To determine the current clinical practices of perinatologists regarding the management of premature rupture of membranes (PROM), 1,041 perinatologists were surveyed by multiple choice questionnaire with regard to induction of labor, use of antibiotics, tocolytic agents, and corticosteroids following uncomplicated PROM occurring between 19 and 36 weeks. The response rate was 51% (557/ 1,041). There was a consensus on expectant management of preterm PROM, except (1) where fetal lungs are found mature between 33 and 35 weeks gestation (51% induction vs. 44% expectant) and (2) at 19-22 weeks (71% undecided). During the expectant management the majority does not at any time use antibiotics, tocolytic agents, or corticosteroids. No uniform protocol has yet evolved for the management of preterm PROM, especially (1) between 33 and 35 weeks with mature fetal lungs, and (2) at 19-22 weeks gestation.

Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg / Background and objectives Prelabour rupture of the membranes (PROM) is a major obstetric problem affecting about 20% of pregnancies. Complications include preterm labour, ascending intrauterine and perinatal infections, and neonatal mortality. Standard guidelines are formulated and continually reviewed to improve the clinical management of PROM and to reduce poor perinatal outcomes associated with this condition. The objectives of this study, conducted using women in Johannesburg as a sample population, were: 1) to audit the implementation of the standard protocol on management of PROM, and 2) to determine the maternal and fetal outcomes of this condition. Methods A cross-sectional descriptive study was done on women admitted to the antenatal wards of Chris Hani Baragwanath Academic Hospital with PROM. Inclusion criteria were that PROM was the main reason for admission, gestation ≥24 weeks, and maternal age 18 years or more. Hospital clinical files were studied for obstetric and clinical characteristics, adherence by doctors to the management protocol, and final outcome including latency period, induction rate, mode of delivery, and neonatal outcome. Results Ninety-seven women participated in the study. Their mean age was 27.0 years, and 37 (38%) were nulliparous. Eighty-five (87%) had attended antenatal clinic. Twenty-nine (30%) were HIV-infected, 23 (79%) of them on highly active antiretroviral treatment. 6 The mean gestational age on admission was 32.8 weeks, with 78 (80%) women having preterm PROM at GA<37 weeks and 52 (54%) at GA <34 weeks. The most frequent methods of diagnosis were visual inspection in 77 (79%), speculum examination in 49 (51%) and ultrasound scan in 81 (84%) of the women. Antibiotics were given to 96 women (99%), and antenatal corticosteroids were used in all women <34 weeks pregnant. No cases of clinical chorioamnionitis were detected. The mean latency from PROM to delivery for women <37 weeks pregnant was 15 days, and for those <34 weeks, it was 19 days. Twenty-nine women (30%) required induction of labour, and 25 (25.8%) had caesarean sections. There were 12 perinatal deaths (with the exclusion of three late neonatal deaths), resulting from prematurity (n=4), congenital anomalies (n=2), neonatal jaundice (n=2), respiratory distress syndrome (n=2) and perinatal asphyxia / hypoxic ischaemic encephalopathy (n=2). There were no recorded cases of either neonatal or puerperal sepsis. Conclusion The study may have under-represented term PROM, so the findings are most applicable to preterm PROM. The condition was mostly managed appropriately within the local protocol, especially in terms of corticosteroid and antibiotic use. Overt or clinically evident chorioamnionitis was not detected. However, the perinatal mortality rate was high, and whatever the causes of perinatal death in this group, it is clear that PROM is a high-risk condition deserving of close clinical attention.

As part of our management protocol for preterm premature rupture of membranes, ceftizoxime and tocolysis were used to prolong the latent period and prevent or treat concomitant infection. Ceftizoxime was selected for this protocol based on its physiochemical properties, which favor placental transfer of the drug. Patients achieving steady-state pharmacodynamics (more than three doses of the drug) were considered eligible for study. Ceftizoxime levels were determined by reverse-phase high-pressure liquid chromatography. All levels measured after the first hour of treatment were indicative of the relative concentration of ceftizoxime in the fetal and amniotic fluid compartments when compared with the maternal compartment. Mean (±SEM) ceftizoxime levels were 11.96 + 2.35 μg/ml in maternal serum, 24.54 ± 4.78 μg/ml in cord serum, and 43.45 ± 4.97 μg/ml in amniotic fluid. Based on its broad antibacterial activity and its high concentration in fetal blood and amniotic fluid, ceftizoxime appears to be an ideal agent for treatment of the intrauterine environment.

Orientador: Lígia Maria S. S. Rugolo / Banca: Cleide Enoir Petean Trindade / Banca: José Carlos Peraçoli / Banca: Maria Fernanda Branco de Almeida / Banca: Lilian dos Santos Rodrigues Sadeck / Resumo: A rotura prematura de membranas pré-termo (RPM-PT) é uma das principais causas de morbimortalidade perinatal e fator de risco para infecção neonatal precoce. As citocinas pró-inflamatórias TNF-α, IL-8 e a antiiflamatória IL-10 são importantes mediadores da resposta imune, e na situação de risco infeccioso podem ser adjuvantes úteis no diagnóstico de infecção neonatal. Investigar se os níveis de TNF-α, IL-8 e IL-10 em sangue de cordão umbilical são marcadores de infecção precoce em prematuros advindos de gestações com RPM-PT. Estudo clínico, prospectivo e do tipo teste diagnóstico, realizado no Serviço de Obstetrícia e Neonatologia da Faculdade de Medicina de Botucatu, envolvendo prematuros de gestantes com rotura de membranas ≥ 12 horas. As citocinas TNF-α, IL-8 e IL-10 foram dosadas em sangue de cordão umbilical pelo método ELISA. Conforme a evolução clínica e laboratorial dos recém-nascidos foram constituídos dois grupos: Infectado e Não infectado, os quais foram comparados quanto às variáveis perinatais e neonatais por análise estatística univariada; com significância em 5%. A acurácia do teste diagnóstico foi obtida pela curva ROC, sendo calculados: sensibilidade, especificidade, valor preditivo positivo (VPP) e negativo (VPN). Foram estudados 55 prematuros: 27 infectados e 28 não infectados. O tempo de rotura não diferiu entre os grupos (54 x 29 hs; p=0,102) mas, no grupo infectado corioamnionite clínica e histológica foi mais frequente; a idade gestacional (31 x 33 semanas; p<0,001) e o peso de nascimento (1707 x 2109g; p=0,003) foram menores; a morbidade foi maior desde o nascimento com necessidade de assistência mais intensiva e o óbito ocorreu somente nesse grupo. As medianas de TNF-α (3.67 vs 1.76 pg/ml; p =0.084) e IL-10 (0 vs 4.10 pg/ml; p=0.291)... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Preterm premature rupture of membranes (PPROM) is one of the major causes of perinatal morbidity and mortality, and an important risk factor for early-onset neonatal infection. The pro-inflammatory cytokines TNF-α, IL-8 and anti-inflammatory cytokine IL-10 are mediators of immune response and may be helpful as early indicator of neonatal infection in the presence of perinatal risk factor. To evaluate umbilical cord blood levels of TNF-α, IL-8 and IL-10 as markers for early-onset infections in premature infants from pregnancies complicated by PPROM. Clinical, prospective and diagnostic test study performed at Obstetrician and Neonatal Unit of Botucatu School of Medicine, enrolling premature infants from pregnant women with ≥ 12 hours of premature rupture of membranes. TNF-α, IL-8 and IL-10 cytokines were measured in umbilical cord blood by ELISA. According to clinical and laboratorial evaluation patients were classified into two groups: infected and noninfected. Perinatal and neonatal variables were studied. Comparisons between groups were performed by univariate statistical analysis; significance at p <0.05. The diagnostic test accuracy was obtained by ROC curve. Sensibility, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated by comparing infected with noninfected group. 55 premature infants were studied: 27 infected and 28 noninfected. There was no difference between the groups in the latency period (54 x 29 hours; p=0,102). In the infected group, clinical and histological chorioamnionitis were more frequent, gestational age (31 x 33 weeks; p<0,001) and birth weight(1707 x 2109g; p=0,003) were lower. Morbidity, mortality and resource use were higher among infected premature infants. The median levels of TNF-α (3.67 vs 1.76 pg/ml; p=0.084)... (Complete abstract click electronic access below) / Doutor

Lic.-avh. Stockholm : Karolinska institutet, 2005.

LabPasteur / Objetivos deste estudo: identificar a prevalÃncia e os fatores de risco da colonizaÃÃo materna e infecÃÃo neonatal por streptococcus do grupo B (SGB), em mulheres com trabalho de parto prematuro (TPP) e/ou ruptura prematura de membranas (RPM); medir e comparar taxas de colonizaÃÃo vaginal e anorretal por SGB, comparar taxas de detecÃÃo do SGB em meio de cultura seletivo (Todd-Hewitt) e nÃo seletivo (Stuart) e com cultivo em Ãgar-sangue e Ãgar- CPS. Estudo transversal de 112 mulheres e 220 recÃm-nascidos realizou-se na Maternidade Escola Assis Chateaubriand da Universidade federal do Cearà (MEAC-UFC), de maio de 2008 a julho de 2009. Amostras vaginais e anorretais foram colhidas de cada mulher, usando swabs estÃreis. Em 71 mulheres, 2 swabs (vaginal e anorretal), colocaram-se separadamente em meio de transporte Stuart e 2 swabs (vaginal e anorretal), inocularam-se separadamente em meio seletivo Todd-Hewitt, todos subcultivados em placas de Ãgar-sangue. Outras gestantes do grupo, 41 mulheres, foram investigadas somente em meio seletivo com subcultivo em placas de Ãgar-CPS. Colheu-se hemocultura de cada recÃm-nascido pretermo com algum sinal de infecÃÃo. A taxa de colonizaÃÃo materna de 71 mulheres foi de 4,2% e do grupo de 41, de 17%. Meio seletivo Todd-Hewitt detectou 4,4% e meio nÃo seletivo, 7,2% das culturas positivas para SGB no grupo de 71 mulheres, resultados sem diferenÃa significativa. Amostras vaginais tiveram taxas de detecÃÃo de 10,7% e anorretais de 7,1%, nÃo alcanÃando significÃncia estatÃstica. Houve diferenÃa significativa no isolamento de SGB, entre o meio Ãgar-CPS e o Ãgar-sangue. InfecÃÃo urinÃria mostrou ser importante fator de risco (P < 0,01) e a profissÃo Do lar tambÃm associou-se significativamente com a colonizaÃÃo por SGB Dos RNs incluÃdos no estudo, nenhuma hemocultura teve resultado positivo para SGB, embora apresentassem sinais de infecÃÃo e hemogramas alterados. à possÃvel que o resultado tenha ocorrido pelo fato de que as mÃes tomaram antibiÃticos antes ou durante o trabalho de parto. As taxas de colonizaÃÃo por SGB, em nosso meio, sÃo semelhantes Ãs encontradas em outras regiÃes do Brasil, podendo ser tambÃm, aqui, agente de relevÃncia na sepse neonatal que requer, sÃrias medidas de prevenÃÃo. / The objectives of this study: to identify the prevalence and the risk factors from maternal colonization and neonatal infection from group B Streptococcus in women with preterm labor and/or premature rupture membranes. It measures and compare vaginal and anorectal colonization rates. It compare detection rates with selective and non-selective culture media and it compare detection rates with blood Ãgar and CPS Ãgar. A transversal study of 112 women and 220 newborns was performed at Maternidade Escola Assis Chateaubriand from Universidade Federal do Cearà (MEAC-UFC) from may /2008 to july/2009. Vaginal and anorectal samples from each woman were collected using sterile swabs. In 71 women two swabs (vaginal and anorectal) were placed separately in Stuart transport medium and two swabs (vaginal and anorectal) were inoculated separately in Todd-Hewitt selective medium. All subcultered in blood agar plates. The other pregnancies 41 women were investigated only in selective medium and subcultered in a CPS agar plates. A blood culture was collected from each preterm newborn that with any sign of infection. The maternal colonization rate from 71 women was of 4,2% and from the 41 women group was of 17%. Todd-Hewitt selective medium detected 4,4% and non-selective medium 7,2% GBS positive culture (not statistical relevant âNSR). Vaginal samples had a detection rate of 10,7% and anorectal samples had detection rate of 7,1% ( NSR). Urinary infection and be a housewife showed to be meaningful risk factors (p < 0,05). From the newborns studied none of them had GBS positive blood culture due to the sign of infection and altered hemogram. It,s possible that the result had occurred for the fact that the mothers had taken antibiotic before or during the labor. The GBS women colonization in our environment is similar to the other regions of Brazil. The GBS could be to here an important agent for neonatal infection disease and its necessary to take serious prevent measures.

The vaginal microbial community is critical to a woman’s health and the health of her family. Bacterial vaginosis (BV) is a polymicrobial syndrome characterized by a shift of the vaginal microbiota from a Lactobacillus dominated community to a dense biofilm containing a complex mixture of organisms. Although BV is an important risk factor for poor reproductive health outcomes, the etiology of BV is poorly understood. Gardnerella vaginalis is a hallmark species of BV. Phylogenetic analysis of cpn60 universal target sequences from metagenomic studies of the vaginal microbiome and from G. vaginalis isolates resolved four subgroups within the species. This subdivision, supported by whole genome similarity comparisons, demonstrated that these subgroups might represent different species. Among a group of African women, only G. vaginalis subgroup B was significantly more abundant in women with BV relative to women with Nugent scores not consistent with BV. To characterize the subgroups further, several phenotypic and molecular factors of G. vaginalis subgroups were assessed. Proteomic profiles of isolates within each subgroup formed unambiguous clusters. Sialidase gene sequences were detected in all subgroups, however enzymatic activity was detected only in subgroup B. Two isolates of subgroup B isolates (N153 and N101) were incapable of growth in 7% CO2. Given the well-known relationship between an anaerobic microbiota and BV, anaerobic isolates of G. vaginalis are potentially important players in the vaginal microbial community. To determine genome content differences that could account for the phenotypic difference, whole genome sequences of four G. vaginalis subgroup B isolates representing facultative and anaerobic phenotypes were determined. Comparison of genomes led to the identification of genes predicted to encode proteins involved in cell wall biogenesis and protection from oxidative damage that might account for the observed phenotypes. The cpn60 universal target based methodology that improved resolution of the vaginal microbiota including G. vaginalis was applied in a prospective study of the vaginal microbiome of women with preterm premature rupture of membranes (PPROM). The objectives were to characterize the vaginal microbiota of women following PPROM, and to determine if microbiome composition at the time of rupture predicts latency duration and perinatal outcomes. Only 13/70 samples collected from 36 women were dominated by Lactobacillus spp., the expected profile for healthy women, while Megasphaera type 1 and Prevotella spp. were detected in all samples. Microbiome profiles at the time of membrane rupture did not cluster by gestational age at PPROM, or latency duration. Microbial profiles were unstable over the latency period, with dramatic shifts in composition between weekly samples, and an overall decrease in Lactobacillus abundance. Mollicutes were detected by PCR in 81% (29/36) of women, and these women had significantly lower gestational age at delivery and correspondingly lower birth weight infants than Mollicutes negative women. Taken together, the results presented in this thesis demonstrate the value of high resolution profiling of the vaginal microbiome using cpn60 UT sequences. The resolution of subgroups within G. vaginalis has potentially significant implications for women's health diagnostics, requiring a shift away from considering G. vaginalis as a single entity. The PPROM study provides foundational information that may lead to the identification of informative sequence patterns, providing clinicians with better tools for expectant management following PPROM.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Made available in DSpace on 2014-06-11T19:33:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-08-01Bitstream added on 2014-06-13T19:26:38Z : No. of bitstreams: 1 hashimoto_m_dr_botfm.pdf: 298656 bytes, checksum: 13b4b2d4d265946e9f647fb2dd27e0e4 (MD5) / A rotura prematura de membranas pré-termo (RPM-PT) é uma das principais causas de morbimortalidade perinatal e fator de risco para infecção neonatal precoce. As citocinas pró-inflamatórias TNF-α, IL-8 e a antiiflamatória IL-10 são importantes mediadores da resposta imune, e na situação de risco infeccioso podem ser adjuvantes úteis no diagnóstico de infecção neonatal. Investigar se os níveis de TNF-α, IL-8 e IL-10 em sangue de cordão umbilical são marcadores de infecção precoce em prematuros advindos de gestações com RPM-PT. Estudo clínico, prospectivo e do tipo teste diagnóstico, realizado no Serviço de Obstetrícia e Neonatologia da Faculdade de Medicina de Botucatu, envolvendo prematuros de gestantes com rotura de membranas ≥ 12 horas. As citocinas TNF-α, IL-8 e IL-10 foram dosadas em sangue de cordão umbilical pelo método ELISA. Conforme a evolução clínica e laboratorial dos recém-nascidos foram constituídos dois grupos: Infectado e Não infectado, os quais foram comparados quanto às variáveis perinatais e neonatais por análise estatística univariada; com significância em 5%. A acurácia do teste diagnóstico foi obtida pela curva ROC, sendo calculados: sensibilidade, especificidade, valor preditivo positivo (VPP) e negativo (VPN). Foram estudados 55 prematuros: 27 infectados e 28 não infectados. O tempo de rotura não diferiu entre os grupos (54 x 29 hs; p=0,102) mas, no grupo infectado corioamnionite clínica e histológica foi mais frequente; a idade gestacional (31 x 33 semanas; p<0,001) e o peso de nascimento (1707 x 2109g; p=0,003) foram menores; a morbidade foi maior desde o nascimento com necessidade de assistência mais intensiva e o óbito ocorreu somente nesse grupo. As medianas de TNF-α (3.67 vs 1.76 pg/ml; p =0.084) e IL-10 (0 vs 4.10 pg/ml; p=0.291)... / Preterm premature rupture of membranes (PPROM) is one of the major causes of perinatal morbidity and mortality, and an important risk factor for early-onset neonatal infection. The pro-inflammatory cytokines TNF-α, IL-8 and anti-inflammatory cytokine IL-10 are mediators of immune response and may be helpful as early indicator of neonatal infection in the presence of perinatal risk factor. To evaluate umbilical cord blood levels of TNF-α, IL-8 and IL-10 as markers for early-onset infections in premature infants from pregnancies complicated by PPROM. Clinical, prospective and diagnostic test study performed at Obstetrician and Neonatal Unit of Botucatu School of Medicine, enrolling premature infants from pregnant women with ≥ 12 hours of premature rupture of membranes. TNF-α, IL-8 and IL-10 cytokines were measured in umbilical cord blood by ELISA. According to clinical and laboratorial evaluation patients were classified into two groups: infected and noninfected. Perinatal and neonatal variables were studied. Comparisons between groups were performed by univariate statistical analysis; significance at p <0.05. The diagnostic test accuracy was obtained by ROC curve. Sensibility, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated by comparing infected with noninfected group. 55 premature infants were studied: 27 infected and 28 noninfected. There was no difference between the groups in the latency period (54 x 29 hours; p=0,102). In the infected group, clinical and histological chorioamnionitis were more frequent, gestational age (31 x 33 weeks; p<0,001) and birth weight(1707 x 2109g; p=0,003) were lower. Morbidity, mortality and resource use were higher among infected premature infants. The median levels of TNF-α (3.67 vs 1.76 pg/ml; p=0.084)... (Complete abstract click electronic access below)

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22322号 / 医博第4563号 / 新制||医||1041(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 竹内 理, 教授 椛島 健治, 教授 安達 泰治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM