multiples from RDS near term. The risk of RDS, defined by the interaction of SP-A and SP-B alleles, was additionally associated with the fetal mass. Thus, the difference in the susceptibility to RDS in premature singletons and multiples may depend on the size of the conceptus. In an evaluation of the genetic risk factors for RDS, the classical twin study method comparing the concordance of a disease between MZ and DZ twins underestimates the extent of heredity. Several predominant intrauterine and perinatal environmental factors contribute to disease susceptibility regardless of zygosity and are suspected to override the hereditary components of RDS. Twin gestation was shown to be an effect modifier in the genetic susceptibility to RDS. / Tiivistelmä Vastasyntyneen hengitysvaikeusoireyhtymä, RDS-tauti, on hyvin monitekijäinen ennenaikaisena syntyneiden lasten sairaus. Taudin tärkein syy on keuhkojen pintajännitystä alentavan aineen, surfaktantin, puute ennenaikaisessa synnytyksessä. Surfaktantti on rasva-proteiiniseos, joka alentaa keuhkorakkuloiden pintajännitystä ja estää rakkuloiden kasaan painumisen hengityksen aikana. Epäkypsyys on tärkein RDS-taudin kehittymiselle altistava tekijä. Viimeisen vuosikymmenen aikana monisikiöiset raskaudet ovat lisääntyneet merkittävästi keinohedelmöitysten ja synnyttäjien kohonneen iän seurauksena. RDS-tauti on monisikiösynnytyksissä tärkeä sairastavuutta aiheuttava tekijä, koska monisikiöraskaudet päättyvät huomattavasti useammin ennenaikaisesti kuin yksösraskaudet. Tämän tutkimuksen tarkoituksena oli selvittää RDS-taudin ilmaantuvuutta ja riskitekijöitä kaksosilla verrattuna yksösiin, tutkia surfaktanttiproteiinien A ja B geenivaihtelua sekä geenien ja ympäristötekijöiden vuorovaikutusta kaksosten ja monisikiöisistä raskauksista syntyneiden lasten RDS-taudissa. Tutkimus osoitti, että viimeisten viidentoista vuoden aikana RDS-taudin raskausikäkohtainen ilmaantuvuus on vähentynyt. Vain hyvin epäkypsillä, ennenaikaisilla kaksosilla on lisääntynyt riski sairastua RDS-tautiin verrattuna yksösiin. 28 raskausviikon jälkeen ensimmäisenä syntyvällä kaksosella on pienempi riski saada RDS-tauti kuin toisena syntyvällä tai yksösellä. Lisäksi surfaktanttiproteiini B:n (SP-B) geenin eksonin 4 monimuotoisuus osoittautui vaikuttavan RDS-taudin alttiuteen erityisesti ensin syntyvällä kaksosella. Surfaktanttiproteiini A:n (SP-A) geenin yhteys RDS-taudin riskiin osoittautui olevan erilainen kaksosilla verrattuna yksösiin. Lähes täysiaikaisilla kaksosilla SP-A1 geenin valta-alleeli ja genotyyppi liittyivät RDS-taudin vähentyneeseen riskiin. SP-B geenin eksonin 4 treoniini alleeli osoittautui liittyvän yhdessä SP-A1 valtagenotyypin kanssa RDS-taudin riskiin sekä yksösillä että kaksosilla: hyvin ennenaikaisilla yksösillä geenien yhteisvaikutus lisäsi riskiä, kun taas lähes täysiaikaisilla kaksosilla sama geenien yhteisvaikutus yllättäen suojeli RDS-taudilta. SP-A ja SP-B geenien vuorovaikutuksen kautta välittyvä RDS-taudin riski oli lisäksi yhteydessä sikiön kokoon. Siten ennenaikaisena syntyneiden yksösten ja monisikiöisten RDS-taudin alttiuden ero voi olla riippuvainen sikiön koosta. Klassinen kaksostutkimusmenetelmä, jossa verrataan identtisten ja ei-identtisten kaksosten sairastuvuutta, aliarvioi perimän määräämien tekijöiden osuutta RDS-taudin synnyssä. Useat hallitsevat kohdunsisäiset ja synnytykseen liittyvät ympäristötekijät vaikuttavat RDS-taudin syntyyn ja kumoavat perimän osuutta. Kaksosuus osoittautui olevan periytymisen vaikutusta muokkaava tekijä RDS-taudissa.

L’objectif de cette étude est d’appréhender le vécu psychoaffectif des pères de bébés prématurés (Lindberg & al., 2008), leurs relations avec le bébé (Morisod-Harari & al., 2013 ; Ibanez & al., 2006), leur conjointe (Frascarolo, 2001) et les professionnels (Tombeur & al., 2007; Fegran & Helseth, 2009) selon l’approche écosystémique (Bronfenbrenner, 2005). Plus spécifiquement, le modèle opérationnel Processus-Personne-Contexte-Temps (Bronfenbrenner, 1996) sur lequel nous prenons appui, a permis, de manière originale, de procéder à l’analyse de la contribution de facteurs d’ordre individuel, familial et contextuel au vécu psychoaffectif de ces pères. Au plan méthodologique, 48 pères ont participé à notre étude au moyen d’un entretien semi-directif basé sur l’Entretien Clinique pour les parents à risque (CLIP) (Meyer, Zeanah, Boukydis & Lester, 1993) et d’une série de questionnaires. Nous avons utilisé des tests standardisés et des questionnaires adaptés à notre problématique : l’Inventaire de l’Alliance Parentale (Abidin & Brunner, 1995), le Parent Medical Interview Satisfaction Scale (P-MISS) (Lewis, Scott, Pantell & Wolf, 1986), le Parenting Sense of Competence Scale (PSOC), (Johnston & Mash, 1989), l’Echelle de Stress Parental : Unité de Néonatologie (Miles, Funk & Carlson, 1993), le Questionnaire Périnatal du Stress Post-traumatique (Quinnell & Hynan, 1999), le Coping Health Inventory for Parents, CHIP (McCubbin, McCubbin, Patterson, Cauble, Wilson & Warwick, 1983) et l’échelle du soutien familial et social, FSS (Dunst, Jenkins & Trivette, 1984). Nos principaux résultats indiquent que les pères construisent un premier lien avec leur bébé mais témoignent également d’un vécu traumatique lié à la prématurité. Les pères présentent une alliance coparentale coopérative et une satisfaction élevée vis-à-vis du personnel soignant. Par ailleurs, les résultats révèlent que le sentiment de compétence paternelle est moins élevé chez les pères de notre échantillon comparé à celui de la population générale. Ils mettent aussi en évidence que le stress paternel est élevé et qu’il va induire un état de stress post-traumatique dès leur séjour dans le service. Pour autant, la majorité des pères adopte des stratégies de coping, telles que le maintien de la cohésion familiale et la communication avec le personnel soignant et les autres parents dans le service. Enfin, nous avons mis en évidence l’influence des caractéristiques du contexte, à savoir le soutien familial et le soutien extrafamilial fourni par l’équipe soignante et les autres parents dans le service, sur l’ensemble de nos variables. L’ensemble des résultats obtenus permet de proposer des perspectives de recherche et des pistes d’intervention auprès des pères de bébés prématurés au sein des services concernés. / The aim of this study is to analyse the life experiences of fathers of prematurely-born infants (Lindberg & al., 2008), their relationship with the baby (Morisod-Harari & al., 2013; Ibanez & al., 2006), their partner (Frascarolo, 2001) and the medical staff (Tombeur & al., 2007; Fegran & Helseth, 2009) based on the theoretical eco-systemic approach (Bronfenbrenner, 2005). Specifically the operational model « Process-Person-Context-Time » (Bronfenbrenner, 1996), on which we are building, in an original manner, to analyse the contribution of personal, contextual and family-related factors on the fathers’ life experiences. As per our methodology, 48 fathers of prematurely-born infants participated in our study through a semi-structured interview, based on the Clinical Interview for parents of high risk infants (Meyer, Zeanah, Boukydis & Lester, 1993), as well as a series of questionnaires. We used standardised tests as well as questionnaires adapted to our study purposes: the Parenting Alliance Inventory (PAI)(Abidin & Brunner, 1995) and the Parent Medical Interview Satisfaction Scale (P-MISS) (Lewis, Scott, Pantell & Wolf, 1986) in order to analyze the proximal processes. Fathers were asked to evaluate their life experiences by completing the Parenting Sense of Competence Scale (PSOC), (Johnston & Mash, 1989), the Parent Stressor Scale: Neonatal Intensive Care Unit (PSS: NICU) (Miles & Davis, 1993), the Perinatal Post-traumatic Questionnaire (PPQ) (Quinnell & Hynan, 1999) and the Coping Health Inventory for Parents (CHIP) (McCubbin, McCubbin, Patterson, Cauble, Wilson & Warwick, 1983). The family and extra family support were measured by the Family Support Scale (FSS) (Dunst, Jenkins & Trivette, 1984). Our principal results indicate that fathers construct an early bond with the infant but also admit to being traumatised by the premature birth. The fathers also exhibit a cooperative parenting alliance with and a high level of satisfaction towards the medical staff. However, the results reveal an inferior sense of paternal competence by the fathers within our sample compared to the general population. The results also show that paternal stress is high and will induce post-traumatic stress symptoms during the hospitalisation of the infant. Though, most fathers adopt a coping strategy, such as maintaining family cohesion and communication with the medical staff and other fathers in the unit. Finally, the impact of the context’s characteristics on all our variables is highlighted, namely family support and extra-family support provided by the medical staff and other parents in the neonatal unit. The results obtained allow us to suggest research themes as well as intervention schemes within the relevant services, towards the fathers of prematurely-born infants.

Cette thèse présente la première évaluation économique de la prématurité en France. La prématurité intervient avant 37 semaines d’aménorrhée. Elle est en constante augmentation dans le monde. Si les enjeux de santé publique sont bien identifiés, la prise en charge et les choix collectifs en matière de prématurité comportent des enjeux économiques importants. La première partie de cette thèse présente les enjeux de santé publique de la prématurité et les efforts restant à fournir en matière de prévention en France. Elle conduit ensuite une réflexion économique sur les moyens d’une utilisation au plus « juste » socialement des ressources dédiées à la santé périnatale, dans le contexte d’augmentation des dépenses de santé. Une mesure de la charge collective de la prise en charge de la prématurité est nécessaire et envisagée au moyen d’une étude Cost-Of-Illness. Enfin elle pose le cadre dans lequel l’éthique et l’évaluation économique sont complémentaires. La deuxième partie présente la méthodologie et les résultats de l’étude, consistant à évaluer les coûts directs hospitaliers et extrahospitaliers des naissances prématurées et à terme, dans la première année de vie, du point de vue de l’Assurance Maladie. Les données sont extraites du Système National d’Information Inter-Régime de l’Assurance Maladie. Les résultats montrent l’ampleur des coûts moyens associés à la grande prématurité et une relation inverse et significative entre les coûts moyens et l’âge gestationnel. Cette étude économique invite à la sensibilisation des décideurs publics à la nécessité d’allouer les moyens financiers et humains pour prévenir la survenue de situations critiques associées à la prématurité. / This thesis focuses on a first economic assessment of prematurity in France. Prematurity is defined as occurring before 37 weeks of gestation. It is increasing in France and worldwide. If the issues of public health are already well identified, medical care and collective choices concerning prematurity matters also involve significant economic challenges. The first part of this thesis attempts to present the public health issues of prematurity and highlights the remaining efforts required to provide prevention in France. It then considers economic issues on the use of socially fairer resources dedicated to perinatal health in a context where current health expenditure is rising. Assessment of the collective burden of care for preterm infants is necessary and envisaged by a Cost-Of-Illness study. Finally it presents a framework where ethical and economic considerations are complementary. The second part addresses the methodology and results of the study. The study assesses the hospital and non-hospital direct costs for preterm and term births, in the first year of life, from health insurance point of view. It is based on an extraction of data from the National Heal Insurance Inter-Regime Information System. The results of the study highlight in particular the level of average costs associated with extreme prematurity (before 32 weeks) and demonstrate an inverse and significant relationship between average costs and the gestational age (GA) at birth. This economic study invites awareness of the policy makers about the need to provide financial and human resources to anticipate and prevent critical situations associated with prematurity.

Orientador: Renato Passini Junior / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-04T01:25:35Z (GMT). No. of bitstreams: 1 Nomura_MarceloLuis_D.pdf: 838174 bytes, checksum: a795b39457b62a18ecb17c4609ece12d (MD5) Previous issue date: 2004 / Resumo: Objetivos: Identificar a taxa de prevalência e fatores de risco de colonização materna por estreptococo do grupo B (EGB) em gestantes com trabalho de parto prematuro (TPP) e/ou ruptura prematura pré-termo de membranas (RPM). Métodos: Foram colhidos dois swabs anais e vaginais de 203 gestantes atendidas no CAISM-UNICAMP. Um swab de cada local foi colocado em meio de transporte e enviados para cultura em placas de ágar-sangue, os outros dois foram incubados por 24 horas em meio de Todd-Hewitt para posterior semeadura em placas de ágar-sangue. Resultados: A prevalência de colonização materna por EGB foi de 27,6% (56 gestantes). As taxas de colonização por diagnóstico foram 34,7% para RPM, 25,2% para TPP e 17,8% para TPP + RPM. As variáveis raça branca, baixo nível de escolaridade e infecção urinária foram associadas a maiores taxas de colonização na análise multivariada. A presença de infecção urinária foi a única variável significativamente associada à colonização materna na análise multivariada. A taxa de detecção do estreptococo do grupo B foi significativamente maior com o uso do meio seletivo e com a associação de coleta de culturas anais e vaginais. A taxa de colonização neonatal foi de 3,1%. Ocorreram dois casos de sepse precoce por EGB nesta amostra, com prevalência estimada de 10,8 casos por mil nascidos vivos e mortalidade de 50%. Conclusão: A amostra avaliada apresenta altas taxas de colonização materna por Streptococcus agalactiae. É necessário o uso de meio de cultura seletivo e a associação de culturas anorretais e vaginais para aumentar a taxa de detecção do EGB. A incidência de sepse neonatal precoce foi elevada nesta população / Abstract: Objective: to study group B streptococcus maternal colonization rates and risk factors in women with preterm labor (PTL) and preterm premature rupture of membranes (PROM). Methods: Vaginal and anal swabs (two of each) were colected from 203 women followed at CAISM-UNICAMP. One of each swab was placed in transport media and then cultured in blood-agar plates, the other swabs were incubated in Todd-Hewitt selective media for 24 hours and then subcultured in blood-agar plates. Results: Maternal colonization rate was 27.6% (56 women). Colonization rates by admission diagnosis were 34.7% in PROM, 25.2% in PTL and 17.8% in PTL and PROM. White race, less than elementary education level and urinary tract infection were associated with maternal colonization in the univariate analysis. Urinary tract infection was the only variable associated with maternal colonization in a multivariate analysis. GBS detection rates were significantly higher with the use of selective culture media and with sampling of both vaginal and anorectal sites. Neonatal colonization rate was 3.1%. There were two cases of early-onset neoanatal sepsis caused by GBS, with an estimated prevalence of 10.8 cases per thousand live borns and a mortality rate of 50%. Conclusions: This sample of women had high GBS colonization rates. The use of selective culture media and collection of both anal and vaginal samples is necessary in order to maximize GBS detection rates. Early-onset neonatal sepsis incidence was high in this population / Doutorado / Tocoginecologia / Doutor em Tocoginecologia

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.