Assessment of Blood Prostaglandin E2 Metabolite Levels among Infants Born Preterm with Patent Ductus Arteriosus: A Prospective Study.

OBJECTIVE: To assess the role of prostaglandin E2 by measuring blood prostaglandin E2 metabolite (PGEM) concentrations in preterm infants with patent ductus arteriosus (PDA). STUDY DESIGN: A prospective observational study of preterm infants born before 32 weeks of gestational age (GA) was performed in a single tertiary hospital in Japan. Blood samples were collected to measure serum concentrations of PGEM, ibuprofen (IBU), and cytokines. Multiple regression analyses assessed associations between blood PGEM levels and perinatal factors, development of hemodynamically significant PDA (hsPDA), and IBU treatment response of hsPDA. RESULTS: Seventy-nine infants (median GA 28 weeks) were enrolled in this study. Forty-seven received IBU for hsPDA treatment 1 d after birth in median. PDA closure occurred in 25 infants after a single IBU treatment. Serum PGEM concentrations were associated with histologic chorioamnionitis (P < .01), but not with GA, respiratory distress syndrome, or serum IL-6 concentrations. Serum PGEM concentrations decreased after initial IBU treatment; however, they were not associated with hsPDA development (P = .39). IBU concentrations correlated with IBU treatment response (aOR 1.29, P < .01). However, pre-IBU serum PGEM levels and PGEM reduction ratio did not (P = .13, .15, respectively). CONCLUSIONS: Serum PGEM concentrations in preterm infants were associated with maternal histologic chorioamnionitis, but not hsPDA development. IBU treatment response was associated with higher blood IBU concentrations, but not PGEM concentrations.

Risk of adverse perinatal outcomes among women with clinical and subclinical histopathological chorioamnionitis.

Introduction: Histologic chorioamnionitis (HCA) is a placental inflammatory condition associated with adverse perinatal outcomes (APOs). This historical cohort study explores the risk of APOs in pregnant women with HCA and compares the impact of clinical chorioamnionitis (CCA) with subclinical chorioamnionitis (SCCA). Methodology: Placentas were evaluated by a perinatal pathologist tand all women with HCA were included. Two groups were integrated: (1) women with clinical chorioamnionitis (CCA) and (2) women with subclinical chorioamnionitis (SCCA). Additionally, we conducted a secondary analysis to compare the prevalence of APOs among stage 1, 2 and 3 of HCA and the risk of APOs between grades 1 and 2 of HCA. The APOs analyzed were preterm birth, stillbirth, neonatal weight < 1,500 g, neonatal sepsis. Relative risk with 95% confidence interval was calculated. Results: The study included 41 cases of CCA and 270 cases of SCCA. The mean gestational age at diagnosis and birth was 30.2 ± 5.4 weeks and 32.5 ± 5.1 weeks, for group 1 and 2, respectively. The study also found that women with HCA stage 3 and grade 2 had a higher prevalence and risk of adverse perinatal outcomes. Discussion: The findings of this study suggest the importance of placental histological study to excluded SCCA, which represents a significant risk to both maternal and neonatal health, contributing to high morbidity and mortality.

Intra-amniotic Candida albicans Infection Treated With Liposomal Amphotericin B With a Successful Neonatal Outcome.

Intra-amniotic infection with Candida species is an uncommon but severe condition with high fetal morbimortality and no established clinical guidelines for its management. We report a Candida albicans intra-amniotic infection diagnosed in a 25-week pregnant woman, successfully treated with high-dose liposomal amphotericin B. Pregnancy was prolonged until 30 weeks, and despite persistently positive Candida cultures in amniotic fluid, a healthy newborn was delivered without evidence of systemic infection. Amphotericin concentration was determined at birth, revealing levels over 30 times higher in mother's and cord blood than in the amniotic fluid, probably explaining the clinical protection despite failure in obtaining fungal clearance.

Clinical Chorioamnionitis and Neurodevelopment at 5 Years of Age in Children Born Preterm: The EPIPAGE-2 Cohort Study.

OBJECTIVE: To assess the association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born preterm. STUDY DESIGN: EPIPAGE 2 is a national, population-based cohort study of children born before 35 weeks of gestation in France in 2011. We included infants born alive between 240/7 and 346/7 weeks after preterm labor or preterm premature rupture of membranes. Clinical chorioamnionitis was defined as maternal fever before labor (>37.8°C) with ≥2 of the following criteria: maternal tachycardia, hyperleukocytosis, uterine contractions, purulent amniotic fluid, or fetal tachycardia. The primary outcome was a composite, including cerebral palsy, coordination disorders, cognitive disorders, sensory disorders, or behavioral disorders. We also analyzed each of these disorders separately as secondary outcomes. We performed a multivariable analysis using logistic regression models. We accounted for the nonindependence of twins and missing data by generalized estimating equation models and multiple imputations, respectively. RESULTS: Among 2927 children alive at 5 years of age, 124 (3%) were born in a context of clinical chorioamnionitis. Overall, 8.2% and 9.6% of children exposed and unexposed, respectively, to clinical chorioamnionitis had moderate-to-severe neurodevelopmental disorders. After multiple imputations and multivariable analysis, clinical chorioamnionitis was not associated with the occurrence of moderate-to-severe neurodevelopmental disorders (aOR, 0.9; 95% CI, 0.5-1.8). CONCLUSIONS: We did not find any association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born at <35 weeks of gestation after preterm labor or preterm premature rupture of membrane.

Improved efficiency in the management of newborns with infectious risk factors by the sepsis risk calculator and clinical observation.

OBJECTIVE: To evaluate the efficiency of the sepsis risk calculator and the serial clinical observation in the management of late preterm and term newborns with infectious risk factors. METHOD: Single-center, observational, two-phase cohort study comparing the rates of neonates born ≥35 weeks' gestation, ≥2000 g birthweight, and without major congenital anomalies, who were screened and/or received antibiotics for early-onset neonatal sepsis risk at our center during two periods, before (January/2018-June/2019) and after (July/2019-December/2020) the implementation of the sepsis risk calculator. RESULTS: A total of 1796 (Period 1) and 1867 (Period 2) patients with infectious risk factors were included. During the second period, tests to rule out sepsis were reduced by 34.0 % (RR, 95 %CI): 0.66 (0.61, 0.71), blood cultures by 13.1 %: 0.87 (0.77, 0.98), hospital admissions by 13.5 %: 0.86 (0.76, 0.98) and antibiotic administration by 45.9 %: 0.54 (0.47, 0.63). Three cases of early-onset neonatal sepsis occurred in the first period and two in the second. Clinical serial evaluation would have detected all true cases. CONCLUSIONS: The implementation of a sepsis risk calculator in the management of newborns ≥35 weeks GA, ≥2000 g birthweight, without major congenital anomalies, with infectious risk factors is safe and adequate to reduce laboratory tests, blood cultures, hospital admissions, and antibiotics administration. Serial clinical observation, in addition, could be instrumental to achieve or even improve this goal.

Improved efficiency in the management of newborns with infectious risk factors by the sepsis risk calculator and clinical observation

Abstract Objective To evaluate the efficiency of the sepsis risk calculator and the serial clinical observation in the management of late preterm and term newborns with infectious risk factors. Method Single-center, observational, two-phase cohort study comparing the rates of neonates born ≥35 weeks' gestation, ≥2000 g birthweight, and without major congenital anomalies, who were screened and/or received antibiotics for early-onset neonatal sepsis risk at our center during two periods, before (January/2018-June/2019) and after (July/2019-December/2020) the implementation of the sepsis risk calculator. Results A total of 1796 (Period 1) and 1867 (Period 2) patients with infectious risk factors were included. During the second period, tests to rule out sepsis were reduced by 34.0 % (RR, 95 %CI): 0.66 (0.61, 0.71), blood cultures by 13.1 %: 0.87 (0.77, 0.98), hospital admissions by 13.5 %: 0.86 (0.76, 0.98) and antibiotic administration by 45.9 %: 0.54 (0.47, 0.63). Three cases of early-onset neonatal sepsis occurred in the first period and two in the second. Clinical serial evaluation would have detected all true cases. Conclusions The implementation of a sepsis risk calculator in the management of newborns ≥35 weeks GA, ≥2000 g birthweight, without major congenital anomalies, with infectious risk factors is safe and adequate to reduce laboratory tests, blood cultures, hospital admissions, and antibiotics administration. Serial clinical observation, in addition, could be instrumental to achieve or even improve this goal.

Predictive value of serum inflammatory markers for histological chorioamnionitis among women with preterm premature rupture of membranes after undergoing cervical cerclage.

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.

Progesterone modulates extracellular heat-shock proteins and interlukin-1ß in human choriodecidual after Escherichia coli infection.

INTRODUCTION: Chorioamnionitis is an adverse condition in human pregnancy caused by many bacterial pathogens including Escherichia coli (E. coli); which has been associated with higher risk of preterm birth. We recently reported that human maternal decidua (MDec) tissue responds to E. coli infection by secreting extracellular heat-shock proteins (eHsp)-60, -70 and interlukin-1ß (IL-1ß). Previous studies have shown that progesterone (P4) regulates the immune response, but it is unknown whether P4 inhibits the secretion of eHsp. The aim of this investigation was to determine the role of P4 on the secretion of eHsp-27, -60, -70 and IL-1ß in MDec after 3, 6, and 24 h of E. coli infection. METHODS: Nine human feto-maternal interface (HFMi) tissues were included and mounted in the Transwell culture system. Only the maternal decidua (MDec) was stimulated for 3, 6 and 24 h with E. coli alone or in combination with progesterone and RU486. After each treatment, the HFMi tissue was recovered to determine histological changes and the culture medium recovered to evaluate the levels of eHsp-27, -60, -70 and IL-1ß by ELISA and mRNA expression by RT-PCR. RESULTS: No structural changes were observed in the HFMi tissue treated with P4 and RU486. However, stimulation with E. coli produces diffuse inflammation and ischemic necrosis. E. coli induced infection decreases, in time- and dose-dependent manner, eHsp-27 and increases eHsp-60, eHsp-70 and IL-1ß levels. In contrast, incubation of HFMi tissue with E. coli + P4 reversed eHsp and IL-1ß secretion levels relative to E. coli stimulation group but not relative to the control group. The same profile was observed on the expression of eHsp-27 and eHsp-60. DISCUSSION: we found that progesterone modulates the anti-inflammatory (eHsp-27) and pro-inflammatory (eHsp-60 and eHsp-70) levels of eHsp induced by E. coli infection in human choriodecidual tissue. eHsp-60 and eHsp-70 levels were not completely reversed; maintaining the secretion of IL-1ß, which has been associated with adverse events during pregnancy.

Variación del perímetro cefálico en prematuros menores de 34 semanas expuestos a corioamnionitis histológica / Variation of head circumference variation in preterm infants less than 34 weeks to histologic chorioamnionitis

RESUMEN Objetivo : Analizar las variaciones del perímetro cefálico (PC) en prematuros menores de 34 semanas expuestos a corioamnionitis histológica (CAH), y observados hasta los 2 años de edad corregida. Material y métodos : Estudio de cohorte secundaria de dos estudios prospectivos. Los datos correspondieron a mediciones del PC al nacimiento, a las 40 semanas y a los 2 años de edad corregida. La variación del PC se analizó en los prematuros con y sin exposición a CAH. La CAH se analizó de acuerdo con los subtipos subcorionitis/corionitis, corioamnionitis y corioamnionitis más funisitis. Resultados : De 91 prematuros incluidos, el 41,8 % (38/91) tuvo CAH. El promedio del PC al nacimiento fue de 27,7 cm (percentil 31,2) en los expuestos y de 28,3 cm (percentil 42,1) en los no expuestos (p = 0,039); a las 40 semanas y a los 2 años, los promedios fueron similares. El subtipo corioamnionitis estuvo asociado con un menor PC (p < 0,05). La menor edad gestacional al nacer (p < 0,005) se relacionó con una mayor velocidad de crecimiento craneal. La CAH y el retardo de crecimiento intrauterino (RCIU) fueron los factores determinantes del menor PC en las tres edades evaluadas, y la sepsis confirmada solo tuvo lugar a las 40 semanas. Conclusiones : Los prematuros menores de 34 semanas expuestos a la CAH tuvieron menor percentil de PC al nacimiento; se observó recuperación del percentil de PC a las 40 semanas; y, finalmente, el subtipo corioamnionitis se relacionó con un menor PC a los 2 años de edad corregida. El factor RCIU potencia esta asociación en las tres edades y la sepsis solo a las 40 semanas. Se recomienda realizar futuros estudios para confirmar estos hallazgos.

SUMMARY Objective : To analyze the variations of head circumference (HC) in preterm infants, born with less than 34 weeks of gestation, exposed to histologic chorioamnionitis (CAH), and observed until 2 years of corrected age. Materials and methods : This is a cohort study derived from two prospective studies. The analyzed data corresponded to HC measures obtained from the subjects at three points: birth, 40 weeks, and 2 years of corrected age. The subjects were classified in two groups: exposed and not exposed to CAH. Preterm infants with CAH were divided according to its subtype in chorioamnionitis, subchorionitis and chorioamnionitis plus funisitis. Results : Out of 91 preterm infants included in the study. 41.8% (38/91) presented CAH. At birth, the average measure of HC in exposed infants was 27.7 cm (31,2 percentile), while in not exposed infants it was 28.3 cm. (42,1 percentile). At 40 weeks and at 2 years, the average measures were similar. The CAH chorioamnionitis subtype was found to be associated with PC growth retardation (p<0,05). A lesser gestational age (p=0.005) was related with greater cranial growth speed. Conclusions : Newborns younger than 34 weeks exposed to CAH had lower HC percentile at birth. We observed a recovery of HC at 40 weeks. The chorioamnionitis subtype was related to lower HC at 2 years of corrected age. Intrauterine growth restriction (IUGR) enhanced this association at these three points, while sepsis did so only at 40 weeks. Further research is required to confirm these findings.

Escala de gravedad según la histología de las estructuras placentarias en la corioamnionitis histológica / Scale of severity according to histology of placental structures in histological chorioamnionitis

Introducción: La infección bacteriana de inicio precoz es una afección del neonato que constituye una causa importante de morbilidad y mortalidad neonatal. Objetivo: Identificar en neonatos pretérminos la corioamnionitis histológica como factor de riesgo y su influencia en la infección neonatal, así como la construcción de una escala de gravedad en la histología de las estructuras placentarias. Método: Se realizó una investigación analítica de casos y controles cuya muestra estuvo constituida por 450 recién nacidos (casos) con infección bacteriana de inicio precoz y 900 recién nacidos (controles) que no presentaron dicha afección en las primeras 72 horas de vida. Resultado: La corioamnionitis histológica se diagnosticó en 96 recién nacidos para el 21,3 por ciento, con odd ratio (OR)= 26,84; intervalo de confianza (IC) 95 %: [13,40-53,75] con p= 0,000; en los controles solo 9 recién nacidos presentaron histología placentaria positiva (1,0 por ciento) de las 96 placentas con histología positiva; 20 pertenecieron al grupo A (ligero) (20,8 por ciento); 45 placentas al grupo B (moderado) (46,9 por ciento) y 31 al grupo C (grave) (32,3 por ciento); de las 9 placentas analizadas en los controles solo 7 pertenecieron al grupo de las ligeras que representan el 77,8 por ciento y en los casos un 20,8 por ciento. Conclusiones: La corioamnionitis histológica constituye un factor de riesgo importante y significativo, se construyó una escala de gravedad en las placentas con histología positivas, esta clasificación representa un aporte teórico, pues al aumentar la gravedad es más evidente la clínica de infección bacteriana en neonatos pretérminos(AU)

Introduction: Early onset bacterial infection is a neonate condition that is an important cause of neonatal morbidity and mortality. Objective: To identify histological chorioamnionitis as a risk factor and its influence on neonatal infection in preterm neonates, as well as the construction of a severity scale in the histology of placental structures. Method: An analytical investigation of cases and controls was carried out, whose sample consisted of 450 newborns (cases) with early bacterial infection of early onset and 900 newborns (controls) who did not present this condition in the first 72 hours of life. Result: Histological chorioamnionitis was diagnosed in 96 newborns for 21.3 percent, with odd ratio (OR) = 26.84; 95 percent confidence interval (CI): [13.40-53.75] with p= 0.000; In controls, only 9 infants had positive placental histology (1.0 percent) of the 96 placentas with positive histology; 20 belonged to group A (light) (20.8 percent); 45 placentas to group B (moderate) (46.9 percent) and 31 to group C (severe) (32.3 percent); Of the 9 placentas analyzed in the controls, only 7 belonged to the group of light placentas that represent 77.8 percent and in cases 20.8 percent. Conclusions: Histological chorioamnionitis is an important and significant risk factor, a severity scale was constructed in placentas with positive histology, this classification represents a theoretical contribution, since when increasing the severity the clinical bacterial infection in preterm neonates is more evident(AU)

Corioamnionitis histológica y neurodesarrollo en niños prematuros menores de 34 semanas, Lima-Perú

Para determinar los efectos de la corioamnionitis histológica en el neurodesarrollo de los prematuros menores de 34 semanas evaluados a los 2 años de edad corregida se realizó un estudio secundario de casos y controles. Fueron analizados los datos clínicos, hallazgos histológicos de la placenta e índices del desarrollo medidos por la Escala Bayley III de 38 niños expuestos y 53 niños no expuestos. Las infecciones genitourinarias de la madre y la sepsis precoz fueron más frecuentes en el grupo expuesto (p<0,005). Las dimensiones del desarrollo cognitivo, motor y lenguaje fueron normales en ambos grupos. Los expuestos al subtipo subcorionitis obtuvieron menor desempeño en las tres dimensiones. La corioamnionitis histológica no mostró influencia sobre el neurodesarrollo en prematuros menores de 34 semanas a los 2 años de edad. Se recomienda estudios longitudinales y multicéntricos para definir los efectos a largo plazo.

SUMMARY The objective of this study was to determine the effects of histologically diagnosed chorioamnionitis on neurodevelopment of premature babies born with less than 34-week gestational age who were assessed at two-year corrected age. A secondary case-control study was carried out. Clinical data, placental histological findings, and development indexes assessed using the Bayley III scale were analyzed in 38 exposed children and 53 non-exposed children. Genitourinary infections in mothers and early sepsis were more frequent in the exposed group (p<0.005). Cognitive development, motor development and language were normal in both groups. Those children exposed to the chorionitis subtype had lower scores in the aforementioned variables. Histologically diagnosed chorioamnionitis did not show any influence on neurodevelopment in premature babies born with less than 34-week gestational age when they were assessed at two years. Longitudinal and multicenter studies are advised in order to define the long-term effects.

Predictive value of serum inflammatory markers for histological chorioamnionitis among women with preterm premature rupture of membranes after undergoing cervical cerclage

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.

Corioamnionitis Histológica Asociada a Muerte Fetal / Histological Chorioamnionitis Associated with Fetal Death

INTRODUCCIÓN. Anualmente ocurren más de 2 millones de muertes fetales a nivel mundial, siendo fundamental el estudio anatomopatológico placentario para disminuir el número de muertes inexplicadas. OBJETIVO. Revisar la literatura existente acerca de corioamnionitis histológica, los criterios para establecer su diagnóstico, su presencia y posible asociación en estudios de causas de muerte fetal. METODOLOGÍA. Se realizaron búsquedas en bases de datos electrónicas para recopilar estudios de causas de muerte fetal que incluyeron corioamnionitis histológica. RESULTADOS. Se encontraron 13 estudios que evaluaron mortalidad fetal y que entre sus causas incluyeron corioamnionitis histológica. DESARROLLO. El estudio microscópico placentario en muertes fetales es esencial al investigar una muerte fetal. Las anomalías placentarias son la causa más común de muerte fetal, la corioamnionitis aguda es la lesión inflamatoria más frecuente. Se detallaron los criterios más relevantes para definir corioamnionitis aguda histológica pero aún no se establece un consenso. Estudios de causas de muerte fetal en años recientes han reportado corioamnionitis histológica entre 6,3% y 41,3% de casos. Las alteraciones inflamatorias del líquido amniótico son una causa importante de muerte fetal, siendo la corioamnionitis la más frecuente en este grupo. CONCLUSIÓN. En estudios para determinar las causas de muerte fetal se evidenció corioamnionitis aguda histológica en hasta el 41,3% de casos, por lo que podría estar asociada a dicho evento. Sin embargo, es necesario establecer un sistema de estadiaje de corioamnionitis histológica mediante un panel de expertos a nivel mundial.

INTRODUCTION. Annually more than 2 million fetal deaths occur worldwide, being fundamental the placental anatomopathological study to reduce the number of unexplained deaths. OBJECTIVE. To review the existing literature on histological chorioamnionitis, the criteria to establish its diagnosis, its presence and possible association in studies of causes of fetal death. METHODOLOGY. Electronic databases were searched to collect studies of causes of fetal death that included histologic chorioamnionitis. RESULTS. Thirteen studies were found that evaluated fetal mortality and that included histologic chorioamnionitis among their causes. DEVELOPMENT: Placental microscopic study in fetal deaths is essential when investigating a fetal death. Placental abnormalities are the most common cause of fetal death, acute chorioamnionitis being the most frequent inflammatory lesion. The most relevant criteria for defining histologic acute chorioamnionitis have been detailed but consensus has not yet been established. Studies of causes of fetal death in recent years have reported histologic chorioamnionitis in between 6,3% and 41,3% of cases. Inflammatory changes in the amniotic fluid are an important cause of fetal death, with chorioamnionitis being the most frequent in this group. CONCLUSIONS. In studies to determine the causes of fetal death, histological acute chorioamnionitis was evidenced in up to 41,3% of cases, so it could be associated with this event. However, it is necessary to establish a histological chorioamnionitis staging system by means of a worldwide panel of experts.

Síndrome de respuesta inflamatoria fetal: fisiopatología, desenlaces y estudio ecográfico prenatal / Feltal inflamatory response syndrome: Pathophysiology, outcomes, and prenatal ultrasound study

Resumen OBJETIVO: Ofrecer al lector información amplia y suficiente acerca de este síndrome, con hincapié en el reconocimiento del daño multiorgánico fetal, que permita darle herramientas para establecer el diagnóstico oportuno y disminuir la morbilidad y mortalidad fetal y neonatal. METODOLOGÍA: Estudio retrospectivo con base en la búsqueda en las bases de datos de PubMed, EBSCO y Ovid de 2016 a 2021 de artículos de revisión, investigaciones originales, guías de práctica clínica y protocolos. Además, artículos clásicos y los correspondientes a búsquedas manuales para lograr la contextualización de los puntos tratados. RESULTADOS: Cuando la infección llega al feto, se despliega una respuesta proinflamatoria con secreción de citocinas, que son la base para el diagnóstico de síndrome de respuesta inflamatoria fetal. Cuando esta respuesta a la infección es desregulada, termina por generar un daño multiorgánico que puede ser reconocido por medio de herramientas no invasivas, como el ultrasonido fetal avanzado. Este reconocimiento permite iniciar la atención oportuna a fin de reducir las tasas de morbilidad y mortalidad perinatal. CONCLUSIÓN: La infección microbiana de la cavidad amniótica y del feto, con la generación subsecuente del síndrome de respuesta inflamatoria fetal, se asocia con daño multiorgánico que puede reconocerse en el ultrasonido avanzado y lograr la atención óptima y mejores desenlaces perinatales.

Abstract OBJECTIVE: To provide the reader with ample and sufficient information about this syndrome, with emphasis on the recognition of fetal multiorgan damage, to provide tools to establish a timely diagnosis and reduce fetal and neonatal morbidity and mortality. METHODOLOGY: Retrospective study based on the search in PubMed, EBSCO and Ovid databases from 2016 to 2021 of review articles, original research, practice guidelines and protocols. In addition, classic articles and those corresponding to manual searches to achieve contextualization of the points discussed. RESULTS: When infection reaches the fetus, a proinflammatory response with cytokine secretion unfolds, which are the basis for the diagnosis of fetal inflammatory response syndrome. When this response to infection is deregulated, it ends up generating multiorgan damage that can be recognized by means of noninvasive tools, such as advanced fetal ultrasound. This recognition allows initiating timely care in order to reduce perinatal morbidity and mortality rates. CONCLUSION: Microbial infection of the amniotic cavity and fetus, with subsequent generation of fetal inflammatory response syndrome, is associated with multiorgan damage that can be recognized on advanced ultrasound and achieve optimal care and better perinatal outcomes.

Induction within or after 12 hours of ≥36 weeks' prelabor rupture of membranes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the incidence of chorioamnionitis in women with singleton gestations with ≥36 weeks' prelabor rupture of membranes induced with oxytocin within or after 12 hours of prelabor rupture of membranes. DATA SOURCES: The search was conducted using MEDLINE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and Cochrane Library as electronic databases from their inception to May 2020. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials of women with singleton cephalic gestations and prelabor rupture of membranes at ≥36 weeks comparing induction of labor with oxytocin either ≤12 hours after prelabor rupture of membranes or >12 hours after prelabor rupture of membranes (expectant management group). STUDY APPRAISAL AND SYNTHESIS METHODS: The risk of bias in each included study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. All analyses were done using an intention-to-treat approach, evaluating women according to the treatment group to which they were randomly allocated in the original trials. The primary outcome was the incidence of chorioamnionitis. RESULTS: After exclusions, 9 randomized controlled trials including 3759 women were analyzed. Women with singleton cephalic gestations and prelabor rupture of membranes at ≥36 weeks who have induction of labor ≤12 hours after prelabor rupture of membranes have shorter time between prelabor rupture of membranes and delivery (-12.68 hours; 95% confidence interval, -16.15 to -9.21) and higher chance of delivering within 24 hours of prelabor rupture of membranes (91% vs 46%; relative risk, 1.93; 95% confidence interval, 1.59-2.35). Cesarean and operative vaginal deliveries were not significantly different between the groups. Induction of labor ≤12 hours after prelabor rupture of membranes was also associated with significantly fewer incidences of chorioamnionitis (5.3% vs 9.9%; relative risk, 0.62; 95% confidence interval, 0.40-0.97), endometritis (2.4% vs 4.2%; relative risk, 0.59; 95% confidence interval, 0.40-0.87), neonatal sepsis (6.1% vs 11.8%; relative risk, 0.46; 95% confidence interval, 0.27-0.79), and admission to neonatal intensive care unit (6.4% vs 12.0%; relative risk, 0.54; 95% confidence interval, 0.43-0.69) compared with women managed expectantly, usually at >24 hours. The subgroup analysis of 3323 women with induction of labor at ≤6 hours showed similar results, including similar significant reductions in chorioamnionitis, endometritis, neonatal sepsis, and admission to neonatal intensive care unit. CONCLUSION: Women with symptoms of prelabor rupture of membranes at ≥36 weeks should be evaluated promptly, and if prelabor rupture of membranes is confirmed, they should have induction of labor within 12 hours and perhaps even within 6 hours since the first symptom of prelabor rupture of membranes. This management is associated with significantly less morbidity, especially in terms of infections, for both the mother and the baby, with no evidence of any harm.

Infección por listeria monocytogenes en el embarazo, asociado a desprendimiento de placenta y complicaciones perinatales: reporte de un caso / Listeria monocytogenes infection in pregnancy, associated with placental abruption and perinatal complications: case report

INTRODUCCIÓN la listeriosis, aunque es una infección infrecuente, debe ser considerada en pacientes inmunocomprometidos y gestantes, especialmente en aquellos que consumen alimentos crudos o productos lácteos no pasteurizados, lo que pone en riesgo a un gran número de mujeres embarazadas en países de habla hispana. Es importante que el médico considere su inclusión en los posibles diagnósticos diferenciales cuando la sospecha clínica lo amerite, lo que permitirá hacer un diagnóstico temprano y por lo tanto un tratamiento oportuno, evitando así las posibles complicaciones en el binomio madre-hijo. CASO CLÍNICO clínico multigestante, con embarazo de 33 + 5 semanas, que ingresó a una institución de alto nivel de complejidad en la ciudad de Medellín, Colombia, por síndrome febril asociado a sepsis obstétrica debido a infección intraamniótica por Listeria monocytogenes, que requirió cesárea de urgencia, en donde se evidenció un desprendimiento placentario del 100 % secundario al proceso infeccioso y asociado a complicaciones neonatales. CONCLUSIONES: el diagnóstico de listeriosis gestacional supone un reto clínico por su presentación inespecífica y baja incidencia. Sin embargo, las consecuencias obstétricas arrastran una gran morbilidad de la madre y morbi-mortalidad neonatal, lo que hace de suma importancia que el clínico lo tenga presente en su arsenal diagnóstico, ya que una vez diagnosticado, el tratamiento oportuno tiene desenlaces clínicos favorables.

INTRODUCTION: although listeriosis is a rare infection, it should be considered in immunocompromised patients and pregnancy, especially in those who consume raw food or unpasteurized dairy, which puts a large number of pregnant women in Hispanic countries at risk. It is of special importance for physicians to include listeriosis among possible diagnoses when clinical suspicion arises in order to timely treat it and thus avoid the complications that may occur in the mother-child binomial. CLINICAL CASE: a pregnant woman (33 + 5 weeks) with multiple gestations, was admitted to a high level of complexity institution in the city of Medellín, Colombia, presenting a febrile syndrome associated with obstetric sepsis due to intra-amniotic infection by Listeria monocytogenes, which required emergency cesarean section where a 100 % placental abruption was evidenced secondary to the infectious process and associated with neonatal complications. CONCLUSIONS: The diagnosis of gestational listeriosis is a clinical challenge due to its nonspecific presentation and low incidence. However, the obstetric consequences drag a great maternal morbidity and neonatal morbidity and mortality, which is why it is important for physicians to consider this in the diagnostic arsenal because once diagnosed, the appropriate treatment has favorable clinical outcomes.

Repercusión de la corioamnionitis como factor de riesgo en la sepsis materna y neonatal temprana / Impact of Chorioamnionitis as a risk factor in early neonatal and maternal sepsis / Impacto da coioamnionite como fator de risco nasepse materna e neonatal precoce

RESUMEN Introducción: se realiza una revisión bibliográfica sobre la repercusión de la corioamnionitis como factor de riesgo en la sepsis neonatal temprana para la madre y el neonato en el Hospital provincial Universitario Docente "Carlos M. de Céspedes" en Bayamo, Granma en los cinco primeros meses del año 2019. Objetivo: profundizar el conocimiento de este factor de riesgo, suetiopatogenia, factores predisponentes, diagnóstico clínico y de laboratorio, riesgos para la madre y repercusión en el recién nacido, su prevención y tratamiento. Métodos: se utilizaron libros de texto específicos de Medicina y se realizó la recopilación de artículos de Internet a través de buscadores como el Servicio de la Editorial Elsevier, Secretaría de Ciencia y Técnica de la Nación, LILACS, MEDLINE con la asistencia del buscador específico PUBMED, IMBIOMED, La Biblioteca Cochrane, SciELO. Resultados: su incidencia en los partos pretérmino es mayor que en las gestaciones a término. Representa una de las tres principales causas de infección antes de término del embarazo con membranas íntegras y en caso de rotura prematura de membranas. Conclusiones: la repercusión en la madre incluye el parto pretérmino, si cesárea (atonía uterina o hemorragia postparto, absceso pélvico, tromboembolismo y endometritis, sepsis puerperal y la infección del torrente sanguíneo, mientras que en el neonato la leucomalacia periventricular con la consiguiente hemorragia periventricular, la broncodisplasia pulmonar, enterocolitis necrotizante, parálisis cerebral y el retraso mental.

ABSTRACT Introduction: a bibliographical review on the impact of Chorioamnionitis as a risk factor in early neonatal sepsis for the mother and the newborn in the provincial University Hospital "Carlos M. de Céspedes" is carried out in Bayamo, Granma in the first five months of the year 2019. Objective: to deepen the knowledge of this risk factor, its pathogenesis, predisposing factors, clinical and laboratory diagnosis, risks to the mother and repercussion in the newborn, its prevention and treatment. Methods: medicine-specific textbooks were used and the collection of Internet articles was made through search engines such as the service of the Editorial Elsevier, Secretariat of Science and Technology of the nation, LILACS, MEDLINE with the assistance of Specific search engine PUBMED, imbiomed, the Cochrane Library, SciELO. Results: its incidence in preterm births is greater than in term gestations. It represents one of the three main causes of infection before the end of pregnancy with intact membranes and in case of premature rupture of membranes. Conclusion: the impact on the mother includes preterm delivery, if caesarean section (uterine sluggishness or postpartum hemorrhage, pelvic abscess, thromboembolism and endometritis, puerperal sepsis and bloodstream infection, while in the neonate the Periventricular periventricular with consequent periventricular hemorrhage, pulmonary broncodisplasia, necrotizing enterocolitis, cerebral palsy and mental retardation.

RESUMO Introdução: uma revisão bibliográfica é realizada sobre o impacto da coioamnionite como fator de risco na sepse neonatal precoce para mãe e recém-nascidos no Hospital Escolar Provincial "Carlos M. de Céspedes" em Bayamo, Granma nos primeiros cinco meses de 2019. Objetivo: aprofundar o conhecimento desse fator de risco, sua etiopatogeneia, fatores predisponderantes, diagnóstico clínico e laboratorial, riscos para a mãe e impacto sobre o recém-nascido, sua prevenção e tratamento. Métodos: foram utilizados livros didáticos específicos de Medicina e o recolhimento de artigosna Internet foi realizado por meio de mecanismos de busca como o Serviço de Publicação Elsevier, Secretaria de Ciência e Técnica da Nação, LILACS, MEDLINE com o auxílio do mecanismo de busca específico PUBMED, IMBIOMED, The Cochrane Library, SciELO. Resultados: sua incidência em partos prematuros é maior do que nas gestações a termo. Representa uma das três principais causas de infecção antes do fim da gravidez com membranas completas e em caso de ruptura prematura de membranas. Conclusões: o impacto sobre a mãe inclui nascimento prematuro, se cesariana (atonia uterina ou hemorragia pós-parto, abscesso pélvico, tromboembolismo e endometrite, sepse pós-parto e infecção por corrente sanguínea, enquanto na leucomalacia periventricular neonate com hemorrhagem periventricular consequente, broncododisplasia pulmonar, enterocolite necrosante, paralisia cerebral e retardo mental.

Association of Chorioamnionitis with Cerebral Palsy at Two Years after Spontaneous Very Preterm Birth: The EPIPAGE-2 Cohort Study.

OBJECTIVE: To assess whether chorioamnionitis is associated with cerebral palsy (CP) or death at 2 years' corrected age in infants born before 32 weeks of gestation after spontaneous birth. STUDY DESIGN: EPIPAGE-2 is a national, prospective, population-based cohort study of children born preterm in France in 2011; recruitment periods varied by gestational age. This analysis includes infants born alive after preterm labor or preterm premature rupture of membranes from 240/7 to 316/7 weeks of gestation. We compared the outcomes of CP, death at 2 years' corrected age, and "CP or death at age 2" according to the presence of either clinical chorioamnionitis or histologic chorioamnionitis. All percentages were weighted by the duration of the recruitment period. RESULTS: Among 2252 infants born alive spontaneously before 32 weeks of gestation, 116 (5.2%) were exposed to clinical chorioamnionitis. Among 1470 with placental examination data available, 639 (43.5%) had histologic chorioamnionitis. In total, 346 infants died before 2 years and 1586 (83.2% of the survivors) were evaluated for CP at age 2 years. CP rates were 11.1% with and 5.0% without clinical chorioamnionitis (P = .03) and 6.1% with and 5.3% without histologic chorioamnionitis (P = .49). After adjustment for confounding factors, CP risk rose with clinical chorioamnionitis (aOR 2.13, 95% CI 1.12-4.05) but not histologic chorioamnionitis (aOR 1.21, 95% 0.75-1.93). Neither form was associated with the composite outcome "CP or death at age 2." CONCLUSIONS: Among infants very preterm born spontaneously, the risk of CP at a corrected age of 2 years was associated with exposure to clinical chorioamnionitis but not histologic chorioamnionitis.

Riesgo de daño cerebral en prematuros menores de 34 semanas expuestos a corioamnionitis histológica, Lima, Perú / Risk of brain damage in premature infants under 34 weeks of gestational age exposed to histological chorioamnionitis Lima, Peru

RESUMEN Objetivos: Evaluar el riesgo de daño cerebral en prematuros menores de 34 semanas expuestos a corioamnionitis histológica (CAH). Materiales y métodos: Se realizó un estudio de cohortes en el Hospital Cayetano Heredia, durante el 2015. Fueron incluidos prematuros menores de 34 semanas que tuvieran examen histopatológico de la placenta. Los tipos de CAH evaluados fueron subcorionitis, corionitis, corioamnionitis, con o sin funisitis. El daño cerebral se evaluó en tres periodos de edad, entre 0 y 7 días, entre 7 y 30 días y a las 40 semanas gestacionales corregidas. Se realizó un seguimiento neurológico y controles con ecografía cerebral. Resultados: Se estudiaron 85 prematuros, 47,1% eran mujeres y la media de la edad gestacional fue de 30,9 semanas. El 42% (36/85) nacieron expuestos a CAH. La ruptura prematura de membrana fue la principal generatriz de sepsis, y la sepsis se relacionó con daño neurológico. La CAH estuvo asociada con hemorragia intraventricular (HIV) durante la primera semana y con lesiones de la sustancia blanca entre los 7 y 30 días de edad (p = 0,035). El tipo corioamnionitis de CAH se asoció al daño neurológico durante la primera semana (RR = 2,11; IC 95%: 1,09-4,11) y entre los 7 y 30 días de vida (RR = 2,72; IC 95%: 1,07-6,88). Conclusiones: La corioamnionitis fue un factor de riesgo para desarrollar lesiones cerebrales en prematuros menores de 34 semanas, para HIV durante los primeros 7 días y lesiones de sustancia blanca entre los 7 y los 30 días de edad. A las 40 semanas de edad corregida, los prematuros extremos con CAH tuvieron lesiones cerebrales más extensas.

ABSTRACT Objectives: To assess the risk of brain damage in premature infants under 34 weeks of gestational age exposed to histological chorioamnionitis (HCA). Materials and methods: A cohort study was conducted at the Hospital Cayetano Heredia, during 2015. Premature infants under 34 weeks of gestational age, who had histopathological examination of the placenta, were included. The types of HCA evaluated were sub-chorionitis, chorionitis, chorioamnionitis, with or without funisitis. Brain damage was evaluated in three age periods, between 0 and 7 days, between 7 and 30 days and at 40 weeks of corrected gestational age. A neurological follow-up and regular controls were performed with brain ultrasound. Results: A total of 85 premature infants were included, 47.1% were women and the mean gestational age was 30.9 weeks. From the total, 42% (36/85) were born exposed to HCA. Premature rupture of membranes was the main cause of sepsis, which was related to neurological damage. HCA was associated with intraventricular hemorrhage (IVH) during the first week and with white matter lesions between 7 and 30 days of age (p = 0.035). The chorioamnionitis type of HCA was associated with neurological damage during the first week (RR = 2.11, 95% CI: 1.09-4.11) and between 7 and 30 days of age (RR = 2.72, 95% CI: 1.07-6.88). Conclusions: Chorioamnionitis was a risk factor for developing brain injuries in premature infants under 34 weeks of gestational age. It was also a risk factor for HIV during the first 7 days and for white matter injuries between 7 and 30 days of age. At 40 weeks of corrected gestational age, extreme premature infants with HCA had more extensive brain damage.

Sepsis neonatal en embarazos a término con corioamnionitis clínica, utilidad de la escala de sepsis / Neonatal sepsis in pregnant at term with clinical chorioamnionitis, utility of sepsis score

RESUMEN Introducción: la corioamnionitis se presenta en 3 a 10 % de los embarazos a término, y los recién nacidos expuestos tienen el riesgo de desarrollar sepsis precoz. Objetivos: determinar la prevalencia de sepsis neonatal en hijos de embarazadas a término con corioamnionitis; describir las características clínicas de las madres y recién nacidos; y evaluar la utilidad de la escala de sepsis (escala de Rodwell y PCR) para el diagnóstico. Metodología: estudio observacional, descriptivo, de recién nacidos a término, producto de madres con corioamnionitis clínica, nacidos e internados en el Servicio de Neonatología del Hospital Nacional desde enero del 2013 a junio del 2016. Fueron excluidos los mortinatos, portadores de infecciones STORCH, y los que no tenían hemocultivo. Resultados: reunieron criterios de inclusión 71 neonatos a término. La población materna estuvo conformada por adolescentes y adultas jóvenes en 98,5 %, nulíparas y primíparas en 94 %, la rotura de membranas fue >18 horas en 34 (47,8 %) y el nacimiento se efectuó por cesárea en 24 (35,2 %). Los motivos de cesárea han sido la dilatación estacionaria y el sufrimiento fetal agudo en 17 (69,8 %). Desarrollaron sepsis neonatal 11 (15,4 %), 3 fueron confirmados con hemocultivo positivo, 10 presentaron síntomas y 7 depresión al nacer. Ninguno falleció. La primera escala de sepsis efectuada en 3,8 ± 1,8 horas de vida, y la segunda en una mediana de 45,5 horas, tuvieron un valor predictivo positivo de 50 % y 60 %. El valor predictivo negativo fue de 85 y 87 % respectivamente. Conclusión: la sepsis neonatal se presentó en 15,4 %. Casi todos fueron sintomáticos y presentaron depresión al nacer. La escala de sepsis no fue útil para confirmar el diagnóstico, sí para descartarla.

ABSTRACT Introduction: chorioamnionitis occurs in 3 to 10 % of full-term pregnancies, and newborns are at risk of developing early sepsis. Objectives: to determine the prevalence of neonatal sepsis in children of term pregnant women with chorioamnionitis; describe the clinical characteristics of mothers and newborns; and evaluate the utility of the sepsis scale (Rodwell scale and PCR) for diagnosis. Methodology: descriptive study, of term newborns, product of mothers with clinical chorioamnionitis, born and admitted to the Servicio de Neonatología del Hospital Nacional from January 2013 to June 2016. Stillbirths, carriers of STORCH infections, and they had no blood culture. Results: 71 term infants met inclusion criteria. The maternal population was made up of adolescents and young adults in 98,5 %, nulliparous and prim parous in 94 %, membrane rupture was >18 hours in 34 (47,8 %) and the birth was performed by caesarean section in 24 (35, 2 %). The reasons for cesarean section were stationary dilation and acute fetal distress in 17 (69,8 %). Neonatal sepsis developed 11 (15,4 %), 3 were confirmed with a positive blood culture, 10 symptoms and 7 depression at birth. Neither died. The first sepsis scale performed at 3,8 ± 1,8 hours of life, and the second at a median of 45,5 hours, had a positive predictive value of 50 % and 60 %. The negative predictive value was 85 and 87 % respectively. Conclusion: neonatal sepsis presented in 15,4 %. Almost all were symptomatic and depressed at birth. The sepsis scale was not useful to confirm the diagnosis, but to rule it out.