Stage III Chorioamnionitis is Associated with Reduced Risk of Severe Retinopathy of Prematurity.

OBJECTIVE: To identify whether histologically confirmed chorioamnionitis (hCAM) is associated with development of retinopathy of prematurity (ROP). STUDY DESIGN: We retrospectively analyzed 2 different cohorts. Cohort 1 was the national database of newborns in Japan born at ≤1500g or <32 weeks' gestation (January 2003 through April 2021, n = 38 013). Cohort 2 was babies born at <1500g from a single institution in Tsuchiura, Japan, (April 2015 through March 2018, n = 118). RESULTS: For Cohort1, after adjusting for potential confounders, stage III CAM (n = 5554) was associated with lower odds of severe ROP (stage ≥3 or required peripheral retinal ablation) by 14% (OR: 0.86; 95% CI: 0.78-0.94]. CAM of stage I (n = 3277) and II (n = 4319) was not associated with the risk of ROP. For Cohort 2, the odds of severe ROP were significantly reduced in moderate to severe hCAM groups (stage II, OR: 0.06, 95% CI: 0.05-0.82; stage III, OR: 0.10, 95% CI: 0.01-0.84). Neonates with funisitis, comorbidity of hCAM, and a finding of fetal inflammatory response had lower odds of severe ROP (OR: 0.11; 95% CI: 0.01-0.93). CONCLUSIONS: After adjusting for confounders, severe hCAM with fetal inflammatory response was associated with reduced risk of ROP.

Placental inflammation in a fetal demise of a SARS-CoV-2-asymptomatic, COVID-19-unvaccinated pregnant woman: a case-report.

BACKGROUND: Intrauterine fetal demise is a recognized complication of coronavirus disease 2019 in pregnant women and is associated with histopathological placental lesions. The pathological mechanism and virus-induced immune response in the placenta are not fully understood. A detailed description of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced inflammation in the placenta during fetal demise is crucial for improved clinical management. CASE PRESENTATION: We report the case of a 27-week gestation SARS-CoV-2-asymptomatic unvaccinated pregnant woman without comorbidities or other risk factors for negative pregnancy outcomes with a diagnosis of intrauterine fetal demise. Histopathological findings corresponded to patterns of subacute inflammation throughout the anatomic compartments of the placenta, showing severe chorioamnionitis, chronic villitis and deciduitis, accompanied by maternal and fetal vascular malperfusion. Our immunohistochemistry results revealed infiltration of CD68+ macrophages, CD56+ Natural Killer cells and scarce CD8+ T cytotoxic lymphocytes at the site of placental inflammation, with the SARS-CoV-2 nucleocapsid located in stromal cells of the chorion and chorionic villi, and in decidual cells. CONCLUSION: This case describes novel histopathological lesions of inflammation with infiltration of plasma cells, neutrophils, macrophages, and natural killer cells associated with malperfusion in the placenta of a SARS-CoV-2-infected asymptomatic woman with intrauterine fetal demise. A better understanding of the inflammatory effects exerted by SARS-CoV-2 in the placenta will enable strategies for better clinical management of pregnant women unvaccinated for SARS-CoV-2 to avoid fatal fetal outcomes during future transmission waves.

Rotura prematura de membranas: diagnóstico y manejo / Premature Rupture of Membranes: Diagnosis and Management

La rotura prematura de membranas se clasifica según la edad gestacional: a término (a partir de las 37 semanas de gestación), y pretérmino (antes de las 37 semanas). Esta se subdivide en cerca del término (34 y menos de 37 semanas), lejos del término (24 a 34 semanas) y previable (antes de las 24 semanas). Afecta a 8 % de las gestaciones; en pretérmino: 2 % y 4 % de las gestaciones únicas, 7 % a 20 % de las gemelares. Conlleva riesgos como corioamnionitis y desprendimiento prematuro de placenta normoinserta. La infección intraamniótica ocurre en 15 % a 35 % de los casos. El diagnóstico oportuno y el manejo adecuado son vitales para reducir la morbimortalidad asociada. El objetivo de esta revisión es abordar el diagnóstico y el manejo de la rotura prematura de membranas de acuerdo a la edad gestacional(AU)

Premature rupture of membranes is classified according to gestational age: term (from 37 weeks of gestation), and preterm (before 37 weeks). This is subdivided into near-term (34 and less than 37 weeks), far from term (24 to 34 weeks), and previable (before 24 weeks). It affects 8% of pregnancies; Preterm: 2% to 4% of singleton pregnancies, 7% to 20% of twins. It carries risks such as chorioamnionitis and normoinserted placental abruption. Intra-amniotic infection occurs in 15% to 35% of cases. Timely diagnosis and appropriate management are vital to reduce associated morbidity and mortality. The aim of this review is to address the diagnosis and management of premature rupture of membranes according to gestational age(AU)

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.

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.

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)

Clinical characteristics, complications, and predictive model of histological chorioamnionitis in women with preterm premature rupture of membranes.

We aimed to analyze the impact of histological chorioamnionitis (HCA) in the presence of preterm premature rupture of the membranes (PPROM) on obstetric and neonatal outcomes, and its possible predictability. A retrospective cohort analysis of PPROM cases (20-37 weeks) was conducted comparing the patients with and without HCA, seeking a predictive model of HCA using logistic regression. A total of 295 cases of PPROM were selected, of which 72 (24.4%) had HCA. The group with HCA had a shorter latency period and a greater number of clinical and laboratory criteria in the evolution. The group with HCA had a worse comparative result and presented: lower gestational age at delivery, lower average birth weight, lower Apgar scores, longer neonatal hospitalization, worse maternal clinical conditions and, higher rates of stillbirth, low birth weight (LBW), very low birth weight (VLBW), complications in pregnancy and childbirth, and cesarean delivery due to fetal distress or chorioamnionitis. A predictive model for HCA was developed, with the following independent variables: abdominal pain (odds ratio [OR] = 11.61), uterine activity (noticeable contractions on physical exam) (OR = 5.97), fever (OR = 5.77), latency > 3 days (OR = 2.13), and C-reactive protein (OR = 1.01). With this model, an adequate receiver operating characteristic curve was found, with an area under the curve of 0.726, and some HCA probability curves were constructed for different clinical situations. In this novel study, we present a non-invasive predictive model, with clinical and laboratory variables, which may help in decision-making in a patient with PPROM.

Immunopathological insights into villitis of unknown etiology on the basis of transplant immunology.

Villitis of unknown etiology (VUE) is an inflammatory disease characterized by the infiltration of maternal CD8 +T cells into the placental villi. Although the pathogenesis of VUE is still debated, dysregulation of the immune system appears to be an important factor in the development of the disease. Interaction of maternal T cells with the fetal antigens seems to be the trigger for the VUE onset. In this context, graft vs host disease (GVHD) and allographic rejection seem to share similarities in the VUE immunopathological mechanism, especially those related to immunoregulation. In this review, we compared the immunological characteristics of VUE with allograft rejection, and GVHD favoring a better knowledge of VUE pathogenesis that may contribute to VUE therapeutics strategies in the future.

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.

¿Son útiles los antimicrobianos en pacientes con trabajo de parto prematuro, espontáneo, membranas intactas e infección bacteriana ascendente? Una revisión narrativa / Are antibiotics useful in patients with preterm and spontaneous labor, intact membranes and ascendant bacterial infection? A narrative review

El parto prematuro (PP) es la principal causa de morbilidad/mortalidad perinatal y frecuentemente es espontáneo, con membranas intactas (MI). La infección intrauterina es su causa más común en un hospital público de Chile. Existe evidencia que la infección bacteriana ascendente desde la vagina es responsable de la infección/inflamación intraamniótica, del PP y de los resultados adversos maternos y perinatales. Esta revisión narrativa incluye ensayos controlados aleatorizados (ECAs), publicados en PubMed, Cochrane, Embase, Scielo, Science Direct, Wiley Online Library, sobre los mecanismos que intervienen en el ascenso de la infección vaginal, los factores infecciosos que participan en el resultado adverso materno-perinatal y la eficacia de los antimicrobianos en estos casos. Estos trabajos no recomiendan usar antimicrobianos profilácticos porque producen daño a corto y largo plazo en los hijos. Pero este resultado tiene sesgo porque no se evaluó la presencia de infección/inflamación subclínica, lo que disminuye el grado de recomendación. También existen ECAs, que erradican la infección/inflamación intraamniótica, reducen la morbilidad/mortalidad neonatal, pero son trabajos aislados, obtenidos de subanálisis, con bajo nivel de evidencia. Se requieren revisiones sistemáticas y metaanális de ECAs con estudio de infección/inflamación subclínica para evaluar si son útiles los antimicrobianos en el PP espontáneo con MI.

Preterm labor (PL) is the leading cause of perinatal morbidity/ mortality and is frequently spontaneous with intact membranes (IM). Intrauterine infection is its most common cause in a public hospital in Chile. There is evidence that ascending bacterial infection from the vagina is responsible for intraamniotic infection/inflammation, PL, and adverse maternal and perinatal outcomes. This narrative review includes randomized controlled trials (RCTs), published in PubMed, Cochrane, Embase, Scielo, Science Direct, Wiley Online Library on the mechanisms involved in the rise of vaginal infection, the infectious factors involved in adverse maternal-perinatal outcomes, and the efficacy of antibiotics in these cases. They do not recommend the use of prophylactic antibiotics because they cause short and long-term damage to children. But this result is biased because the presence of subclinical infection/inflammation was not evaluated, which lowers the degree of recommendation. There are also RCTs that eradicate intra-amniotic infection/inflammation, reduce neonatal morbidity/ mortality, but they are isolated studies, obtained from subanalyses, with a low level of evidence. Systematic reviews and meta-analyses of RCTs with subclinical infection/inflammation study are required to assess whether antibiotics are useful in spontaneous PL with IM.

Comparing maternal outcomes in spontaneous singleton pregnancies versus in vitro fertilization conception: Single-center 10-year cohort study.

OBJECTIVE: A successful assisted reproductive technique (ART) cycle is not flawless, and several studies have reported high incidences of maternal complications, but the association is inconclusive. In addition, the racial and ethnic effects of the Asian population undergoing ART on maternal outcomes is not well studied. This study attempts to compare various maternal outcome parameters ART and spontaneously conceived singleton pregnancies from a single high volume tertiary care centre. METHODS: A retrospective cohort study from a single tertiary infertility center was conducted from January 2011 to September 2020. The study included 1125 IVF conceived singletons (AP group) and 7193 spontaneous conceived singletons (SP group). The groups were compared using the Pearson Chi-square test and the adjusted odds ratio calculated using multivariate analysis. RESULTS: Maternal outcomes like gestational hypertension, pre-eclampsia, gestational diabetes (GDM), oligohydramnios, chorioamnionitis, operative, and instrumental delivery were significantly different in the two groups (p<0.05). The AP group had a significantly increased risk of GDM (aOR 1.093; 95% CI 1.076-1.110) and pregnancy-induced hypertension (PIH) (aOR 1.577; 95% CI 1.288-1.930) as compared to the SP group. IVF significantly increases the risk of abruption by 2 times (p=0.028), and independently increases the risk of caesarean section by 3.1-fold (p<0.001). But overall the IVF is the protective factor for oligohydramnios (p=0.024). CONCLUSIONS: ART increases the likelihood of pregnancy-related maternal complications, such as PIH, GDM, abruption, chorioamnionitis, and an increased rate of caesarean delivery. Thus, all patients undergoing ART procedures should receive pre-conceptional counselling regarding the associated obstetric risks and consider ART pregnancy as a high-risk pregnancy.

Parámetros del líquido amniótico para diagnóstico de respuesta inflamatoria en parto pretérmino / Amniotic fluid parameters for the diagnosis of inflammatory response in preterm delivery

OBJETIVO: Evaluar el rendimiento del Gram, la glucosa y los leucocitos en líquido amniótico para el diagnóstico de respuesta inflamatoria fetal y materna en pacientes con parto pretérmino. MÉTODO: Estudio de rendimiento de pruebas diagnósticas. Se incluyeron 63 pacientes a quienes se les realizó amniocentesis por sospecha de infección intraamniótica. Se estudió la placenta y se comparó con el Gram, la glucosa y el recuento de leucocitos en líquido amniótico para ver su relación con la respuesta inflamatoria. Se evaluaron la sensibilidad, la especificidad, las razones de verosimilitud (LR, likelihood ratio), los valores predictivos y el valor de kappa. RESULTADOS: Las pruebas con mejor rendimiento fueron en conjunto la glucosa 50/mm3 en líquido amniótico, con una especificidad del 94,3% (intervalo de confianza del 95% [IC95%]: 84,6-98,1), LR + 8,83 (IC95%: 2,5-31,2) y kappa de 0,48 (IC95%: 0,15-0,82). También se consideró la propuesta de un nuevo punto de corte para el recuento de leucocitos en líquido amniótico en la respuesta inflamatoria fetal. CONCLUSIONES: La combinación del recuento de leucocitos en líquido amniótico y los valores de glucosa mejora el rendimiento para el diagnóstico de respuesta inflamatoria fetal en comparación con la histopatología de la placenta, lo que proporciona información útil para el enfoque de los recién nacidos.

OBJECTIVE: To evaluate the performance of Gram, glucose and leukocytes in amniotic fluid for the diagnosis of fetal and maternal inflammatory response in patients with preterm delivery. METHOD: A diagnostic performance test study was carried out. Sixty-three patients with preterm labor were included who underwent amniocentesis due to suspected intra-amniotic infection. Histopathology of the placenta was studied and compared with the Gram result, glucose and leukocyte count in amniotic fluid, and their relationship with the maternal and fetal inflammatory response. Sensitivity, specificity, likelihood ratios, predictive values, and kappa were evaluated. RESULTS: The tests with the best performance were overall glucose 50/mm3 in amniotic fluid for the diagnosis of the fetal inflammatory response, with a specificity of 94.3% (95% confidence interval [95% CI]: 84.6-98.1%), likelihood positive ratio 8.83 (95% CI: 2.5-31.2) and kappa of 0.48 (95% CI: 0.15-0.82). A new cut-off point for leukocyte count in amniotic fluid to diagnose fetal inflammatory response was proposed. CONCLUSIONS: The combination of amniotic fluid leukocyte count and amniotic fluid glucose values improves performance for the diagnosis of inflammatory response compared with placental histopathology, providing useful information for newborns approach.

Sepsis neonatal precoz: recomendaciones para su abordaje en la práctica clínica / Early neonatal sepsis: recommendations for approach in clinical practice / Sepse neonatal precoce: recomendações para sua abordagem na prática clínica

La sepsis neonatal precoz se define como la que se manifiesta en las primeras 72 horas de vida. Es una importante causa de morbilidad y mortalidad neonatal. Su incidencia es inversamente proporcional a la edad gestacional. Los microorganismos considerados como frecuentes son Streptoccocus del grupo B, Escherichia coli y Listeria monocytogenes. El diagnóstico de sepsis precoz se basa principalmente en la presencia de factores de riesgo como la corioamnionitis y la edad gestacional. Los signos clínicos son inespecíficos y los exámenes paraclínicos disponibles actualmente, como los reactantes de fase aguda (proteína C reactiva y procalcitonia) tienen escaso valor predictivo positivo. Se realizó una revisión bibliográfica de las últimas publicaciones disponibles sobre sepsis neonatal precoz en recién nacidos, en cuanto a su sospecha, confirmación diagnóstica y tratamiento. A partir de las últimas publicaciones se confeccionó una guía para el manejo clínico de los recién nacidos con sospecha de sepsis precoz.

Early neonatal sepsis is defined as that type of sepsis with an onset within the first 72 hours of life and that is a major cause of neonatal morbidity and mortality. Its incidence is inversely proportional to its gestational age. Frequent microorganisms are group B Streptococcus, Escherichia coli and Listeria monocytogenes. Early sepsis diagnosis is mainly based on the presence of risk factors such as chorioamnionitis and gestational age. Clinical signs are non-specific and currently available paraclinical tests such as acute phase reactants (C-reactive protein and procalcitonin) have little positive predictive value. A bibliographic review of the suspicion, diagnostic confirmation and treatment on Early Neonatal Sepsis in newborns in the latest papers and guidelines were prepared for the clinical treatment of newborns with suspected early sepsis.

A sepse neonatal precoce é definida como aquela que se manifesta nas primeiras 72 horas de vida e que é uma das principais causas de morbidade e mortalidade neonatal. Sua incidência é inversamente proporcional à idade gestacional. Os microrganismos considerados frequentes são o Streptococcus grupo B, Escherichia coli e Listeria monocytogenes. O diagnóstico de sepse precoce baseia-se principalmente na presença de fatores de risco como a coioamnionite e a idade gestacional. Os sinais clínicos são inespecíficos e os testes para-clínicos atualmente disponíveis, como reagentes de fase aguda (proteína C-reativa e procalcitonia) têm pouco valor preditivo positivo. Fizemos uma revisão bibliográfica das últimas publicações disponíveis sobre sepse neonatal precoce em recém-nascidos em termos de suspeita e confirmação diagnóstica e tratamento. Com base nas últimas publicações, elaboramos um guia para o manejo clínico de recém-nascidos com suspeita de sepse precoce.

Characterization of amniotic fluid sludge in preterm and term gestations.

OBJECTIVE: To describe the characteristics of amniotic fluid sludge obtained from patients in term and preterm gestations. METHODS: This cross-sectional study included patients with dense aggregates of particulate matter detected in amniotic fluid, observed with transvaginal sonography. All patients were in labor and had an impending delivery, either preterm or at term. Echogenic material contained within amniotic fluid was retrieved transvaginally by needle amniotomy under direct visualization. The amniotic fluid analysis consisted of a Gram stain, cultures for aerobic/anaerobic bacteria and genital mycoplasmas, and a white blood cell count. RESULTS: Twenty-five patients ranging from 18 to 41 weeks of gestation were included in the study. We observed the following: (1) the appearance of amniotic fluid was consistent with pus-like material, vernix, or meconium by naked eye examination; (2) samples collected before 33 weeks of gestation (n = 13) had a pus-like appearance; however, after this gestational age, most of the samples [83% (10/12)] appeared to be consistent with vernix; (3) amniotic fluid cultures were positive for microorganisms in 13 patients, of which 10 were preterm gestations before 33 weeks; (4) the most frequent microorganisms retrieved by culture were genital mycoplasmas (Ureaplasma urealyticum [46% (6/13)]), followed by Mycoplasma hominis [31% (4/13)] and Candida albicans [15% (2/13)]; and (5) patients with sonographic particulate matter in preterm gestations frequently presented acute histologic chorioamnionitis and funisitis, but these conditions were rare in patients at term. CONCLUSION: The nature of amniotic fluid particulate material varies as a function of gestational age. The material obtained in preterm gestations is frequently related to an inflammatory process, while that obtained at term is often consistent with vernix and appears to represent a maturational process.

Placental Findings in Infants with Hypoxic-Ischemic Encephalopathy: The Importance of the Comparison Group.

OBJECTIVE: To determine the effect of 3 distinct comparison groups on associations between placental abnormalities and neonatal hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: This single-center, prospective case-control study of singletons of gestational age ≥36 weeks with predefined criteria for HIE (n = 30) and 3 control groups was conducted from June 2015 to January 2018. The control groups were infants born by repeat cesarean delivery (n = 60), infants born small for gestational age (SGA; n = 80), and infants receiving positive-pressure ventilation (PPV) at birth (n = 70). One pathologist blinded to infant category reviewed placental sections using the Amsterdam Placental Workshop criteria. Logistic regression with group contrasts relative to HIE was used to analyze primary placental pathologies, and ORs with 95% CIs provided effect sizes. RESULTS: The odds of maternal vascular malperfusion were increased among HIE group placentas compared with placentas of the repeat cesarean delivery (OR, 4.50; 95% CI, 1.45-14.00) and PPV (3.88; 1.35-11.16) groups, but not those of the SGA group. The odds of fetal vascular malperfusion were increased in the HIE group compared with the SGA group (OR, 9.75; 95% CI, 1.85-51.51). The odds of acute chorioamnionitis were higher in the HIE group compared only with the repeat cesarean delivery group, reflecting a similar incidence of chorioamnionitis in SGA group and PPV group placentas. The absence of placental findings was lowest in the HIE group (6.7%), followed by the SGA (18.8%), PPV (31.4%), and repeat cesarean delivery (75%) groups. CONCLUSIONS: Associations with placental abnormalities among infants with HIE varied based on the specific placental abnormality and the control group. Potentially important associations between placental pathology and HIE may be obscured if control groups are not well designed.

M1 macrophages involved in the pathogenesis of placental chronic villitis of unknown etiology.

INTRODUCTION: Placental villitis is characterized by the presence of inflammatory infiltrate in the placental villous. The objective of this study was to characterize in villitis of unknown etiology (VUE) of the human placentas the subpopulation of M1, important effector cells, and M2 macrophages, immunoregulatory cells. METHODS: Sixteen cases of VUE and three control placentas were examined using immunohistochemistry with antibodies for CD3, CD68, CD11c, and CD163. RESULTS: CD11c appeared predominantly in the inflamed villi when compared to the normal areas (p<.001). These cells corresponded to 41.2% of the macrophage population in the inflamed area and were mainly present inside the villi (36%). With regards to CD163, these cells tended to be in higher amounts in the inflamed villi when compared to CD11c and normal areas. DISCUSSION: We conclude that the almost exclusive presence of M1 macrophages in the inflamed areas suggests the influence of these cells in the pathogenesis VUE. The greater amount of M2 in villitis and normal areas suggests a possible immunoregulatory mechanism of the inflammatory process in VUE.

Beneficios de los antibióticos en la rotura prematura de membranas de pretérmino y factores que intervienen en la eficacia del tratamiento: revisión narrativa / Benefits of antibiotics in preterm premature rupture of membranes and factors involved in the efficacy of the treatment: narrative review

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.

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.