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PURPOSE: To determine the predictive value of maternal White Blood Cells (WBC), neutrophils, and C-Reactive Protein (CRP) for diagnosing Histological Chorioamnionitis (HCA) among women with Preterm Premature Rupture of Membranes (PPROM) who underwent cervical cerclage. METHODS: A retrospective cross-sectional study was conducted among women with singleton pregnancy and PPROM, who underwent cervical cerclage during 2018-2020. RESULTS: A total of 55 eligible women were included in the final analysis, including 36 (61.02%) cases with HCA and 19 (38.98%) without HCA. Women with HCA had higher WBC count (12.31 ± 2.80) × 109/L and neutrophil count (9.67 ± 2.90)×109/L than those without HCA (10.35 ± 2.53) × 109/L and 7.82 ± 2.82 × 109/L, respectively) (both p < 0.05). The cut-off value of WBC count at 10.15×109/L was found to be the most effective in identifying HCA, with an Area Under Curve (AUC) of 0.707 (95% CI: 0.56-0.86; p = 0.012), sensitivity of 86.11%, specificity of 57.90%, Positive Predictive Value (PPV) of 79.49%, Negative Predictive Value (NPV) of 68.75%, and Youden index of 0.44. The combination of WBC + neutrophil had a slightly higher (AUC = 0.711, 95% CI: 0.57-0.86; p = 0.011), specificity (68.42%), and PPV (81.25%), but lower sensitivity (72.22%), than the WBC count alone. A cut-off value of neutrophil at 7.46 × 109/L was effective in identifying HCA, with an AUC of 0.689 (95% CI: 0.53-0.84; p = 0.022). DISCUSSION: Combination use of WBC+neutrophil was found to be the most accurate predictor of HCA among women with PPROM after surgery of cervical cerclage.

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Preterm labor (PTL) and preterm premature rupture of membranes (PPROM) lead to high perinatal morbidity/mortality rates worldwide. Small extracellular vesicles (sEV) act in cell communication and contain microRNAs that may contribute to the pathogenesis of these complications. We aimed to compare the expression, in sEV from peripheral blood, of miRNAs between term and preterm pregnancies. This cross-sectional study included women who underwent PTL, PPROM, and term pregnancies, examined at the Botucatu Medical School Hospital, SP, Brazil. sEV were isolated from plasma. Western blot used to detect exosomal protein CD63 and nanoparticle tracking analysis were performed. The expression of 800 miRNAs was assessed by the nCounter Humanv3 miRNA Assay (NanoString). The miRNA expression and relative risk were determined. Samples from 31 women-15 preterm and 16 term-were included. miR-612 expression was increased in the preterm groups. miR-612 has been shown to increase apoptosis in tumor cells and to regulate the nuclear factor κB inflammatory pathway, processes involved in PTL/PPROM pathogenesis. miR-1253, miR-1283, miR378e, and miR-579-3p, all associated with cellular senescence, were downregulated in PPROM compared with term pregnancies. We conclude that miRNAs from circulating sEV are differentially expressed between term and preterm pregnancies and modulate genes in pathways that are relevant to PTL/PPROM pathogenesis.

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ABSTRACT Purpose: To determine the predictive value of maternal White Blood Cells (WBC), neutrophils, and C-Reactive Protein (CRP) for diagnosing Histological Chorioamnionitis (HCA) among women with Preterm Premature Rupture of Membranes (PPROM) who underwent cervical cerclage. Methods: A retrospective cross-sectional study was conducted among women with singleton pregnancy and PPROM, who underwent cervical cerclage during 2018-2020. Results: A total of 55 eligible women were included in the final analysis, including 36 (61.02%) cases with HCA and 19 (38.98%) without HCA. Women with HCA had higher WBC count (12.31 ± 2.80) × 109/L and neutrophil count (9.67 ± 2.90)×109/L than those without HCA (10.35 ± 2.53) × 109/L and 7.82 ± 2.82 × 109/L, respectively) (both p < 0.05). The cut-off value of WBC count at 10.15×109/L was found to be the most effective in identifying HCA, with an Area Under Curve (AUC) of 0.707 (95% CI: 0.56-0.86; p = 0.012), sensitivity of 86.11%, specificity of 57.90%, Positive Predictive Value (PPV) of 79.49%, Negative Predictive Value (NPV) of 68.75%, and Youden index of 0.44. The combination of WBC + neutrophil had a slightly higher (AUC = 0.711, 95% CI: 0.57-0.86; p = 0.011), specificity (68.42%), and PPV (81.25%), but lower sensitivity (72.22%), than the WBC count alone. A cut-off value of neutrophil at 7.46 × 109/L was effective in identifying HCA, with an AUC of 0.689 (95% CI: 0.53-0.84; p = 0.022). Discussion: Combination use of WBC+neutrophil was found to be the most accurate predictor of HCA among women with PPROM after surgery of cervical cerclage.

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Resumen El parto prematuro es la principal causa de morbilidad y de mortalidad perinatal, y hasta un tercio de los casos presentan rotura prematura de membranas. La infección intrauterina que asciende desde la vagina es su principal causa en un hospital público de Chile. Esta revisión narrativa mediante búsqueda en PubMed, Cochrane, Embase, Scielo, Science Direct y Wiley Online Library incluye estudios publicados sobre los diferentes factores infecciosos que intervienen en el resultado adverso perinatal y la eficacia de los antibióticos en la rotura prematura de membranas de pretérmino. Además, contiene recomendaciones de sociedades científicas sobre el uso de antibióticos en estos casos. Los ensayos concluyen que los antimicrobianos prolongan el embarazo, disminuyen la corioamnionitis clínica y reducen variadas morbilidades neonatales, pero no reducen la mortalidad perinatal ni las secuelas tardías en la infancia. Los resultados adversos obstétricos, especialmente los neonatales, y las secuelas dependen de la existencia de invasión microbiana de la cavidad amniótica o de infección cérvico-vaginal, de la virulencia de los microorganismos aislados, del compromiso inflamatorio/infeccioso de la placenta (corioamnionitis histológica, funisitis) y de la respuesta inflamatoria fetal. Para mejorar los resultados adversos obstétricos neonatales en la rotura prematura de membranas de pretérmino, los esquemas de antibióticos deben ser eficaces, cubriendo el amplio espectro microbiológico existente y actuando sobre los factores infecciosos implicados en la gravedad de la infección. Además, deben administrarse de manera intensiva y prolongada hasta el parto.

Abstract Preterm birth is the leading cause of perinatal morbidity and mortality, and up to a third of them have premature rupture of membranes. Intrauterine infection that rises from the vagina is its main cause in a public hospital in Chile. This narrative review by searching PubMed, Cochrane, Embase, Scielo, Science Direct and Wiley Online Library includes published studies of the different infectious factors involved in perinatal adverse outcome and of the efficacy of antibiotics in preterm premature rupture of membranes. It also contains recommendations from scientific societies on the use of antibiotics in these cases. These trials conclude that antimicrobials prolong pregnancy, decrease clinical chorioamnionitis, and reduce various neonatal morbidities, but do not reduce perinatal mortality or infant sequelae. Obstetric and especially neonatal adverse outcomes in these patients depend on the existence of microbial invasion of the amniotic cavity and/or cervicovaginal infection, of the virulence of the isolated microorganisms, of inflammatory/infectious involvement of the placenta (histological chorioamnionitis, funisitis) and fetal inflammatory response. To improve adverse neonatal obstetric outcomes in preterm premature rupture of membranes, antibiotic regimens must be effective, covering the wide existing microbiological spectrum and acting on infectious factors responsible for the severity of the infection. In addition, they must be administered aggressively and for a long time until delivery.

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BACKGROUND: Following the destruction of pharmaceutical production facilities in Puerto Rico by Hurricane Maria in September 2017, a shortage of small-volume bags of sterile intravenous fluid for infusion led to a decreased ability to administer intravenous azithromycin and ampicillin efficiently for use in the treatment of patients with preterm premature rupture of membranes. OBJECTIVE: This study aimed to assess pregnancy latency after preterm premature rupture of membranes following treatment with oral-only antibiotics compared with treatment with intravenous antibiotics followed by oral antibiotics. STUDY DESIGN: This is a retrospective historic control study comparing women with preterm premature rupture of membranes who were initiated on a 7-day oral-only regimen of azithromycin and amoxicillin (modified regimen) during a 12-month period beginning December 2017 (during which time there was a shortage of small-volume bags of intravenous fluid) to women with preterm premature rupture of membranes who were initiated on a 2-day regimen of intravenous ampicillin and azithromycin followed by 5 days of oral amoxicillin and azithromycin (standard regimen) from December 2016 to December 2018. Women were included in the study if they were diagnosed with preterm premature rupture of membranes at <34 weeks' gestation and were started on latency antibiotics, and women were excluded from the study if they had a contraindication to expectant management, a cerclage, or suspected fetal anomalies. The primary outcome was pregnancy latency, defined as time from the first dose of antibiotics to delivery. RESULTS: The 37 women who received the modified regimen and the 79 women who received the standard regimen had similar baseline characteristics. Mean (standard deviation) gestational age at time of preterm premature rupture of membranes was similar between the modified (30.5 weeks' gestation [±3.1]) and standard regimen groups (30.2 weeks' gestation [±3.2]), and the rate of group B streptococcus rectovaginal colonization was similar for both groups (27% vs 24%; P=.95). Pregnancy latency did not differ in the modified vs standard regimen (mean difference, -0.15 days; 95% confidence interval, -4.87 to 4.58) There was no statistically significant difference in the relative risk of composite maternal infection (relative risk, 0.43; 95% confidence interval, 0.05-3.53) or composite neonatal infection (relative risk, 0.43; 95% confidence interval, 0.05-3.52). CONCLUSION: Although limited by small sample size, our study suggested that adoption of an oral-only antibiotic regimen for pregnancy latency following preterm premature rupture of membranes is worthy of further study.

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Abstract Objective: To compare the type of management (active versus expectant) for preterm premature rupture of membranes (PPROM) between 34 and 36 + 6 weeks of gestation and the associated adverse perinatal outcomes in 2 tertiary hospitals in the southeast of Brazil. Methods: In the present retrospective cohort study, data were obtained by reviewing the medical records of patients admitted to two tertiary centers with different protocols for PPROM management. The participants were divided into two groups based on PPROM management: group I (active) and group II (expectant). For statistical analysis, the Student t-test, the chi-squared test, and binary logistic regression were used. Results: Of the 118 participants included, 78 underwent active (group I) and 40 expectant management (group II). Compared with group II, group I had significantly lower mean amniotic fluid index (5.5 versus 11.3 cm, p = 0.002), polymerase chain reaction at admission (1.5 versus 5.2 mg/dl, p = 0.002), time of prophylactic antibiotics (5.4 versus 18.4 hours, p < 0.001), latency time (20.9 versus 33.6 hours, p = 0.001), and gestational age at delivery (36.5 versus 37.2 weeks, p = 0.025). There were no significant associations between the groups and the presence of adverse perinatal outcomes. Gestational age at diagnosis was the only significant predictor of adverse composite outcome (x2 [1] = 3.1, p = 0.0001, R2 Nagelkerke = 0.138). Conclusion: There was no association between active versus expectant management in pregnant women with PPROM between 34 and 36 + 6 weeks of gestation and adverse perinatal outcomes.

Resumo Objetivo: Comparar o tipo de manejo (ativo versus expectante) para ruptura prematura de membranas (PPROM, na sigla em inglês) entre 34 e 36 semanas e 6 dias de gestação e os resultados perinatais adversos relacionados, em 2 hospitais terciários do sudeste brasileiro. Métodos: No presente estudo de coorte retrospectivo, os dados foram obtidos através da revisão dos prontuários de gestantes internadas em dois centros terciários com protocolos diferentes para o seguimento da PPROM. As gestantes foram divididas em dois grupos com base no manejo da PPROM: grupo I (ativo) e grupo II (expectante). Para análise estatística, foram utilizados o teste t de Student, qui-quadrado e regressão logística binária. Resultados: Das 118 gestantes incluídas, 78 foram submetidas a tratamento ativo (grupo I) e 40 a seguimento expectante (grupo II). Comparado ao grupo II, o grupo I apresentou índice de líquido amniótico médio significativamente menor (5,5 versus 11,3 cm, p = 0,002), reação em cadeia da polimerase na admissão (1,5 versus 5,2 mg/dl, p = 0,002), tempo de antibióticos profiláticos (5,4 versus 18,4 horas, p < 0,001), tempo de latência (20,9 versus 33,6 horas, p = 0,001) e idade gestacional no parto (36,5 versus 37,2 semanas, p = 0,025). Não houve associações significativas entre os grupos e a presença de resultados perinatais adversos. A idade gestacional no diagnóstico foi o único preditor significativo de desfecho composto adverso (x2 [1] = 3,1, p = 0,0001, R2 Nagelkerke = 0,138). Conclusão: Não houve associação entre manejo ativo e expectante em gestantes com PPROM entre 34 e 36 semanas e 6 dias de gestação e resultados perinatais adversos.

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AIM: Preterm premature rupture of membranes (PPROM) is responsible for approximately one-third of premature births worldwide, and although the diagnosis is often straightforward, this condition can still present difficulties. The purpose of this research was to compare the accuracy of several PPROM diagnostic tests. METHODS: A total of 94 pregnant women with clinical suspicion of PPROM who were between 20 and 36 weeks of pregnancy were examined by vaginal speculum, and tests were performed for phenol, pH, insulin-like growth factor binding protein-1 (IGFBP-1) and placental alpha-microglobulin-1 (PAMG-1). All patients were followed up until the diagnosis was fully defined, and a diagnosis of PROM was confirmed by a definitive evolution of the clinical symptoms (visualization of vaginal amniotic fluid or persistence of oligohydramnios). RESULTS: After excluding the cases that could not be definitively diagnosed, a good diagnostic performance of the immunochromatographic tests was observed that was superior to that of the clinical tests. Similar accuracies were observed for IGFBP-1 (98.7%) and PAMG-1 (93.9%). However, while the IGFBP-1 test differed from a vaginal pH ≥7 (88.9%) and the phenol test (85.7%), this did not occur for the PAMG-1 test. The performance of the tests was modified only by the presence of bleeding (with lower specificity rates for pH and phenol), without interference of gestational age or maternal morbidities. CONCLUSION: Immunochromatographic tests are good tools but should be used sparingly in resource-poor settings because they are expensive, and there is no significant difference between PAMG-1 and traditional tests.

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Background: Despite improvements in fetal survival for pregnancies affected by twin-twin transfusion syndrome since the introduction of laser photocoagulation, prematurity remains a major source of neonatal morbidity and mortality. Objective: To investigate the indications and factors influencing the timing of delivery following laser treatment, we collected delivery information regarding twin-twin transfusion syndrome cases in a large multicenter cohort. Study Design: Eleven North American Fetal Therapy Network (NAFTNet) centers conducted a retrospective review of twin-twin transfusion syndrome patients who underwent laser photocoagulation. Clinical, demographic and ultrasound variables including twin-twin transfusion syndrome stage, and gestational age at treatment and delivery were recorded. Primary and secondary maternal and fetal indications for delivery were identified. Univariate analysis was used to select candidate variables with significant correlation with latency and GA at delivery. Multivariable Cox regression with competing risk analysis was utilized to determine the independent associations. Results: A total of 847 pregnancies were analyzed. After laser, the average latency to delivery was 10.11 ± 4.8 weeks and the mean gestational age at delivery was 30.7 ± 4.5 weeks. Primary maternal indications for delivery comprised 79% of cases. The leading indications included spontaneous labor (46.8%), premature rupture of membranes (17.1%), and placental abruption (8.4%). Primary fetal indications accounted for 21% of cases and the most frequent indications included donor non-reassuring status (20.5%), abnormal donor Dopplers (15.1%), and donor growth restriction (14.5%). The most common secondary indications for delivery were premature rupture of membranes, spontaneous labor and donor growth restriction. Multivariate modeling found gestational age at diagnosis, stage, history of prior amnioreduction, cerclage, interwin membrane disruption, procedure complications and chorioamniotic membrane separation as predictors for both gestational age at delivery and latency. Conclusion: Premature delivery after laser therapy for twin-twin transfusion syndrome is primarily due to spontaneous labor, preterm premature rupture of membranes and non-reassuring status of the donor fetus. Placental abruption was found to be a frequent complication resulting in early delivery. Future research should be directed toward the goal of prolonging gestation after laser photocoagulation to further reduce morbidity and mortality associated with twin-twin transfusion syndrome.

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Resumen OBJETIVO Ofrecer al clínico la evidencia científica más reciente en lo relativo a algunos aspectos de la atención de pacientes con ruptura prematura pretérmino de membranas que han generado debate, controversia y, en algunos momentos, opiniones divergentes que condicionan la toma de decisiones basadas en criterios con un débil rigor científico que se reflejan en morbilidad perinatal significativa. MÉTODO Búsqueda en PubMed, The Cochrane Library, OVID, Science Direct, Practice Guidelines Internacional Networks de artículos publicados en inglés entre los años 2014 a 2016 con las siguientes palabras clave (Mesh): Preterm premature rupture of membranes; diagnostic tests in premature rupture of preterm membranes; pulmonary maturity scheme; antibiotic therapy in premature rupture of preterm membranes; pulmonary maturity tests; fetal inflammatory response syndrome; fetal well-being tests; chorioamnionitis. Criterios de inclusión: revisiones sistemáticas, metanálisis y ensayos clínicos controlados con metodología de medicina basada en evidencias, con consistencia y claridad en las recomendaciones seleccionadas. RESULTADOS Se seleccionaron 70 artículos, entre estos 5 guías internacionales de práctica clínica y 45 artículos. Al final se excluyeron 20 artículos porque el diseño era de casos y controles, ensayos clínicos no controlados y sus recomendaciones no eran concluyentes porque su nivel de evidencia era bajo. CONCLUSIONES El uso racional de los diversos instrumentos de diagnóstico permite ser más eficaces y eficientes en la utilización de los recursos, y la identificación de fetos que podrían beneficiarse de una conducta expectante versus resolutiva y, viceversa. La comprensión y aplicación de lo aquí expuesto puede contribuir a disminuir la incidencia de desenlaces neonatales adversos asociados con procesos infecciosos directamente relacionados con la morbilidad y secuelas neurológicas a corto y mediano plazo. Se planteó el tratamiento de la ruptura prematura pretérmino de membranas en algoritmos aplicables en la práctica clínica.

Abstract OBJECTIVE To provide the clinician the most recent scientific evidence regarding some aspects of the management of patients with preterm premature rupture ofmembranes. Those aspects have generated debate, controversy and sometimes divergent opinions leading to medical decisions based on weak criteria and as consequence significant perinatal morbidity. METHOD We searched databases in PubMed, The Cochrane Library, OVID, Science Direct, Practice Guidelines International Networks from 2014 to 2016 with the following keywords: preterm premature rupture of membranes, diagnostic tests for preterm premature rupture of membranes, antenatal corticosteroids, antibiotic therapy in preterm premature rupture of membranes, fetal pulmonary maturity tests, fetal inflammatory response syndrome, fetal well-being tests, chorioamnionitis. RESULTS We extracted 70 studies, information was collected with emphasis on several controversial themes. Inclusion criteria were systematic reviews, meta-analysis and clinical controlled trials from 2014 to 2016, languages spanish or english, articles with evidence-based medicine methodology with strong recommendations. The final selection includes 5 international clinical practice guidelines and. 45 articles from 2014-2016. Articles which methodology consisted in case-control design, uncontrolled or unrandomized clinical trials or with level of evidence D were excluded. CONCLUSIONS The appropriate use of diagnostic tools will allow us to become more efficient in the use of resources, also allowing the identification of fetuses that would benefit from an expectant versus resolute management and vice versa. The review aims, among other things, to reduce the incidence of adverse neonatal outcomes associated with infectious processes, which are directly related to morbidity and neurological sequelae in short and mid-term. The management of PPROM is proposed in algorithms applicable in clinical practice.

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Resumen ANTECEDENTES La incidencia de acretismo placentario se ha elevado en países industrializados debido al incremento en la tasa de cesáreas. La ruptura prematura de membranas pretérmino se asocia con complicaciones en 3% de todos los embarazos. En la actualidad no existen publicaciones que documenten la atención médica de ambas alteraciones en conjunto. CASO CLÍNICO Paciente de 31 años, en curso del segundo embarazo (30.2 semanas de gestación), que acudió al servicio médico por salida de líquido transvaginal. Se confirmó la ruptura prematura de membranas pretérmino por cristalografía y determinación de microglobulina alfa 1 placentaria por tira reactiva Amnisure®. La valoración de los médicos del servicio de Medicina Materno-Fetal fue: placenta previa total, con lagunas placentarias y flujo turbulento, grosor miometrial menor de 1 mm y pérdida de la interfase deciduomiometrial. Después de comprobar el bienestar fetal se inició el tratamiento conservador de la ruptura prematura de membranas pretérmino. Se decidió finalizar el embarazo a las 31 semanas, debido a que se confirmó el inicio del trabajo de parto y actividad uterina normal; se efectuó cesárea-histerectomía sin complicaciones maternas. CONCLUSIÓN La placenta previa total con datos de acretismo, concomitante con ruptura prematura de membranas pretérmino, es una complicación poco común. Estas pacientes deben recibir tratamiento conservador y adecuada vigilancia materno-fetal. A pesar de los buenos resultados obtenidos en este caso, se requiere mayor evidencia para indicar el tratamiento conservador en estas pacientes.

Abstract BACKGROUND The incidence of placental accreta has increased in industrialized countries, due to the increase in the rate of cesarean sections. On the other hand, the premature rupture of membranes (PPROM), complicate approximately 3% of all pregnancies and is associated mainly with neonatal complications related to prematurity. At present, there is no documented evidence in the medical literature of the approach of both pathologies together. CLINICAL CASE 31-year-old woman at 30.2 weeks' gestation in her second pregnancy is admitted to the hospital with vaginal discharge. PROM is confirmed by fern-type crystallization and quantification of placental alpha macroglobulin-1 (PAMG-1) microglobulin by Amnisure® test strip. Medical assessment is performed by the maternal-fetal specialists, finding complete placenta praevia with the presence of vascular lacunae with turbulent lacunar flow, myometrium thickness < 1mm and loss of the clear space. Fetal well-being is confirmed and conservative management of PPROM is initiated. Obstetric delivery is conducted at 31 weeks of gestation with Caesarean section - Hysterectomy without complications. CONCLUSIONS The premature rupture of membranes in presence of placenta accreta is a rare complication. In this patients, conservative management is a suitable alternative, with an appropriate maternal and fetal surveillance. More evidence is required to indicate the conservative treatment in these patients.

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RESUMEN Introducción: La ruptura prematura de membranas pretérmino (PPROM) es una patología obstétrica que genera un alto riesgo de morbilidad fetal. Pese a esto, actualmente prevalece la incertidumbre ante el manejo adecuado para ésta entidad. Objetivo: Comparar los desenlaces materno-fetales de la inducción del parto (IL) y manejo expectante (EM) Metodología: Revisión sistemática y metanálisis Fuentes de datos: Se buscó en las bases de datos MEDLINE, EMBASE, SCIELO y Google Académico. Criterios de elección, pacientes e intervenciones: Se incluyeron ensayos clínicos aleatorizados controlados y estudios de cohortes que compararan el EM e IL en pacientes con PPROM entre la semana 24 a 36 6/7, y que adicionalmente tuvieran en cuenta como desenlaces analizados: sepsis neonatal (NS), síndrome de distrés respiratorio (SDR), muerte neonatal y corioamionitis. Recolección de datos y análisis: La extracción y registro de datos se ejecutó por dos revisores de forma independiente. La evaluación de calidad se realizó con CONSORT y STROBE, según corresponda. Metanálisis: Para cada desenlance, se realizó la estimación del Riesgo Relativo (RR) consolidado, usando modelos de efectos aleatorios. Resultados: Un total de 3378 mujeres con PPROM fueron incluidas en los 9 estudios (8 ensayos clínicos). En el meta-análisis no se encontraron diferencias significativas en la ocurrencia de SDR (RR= 1,08; IC 95%: 0,89-1,31), ni de sepsis neonatal (RR= 0,92; IC 95%: 0,61-1,39), en los tratados con IL comparados con el EM. Tampoco se encontraron diferencias significativas en la ocurrencia de muertes neonatales (RR= 1,34; IC 95%: 0,93-1,93) ni corioamnionitis (RR= 0,88; IC 95%: 0,58-1,35). Conclusiones: Los resultados sugieren que no existe evidencia de diferencias estadísticamente significativas en la ocurrencia de los principales desenlaces cuando se compara EM con IL. Más estudios y con mayores tamaños de muestras son necesarios.

ABSTRACT Introduction: Preterm premature rupture of membranes (PPROM), is an obstetric pathology that causes a high-risk of morbidities and higher rate of hospital readmission in the first month of life. However, the management of this patology is still uncertain. Objetive: To compare maternal-fetal outcomes of induction of labor (IL) and expectant management (EM) in order to determine the actions to follow. Methodology: Systematic review and meta-analysis Data collection: We searched MEDLINE, EMBASE, SCIELO and Google Scholar. Selection Criteria, patients and interventions: Controlled randomized clinical trial and cohort studies were included. These studies compared the EM and IL in patients with PPROM within 24 to 36 6/7 weeks and take into account outcomes such as neonatal sepsis (NS), respiratory distress syndrome (RDS), neonatal death or chorioamnionitis. Analysis and data collection: Two authors independently executed the extraction and recording of data. Quality assessment was performed with the CONSORT or STROBE score, accordingly. Meta-analysis: For each outcome, a pooled Relative Risk was estimated using random effects models. Results 3378 women with PPROM were included in 9 studies (8 clinical trials). In the meta-analysis, we did not find a statistically significant differences in the occurrence of RDS (RR =1.08; 95% CI: 0.89-1.31 or NS (RR= 0.92; IC 95%: 0.61-1.39), in the IL group in comparison with EM. We did not find either differences in the occurrence of neonatal deaths (RR= 1.34; IC 95%: 0.93-1.93) or chorioamnionitis ( RR= 0.88; IC 95%: 0.58-1.35). Conclusions: The results suggest that there is no evidence of statistically significant differences in the occurrence of major outcomes when comparing MS with IL. Further studies and larger sample sizes will be necesary.

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OBJECTIVE: To assess the impact of latency duration on survival, survival without severe morbidity, and early-onset sepsis in infants born after preterm premature rupture of membranes (PPROM) at 24-32 weeks' gestation. STUDY DESIGN: This study was based on the prospective national population-based Etude Épidémiologique sur les Petits Ȃges Gestationnels 2 cohort of preterm births and included 702 singletons delivered in France after PPROM at 24-32 weeks' gestation. Latency duration was defined as the time from spontaneous rupture of membranes to delivery, divided into 4 periods (12 hours to 2 days [reference], 3-7 days, 8-14 days, and >14 days). Multivariable logistic regression was used to assess the relationship between latency duration and survival, survival without severe morbidity at discharge, or early-onset sepsis. RESULTS: Latency duration ranged from 12 hours to 2 days (18%), 3-7 days (38%), 8-14 days (24%), and >14 days (20%). Rates of survival, survival without severe morbidity, and early-onset sepsis were 93.5% (95% CI 91.8-94.8), 85.4% (82.4-87.9), and 3.4% (2.0-5.7), respectively. A crude association found between prolonged latency duration and improved survival disappeared on adjusting for gestational age at birth (aOR 1.0 [reference], 1.6 [95% CI 0.8-3.2], 1.2 [0.5-2.9], and 1.0 [0.3-3.2] for latency durations from 12 hours to 2 days, 3-7 days, 8-14 days, and >14 days, respectively). Prolonged latency duration was not associated with survival without severe morbidity or early-onset sepsis. CONCLUSION: For a given gestational age at birth, prolonged latency duration after PPROM does not worsen neonatal prognosis.

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BACKGROUND: Since the results of the Management of Myelomeningocele Study were published, maternal-fetal surgery for the in utero treatment of spina bifida has become accepted as a standard of care alternative. Despite promise with fetal management of myelomeningocele repair, there are significant complications to consider. Chorioamniotic membrane separation and preterm premature rupture of membranes are known complications of invasive fetal procedures. Despite their relative frequency associated with fetal procedures, few data exist regarding risk factors that may be attributed to their occurrence or the natural history of pregnancies that are affected with chorionic membrane separation or preterm premature rupture of membranes related to the procedure. OBJECTIVE: The objective of this study was to review chorioamniotic membrane separation and preterm premature rupture of membranes in a cohort of patients undergoing fetal management of myelomeningocele repair including identification of risk factors and outcomes. STUDY DESIGN: This was a retrospective review of patients undergoing fetal management of myelomeningocele repair and subsequent delivery from January 2011 through December 2013 at 1 institution. Patients were identified through the institutional fetal management of myelomeningocele repair database and chart review was performed. Perioperative factors and outcomes among patients with chorioamniotic membrane separation and preterm premature rupture of membranes were compared to those without. Risk factors associated with the development of chorioamniotic membrane separation and preterm premature rupture of membranes were determined. RESULTS: A total of 88 patients underwent fetal management of myelomeningocele repair and subsequently delivered during the study period. In all, 21 patients (23.9%) were diagnosed with chorioamniotic membrane separation by ultrasound and preterm premature rupture of membranes occurred in 27 (30.7%). Among the chorioamniotic membrane separation patients, 10 (47.6%) were diagnosed with global chorioamniotic membrane separation and 11 (52.4%) with local chorioamniotic membrane separation. Earlier gestational age at the time of fetal surgery was a significant risk factor for the development of chorioamniotic membrane separation (P = .01) and preterm premature rupture of membranes (P < 0.0001). Chorioamniotic membrane separation was significantly associated with preterm premature rupture of membranes (59.1% vs 21.2%, P = .008) and earlier gestational age at delivery (32.1 ± 4.2 vs 34.4 ± 3.5 weeks, P = .01). The average number of days from chorioamniotic membrane separation to preterm premature rupture of membranes was 11.0 ± 10.1 and from chorioamniotic membrane separation to delivery was 31.0 ± 22.5. The mean time interval between fetal management of myelomeningocele repair and preterm premature rupture of membranes was 47.9 days. Mean latency period from preterm premature rupture of membranes to delivery was 25 days. Gestational age at delivery was significantly lower in patients with preterm premature rupture of membranes (31.6 ± 3.4 vs 34.9 ± 3.5 weeks, P = .0001). Using logistic regression analysis, nulliparity, gestational age at fetal management of myelomeningocele repair, and membrane separation remained significant risk factors for preterm premature rupture of membranes. CONCLUSION: Chorioamniotic membrane separation after fetal management of myelomeningocele repair is a significant risk factor for subsequent development of preterm premature rupture of membranes and preterm delivery. Fetal management of myelomeningocele repair <23 weeks is associated with higher rates of preterm premature rupture of membranes and chorioamniotic membrane separation. Therefore fetal management of myelomeningocele repair should be deferred until ≥23 weeks to mitigate these complications. Nulliparity also appears to increase the risk for preterm premature rupture of membranes.

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Introducción. El parto prematuro es la causa principal de morbilidad y mortalidad neonatales. Objetivo. Determinar los resultados maternos y perinatales del manejo conservador de la ruptura prematura de membranas pretérmino en gestantes de 24 a 33 semanas, en el período 2010-2011, en el Instituto Nacional Materno Perinatal (INMP). Material y método. Estudio no experimental, observacional, retrospectivo, transversal, descriptivo desarrollado en el INMP. La población estuvo compuesta por gestantes pretérmino con ruptura prematura de membranas. Se recolectó datos registrados en las historias clínicas. Resultados. Fueron 142 casos los que culminaron el parto por cesárea (71,8 %), con edad de 26,36 ± 7,418 años. Las nulíparas fueron más frecuentes (45,8 %). La edad gestacional promedio fue 29,06 ± 2,590 semanas; el control prenatal promedio, 2,35 ± 2,101; el período de latencia promedio, 10,68 ± 12,305 días. Hubo resultados maternos en 34,5 % (49 casos), donde la coriamnionitis fue el más frecuente (23,9 %). Hubo resultados perinatales en 32,4 % (46 casos), donde el síndrome de dificultad respiratoria fue el más frecuente (21,8 %). El peso promedio al nacer fue de 1 653,14 g ± 460,219 g. La mayoría de los recién nacidos pretérminos al nacer tuvieron buen Apgar. El promedio de días de internamiento de la madre fue de 15,30 días ± 12,912. Conclusiones. La coriamnionitis y el síndrome de dificultad respiratoria fueron los resultados maternos y perinatales más frecuentes.

Introduction. Preterm birth is the leading cause of neonatal morbidity and mortality. Objectives. Determine maternal and perinatal outcomes of conservative management of preterm premature rupture of membranes in pregnancies of 24-33 weeks in the period 2010-2011. Material and method. Non-experimental, observational, retrospective, cross-sectional, descriptive from National Institute Maternal Perinatal. Pregnancies with preterm premature rupture of membranes. I collect it of data from medical records. Results. There were 142 cases, the culmination of the delivery via was the cesarean (71,8 %), the mean age was 26,36 + 7,418 years. The nulliparous were more frequent 45,8 %. The mean gestational age was 29,06 + 2,590 weeks. The mean birth control was 2,35 + 2,101. The mean latency period was 10,68 + 12,305 days. Maternal outcomes were 34,5 % (49 cases) where the chorioamnionitis was most frequent 23,9 %. Perinatal outcome was 32,4 % (46 cases) where respiratory distress syndrome was the most frequent 21,8 %. The mean birth weight was 1 653,14 g + 460,219. Most preterm infants had good Apgar scores at birth. The mean days of hospitalization of the mother were of 15,30 days + 12,912. Conclusions. The chorioamnionitis and respiratory distress syndrome were the maternal and perinatal outcomes more frequent.

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INTRODUCTION: Nicotinamide adenine dinucleotide phosphate oxidases (NOX 1-5) are enzymes that generate cellular reactive oxygen species (ROS) besides mitochondria and might be important ROS sources associated with pregnancy complications, particularly preterm premature rupture of membranes (pPROM), that has been related to ROS. OBJECTIVE: To characterize NOX enzymes expression in human fetal membranes. METHODS: Differential expression and localization of NOX isoforms in human fetal membranes collected from women with uncomplicated pregnancies at term, preterm birth (PTB) or pPROM and in vitro in normal term membranes maintained in an organ explant system stimulated with water-soluble cigarette smoke extract (wsCSE) were documented by real time PCR and immunohistochemistry. RESULTS: Fetal membranes from term deliveries, PTB and pPROM expressed NOX 2, 3 and 4 mRNAs whereas NOX 1 and 5 were not detected. NOX 2 expression was 2.3-fold higher in PTB than pPROM (p = 0.005) whereas NOX 3 was 2.2-fold higher in pPROM compared to PTB (p = 0.04). NOX 2 and 3 expressions at term mimicked pPROM and PTB, respectively. No difference in NOX 4 expression was observed among the studied groups. NOX 2, 3 and 4 were localized to both amniotic and chorionic cells. Expression of NOX 2, 3 and 4 were not significant in wsCSE-stimulated membranes compared to untreated controls. DISCUSSION/CONCLUSIONS: NOX enzymes are present in the fetal membranes and are differentially expressed in PTB and pPROM. Absence of any changes in NOXs expression after wsCSE stimulation suggests ROS generation in the membranes does not always correlate with NOX expression.

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OBJECTIVE: To evaluate the relationship between preterm premature rupture of membranes (PPROM) and cognitive impairment in 5-year-old children born very preterm. STUDY DESIGN: The Etude Epidémiologique sur les Petits Ages Gestationnels Study is a population-based cohort of children followed up from birth to age 5 years recruited in 9 French regions in 1997. We analyzed data from singletons born between 24 and 32 weeks gestation categorized into 4 groups according to etiology of prematurity: infants born after PPROM, after idiopathic preterm labor, in a vascular context (Vasc), and to women with other complications (Other). Cognitive development at age 5 years was assessed using the Mental Processing Composite score of the Kaufman-Assessment Battery for Children. RESULTS: Among the 1051 children followed up to age 5 years, the mean Mental Processing Composite score was 93.6 ± 19.7, and 13.3% of the children (140 of 1051) had cognitive impairment. After adjustment for potential confounders, the risk of cognitive impairment among infants in the PPROM group was not significantly different than that in the idiopathic preterm labor group (OR, 1.09; 95% CI, 0.62-1.92) and the Other group (OR, 1.36; 95% CI, 0.75-2.47), but was lower than that in the Vasc group (OR, 1.86; 95% CI, 1.16-2.97). In the PPROM group, the risk of cognitive impairment was greater when the latency period (ie, time from rupture to delivery) was <3 days (OR, 2.32; 95% CI, 1.07-5.02). CONCLUSION: Preterm infants born after PPROM are not at increased risk for cognitive impairment in childhood, but the time between PPROM and birth may influence that risk.

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El cerclaje es un factor de riesgo de rotura prematura pretérmino de membranas (RPPM). La RPPM ocurre en aproximadamente un 38-65 por ciento de los embarazos con cerclaje y no existe consenso aún sobre cuál es el manejo más adecuado: retirar o mantener el cerclaje. En esta revisión presentamos la evidencia disponible en relación al retiro versus mantención del cerclaje y su directa influencia sobre el resultado materno-perinatal, con el objetivo de proponer una pauta de manejo. La mantención del cerclaje se asoció a un aumento de la latencia al parto mayor a 48 horas, a un aumento en la incidencia de corioamnionitis clínica, y aumento en la incidencia de mortalidad neonatal por sepsis. Conclusión: en pacientes embarazadas con cerclaje que presentan RPPM antes de las 34 semanas proponemos como la conducta más adecuada la mantención del cerclaje sólo hasta completar la inducción de madurez pulmonar con corticoides, luego retirar el cerclaje y proceder al manejo habitual de un embarazo con RPPM antes de las 34 semanas.

Cervical cerclage is a risk factor for preterm premature rupture of membranes (PPROM). PPROM occurs in about 38-65 percent of pregnancies with cerclage. There is no consensus on whether to remove or retain the cerclage after PPROM. Here we review the evidence about clinical management of PPROM in women with cerclage and its influence on maternal and neonatal outcome. Retained cerclage was found to be associated to a prolongation of pregnancy by more than 48 hours, to a higher incidence of maternal chorioamnionitis and to a higher incidence of neonatal mortality from sepsis. In pregnancies with cerclage complicated with PPROM before 34 weeks we propose to retain the cerclage just enough time to complete fetal lung maturation with corticosteroid therapy, then remove the cerclage and manage pregnancy as any PPROM before 34 weeks.

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