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1.
Z Geburtshilfe Neonatol ; 223(6): 373-394, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31801169

RESUMO

AIMS: This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recently published scientific literature, the experience of the members of the guideline commission and the views of self-help groups. METHODS: The members of the participating medical societies and organizations developed Recommendations and Statements based on the international literature. The Recommendations and Statements were adopted following a formal consensus process (structured consensus conference with neutral moderation, voting done in writing using the Delphi method to achieve consensus). RECOMMENDATIONS: Part 2 of this short version of the guideline presents Statements and Recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes.


Assuntos
Ruptura Prematura de Membranas Fetais , Trabalho de Parto Prematuro/prevenção & controle , Guias de Prática Clínica como Assunto , Nascimento Prematuro , Sociedades Médicas , Prevenção Terciária , Incompetência do Colo do Útero , Áustria , Feminino , Ruptura Prematura de Membranas Fetais/prevenção & controle , Ruptura Prematura de Membranas Fetais/terapia , Humanos , Recém-Nascido , Obstetrícia , Gravidez , Nascimento Prematuro/prevenção & controle , Nascimento Prematuro/terapia , Sistema de Registros
2.
Geburtshilfe Frauenheilkd ; 79(11): 1171-1175, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31736505

RESUMO

This position paper describes clinically important, practical aspects of cervical pessary treatment. Transvaginal ultrasound is standard for the assessment of cervical length and selection of patients who may benefit from pessary treatment. Similar to other treatment modalities, the clinical use and placement of pessaries requires regular training. This training is essential for proper pessary placement in patients in emergency situations to prevent preterm delivery and optimize neonatal outcomes. Consequently, pessaries should only be applied by healthcare professionals who are not only familiar with the clinical implications of preterm birth as a syndrome but are also trained in the practical application of the devices. The following statements on the clinical use of pessary application and its removal serve as an addendum to the recently published German S2-consensus guideline on the prevention and treatment of preterm birth.

3.
Z Geburtshilfe Neonatol ; 223(5): 304-316, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31623006

RESUMO

AIMS: This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recent scientific literature, the experience of the members of the guideline commission and the views of self-help groups. METHODS: Based on the international literature, the members of the participating medical societies and organizations developed Recommendations and Statements. These were adopted following a formal process (structured consensus conference with neutral moderation, voting was done in writing using the Delphi method to achieve consensus). RECOMMENDATIONS: Part I of this short version of the guideline lists Statements and Recommendations on the epidemiology, etiology, prediction and primary and secondary prevention of preterm birth.


Assuntos
Guias de Prática Clínica como Assunto , Nascimento Prematuro , Áustria , Feminino , Humanos , Recém-Nascido , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/prevenção & controle , Prevenção Primária , Sistema de Registros , Prevenção Secundária , Sociedades Médicas
4.
Geburtshilfe Frauenheilkd ; 79(8): 800-812, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31423016

RESUMO

Aims This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recent scientific literature, the experience of the members of the guideline commission and the views of self-help groups. Methods Based on the international literature, the members of the participating medical societies and organizations developed Recommendations and Statements. These were adopted following a formal process (structured consensus conference with neutral moderation, voting was done in writing using the Delphi method to achieve consensus). Recommendations Part I of this short version of the guideline lists Statements and Recommendations on the epidemiology, etiology, prediction and primary and secondary prevention of preterm birth.

5.
Geburtshilfe Frauenheilkd ; 79(8): 813-833, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31423017

RESUMO

Aims This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recently published scientific literature, the experience of the members of the guideline commission and the views of self-help groups. Methods The members of the participating medical societies and organizations developed Recommendations and Statements based on the international literature. The Recommendations and Statements were adopted following a formal consensus process (structured consensus conference with neutral moderation, voting done in writing using the Delphi method to achieve consensus). Recommendations Part 2 of this short version of the guideline presents Statements and Recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes.

6.
Dtsch Arztebl Int ; 116(50): 858-864, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931955

RESUMO

BACKGROUND: The preterm birth rate in Germany has remained unchanged at 8-9% since 2009. Preterm birth is the most common cause of neonatal morbidity and mortality. In the absence of a causal treatment, it is important to lower the risk of preterm birth by preventive measures in prenatal outpatient care. METHODS: This review is based on pertinent publications from the years 2000-2019 that were retrieved by a selective search in PubMed. RESULTS: The clinical risk factors for preterm birth-known mainly from retrospective cohort studies-include previous preterm birth (adjusted odds ratio [aOR]: 3.6), multiple pregnancy (relative risk [RR]: 7.7), nicotine consumption (aOR: 1.7), and a short uterine cervix, i.e., <25 mm in the second trimester (aOR: 6.9). In women with a short cervix, vaginally administered progesterone significantly lowers the preterm birth rate (22.5% vs. 14.1% for birth before 33 weeks of gestation, RR: 0.62; 95% confidence interval [0.47; 0.81]). Nicotine abstinence is associated with a lower pre- term birth rate as well (aOR: 0.91; [0.88; 0,.94]), while working more than 40 hours per week (aOR: 1.25; [1,.01; 1,.54]) and heavy lifting during pregnancy (hazard ratio [HR]: 1.43; [1.13; 1.80]) are associated with a higher preterm birth rate. Avoidance of physical exertion, or bed rest, in the face of impending preterm birth does not lower the preterm birth rate, but it does increase the risk of complications, such as thromboembolism. CONCLUSION: The meticulous assessment and elimination of treatable risk factors at the outset of ambulatory prenatal care can help lower the preterm birth rate. Further velopment of causally directed treat- ments (e.g., changes of relevant environmental and epigenetic factors).

7.
Pregnancy Hypertens ; 14: 228-233, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29627351

RESUMO

OBJECTIVES: Placental Growth Factor (PlGF) has been shown to be beneficial in diagnosing pre-eclampsia. We performed a prospective cohort study of revealed PlGF in standard clinical use in four teaching hospitals in UK, Germany, Austria and Australia. STUDY DESIGN: Clinical data from women with suspected pre-eclampsia or fetal growth restriction <35 weeks' gestation with revealed PlGF measurement were collected (MAPPLE study). MAIN OUTCOME MEASURES: Data were compared to the PELICAN study (PlGF concealed). Pre-specified outcomes were compared using standard statistical tests (median difference or Risk Ratio). The results were further categorised by PlGF concentration: i) very low (<12 pg/ml), ii) low (12-100 pg/ml), iii) normal (>100 pg/ml). RESULTS: 396 women managed with revealed PlGF (MAPPLE) were compared with 287 women with concealed PlGF (PELICAN). Revealed PlGF led to delivery 1.4 weeks earlier (-2.0 to -0.9, 34.9 weeks vs 36.7 weeks). There were no significant differences in maternal adverse outcomes (11.9% vs 10.1%, Risk Ratio (RR) 1.17, 95% CI 0.76-1.82) or caesarean sections (73.8% vs 64.5%; RR 1.14, 95% CI 1.03-1.26). Revealed PlGF led to fewer perinatal deaths (2 vs 9; RR 0.16, 95% CI 0.03-0.74) and fewer babies with birthweight <3rd centile (28.9% vs 36.1%; RR 0.80, 0.65-0.99), but with more neonatal adverse outcomes (30.4% vs 17.1%; RR 1.78, 95% CI 1.32-2.41). CONCLUSIONS: Revealed PlGF may be associated with lower perinatal mortality and birthweight <3rd centile but appears to lead to earlier delivery with more neonatal respiratory morbidity. Randomised trials with adequate power for clinical outcomes are needed. FUNDING: Financial assistance was received from Alere to support the running of the MAPPLE database. Alere had no access to the information or control over the database itself.


Assuntos
Retardo do Crescimento Fetal/sangue , Fator de Crescimento Placentário/sangue , Pré-Eclâmpsia/sangue , Resultado da Gravidez , Adulto , Biomarcadores/sangue , Peso ao Nascer , Cesárea/estatística & dados numéricos , Feminino , Retardo do Crescimento Fetal/diagnóstico , Humanos , Recém-Nascido , Pré-Eclâmpsia/diagnóstico , Valor Preditivo dos Testes , Gravidez
8.
Front Biosci (Elite Ed) ; 4: 2745-53, 2012 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-22652683

RESUMO

Infections during pregnancy can adversely affect the development of the fetal brain. This may contribute to disease processes such as schizophrenia in later life. Changes in the (cyto-) architecture of the anterior cingulate cortex (ACC), particularly in GABA-ergic interneurons, play a role in the pathogenesis of schizophrenia. We hypothesized that exposure to infection during pregnancy could result in cyto-architectural changes in the fetal ACC, similar to the pathogenesis seen in schizophrenia. Fetal sheep of 110 days GA (term=150 days GA) received an intravenous injection of 100 ng or 500 ng lipopolysaccharide (LPS) or saline as control. After delivery at 113 days GA, the cyto-architecture of the cingulate cortex (CC) was examined by immunohistochemistry. High dose LPS exposure resulted in a decreased density of GFAP-, calbindin D-28K- and parvalbumin-immunoreactive cells in the CC. In addition, these cells and calretinin-immunoreactive cells showed a changed morphology with reduced cell processes. This study provides further evidence that intra-uterine endotoxemia can induce changes in the fetal brain which correspond with changes seen in schizophrenia.


Assuntos
Encéfalo/embriologia , Modelos Animais de Doenças , Endotoxemia/patologia , Esquizofrenia/patologia , Ovinos/embriologia , Animais , Feminino , Imuno-Histoquímica , Gravidez
9.
Neonatology ; 102(2): 81-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22614058

RESUMO

BACKGROUND: Chorioamnionitis is a major risk factor for preterm birth in multifetal pregnancies. However, there is little clinical data whether chorioamnionitis is restricted to one amniotic compartment in multifetal pregnancies. OBJECTIVE: To explore whether chorioamnionitis is confined to the exposed compartment and does not cross to the unaffected fetus in twin pregnancy. METHODS: In twin pregnant sheep, one of the twins was exposed to either 2 or 14 days of intra-amniotic lipopolysaccharide (LPS) while the co-twin was exposed to either 2 or 14 days of intra-amniotic saline (n = 3 for each exposure). Singletons were included in this study to compare the grade of inflammation with twins. All fetuses were delivered at 125 days of gestation (term = 150 days). Chorioamnionitis was confirmed by histological examination. Lung inflammation was assessed by cell count in bronchoalveolar lavage. Lung compliance was assessed at 40 cm H(2)O. Results were compared using analysis of variance (ANOVA) with a post-hoc Tukey analysis. RESULTS: Inflammation in placenta, membranes and lung of LPS-exposed twins was significantly higher after 2 and 14 days of exposure when compared to the saline-exposed co-twins. Lung compliance in LPS-exposed twins was significantly increased after 14 days when compared to saline-exposed co-twins. Intrauterine LPS exposure increased lung compliance and inflammation in the membranes, placenta and lung to the same extent in twins as in singletons. CONCLUSION: In twin pregnant sheep, inflammation of the membranes, placenta and fetal lung was strictly limited to the exposed fetus in the amniotic compartment in which the LPS was injected.


Assuntos
Âmnio/patologia , Corioamnionite/patologia , Lipopolissacarídeos , Pulmão/patologia , Placenta/patologia , Âmnio/imunologia , Análise de Variância , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Corioamnionite/induzido quimicamente , Corioamnionite/imunologia , Modelos Animais de Doenças , Feminino , Idade Gestacional , Contagem de Leucócitos , Pulmão/embriologia , Pulmão/imunologia , Complacência Pulmonar , Neutrófilos/imunologia , Placenta/imunologia , Gravidez , Gravidez Múltipla , Carneiro Doméstico
10.
Cerebellum ; 11(1): 132-44, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21773814

RESUMO

Chorioamnionitis is an important problem in perinatology today, leading to brain injury and neurological handicaps. However, there are almost no data available regarding chorioamnionitis and a specific damage of the cerebellum. Therefore, this study aimed at determining if chorioamnionitis causes cerebellar morphological alterations. Chorioamnionitis was induced in sheep by the intra-amniotic injection of lipopolysaccharide (LPS) at a gestational age (GA) of 110 days. At a GA of 140 days, we assessed the mean total and layer-specific volume and the mean total granule cell (GCs) and Purkinje cell (PC) number in the cerebelli of LPS-exposed and control animals using high-precision design-based stereology. Astrogliosis was assessed in the gray and white matter (WM) using a glial fibrillary acidic protein staining combined with gray value image analysis. The present study showed an unchanged volume of the total cerebellum as well as the molecular layer, outer and inner granular cell layers (OGL and IGL, respectively), and WM. Interestingly, compared with controls, the LPS-exposed brains showed a statistically significant increase (+20.4%) in the mean total number of GCs, whereas the number of PCs did not show any difference between the two groups. In addition, LPS-exposed animals showed signs of astrogliosis specifically affecting the IGL. Intra-amniotic injection of LPS causes morphological changes in the cerebellum of fetal sheep still detectable at full-term birth. In this study, changes were restricted to the inner granule layer. These cerebellar changes might correspond to some of the motor or non-motor deficits seen in neonates from compromised pregnancies.


Assuntos
Astrócitos/patologia , Córtex Cerebelar/citologia , Córtex Cerebelar/patologia , Doenças Cerebelares/patologia , Corioamnionite/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Animais , Astrócitos/efeitos dos fármacos , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Córtex Cerebelar/efeitos dos fármacos , Doenças Cerebelares/induzido quimicamente , Corioamnionite/induzido quimicamente , Modelos Animais de Doenças , Feminino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Carneiro Doméstico , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia
11.
Pediatr Res ; 70(3): 242-6, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21629153

RESUMO

Exposure of the fetus to antenatal inflammation can occur from chorioamnionitis, which may progress to a fetal inflammatory response syndrome (FIRS) and to fetal sepsis. We tested whether the fetal myocardium responded to systemic Gram-negative endotoxinaemia. We hypothesized that the myocardium would respond to inflammation by changes in hypoxia-inducible factor-α (HIF-1α), inducible NO-synthase (iNOS), Toll-like receptors 2 and 4 (TLR2 and TLR4), IL-6, and phosphorylated signal transducer and activator of transcription-3 (pSTAT3). To model systemic endotoxinaemia, fetal sheep were exposed to Gram-negative endotoxin or saline i.v. 3 d before preterm delivery at 113 d of gestation (term = 147 d). All endotoxin-exposed animals developed cardiac dysfunction within these 72 h. Cardiac mRNA and protein levels of HIF-1α and TLR2 and TLR4 mRNA increased, whereas STAT3 phosphorylation decreased significantly. IL-6 and iNOS mRNA remained unchanged. Fetal systemic endotoxinaemia induced myocardial inflammation by activating TLR2 and 4. The following cardiac dysfunction seems not to be mediated via cardiac iNOS.


Assuntos
Endotoxinas/sangue , Endotoxinas/imunologia , Endotoxinas/farmacologia , Feto/efeitos dos fármacos , Feto/imunologia , Miocárdio/metabolismo , Ovinos , Animais , Feminino , Feto/anatomia & histologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/imunologia , Inflamação/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Miocárdio/citologia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Gravidez , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia
12.
PLoS One ; 4(6): e5837, 2009 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-19503810

RESUMO

Chorioamnionitis is the most significant source of prenatal inflammation and preterm delivery. Prematurity and prenatal inflammation are associated with compromised postnatal developmental outcomes, of the intestinal immune defence, gut barrier function and the vascular system. We developed a sheep model to study how the antenatal development of the gut was affected by gestation and/or by endotoxin induced chorioamnionitis.Chorioamnionitis was induced at different gestational ages (GA). Animals were sacrificed at low GA after 2d or 14d exposure to chorioamnionitis. Long term effects of 30d exposure to chorioamnionitis were studied in near term animals after induction of chorioamnionitis. The cellular distribution of tight junction protein ZO-1 was shown to be underdeveloped at low GA whereas endotoxin induced chorioamnionitis prevented the maturation of tight junctions during later gestation. Endotoxin induced chorioamnionitis did not induce an early (2d) inflammatory response in the gut in preterm animals. However, 14d after endotoxin administration preterm animals had increased numbers of T-lymphocytes, myeloperoxidase-positive cells and gammadelta T-cells which lasted till 30d after induction of chorioamnionitis in then near term animals. At early GA, low intestinal TLR-4 and MD-2 mRNA levels were detected which were further down regulated during endotoxin-induced chorioamnionitis. Predisposition to organ injury by ischemia was assessed by the vascular function of third-generation mesenteric arteries. Endotoxin-exposed animals of low GA had increased contractile response to the thromboxane A2 mimetic U46619 and reduced endothelium-dependent relaxation in responses to acetylcholine. The administration of a nitric oxide (NO) donor completely restored endothelial dysfunction suggesting reduced NO bioavailability which was not due to low expression of endothelial nitric oxide synthase.Our results indicate that the distribution of the tight junctional protein ZO-1, the immune defence and vascular function are immature at low GA and are further compromised by endotoxin-induced chorioamnionitis. This study suggests that both prematurity and inflammation in utero disturb fetal gut development, potentially predisposing to postnatal intestinal pathology.


Assuntos
Corioamnionite/imunologia , Corioamnionite/veterinária , Endotoxinas/metabolismo , Intestinos/embriologia , Animais , Artérias/patologia , Feminino , Imuno-Histoquímica/métodos , Inflamação , Microscopia de Fluorescência/métodos , Óxido Nítrico Sintase Tipo III/metabolismo , Gravidez , Prenhez , Ovinos , Junções Íntimas/patologia , Fatores de Tempo
13.
Reprod Sci ; 16(8): 758-66, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19525402

RESUMO

OBJECTIVE: Intrauterine infection is suggested to cause perinatal brain white matter injury. In the current study, we evaluated whether S100B, a brain damage marker, may be also assessed in maternal bloodstream after white matter injury induced by fetal intravenous application of lypopolisaccharide (LPS) endotoxin. METHODS: Fourteen fetal sheeps were chronically catheterized at a mean gestational age of 107 days. Three days after surgery, fetuses (n = 7) received 500 ng of LPS or 2 mL 0.9% saline (n = 7) intravenously (IV). Lypopolisaccharide and placebo groups were monitored by continuous hemodynamic data recordings and at 6 predetermined time points (control value; 3, 6, 24, 48, and 72 hours after LPS/placebo administration) blood was drawn for laboratory parameters and S100B assessment. Brain damage was evaluated by light microscopy after Klüver-Barrera staining. Selected areas of the periventricular white matter were also examined by electron microscopy. RESULTS: White matter injury was detected in all LPS-treated fetuses, whereas no abnormalities were seen in control animals or in LPS-treated mothers. Maternal and fetal S100B protein levels were significantly higher in the LPS group than in the control group at all monitoring time points (P < .001). The highest fetal-maternal S100B levels were observed at 3-hour time-point (P < .001). CONCLUSIONS: We found that S100B protein is increased in the maternal district in presence of fetal periventricular brain white matter injury induced by endotoxin. The present data offer additional support for S100B assessment in the maternal circulation in pregnancies complicated by intrauterine infection at risk of white matter injury.


Assuntos
Lesões Encefálicas/sangue , Endotoxemia/sangue , Sangue Fetal/metabolismo , Fatores de Crescimento Neural/sangue , Proteínas S100/sangue , Equilíbrio Ácido-Base , Animais , Biomarcadores/sangue , Pressão Sanguínea , Encéfalo/ultraestrutura , Lesões Encefálicas/induzido quimicamente , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Dióxido de Carbono/sangue , Modelos Animais de Doenças , Endotoxemia/induzido quimicamente , Endotoxemia/patologia , Endotoxemia/fisiopatologia , Feminino , Idade Gestacional , Frequência Cardíaca Fetal , Lipopolissacarídeos , Oxigênio/sangue , Gravidez , Subunidade beta da Proteína Ligante de Cálcio S100 , Ovinos , Fatores de Tempo , Regulação para Cima
14.
Am J Obstet Gynecol ; 200(4): 437.e1-8, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19217590

RESUMO

OBJECTIVE: We quantified the impact of chorioamnionitis on both the white and gray matter structures of the preterm ovine central nervous system (CNS). STUDY DESIGN: The CNS was studied at 125 days of gestation, either 2 or 14 days after the intraamniotic administration of 10 mg of lipopolysaccharide (LPS) (Escherichia coli) or saline. Apoptotic cells and cell types were analyzed in the brain, cerebellum, and spinal cord using flow cytometry. RESULTS: Apoptosis and microglial activation increased in all regions with prolonged exposure to LPS-induced chorioamnionitis. Astrocytes were increased in the brain and cerebellum of LPS-exposed fetuses but not in the spinal cord. Mature oligodendrocytes decreased in the cerebral and cerebellar white matter, the cerebral cortex, caudate putamen, and hippocampus 14 days after LPS. Neurons in the cerebral cortex, hippocampus, and substantia nigra were reduced 14 days after LPS. CONCLUSION: Fetal inflammation globally but differentially affected the CNS depending on the maturational stage of the brain region.


Assuntos
Encéfalo/patologia , Corioamnionite , Medula Espinal/patologia , Âmnio , Animais , Cerebelo/patologia , Corioamnionite/etiologia , Feminino , Injeções , Lipopolissacarídeos/administração & dosagem , Gravidez , Ovinos , Fatores de Tempo
15.
Am J Obstet Gynecol ; 200(2): 195.e1-10, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19110233

RESUMO

BACKGROUND: Antenatal pulmonary inflammation is associated with reduced risk for respiratory distress syndrome but with an increased risk for bronchopulmonary dysplasia (BPD) with impaired alveogenesis. OBJECTIVE: We hypothesized that fetal systemic inflammation induced by intravenous (IV) lipopolysaccharide (LPS) would affect lung development in utero. STUDY DESIGN: Twenty-one fetal sheep were instrumented (107 days gestational age). Control fetuses received saline (N = 12) and 9 in the study group received 100 ng of LPS IV 3 days after surgery. Animals were assessed for lung maturation and structure after 3 (N = 5) and 7 (N = 4) days. RESULTS: Interleukin-6 concentration increased in the bronchoalveolar lavage more than 40-fold 3 days after LPS IV. Processing of pro-surfactant protein (SP)-B to mature SP-B and increased SP-B concentrations were shown 7 days after LPS IV. Deposition of elastin fibers at sites of septation was disturbed within 3 days after LPS IV. CONCLUSION: Lung maturation and disturbed lung structure occurred after short-term exposure to fetal inflammation and suggests new targeted therapies for BPD.


Assuntos
Doenças Fetais/imunologia , Maturidade dos Órgãos Fetais/imunologia , Lipopolissacarídeos/administração & dosagem , Pneumopatias/imunologia , Pulmão/imunologia , Animais , Proliferação de Células , Elastina/imunologia , Feminino , Feto , Pulmão/crescimento & desenvolvimento , Complacência Pulmonar , Proteína B Associada a Surfactante Pulmonar/imunologia , Ovinos
16.
Eur J Obstet Gynecol Reprod Biol ; 141(1): 3-9, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18783866

RESUMO

Spontaneous preterm labour and preterm births are still the leading cause of perinatal morbidity and mortality in the developed world. Previous efforts to prevent preterm birth have been hampered by a poor understanding of the underlying pathophysiology, inadequate diagnostic tools and generally ineffective therapies. Clinical, epidemiological and experimental studies indicate that genito-urinary tract infections play a critical role in the pathogenesis of preterm birth. Moreover, intrauterine infection increases perinatal mortality and morbidity, such as cerebral palsy and chronic lung disease, significantly. It has recently been suggested that gene-environment interactions play a significant role in determining the risk of preterm birth. Polymorphisms of certain critical genes may be responsible for a harmful inflammatory response in those who possess them. Accordingly, polymorphisms that increase the magnitude or the duration of the inflammatory response were associated with an increased risk of preterm birth. In contrast polymorphisms that decrease the inflammatory response were associated with a lower risk of preterm birth. This article will review the current understanding of pathogenetic pathways in the aetiology of preterm birth.


Assuntos
Ruptura Prematura de Membranas Fetais/genética , Predisposição Genética para Doença/genética , Inflamação/genética , Nascimento Prematuro/genética , Corioamnionite/imunologia , Citocinas/genética , Feminino , Ruptura Prematura de Membranas Fetais/imunologia , Ruptura Prematura de Membranas Fetais/microbiologia , Humanos , Metaloproteinases da Matriz/genética , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Gravidez , Nascimento Prematuro/imunologia , Nascimento Prematuro/microbiologia , Vaginose Bacteriana/imunologia
17.
Eur J Obstet Gynecol Reprod Biol ; 138(2): 152-7, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17942214

RESUMO

OBJECTIVES: Antenatal infections are associated with an increased risk of perinatal morbidity and mortality. Systemic application of endotoxins to the fetus results in an increase in placental vascular resistance and chronic reduction in umbilical blood flow. We studied morphological alterations of the placenta in response to fetal inflammation in the preterm sheep. STUDY DESIGN: Therefore, 14 fetal sheep were chronically instrumented at a mean gestational age of 107+/-1 days (term is 147 days). Four days after surgery fetuses received 100 ng lipopolysaccharide (LPS; n=8) or saline (control; n=6) intravenously. Fetal heart rate and arterial blood pressure were monitored continuously while blood gases and acid-base balance were measured at time points 0, +1, +3, +6, +12, +24, +48 and +72 h. Three days after LPS application placental cotyledons were analyzed by immunohistochemistry and morphometry. Different primary antibodies like AE 1 and AE 3 against cytokeratins were used. Secondary antibodies were visualized with 3-amino-9-ethylcarbazole (AEC) or using the Vectastain kit (Vector Laboratories, Burlingame, CA). Double staining was carried out first by utilizing Vectastain kit (black), followed by AEC staining (red). Counterstaining was performed with haematoxylin. RESULTS: Fetal tachycardia and hypertension were induced transiently during the first 12h after LPS application. Fetuses suffered from mild hypoxaemia while acidemia was absent. Morphometry revealed a non-significant shift in the relation of maternal and fetal placental compartments towards the maternal parts in response to LPS treatment. Endotoxin induced an increased proliferation in both compartments of the placenta with a 3.2-fold increase on the maternal and a 1.8-fold increase on the fetal side. CONCLUSIONS: Systemic endotoxin exposure of the preterm fetal sheep leads to a change in the gross organization of the placenta and changes in the proliferation patterns in both placental compartments. These rearrangements inside the placenta may disturb its organ function and subsequently lead to fetal morbidity associated with the fetal inflammatory response syndrome and chronic placental dysfunction, respectively.


Assuntos
Feto/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Placenta/patologia , Equilíbrio Ácido-Base/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Endotelina-1/fisiologia , Feminino , Frequência Cardíaca Fetal/efeitos dos fármacos , Inflamação/etiologia , Placenta/efeitos dos fármacos , Gravidez , Ovinos
18.
Clin Nucl Med ; 32(8): 663-5, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17667449

RESUMO

A 31-year-old woman with a history of infection with human papilloma virus was found to have an elevated human chorionic gonadotropin level (beta-HCG) of more than 9000 IU/L in January 2006. The patient reported an irregular menstrual cycle. Extensive clinical work-up including gynecologic examinations with laparoscopy, hysteroscopy, and curettage were performed but no pathologic explanation of this elevated beta-HCG could be found. In the initial computed tomography (CT) of the abdomen and the thorax, a tumor could not be detected. Based on a clinical decision, chemotherapy with methotrexate in a dose of 1 mg/kg body weight was started. Four months after beginning of the chemotherapy the beta-HCG level dropped to 3048 IU/L. At this time a first F-18 FDG PET was performed and the findings were negative. After completion of 7 cycles of chemotherapy the beta-HCG level rose again. In a second F-18 FDG PET in August 2006 focal, intense and pathologic F-18 FDG accumulation with a SUV max. of 5.4 was seen in the mediastinum in the region of the thymus. At this time the beta-HCG level was 7000 IU/L. In a subsequent CT of the chest a retrosternal mass of 4 x 1.7 cm was detected with contrast enhancement. Resection of the tumor and thymus gland demonstrated a choriocarcinoma in part adjacent to the thymus and in part in the thymus. Postoperative beta-HCG levels dropped to 105 IU/L.


Assuntos
Coriocarcinoma não Gestacional/diagnóstico por imagem , Fluordesoxiglucose F18 , Neoplasias do Mediastino/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Neoplasias do Timo/diagnóstico por imagem , Adulto , Feminino , Humanos , Compostos Radiofarmacêuticos
19.
Eur J Obstet Gynecol Reprod Biol ; 124(1): 15-22, 2006 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-16386654

RESUMO

OBJECTIVE: Intrauterine infection is suggested to cause perinatal brain white matter injury. The aim of the present study was to clarify, whether intravenous application of endotoxin results in neuropathological findings and increased blood levels of the S100B protein, which is a consolidated marker of brain injury. METHODS: Twenty-one fetal sheep were chronically catheterized at a mean gestational age of 107+/-1 days (0.7 of gestation). Three days after surgery fetuses received either 100 (n = 9), 500 (n = 5) or 2500 ng (n = 1) lipopolysaccharide (LPS; E. coli; O127:B8, Sigma-Aldrich) or 2 ml 0.9% saline (n = 6) i.v. S100B protein blood levels were assessed before during and after LPS or placebo administration. Brain damage was evaluated by light microscopy. Selected areas of the periventricular white matter were also examined by electron microscopy. RESULTS: Histopathological screening revealed no evidence for cortical neuronal cell damage in both groups. However, LPS treatment resulted in inflammatory infiltrates in all animals and cystic lesions in the periventricular brain white matter in two fetuses. On electron micrographs, infiltrate forming cells appeared to be activated microglia. S100B protein blood levels were significantly higher in the LPS group at 1h (p < 0.01) after LPS injection, peaking at 3h (p < 0.001) and returning to baseline between 12 and 72 h. CONCLUSION: Intravenous application of endotoxin caused focal periventricular brain white matter injury, inflammation and an increase in S100B protein release. It is suggested that longitudinal investigations of S100B protein blood levels offer a tool for the early detection of white matter injury.


Assuntos
Lesões Encefálicas/induzido quimicamente , Feto/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Fatores de Crescimento Neural/sangue , Proteínas S100/sangue , Animais , Lesões Encefálicas/patologia , Feminino , Feto/patologia , Hemodinâmica/efeitos dos fármacos , Microscopia Eletrônica , Gravidez , Subunidade beta da Proteína Ligante de Cálcio S100 , Ovinos
20.
Eur J Obstet Gynecol Reprod Biol ; 124(2): 150-7, 2006 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-16054285

RESUMO

OBJECTIVE: To study endotoxin induced changes in pulmonary blood flow during normoxia and hypoxia and analyzed the role of nitric oxide (NO) and endothelin (ET) in this process. STUDY DESIGN: Twenty-seven fetal sheep were chronically instrumented at 107+/-1 days (term is 147 days). Experiments were performed 3 days after surgery. Fetuses were randomized into four groups. Group 1: control group (n=5); Group 2: LPS group (n=6) with lipopolysaccharide (LPS) injection at t -60min; Group 3: L-NAME (n=6) with nitro-l-arginine methyl ester (l-NAME) treatment at t -75min; Group 4: l-NAME+LPS group (n=6) with nitro-l-arginine methyl ester (l-NAME) pre-treatment at t -75min and LPS administration at t -60min as described above; Group 5: BQ123+LPS group (n=4) with BQ123 pre-treatment at t -75min and LPS injection at t -60min as described above. RESULTS: Unlike in control fetuses, there was a marked elevation in pulmonary perfusion in response to LPS induced endotoxemia during normoxia (+112%; p<0.01), which was even further increased during hypoxia (+434%; p<0.001). This increase was partially blocked by BQ123 (p<0.05) and completely abolished by pre-treatment with l-NAME (p<0.001). CONCLUSION: During fetal endotoxemia, pulmonary perfusion is increased by LPS induced production of nitric oxide. This may have a significant impact in the fetal inflammatory response syndrome, particularly in the inflammation of the fetal lungs observed in response to intrauterine infection.


Assuntos
Endotelinas/fisiologia , Endotoxemia/fisiopatologia , Hipóxia Fetal/fisiopatologia , Lipopolissacarídeos/toxicidade , Pulmão/irrigação sanguínea , Óxido Nítrico/fisiologia , Equilíbrio Ácido-Base/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Feminino , Feto/irrigação sanguínea , Frequência Cardíaca Fetal/efeitos dos fármacos , Lipopolissacarídeos/administração & dosagem , Pulmão/efeitos dos fármacos , Pulmão/embriologia , NG-Nitroarginina Metil Éster/farmacologia , Peptídeos Cíclicos/farmacologia , Distribuição Aleatória , Fluxo Sanguíneo Regional/efeitos dos fármacos , Ovinos
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