Introdução: A infecção amniótica e a corioamnionite (CAM) são determinantes de infecções materna e do recém-nascido, parturição e nascimento prematuro, morbidade e mortalidade pós-natal. Embora métodos clínicos, histopatológicos, microbiológicos, bioquímicos e moleculares possam diagnosticar CAM, muitos serviços hospitalares não examinam as placentas das parturientes, permanecendo muitos casos sem diagnóstico. O presente estudo utiliza o exame extemporâneo do cório placentário (EECP) proposto por Blanc em 1959 para o diagnóstico de CAM em mães que tiveram Recém-Nascido Pré- Termo (RNPT) e avaliou a morbidade e mortalidade nesse grupo de pacientes. Objetivo: Verificar a relação entre a CAM histológica e o prognóstico do RNPT nascidos no ano de 2012 no Hospital Universitário Cassiano Antônio de Moraes (HUCAM) em Vitória - ES. Justificativa: A maioria dos óbitos do período neonatal continua sendo por sepse, e esta também leva muitas sequelas no RNPT, assim exames que possam auxiliar no diagnóstico precoce da sepse neonatal ajudarão na instituição rápida do tratamento e consequentemente redução das sequelas, da mortalidade neonatal e redução dos índices de mortalidade neonatal e mortalidade infantil. Hipótese: RNPT filhos de mães com CAM terão mais complicações pós-parto, tais como: sepse neonatal, insuficiência respiratória, asfixia perinatal e óbito do que aqueles cujas mães não tiveram CAM. Metodologia: Estudo transversal, onde todas as placentas examinadas e laudadas no ano de 2012, no laboratório de Patologia do HUCAM em Vitória, ES, foram analisadas em conjunto com a evolução dos RNPT. Os casos foram categorizados por idade gestacional, desfecho perinatal e presença ou ausência de CAM. Resultados: No presente estudo foram selecionados 274 RNPT, desses 61 (22,2%) as placentas foram positivas para CAM e 213 (77,8%) as placentas foram negativas CAM. Quanto ao sexo (51,5%) eram masculinos (48,5%) eram femininos e não houve diferença estatiscamente significante.Quanto ao Apgar 5\', 14 (5,1%) tiveram Apgar menor ou igual a 5 e 260 (94,9%) tiveram Apgar maior do que 5.Quanto ao peso, nos RNPT selecionados 82 (29,9%) foram classificados como PIG, 184 (67,2%) foram classificados como AIG e 8 (2,9%) foram classificados como GIG.Quanto a necessidade de oxigenioterapia 154 (56,2%) necessitaram de suporte ventilatório e oxigênio nas primeiras 72 horas de vida e 116 (42,4%) ficaram em ar ambiente, sem necessidade de oxigênio nas primeiras 72 hs de vida. Quanto a sepse neonatal 140 (51%) tiveram hemograma classificado pelo Escore de Rodwell menor ou igual a 3, ou seja, sem risco para sepse neonatal precoce e 16 (5,9%) tiveram Escore Rodwell maior ou igual a 3, com risco para sepse neonatal precoce. Quanto o desfecho do RNPT, 169 (61,7%) dos casos receberam alta, 78 (28,5%) foram transferidos para outras Unidade de Terapia intensiva Neonatal (UTIN) devido superlotação do HUCAM e 27 (9,9%) dos casos foram a óbito.Teste t para médias e Teste de Mann-Whitney, foi encontrada diferença estatisticamente significante nas variáveis: Idade gestacional, Peso ao nascer, Estatura ao nascimento (EM), Pressão Arterial Média (PAM), número total de leucócitos (LEUCO) e proteína C reativa (PCR), já as variáveis frequência cardíaca (FC), temperatura axilar (TAX), leucócitos imaturos (IMAT), leucócitos segmentados (SEG) e plaquetas (PLAQ) não houve diferença estatística significante entre os grupos com CAM e sem CAM. Discussão: O estudo demonstrou que os RNPT nascidos de mães com CAM são mais graves, pois tem mais chances de nascerem asfixiados, ter insuficiência respiratória grave com necessidade de VPM, sepse neonatal precoce e vão mais a óbito do que os RNPT de mães sem CAM. Conclusão: Se a gestante apresentar sinais clínicos de infecção no trabalho de parto, deve-se ficar atento ao suporte que será dado ao RNPT, pois ele tem mais chances de apresentar complicações ao nascimento tais como, asfixia e insuficiência respiratória. Assim o EECP deve ser feito o mais rápido possível e o resultado entregue a equipe de Neonatologia do serviço para que a terapêutica antimicrobiana seja instituída precocemente e não precise aguardar alterações no hemograma e PCR e/ou na clínica do paciente para ter o início do tratamento da infecção / Introduction: Amniotic infection and chorioamnionitis (CAM) are determinants of maternal and newborn infections, parturition and preterm birth, postnatal morbidity and mortality. Although clinical, histopathological, microbiological, biochemical and molecular methods can diagnose CAM, many hospital services do not examine the placenta of the parturients, many cases remain undiagnosed. The present study utilizes extemporaneous placental laryngoscopy (ECC) proposed by Blanc in 1959 for the diagnosis of CAM in mothers who had Preterm Newborn (PTNB) and evaluated morbidity and mortality in this group of patients. Objective: To verify the relationship between the histological CAM and the prognosis of the PTNB born in 2012 at the Cassiano Antônio de Moraes University Hospital (HUCAM) in Vitória - ES. Rationale: Most neonatal deaths continue to be sepsis, and this also leads to many sequels in PTNB, so tests that may help in the early diagnosis of neonatal sepsis will aid in the rapid institution of treatment and consequently reduction of sequelae, neonatal mortality, and Reduction of neonatal mortality rates and infant mortality. Hypothesis: Children born to mothers with CAM will have more postpartum complications such as: neonatal sepsis, respiratory failure, perinatal asphyxia and death than those whose mothers did not have CAM. Methodology: Cross-sectional study, in which all the placentas examined and lauded in 2012, in the HUCAM pathology laboratory in Vitória, ES, were analyzed together with the evolution of the PTNBs. The cases were categorized by gestational age, perinatal outcome and presence or absence of CAM. Results: In the present study, 274 PTNBs were selected, of which 61 (22.2%) placentas were positive for CAM and 213 (77.8%) placentas were CAM negative. As for the gender (51.5%) were male (48.5%) were female and there was no statistically significant difference. As for Apgar 5 \', 14 (5.1%) had Apgar less than or equal to 5 and 260 9%) had Apgar greater than 5. Regarding weight, 82 (29.9%) were classified as PIG, 184 (67.2%) were classified as AIG, and 8 (2.9%) were (56.2%) required ventilatory support and oxygen in the first 72 hours of life, and 116 (42.4%) remained in ambient air, with no need for oxygen in the first 72 hours of life. life. As for neonatal sepsis, 140 (51%) had a hemogram classified by Rodwell score less than or equal to 3, that is, without risk for early neonatal sepsis, and 16 (5.9%) had Rodwell score greater than or equal to 3, with risk For early neonatal sepsis. Regarding the outcome of the PTNB, 169 (61.7%) of the cases were discharged, 78 (28.5%) were transferred to other NICUs due to overcrowding of HUCAM and 27 (9.9%) of the cases died. For mean and Mann-Whitney tests, a statistically significant difference was found in the following variables: gestational age, birth weight, height at birth, mean arterial pressure (MAP), total leukocyte count (LEUCO) and C-reactive protein PCR), the variables heart rate (HR), axillary temperature (TAX), immature leukocytes (IMAT), segmented leukocytes (SEG) and platelets (PLAQ) were not statistically significant between CAM and CAM groups. Discussion: The study showed that the infants born to mothers with CAM are more severe, as they are more likely to be asphyxiated, have severe respiratory insufficiency with need for MVP, early neonatal sepsis and more than death of the infants of mothers without CAM. Conclusion: If the pregnant woman presents clinical signs of infection in labor, one should be aware of the support that will be given to the PTNB, since it is more likely to present complications at birth, such as asphyxia and respiratory failure. Thus the EECP must be done as soon as possible and the result delivered to the Neonatology team of the service so that the antimicrobial therapy is instituted early and does not have to wait for changes in the blood count and PCR and / or in the patient\'s clinic to have the beginning of the treatment Infection

Biofilme subgengival, conteúdo vaginal, âmnio e parênquima placentários foram obtidos de 93 puérperas. Os periodontopatógenos (BPPG) P.g., A.a, F.n e T.f foram identificadas por PCR, corioamnionite e vilosite por histopatologia e analisados estatisticamente. Roturas de membranas (22,2%), cesáreas (65,6%), pretermo (36,6%), baixo peso (34,4%), morte perinatal (5,4%), CAM (34,4%) e vilosite (5,5%) foram observados. Periodontite agressiva (62,4%) e cáries (83,9%). Periodontite ou BPPG em qualquer sitio não se associou com maior freqüência ou com maior risco de corioamnionite ou de desfecho reprodutivo ruim. No biofilme observou-se Aa em 2 (2,1%), Fn em 16 (17,20%), Pg em 30 (32,30%) e Tf em 29 (31.2%); na vagina, Aa em 3 (3,2%), Fn em 2 (2,1%), Pg em 16 (17,2%) e Tf em 3 (3,2%); no âmnio, Fn em 4 (4,2%) e Pg em 9 (9,7%); na placenta, Fn em 1 (1,07%), Pg em 4 (4,3%) e Tf em 1 (1,1%). P.g e F.n foram observados simultaneamente: 6/30 casos de Pg na boca estavam na vagina, 3 no âmnio e 1 na placenta; dos 16 Fn na boca, 1 foi encontrado na placenta. Esta taxa de disseminação sugere que as BPPG na vagina, âmnio ou placenta não se originaram na boca das puérperas. / Subgingival biofilm and buccal samples, vaginal contents, amnion and placental parenchyma were obtained from 93 pregnant. The periodontopathogens (PPG) Pg, Aa, Fn, and Tf were identified by PCR, the diagnosis of chorioamnionitis (CAM) and villitis by histopathology methods and its relationships with adverse perinatal outcome (APO) statically analyzed. Rupture of membranes (22.2%), cesarean (65.6%), preterm (36.6%), low fetal weight (34.4%), perinatal death (5.4%), CAM (34.4%), and villitis (5.5%) were observed. Aggressive periodontitis (62,4%), and 83.9% had caries. Periodontitis or PPG (Aa, Fn, Pg, and Tf) in any site not associated with greater frequency or at greater risk of CAM or APO. In the subgingival biofilm Aa was observed in 2 (2.1%), Fn in 16 (17.20%), Pg in 30 (32.30%) and Tf in 29 (31.2%); in the vagina, 3 in Aa (3.2%), Fn 2 (2.1), Pg 16 (17.2%) and Tf 3 (3.2%); amnion, Fn in 4 (4.2%) and Pg 9 (9.7%); in the placenta, Fn 1 (1.07%), Pg 4 (4.3%) and Tf 1 (1.1%). Only Fn and Pg were observed simultaneously: 30 mothers with Pg in the mouth, 6 were detected in the vagina, 3 in amnion and 1 in the placenta; Fn 16 with the mouth, 1 was found in the placenta. This low rate of spread suggests that most of periodontopathogens present in vagina, amnion or placenta did not belong to the pregnant mouth.

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

Biofilme subgengival, conteúdo vaginal, âmnio e parênquima placentários foram obtidos de 93 puérperas. Os periodontopatógenos (BPPG) P.g., A.a, F.n e T.f foram identificadas por PCR, corioamnionite e vilosite por histopatologia e analisados estatisticamente. Roturas de membranas (22,2%), cesáreas (65,6%), pretermo (36,6%), baixo peso (34,4%), morte perinatal (5,4%), CAM (34,4%) e vilosite (5,5%) foram observados. Periodontite agressiva (62,4%) e cáries (83,9%). Periodontite ou BPPG em qualquer sitio não se associou com maior freqüência ou com maior risco de corioamnionite ou de desfecho reprodutivo ruim. No biofilme observou-se Aa em 2 (2,1%), Fn em 16 (17,20%), Pg em 30 (32,30%) e Tf em 29 (31.2%); na vagina, Aa em 3 (3,2%), Fn em 2 (2,1%), Pg em 16 (17,2%) e Tf em 3 (3,2%); no âmnio, Fn em 4 (4,2%) e Pg em 9 (9,7%); na placenta, Fn em 1 (1,07%), Pg em 4 (4,3%) e Tf em 1 (1,1%). P.g e F.n foram observados simultaneamente: 6/30 casos de Pg na boca estavam na vagina, 3 no âmnio e 1 na placenta; dos 16 Fn na boca, 1 foi encontrado na placenta. Esta taxa de disseminação sugere que as BPPG na vagina, âmnio ou placenta não se originaram na boca das puérperas. / Subgingival biofilm and buccal samples, vaginal contents, amnion and placental parenchyma were obtained from 93 pregnant. The periodontopathogens (PPG) Pg, Aa, Fn, and Tf were identified by PCR, the diagnosis of chorioamnionitis (CAM) and villitis by histopathology methods and its relationships with adverse perinatal outcome (APO) statically analyzed. Rupture of membranes (22.2%), cesarean (65.6%), preterm (36.6%), low fetal weight (34.4%), perinatal death (5.4%), CAM (34.4%), and villitis (5.5%) were observed. Aggressive periodontitis (62,4%), and 83.9% had caries. Periodontitis or PPG (Aa, Fn, Pg, and Tf) in any site not associated with greater frequency or at greater risk of CAM or APO. In the subgingival biofilm Aa was observed in 2 (2.1%), Fn in 16 (17.20%), Pg in 30 (32.30%) and Tf in 29 (31.2%); in the vagina, 3 in Aa (3.2%), Fn 2 (2.1), Pg 16 (17.2%) and Tf 3 (3.2%); amnion, Fn in 4 (4.2%) and Pg 9 (9.7%); in the placenta, Fn 1 (1.07%), Pg 4 (4.3%) and Tf 1 (1.1%). Only Fn and Pg were observed simultaneously: 30 mothers with Pg in the mouth, 6 were detected in the vagina, 3 in amnion and 1 in the placenta; Fn 16 with the mouth, 1 was found in the placenta. This low rate of spread suggests that most of periodontopathogens present in vagina, amnion or placenta did not belong to the pregnant mouth.

Depuis les dernières décennies, plusieurs études épidémiologiques montrent des associations entre l’infection/inflammation durant la grossesse, les accouchements prématurés, les lésions cérébrales périnatales et les troubles neuro-développementaux ultérieurs tels que l’autisme. Le pathogène le plus fréquemment rencontré durant la grossesse est le streptocoque de groupe B (SGB). Le SGB colonise le tractus gastro-intestinal et/ou vaginal de 10 à 30% des femmes enceintes et provoque une combinaison d’infection et d’inflammation dont la cible la plus fréquente est le placenta (chorioamnionite). Nous avions précédemment montré, à l’aide d’un modèle animal pré-clinique (rat), que l’exposition systémique au SGB inactivé en fin de gestation induit une chorioamnionite, des lésions cérébrales ainsi que des traits comportementaux de type autistique dans la progéniture mâle. Dans le cadre de ce travail, nous avons précisé la nature de la réaction inflammatoire sous-jacente à l’exposition maternelle au SGB inactivé en fin de gestation. Cette réaction inflammatoire est caractérisée par une surexpression d’IL-1β à la fois dans le plasma maternel, le placenta et le plasma foetal. Les placentas présentent une chorioamnionite sévère, principalement caractérisée par des infiltrations de cellules inflammatoires (majoritairement des cellules polymorphonucléaires neutrophiles (PMN), s’étendant jusqu’au versant foetal placentaire. De manière générale, les tissus associés aux foetus mâles présentent des niveaux d’inflammation supérieurs, autant par le profil d’expression des cytokines pro-inflammatoires (IL-1β, IL-6 et TNF-α) que par les infiltrations de PMN. Puisque l’IL-1 est une cytokine pro-inflammatoire associée au travail préterme, aux lésions cérébrales ainsi qu’à l’autisme, nous avons tenté de valider son rôle dans la genèse des troubles neuro-développementaux SGB-induits dans notre modèle. Toutefois, le rôle de l’IL-1 n’a pu être élucidé. Ces résultats supportent les évidences croissantes que le sexe foetal impacte la susceptibilité du foetus face aux agressions inflammatoires. Ces résultats ouvrent plusieurs nouvelles avenues de recherche, notamment sur l’identification de joueurs clés dans la réaction inflammatoire materno-foetale suivant l’exposition au SGB et ainsi développer de nouvelles mesures pour protéger le placenta et le cerveau du foetus en développement. / Abstract : For the last decades, epidemiological studies have associated preterm birth, cerebral lesions and neurodevelopmental disorders to infection and/or inflammation during pregnancy. One of the most common pathogen encountered during gestation is Group B Streptococcus (GBS), which colonizes 10 to 30% of pregnant women’s gastro-intestinal and/or vaginal tracts. We have previously shown - with a preclinical rat model - that exposure to killed GBS at the end of gestation leads to placental and cerebral lesions. Moreover, only male offspring from mothers who experienced GBS-induced gestational inflammation displayed autistic-like behavior. In this work, we analyzed the inflammatory response to maternal inactivated GBS exposure at the end of gestation. This inflammatory response involves IL-1β, which is over expressed in maternal plasma, placenta and fetal plasma. Placentas displayed acute signs of histological chorioamnionitis, with polymorphonuclear cells (PMN) infiltrations even on the fetal side of placenta. Following GBS-induced inflammation, tissues associated to male fetuses generally showed increased inflammatory response as compared to females (IL-1β, IL-6 and TNF-α) and higher PMN placental infiltrations. Because IL-1β is associated to preterm birth, cerebral damage and autism, we wanted to validate the role of IL-1 in the onset of GBS-induced autism-like behavior in our animal model. However, at this stage, we have not been able to demonstrate this role. These results support the evidences that fetal sex matters for fetal susceptibility to inflammatory aggressions during pregnancy. These results pave the way toward the identification of key molecules in chorioamnionitis, brain damage and subsequent neurobehavioral disorders. This will help to find new strategies to protect the placenta and the fetal brain.

No description available.

Abstract Deficiency of pulmonary surfactant is the main cause of respiratory distress syndrome (RDS) in premature newborn infants, which is often complicated by chronic lung disease (CLD). Preterm birth is often associated with intra-amniotic infection (IUI), which is characterized by increased proinflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α), in the amniotic fluid. In very preterm birth due to IUI, the incidence of RDS is decreased, while the incidence of CLD is increased. Maternal glucocorticoids are used in imminent preterm birth to prevent RDS. This study was designed to clarify the contrasting association of these perinatal pulmonary diseases with IUI and the pathogenesis of these lung diseases using an in vitro rabbit model. IL-1 increased the expression of surfactant protein (SP)-A and SP-B in very immature lung. Contrariwise, in transitional and mature fetal lung as well as in newborn lung, IL-1 additively with TNF-α decreased the expression of SP-B and SP-C. Bacterial lipopolysaccharide (LPS) decreased SP-A, -B and -C mRNAs in mature fetal and newborn lung, but had no effect on SP expression in immature lung. Interferon-γ (IFN-γ) had no effect on SP expression at any gestational age, but it modified the effects of the other cytokines. Dexamethasone (Dx) and IL-1 in combination additively increased SP-A and SP-B mRNAs in immature lung. Dx abolished the inhibitory effect of IL-1 on SP-B and SP-C in mature lung. Dx and IL-1 together tended to stabilize SP mRNAs. The present findings provide additional evidence of the role of the transcription factors nuclear factor-κB (NF-κB) and C/CAAT enhancer-binding protein δ (C/EBPδ) in the upregulation of SP-A by IL-1 in immature lung. Proinflammatory cytokines profoundly influence the expression of surfactant proteins in a manner that is strictly dependent on the length of gestation. The present findings help to explain the differences in the incidence of RDS and CLD in preterm births caused by IUI, and they may clarify further the role of surfactant in the pathogenesesis of lung diseases in neonatal infants. / Tiivistelmä Keuhkosurfaktantin puute aiheuttaa ennenaikaisesti syntyville keskosille vastasyntyneen hengitysvaikeusoireyhtymää eli RDS-tautia (Respiratory Distress Syndrome). Toinen keskosilla esiintyvä keuhkosairaus on krooninen keuhkosairaus eli CLD (Chronic Lung Disease). Glukokortikoideja käytetään hoitona ennenaikaisen synnytyksen uhatessa, koska niiden tiedetään vähentävän RDS-taudin riskiä. Kohdunsisäinen infektio on huomattava ennenaikaisen synnytyksen aiheuttaja. Infektiossa tulehduksen välittäjäaineet, kuten sytokiinit interleukiini-1 (IL-1) ja tuumorinekroositekijä alfa (TNF-α) lisääntyvät lapsivedessä. Infektiosta aiheutunut ennenaikainen synnytys vähentää RDS-taudin ilmaantumista pienille keskosille ja toisaalta lisää kroonisen keuhkosairauden riskiä. Tutkimuksen oli tavoitteena selvittää, miksi RDS ja CLD ilmaantuvat eriävästi infektion vuoksi ennenaikaisesti syntyneille vauvoille. Viljelemällä eri-ikäisten kanin sikiöiden sekä vastasyntyneiden kanin poikasten keuhkon kappaleita tutkittiin tulehduksen välittäjäaineiden sekä anti-inflammatorisen glukokortikoidin (deksametasonin) vaikutusta surfaktantin toiminnalle tarpeellisten surfaktanttiproteiinien (SP) ilmentymiseen. IL-1 lisäsi SP-A:n ja SP-B:n ilmentymistä erittäin epäkypsässä kanin sikiön keuhkossa. Toisaalta IL-1 ja TNF-α vähensivät SP-B:n ja SP-C:n ilmentymistä kypsemmässä sikiön sekä vastasyntyneen kanin keuhkossa. Interferoni-gamma (IFN-γ) ei vaikuttanut surfaktanttiproteiinien ilmentymiseen missään gestaatioiässä, mutta se muunsi muiden sytokiinien surfaktanttivaikutusta. Gram-negatiivisten bakteerien soluseinän tuote, lipopolysakkaridi (LPS) vähensi SP-A:n, SP-B:n ja SP-C:n ilmentymistä kypsässä kanin sikiön ja vastasyntyneen kanin keuhkossa. IL-1:llä ja deksametasonilla oli positiivinen yhteisvaikutus surfaktanttiproteiinien ilmentymiseen. Tämän surfaktanttiproteiineja lisäävän vaikutuksen mekanismiksi havaittiin pääasiallisesti lisääntynyt mRNA:n stabiliteetti. Lisäksi tutkimus antaa lisätietoa kahden transkriptiofaktorin, NF-κB:n (nuclear factor kappa B) ja C/EBPγ:n (C/CAAT enhancer binding protein delta), osuudesta IL-1:n aiheuttamassa SP-A:n ilmentymisen lisääntymisessä. Sytokiinien vaikutukset surfaktanttiproteiinien ilmentymiseen ovat riippuvaisia gestaatioiästä. Tutkimuksen löydökset auttavat ymmärtämään RDS:n ja CLD:n vastakohtaista esiintymismäärää keskosilla, joiden ennenaikainen synnytys on aiheutunut kohdunsisäisestä tulehduksesta. Edelleen tutkimus selittää glukokortikoidien positiivista vaikutusta hengitysvajaukseen johtavassa keuhkotulehduksessa.

Résumé : Le streptocoque de groupe B (SGB) est une bactérie commensale présente dans le tractus génito-urinaire de 10 à 30 % des femmes enceintes en santé. Ce pathogène est responsable de chorioamnionite, associée aux naissances prématurées et aux dommages cérébraux du nouveau-né. Les infections durant la grossesse, la chorioamnionite et la prématurité sont associées au développement de troubles du spectre de l’autisme. Notre hypothèse est qu’une exposition subclinique au SGB induit une réponse inflammatoire maternofoetale, menant à des troubles neurodéveloppementaux et comportementaux de type autistique dans la progéniture. L’objectif principal est d’étudier, à l’aide d’un nouveau modèle animal (rat) préclinique, les impacts d’une exposition au SGB en période prénatale sur le développement cérébral de la progéniture. Les rates Lewis gestantes sont injectées au jour de gestation 19 avec une dose de SGB de sérotype Ia (108 UFC/100µl) ou de saline. La réponse inflammatoire placentaire est caractérisée par immunohistochimie. Des tests comportementaux sont effectués entre les jours postnataux 7 et 40 afin d’évaluer la communication, le comportement exploratoire, l’intégration sensorielle et les interactions sociales. Une chorioamnionite dichotomique selon le genre est observée dans les placentas exposés au SGB, via une infiltration de cellules polymorphonucléaires. Cette infiltration est significativement plus proéminente dans les placentas associés aux fœtus mâles que ceux des fœtus femelles. Les mâles exposés au SGB ont un amincissement de la substance blanche cérébrale adjacente aux ventricules latéraux élargis. La progéniture mâle exposée au SGB présente des anomalies comportementales associées aux traits cardinaux des troubles du spectre de l’autisme, soit des déficits au niveau de la communication, des interactions sociales, du traitement de l’information sensorielle ainsi qu’au niveau d’autres comorbidités classiques de l’autisme, comme l’hyperactivité. Ces données démontrent pour la première fois que l’activation immune maternelle induite par l’infection au SGB joue un rôle dans l’induction d’anomalies neurodéveloppementales récapitulant celles observées chez les patients autistes, incluant la dichotomie de genre et le phénotype neurocomportemental. Ces résultats fournissent de nouvelles évidences en faveur du rôle dans la physiopathologie de l’autisme d’un facteur environnemental commun, et modifiable, d’inflammation gestationnelle. / Abstract : Group B Streptococcus (GBS) is a commensal bacterium present in the vagina of 10 to 30% of healthy pregnant women. GBS is responsible for chorioamnionitis, which can cause preterm birth and cerebral injuries in the newborn most often in the absence of maternofetal pathogen translocation. Maternal infection, chorioamnionitis and preterm birth are associated to autism spectrum disorders (ASD) in the progeny. Our hypothesis is that GBS-induced gestational infection induces a maternofetal inflammatory response leading to neurodevelopmental impairments and ASD-like behaviour in the offspring. Our goal was to study, with a new preclinical animal model, the impacts of GBS-induced gestational inflammation on the neurodevelopmental features in the offspring. We characterized GBS-induced placental and neurobehavioural outcomes. Dams were exposed at gestational day 19 to live GBS or saline. The placental inflammatory response was studied by immunohistochemistry. Behavioural tests were performed between postnatal days 7 and 40 to assess communication, exploratory abilities, sensory integration and social interactions. GBS-exposed placentas displayed chorioamnionitis featured by infiltration of polymorphonuclear cells, which was significantly more prominent in males than in females. GBS-exposed males showed a reduced thickness of periventricular white matter. Male offspring exposed to GBS had early onset of cardinal ASD-like traits affecting social interaction, communication (ultrasonic vocalizations), treatment of sensory information (prepulse inhibition), preference toward mother cue (nest-seeking), and some other classic ASD comorbidities such as hyperactivity (open field). Overall, these data show for the first time that maternal immune activation due to live GBS plays a key role in the induction of neurodevelopmental abnormalities recapitulating those of human ASD, including gender dichotomy and neurobehavioural phenotype. These results provide new evidence in favor of the role of a common and modifiable infectious/inflammatory environmental factor in human ASD pathophysiology.

[Truncated abstract] Fetal inflammatory response syndrome (FIRS) has only recently been recognised as an important cause of spontaneous preterm delivery (PTD). In addition, it has been associated with a number of other short-term and long-term adverse neonatal outcomes, including early onset neonatal sepsis, necrotising enterocolitis, periventricular leucomalacia, cerebral palsy, and bronchopulmonary dysplasia, although the causal mechanisms are unclear. The hallmark of FIRS is histologic chorioamnionitis (HCA). Mothers with HCA are often asymptomatic and it remains unclear whether elevated maternal inflammatory markers, such as C-reactive protein (CRP) and procalcitonin (PCT), are predictive of preterm birth. Furthermore neonatal inflammatory markers such as CRP, PCT, white cell count (WCC) and absolute neutrophil count (ANC), are commonly used in clinical practice to diagnose infection in the neonatal period. Although both intrauterine inflammation and FIRS may have effects on inflammatory markers for up to 10 days following delivery, the extent to which intrauterine infection and FIRS confound these diagnostic surrogates of neonatal infection is unknown. This work addressed the hypothesis that HCA is associated with inflammatory changes that may be detected in the: (a) maternal circulation at the time of delivery, (b) umbilical cord blood at delivery and (c) post-natal circulation within the first 48 hours of life. The primary aim of this study was to investigate the relationship between the presence of HCA and maternal inflammatory markers (serum CRP and PCT on the day of delivery) as well as neonatal inflammatory markers (haematological parameters, CRP and PCT up to 48 hours following delivery). ... Cord platelet counts were likely affected by platelet activation. For both intra-rater and inter-rater reproducibility, the corrected WCC, ANC and NRBC were shown to be reliable with an ICC of >0.90 for all comparisons. However, I:T ratio was poorly reproducible. HCA appears to be a minor inflammatory insult for the mother. In the majority of cases it is asymptomatic and results in minor increases in PCT and CRP levels on the day of delivery. Conversely HCA results in significant inflammatory changes in the newborn that can be seen in the cord blood. Sensitive markers of inflammation in the cord blood are significantly higher in affected infants (CRP and PCT), while less sensitive markers, such as WCC and ANC are not significantly different. This study has shown that fetal inflammation has sustained effects on CRP and haematological parameters in early neonatal life; CRP, WCC and ANC are significantly higher in newborns exposed to HCA, peaking 24 hours following delivery. These effects may confound the interpretation of common diagnostic tests for early onset neonatal sepsis. Conclusion: HCA results in mild elevations in CRP and PCT in the cord blood. Over the subsequent 24 hours CRP, WCC and ANC increase significantly in these neonates. Intrauterine exposure to HCA may influence surrogate diagnostic markers for early onset sepsis in newborn infants. Future research to investigate novel diagnostic markers, such as CD64 and soluble triggering receptor expressed on myeloid cells (TREM-1), or enhanced microbiological molecular diagnosis, will help distinguish true invasive infection from HCA-driven inflammation in the newborn infant.

Made available in DSpace on 2016-12-23T13:55:59Z (GMT). No. of bitstreams: 1 Laura Fregonassi Ribeiro Fraga.pdf: 4567995 bytes, checksum: 80f83feca246031271e511fadd682376 (MD5) Previous issue date: 2013-08-30 / A infecção amniótica e a corioamnionite (CAM) são determinantes de infecções materna e perinatal, parturição e nascimento pretermo e morbi-mortalidade pós-natal. Embora métodos clínicos, histopatológicos, microbiológicos, bioquímicos e moleculares possam diagnosticar CAM, nenhum logrou amplo emprego, permanecendo muitos casos clínica e epidemiologicamente ocultos. O presente estudo analisa o exame do cório placentário (EECP) proposto por Blanc (1953) para o diagnóstico de CAM a tempo de orientar o manejo da puérpera e do neonato sob risco. Objetivo. Determinar o valor e a reprodutibilidade do EECP em comparação com a histopatologia convencional (HP). Material e métodos. Dentre as placentas examinadas entre 2008 e 2012, em dois laboratórios de Vitória, ES, um público (HUCAM) e um privado (PAT), foram selecionadas 1626, incluindo: uma amostra de corte transversal (HCT, n: 108) e duas séries consecutivas examinadas por suspeita neonatal de CAM (HIB, n: 193) e por variadas indicações obstétricas (PIV, n: 1325). O EECP foi realizado no puerpério imediato (HIB e HCT) ou como primeira etapa da HP (PIV). Os casos foram categorizados por procedência, idade gestacional, desfecho perinatal, método de exame, estágio e grau da CAM e foram calculados índices de valor diagnóstico e concordância entre os dois métodos (EECP e HP). Resultados. CAM por HP foi observada em 12,8% dos casos (HCT: 31,5% e PIV: 11,3%) dos quais 2,4% com resposta inflamatória fetal; CAM pelo EECP foi observada em 14,2% (HCT: 41,7%, HIB: 31,1% e PIV: 9,1%). O EECP revelou-se exequível e rápido, com sensibilidade 50,0%, especificidade 93,7%, valores preditivos positivo 53,8% e negativo 92,7% e razões de verossimilhança positiva 7,9 e negativa 0,53. Concordância entre EECP e HP foi observada em 88,8%, diagnóstico apenas pelo EECP em 5,7% e apenas pela HP em 5,5% (kappa: 0,45). Conclusão. O EECP pode ser empregado para o diagnóstico rápido de CAM. Trata-se de método exequível, que tem bons índices de valor diagnóstico e pode ser útil para orientar a conduta no puerpério e período neonatal imediatos / Amniotic infection and chorioamnionitis (CAM) are determining factors of maternal and perinatal infections, preterm births and postnatal mortality and morbidity. As none of clinical, microbiological, biochemical, molecular and histopathological proposed methods for CAM diagnosis has achieved broad and routine employment, many cases remain clinical and epidemiologically occult. After Blanc s proposal (1959), this study analysis the placental chorionic sampling and microscopical examination (EECP) at early postpartum period to CAM diagnosis in order to help a timely clinical decision to treat the risk mother and newborn infant. Objectives. To establish the diagnostic value and the reproducibility of EECP compared to conventional histopathology (HP) CAM diagnosis. Material e Methods. Out from all placentas examined between 2008 and 2012, in two Pathology laboratories at Vitória City, southwestern Brazil, one public (HUCAM) and one private (PAT), 1626 were selected including: a cross-sectional sampling (HCT, n: 108) and two consecutive cases series examined after neonatal clinical infection suspicion (HIB, n: 193) and varied others obstetrical indications (PIV, n: 1325). The EECP was done at immediate postpartum period (HIB and HCT) or as the first step of HP examination (PIV). The cases were categorized by study groups, gestational age, perinatal outcome, method of examination, CAM stage and grade, and the statistic indexes of agreement and diagnostic value between the two methods (EECP and HP) were calculated. Results. In overall cases, CAM diagnosis by HP were observed in 12.8% (HCT: 31.5% e PIV: 11.3%) from which 2.4% with a fetal inflammatory response; CAM diagnosis by EECP were observed in 14.2% (HCT: 41.7%, HIB: 31.1% e PIV: 9.1%). The EECP revealed itself to be a fast and easy to perform method, with 50.0% sensitivity, 93.7% specificity, 53.8 predictive positive and 92.7% predictive negative values, and 7.9 likelihood positive and 0.53 likelihood negative ratios. Agreement between EECP and HP were observed in 88.8%, CAM diagnosis only by EECP in 5.7% and only by HP in 5.5% (kappa: 0,45). Conclusion. The EECP method could be an important contribution to fast CAM diagnosis. It is easy to perform, with significant statistic indexes of diagnosis value and can be helpful to guide the clinical decision at early postpartum period