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Introducción. La cesárea es uno de los procedimientos quirúrgicos más predominante a nivel mundial. En el Perú, con datos nacionales, muestran que nuestros valores oscilan en 36% y un factor prevalente en la indicación de parto por cesárea es la cesárea previa. Objetivo. Determinar la prevalencia de cesárea previa como indicación de parto por cesárea en un hospital peruano en el periodo de enero a diciembre del año 2022. Materiales y Métodos. Se realizó un estudio descriptivo a partir de la información de las historias clínicas de las gestantes con indicación de parto por cesárea atendidas en un hospital. De una población de 6100 gestantes atendidas en el 2022 se obtuvo un total de 236 historias clínicas de pacientes que se les realizó cesárea con antecedente de cesárea. Se extrajo información sociodemográfica y clínica. Resultados. Se encontró que la prevalencia de cesárea previa como indicación de parto por cesárea fue de un 21.6%. La edad media de las pacientes atendidas fue de 32.5 años, el grado de instrucción más prevalente fue de secundaria completa con un 57.6%, el 75.4% de pacientes fueron convivientes, finalmente el número de gestaciones prevalente que tuvieron estas pacientes fue dos. Conclusiones. Aproximadamente la quinta parte de las pacientes con indicación de parto por cesárea tuvieron la indicación por la cesárea previa. Palabras clave: Cesárea previa, indicación de cesárea, gestantes.

En condiciones de ayuno, se extrajeron muestras sanguíneas de 1,560 gestantes peruanas no diabéticas residentes a nivel del mar, en semana 26 a 36 de gestación a fin de establecer valores normales para la glicemia en ayunas en la gestación (método o-toluidina) y comprobar si el pronóstico materno-fatal variaba cuando los valores de glicenúa en ayunas (GA) se encontraban fuera de estos límites. Los percentiles 3, 50, 90 y 95 para GA fueron 50, 67, 80 y 85 mg/d~ respectivamente. Las gestantes con factores de riesgo para diabetes tuvieron GA significativamente mayores aquellas que no los tenían 68 ± 10 versus 66 ± 9 mg/dl, p < 0.02), Se siguió a 1,415 (90.7%) de las gestantes y a 1,043 (67%) de los recién nacidos. La GA mostró una asociación positiva con la presencia de factores de riesgo para diabetes, complicaciones obstétricas, cesárea por desproporción fetopélvica, distocia de hombro y morbi-mortalidad perinatal. Un incremento significativo en el riesgo materno-fetal ocurrió cuando la glicemia en ayunas se encontraba fuera de los límites SO - 79 mg,ldl (2.8 - 4.4 mmol/L). Valores de glicemia en ayunas fuera de estos límites debe considerarse como un indicador pronóstico de mayor riesgo obstétrico y perinatal.

Las competencias investigativas son el dominio de actitudes cognitivas puestas en prácticas por los estudiantes. El objetivo fue analizar la validez de constructo de una rúbrica analítica para evaluar las competencias investigativas de estudiantes de posgrado. Docentes asesores evaluaron 260 tesis mediante la rúbrica. El análisis de validez de constructo se efectuó mediante un proceso de validación cruzada entre el análisis factorial exploratorio, que es una técnica estadística que explora con precisión las dimensiones subyacentes de las variables latentes de las variables observadas y el análisis factorial comprobatorio, que encuadra los modelos de ecuaciones estructurales, analizando las relaciones entre los indicadores de las variables observadas y las variables latentes. Los resultados del análisis factorial exploratorio mostraron correspondencia con la propuesta teórica, donde un solo factor explicó el 51% de la varianza que fue representado por la totalidad de ítems. La evaluación de este modelo mediante el análisis factorial comprobatorio reveló un buen ajuste (X2/gl: 2.197; RMSA: 0,085; GFI: 0,902; CFI: 0,932; TLI: 0,912), y se encontró evidencia de validez convergente (CFE>0,50; CC: 0,902; VME: 0,464). La confiabilidad de la rúbrica fue óptima (α=0,903). Se concluye que el constructo formulado está representado en la estructura del instrumento.

Abstract Background Migraine, a common chronic-intermittent disorder of idiopathic origin characterized by severe debilitating headaches and autonomic nervous system dysfunction, and placental abruption, the premature separation of the placenta, share many common pathophysiological characteristics. Moreover, endothelial dysfunction, platelet activation, hypercoagulation, and inflammation are common to both disorders. We assessed risk of placental abruption in relation to maternal history of migraine before and during pregnancy in Peruvian women. Methods Cases were 375 women with pregnancies complicated by placental abruption, and controls were 368 women without an abruption. During in-person interviews conducted following delivery, women were asked if they had physician-diagnosed migraine, and they were asked questions that allowed headaches and migraine to be classified according to criteria established by the International Headache Society. Logistic regression procedures were used to calculate odds ratios (aOR) and 95% confidence intervals (CI) adjusted for confounders. Results Overall, a lifetime history of any headaches or migraine was associated with an increased odds of placental abruption (aOR = 1.60; 95% CI 1.16-2.20). A lifetime history of migraine was associated with a 2.14-fold increased odds of placental abruption (aOR = 2.14; 95% CI 1.22-3.75). The odds of placental abruption was 2.11 (95% CI 1.00-4.45) for migraineurs without aura; and 1.59 (95% 0.70-3.62) for migraineurs with aura. A lifetime history of tension-type headache was also increased with placental abruption (aOR = 1.61; 95% CI 1.01-2.57). Conclusions This study adds placental abruption to a growing list of pregnancy complications associated with maternal headache/migraine disorders. Nevertheless, prospective cohort studies are needed to more rigorously evaluate the extent to which migraines and/or its treatments are associated with the occurrence of placental abruption.

Objetivo: Describir los resultados de la biopsia prostática transperineal por fusión de la resonancia magnética cognitiva y ultrasonido en la detección del cáncer. Materiales y métodos: Estudio de serie de casos, retrospectivo, realizado en Clínica Delgado entre julio del 2019 y octubre del 2021. Se incluyó pacientes con examen digital de próstata y/o Antígeno Prostático Específico anormal e imágenes de Resonancia Magnética de próstata con lesiones categoría PI-RADS 4 o 5. Excluyendo a pacientes con trastorno de coagulación, lesiones rectales, imposibilidad para abducción, comorbilidades para anestesia. Registramos las características clínicas, demográficas, datos de antígeno prostático específico, volumen de la próstata, lesiones PI-RADS, tasas de cáncer, complicaciones. Resultados: Se evaluaron 18 pacientes, con edad media de 69,33 ± 7,67 años. La media del antígeno prostático específico de 14,94 ± 12,42 ng/mL. La media del volumen de próstata de 57,72 ± 28,68 cc. Al examen digital de la próstata 16/18 (88.88 %) pacientes tenían sospecha de cáncer. Biopsias en pacientes con lesiones PI-RADS 4 en 6/18 (33,33%) y 5 en 12/18 (66,67%). Biopsia con 19 núcleos a 6/18 (33,33%) y 16 núcleos a 12/18 (66,67%) pacientes. Pacientes con cáncer 15/18 (83,33%), todos Adenocarcinoma Acinar, con Gleason 6 en 2/18 (11,11%) y Gleason ≥ 7 en 13/18 (72,22%) pacientes. Complicaciones leves como hematuria 1/18 (5,6%), disuria terminal 8/18 (44,4%) y molestia perineal 7/18 (38,8%) y ninguna infecciosa. Conclusiones: la biopsia prostática transperineal por fusión de imágenes de resonancia magnética cognitiva y ultrasonido es factible, segura, con tasas altas de positividad y sin infecciones.

Purpose: Despite the call to increase the number of radiation oncologists in Latin America, the quality, similarity, and number of residency training programs are unknown. We seek to describe the current state of residency programs in radiation oncology in Latin America. Methods and Materials: Latin American Residents in Radiation Oncology performed a cross-sectional analysis of universities and training centers for radiation oncologists in Latin America. Latin American Residents in Radiation Oncology members identified and contacted current residents and specialists at each center to obtain information and documents that described their training curricula. Results: As of 2020, 13 of 23 (56.5%) Latin American countries have radiation oncology training. Seventy-three training centers were identified (59 active and 14 inactive), associated with 28 universities. On average, each active center trains 2.6 new residents per year, and in total, 156 residents are trained annually. The average length of training programs is 3.6 years. Brazil and Mexico comprise 31 (52.5%) and 7 (11.9%) of active programs, respectively, and 64 (41.8%) and 50 (32.7%) residents, respectively. Training is available in 38 cities in 13 countries, and outside Brazil and Mexico, only 13 cities in 11 countries (9 capitals and 4 noncapital cities). Individualized curriculum documents were provided by 20 (83.3%) of 24 non-Brazilian programs, while 1 standardized guideline was provided for Brazilian training programs. These demonstrated variation between subjects taught, their devoted time, outside specialty rotations, and experiences in modern techniques. Seventy-five percent include volumetric modulated arc therapy, 70% stereotactic radiosurgery, and 55% stereotactic body radiation therapy training. One-hundred percent include gynecologic brachytherapy education and

Objetivo. Evaluar las estrategias didácticas usadas en las sesiones de aprendizaje del área de comunicación para desarrollar el pensamiento crítico en estudiantes de educación secundaria de instituciones educativas de la jurisdicción de Ocros. El desarrollo del aprendizaje en el siglo XXI exige que sus estudiantes desarrollen altos niveles de pensamiento y creatividad, utilizando diversas estrategias pedagógicas por parte de la comunidad docente. Metodología. Se utilizaron los diseños cuantitativo y cualitativo, por lo tanto, este estudio se caracteriza por ser de naturaleza mixta; triangulándose no solo datos, eventos y entrevistas aisladas, sino también el análisis y la reflexión pedagógica. Se utilizaron los diseños cuantitativo y cualitativo, los cuales permiten analizar e inferir cómo los docentes de la provincia de Ocros-Huaraz-Perú desarrollan la gestión del aula. Resultados y conclusión. El pensamiento crítico, en sus tres subcategorías: razonamiento, argumentación y toma de decisiones, permite afirmar que los docentes presentan fuertes debilidades en su proceso de conducción de los aprendizajes y los estudiantes carecen de herramientas cognitivas que posibiliten realizar una lectura crítica.

Abstract Background The amniotic fluid (AF) cell-free transcriptome is modulated by physiologic and pathologic processes during pregnancy. AF gene expression changes with advancing gestation reflect fetal development and organ maturation; yet, defining normal expression and splicing patterns for biomarker discovery in obstetrics requires larger heterogeneous cohorts, evaluation of potential confounding factors, and novel analytical approaches. Methods Women with a normal pregnancy who had an AF sample collected during midtrimester (n = 30) or at term gestation (n = 68) were included. Expression profiling at exon level resolution was performed using Human Transcriptome Arrays. Differential expression was based on moderated t-test adjusted p 1.25; for differential splicing, a splicing index > 2 and adjusted p 0.79, p

OBJECTIVE:To predict spontaneous preterm birth among pregnant women in an African American population using first trimester peripheral blood maternal immune cell microRNA. STUDY DESIGN:This was a retrospective nested case-control study in pregnant patients enrolled between March 2006 and October 2016. For initial study inclusion, samples were selected that met the following criteria: 1) singleton pregnancy; 2) maternal body mass index (BMI)

ObjectiveAmniotic fluid cytokines have been implicated in the mechanisms of preterm labor and birth. Cytokines can be packaged within or on the surface of extracellular vesicles. The main aim of this study was to test whether the protein abundance internal to and on the surface of extracellular vesicles changes in the presence of sterile intra-amniotic inflammation and proven intra-amniotic infection in women with preterm labor as compared to the women with preterm labor without either intra-amniotic inflammation or proven intra-amniotic infection.Study designWomen who had an episode of preterm labor and underwent an amniocentesis for the diagnosis of intra-amniotic infection or intra-amniotic inflammation were classified into three groups: 1) preterm labor without either intra-amniotic inflammation or proven intra-amniotic infection, 2) preterm labor with sterile intra-amniotic inflammation, and 3) preterm labor with intra-amniotic infection. The concentrations of 38 proteins were determined on the extracellular vesicle surface, within the vesicles, and in the soluble fraction of amniotic fluid.Results1) Intra-amniotic inflammation, regardless of detected microbes, was associated with an increased abundance of amniotic fluid cytokines on the extracellular vesicle surface, within vesicles, and in the soluble fraction. These changes were most prominent in women with proven intra-amniotic infection. 2) Cytokine changes on the surface of extracellular vesicles were correlated with those determined in the soluble fraction; yet the magnitude of the increase was significantly different between these compartments. 3) The performance of prediction models of early preterm delivery based on measurements on the extracellular vesicle surface was equivalent to those based on the soluble fraction.ConclusionsDifferential packaging of amniotic fluid cytokines in extracellular vesicles during preterm labor with sterile intra-amniotic inflammation or proven intra-amniotic infection is reported herein for the first time. The current study provides insights into the biology of the intra-amniotic fluid ad may aid in the development of biomarkers for obstetrical disease.

BackgroundIn comparison to the non-pregnant state, the first trimester of pregnancy is characterized by systemic adaptation of the mother. The extent to which these adaptive processes are reflected in the maternal blood metabolome is not well characterized.ObjectiveTo determine the differences between the plasma metabolome of non-pregnant and pregnant women before 16 weeks gestation.Study designThis study included plasma samples from 21 non-pregnant women and 50 women with a normal pregnancy (8-16 weeks of gestation). Combined measurements by ultrahigh performance liquid chromatography/tandem mass spectrometry and by gas chromatography/mass spectrometry generated molecular abundance measurements for each sample. Molecular species detected in at least 10 samples were included in the analysis. Differential abundance was inferred based on false discovery adjusted p-values (FDR) from Mann-Whitney-Wilcoxon U tests ResultsOverall, 637 small molecules met the inclusion criteria and were tested for association with pregnancy; 44% (281/637) of small molecules had significantly different abundance, of which 81% (229/281) were less abundant in pregnant than in non-pregnant women. Eight percent (14/169) of the metabolites that remained significant in the adjusted analysis also changed as a function of gestational age. A pathway analysis revealed enrichment in steroid metabolites related to sex hormones, caffeine metabolites, lysolipids, dipeptides, and polypeptide bradykinin derivatives (all, FDR < 0.1).ConclusionsThis high-throughput mass spectrometry study identified: 1) differences between pregnant vs. non-pregnant women in the abundance of 44% of the profiled plasma metabolites, including known and novel molecules and pathways; and 2) specific metabolites that changed with gestational age.

ObjectivesTo identify maternal plasma protein markers for early preeclampsia (delivery Study designThis longitudinal case-control study included 90 patients with a normal pregnancy and 33 patients with early preeclampsia. Two to six maternal plasma samples were collected throughout gestation from each woman. The abundance of 1,125 proteins was measured using high-affinity aptamer-based proteomic assays, and data were modeled using linear mixed-effects models. After data transformation into multiples of the mean values for gestational age, parsimonious linear discriminant analysis risk models were fit for each gestational-age interval (8-16, 16.1-22, 22.1-28, 28.1-32 weeks). Proteomic profiles of early preeclampsia cases were also compared to those of a combined set of controls and late preeclampsia cases (n = 76) reported previously. Prediction performance was estimated via bootstrap.ResultsWe found that 1) multi-protein models at 16.1-22 weeks of gestation predicted early preeclampsia with a sensitivity of 71% at a false-positive rate (FPR) of 10%. High abundance of matrix metalloproteinase-7 and glycoprotein IIbIIIa complex were the most reliable predictors at this gestational age; 2) at 22.1-28 weeks of gestation, lower abundance of placental growth factor (PlGF) and vascular endothelial growth factor A, isoform 121 (VEGF-121), as well as elevated sialic acid binding immunoglobulin-like lectin 6 (siglec-6) and activin-A, were the best predictors of the subsequent development of early preeclampsia (81% sensitivity, FPR = 10%); 3) at 28.1-32 weeks of gestation, the sensitivity of multi-protein models was 85% (FPR = 10%) with the best predictors being activated leukocyte cell adhesion molecule, siglec-6, and VEGF-121; 4) the increase in siglec-6, activin-A, and VEGF-121 at 22.1-28 weeks of gestation differentiated women who subsequently developed early preeclampsia from those who had a normal pregnancy or developed late preeclampsia (sensitivity 77%, FPR = 10%); 5) the sensitivity of risk models was higher for early preeclampsia with placental MVM lesions than for the entire early preeclampsia group (90% versus 71% at 16.1-22 weeks; 87% versus 81% at 22.1-28 weeks; and 90% versus 85% at 28.1-32 weeks, all FPR = 10%); and 6) the sensitivity of prediction models was higher for severe early preeclampsia than for the entire early preeclampsia group (84% versus 71% at 16.1-22 weeks).ConclusionWe have presented herein a catalogue of proteome changes in maternal plasma proteome that precede the diagnosis of preeclampsia and can distinguish among early and late phenotypes. The sensitivity of maternal plasma protein models for early preeclampsia is higher in women with underlying vascular placental disease and in those with a severe phenotype.

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BackgroundLate-onset preeclampsia is the most prevalent phenotype of this syndrome; nevertheless, only a few biomarkers for its early diagnosis have been reported. We sought to correct this deficiency using a high through-put proteomic platform.MethodsA case-control longitudinal study was conducted, including 90 patients with normal pregnancies and 76 patients with late-onset preeclampsia (diagnosed at ≥34 weeks of gestation). Maternal plasma samples were collected throughout gestation (normal pregnancy: 2-6 samples per patient, median of 2; late-onset preeclampsia: 2-6, median of 5). The abundance of 1,125 proteins was measured using an aptamers-based proteomics technique. Protein abundance in normal pregnancies was modeled using linear mixed-effects models to estimate mean abundance as a function of gestational age. Data was then expressed as multiples of-the-mean (MoM) values in normal pregnancies. Multi-marker prediction models were built using data from one of five gestational age intervals (8-16, 16.1-22, 22.1-28, 28.1-32, 32.1-36 weeks of gestation). The predictive performance of the best combination of proteins was compared to placental growth factor (PIGF) using bootstrap.Results1) At 8-16 weeks of gestation, the best prediction model included only one protein, matrix metalloproteinase 7 (MMP-7), that had a sensitivity of 69% at a false positive rate (FPR) of 20% (AUC = 0.76); 2) at 16.1-22 weeks of gestation, MMP-7 was the single best predictor of late-onset preeclampsia with a sensitivity of 70% at a FPR of 20% (AUC = 0.82); 3) after 22 weeks of gestation, PlGF was the best predictor of late-onset preeclampsia, identifying 1/3 to 1/2 of the patients destined to develop this syndrome (FPR = 20%); 4) 36 proteins were associated with late-onset preeclampsia in at least one interval of gestation (after adjustment for covariates); 5) several biological processes, such as positive regulation of vascular endothelial growth factor receptor signaling pathway, were perturbed; and 6) from 22.1 weeks of gestation onward, the set of proteins most predictive of severe preeclampsia was different from the set most predictive of the mild form of this syndrome.ConclusionsElevated MMP-7 early in gestation (8-22 weeks) and low PlGF later in gestation (after 22 weeks) are the strongest predictors for the subsequent development of late-onset preeclampsia, suggesting that the optimal identification of patients at risk may involve a two-step diagnostic process.

A propósito de la reciente promulgación de la Resolución Ministerial N.º 486-2014/Minsa, que aprueba la guía técnica nacional para el aborto terapéutico, se ha generado un gran debate al respecto. Como un aporte a la discusión, se presenta una revisión sobre las definiciones y tipos de aborto, para luego centrarse en el denominado ‘aborto terapéutico’ y explorar las dificultades que existen para definirlo. Finalmente, sepresentan algunas observaciones a esta Guía técnica emitida por el Minsa. Se concluye que el término ‘aborto terapéutico’ es anacrónico y contradictorio porque el aborto no es un tratamiento que asegure mejorar la salud de la mujer ni la del niño. El término apropiado debería ser ‘interrupción del embarazo por razones médicas’.

This article, published in the journal Ultrasound in Obstetrics & Gynecology, examines the effects of serial amnioinfusions (AI) on fetal lung size/volume and intrapulmonary circulation in fetuses diagnosed with anhydramnios before 22 weeks of gestation. The study involved nine fetuses with anhydramnios due to renal agenesis or renal dysplasia, who received serial AI to maintain an amniotic fluid index (AFI) of 15-17 cm until 32 weeks or preterm premature rupture of membranes (PPROM). The results showed that there was an increase in lung size and improvement in intrapulmonary circulation after the AI, but the lung measurements remained below the expected mean for gestational age. [Extracted from the article]

Objetivo: Determinar si el empleo de la sutura compresiva del útero (técnica de B-Lynch) durante la cesárea en casos de atonía uterina disminuye la pérdida sanguínea y evita la histerectomía posparto. Material y Métodos: Estudio retrospectivo de las cesáreas que cursaron con atonía uterina durante la intervención, desde el 1 de enero de 1990 al 31 de diciembre de 2003, en el Hospital San Bartolomé de Lima. El método estándar de manejo de la atonía uterina en la cesárea consiste en el masaje uterino, el empleo de agentes uterotónicos (ocitocina, prostaglandinas), ligadura de arterias uterinas/hipogástricas y la histerectomía posparto. Las variables maternas y perinatales obtenidas de las historias clínicas fueron ingresadas a una base de datos computarizado (SPSS versión 10). Resultados: Se identificó 46 casos: en 30 se empleó la técnica B-Lynch y en 16 el método estándar. No hubo diferencias en las características maternas entre ambos grupos. El grupo de B-Lynch presentó subjetivamente menor perdida sanguínea, recibió menor número de unidades de sangre transfundida y presentó significativo menor riesgo de histerectomía posparto comparado con el método estándar (promedio ± DE: 1144,4±311,7 mL vs 1666,9±794,4 mL, p

Objetivo: Identificar los factores etiopatogénicos asociados a la muerte fetal y neonatal de una población de la ciudad de Lima, Perú. Lugar: Hospital San Bartolomé en Lima, entre 1 de enero de 1996 y 31 de diciembre de 2000. Material y Métodos: Estudio retrospectivo de todos los casos de muerte fetal mayor de 20 semanas de gestación y muerte neonatal antes de los 28 días de nacimiento sometidos a estudio de autopsia y anatomía patológica. Resultados: La prevalencia de muerte fetal fue 1,68% (508/30125) y de muerte neonatal 1,44% (434/30125). Todas las muertes fetales y 58,8% (255/434) de las muertes neonatales tuvieron autopsia. De 508 muertes fetales, 92 (18%) presentaron signos de autólisis, que no permitieron una apropiada identificación de los procesos etiopatogénicos involucrados. Las muertes fetales estuvieron asociadas a prematuridad (60,5%), defecto nutricional/vascular (78,1%), privación social (60,8%), anomalías congénitas anatómicas (14,6%) y respuesta inflamatoria (12,9%). La muerte neonatal estuvo asociada a la prematuridad (71,7%), privación social (61,1%), defecto nutricional/vascular (59,6%), anomalía congénita anatómica (28,6%), respuesta inflamatoria (20,0%). Conclusiones: La muerte fetal es consecuencia de factores patogénicos que interactúan tempranamente con la unidad madre-embrión/feto. La mayoría de los tejidos muertos de los fetos/neonatos muestra manifestaciones de varios factores etiopatogénicos en forma simultánea.

Abstract The cell-free transcriptome in amniotic fluid (AF) has been shown to be informative of physiologic and pathologic processes in pregnancy; however, the change in AF proteome with gestational age has mostly been studied by targeted approaches. The objective of this study was to describe the gestational age-dependent changes in the AF proteome during normal pregnancy by using an omics platform. The abundance of 1310 proteins was measured on a high-throughput aptamer-based proteomics platform in AF samples collected from women during midtrimester (16–24 weeks of gestation, n = 15) and at term without labor (37–42 weeks of gestation, n = 13). Only pregnancies without obstetrical complications were included in the study. Almost 25% (320) of AF proteins significantly changed in abundance between the midtrimester and term gestation. Of these, 154 (48.1%) proteins increased, and 166 (51.9%) decreased in abundance at term compared to midtrimester. Tissue-specific signatures of the trachea, salivary glands, brain regions, and immune system were increased while those of the gestational tissues (uterus, placenta, and ovary), cardiac myocytes, and fetal liver were decreased at term compared to midtrimester. The changes in AF protein abundance were correlated with those previously reported in the cell-free AF transcriptome. Intersecting gestational age-modulated AF proteins and their corresponding mRNAs previously reported in the maternal blood identified neutrophil-related protein/mRNA pairs that were modulated in the same direction. The first study to utilize an aptamer-based assay to profile the AF proteome modulation with gestational age, it reveals that almost one-quarter of the proteins are modulated as gestation advances, which is more than twice the fraction of altered plasma proteins (~ 10%). The results reported herein have implications for future studies focused on discovering biomarkers to predict, monitor, and diagnose obstetrical diseases.

Abstract The amniotic fluid (AF) cell-free RNA was shown to reflect physiological and pathological processes in pregnancy, but its value in the prediction of spontaneous preterm delivery is unknown. Herein we profiled cell-free RNA in AF samples collected from women who underwent transabdominal amniocentesis after an episode of spontaneous preterm labor and subsequently delivered within 24 h (n = 10) or later (n = 28) in gestation. Expression of known placental single-cell RNA-Seq signatures was quantified in AF cell-free RNA and compared between the groups. Random forest models were applied to predict time-to-delivery after amniocentesis. There were 2385 genes differentially expressed in AF samples of women who delivered within 24 h of amniocentesis compared to gestational age-matched samples from women who delivered after 24 h of amniocentesis. Genes with cell-free RNA changes were associated with immune and inflammatory processes related to the onset of labor, and the expression of placental single-cell RNA-Seq signatures of immune cells was increased with imminent delivery. AF transcriptomic prediction models captured these effects and predicted delivery within 24 h of amniocentesis (AUROC = 0.81). These results may inform the development of biomarkers for spontaneous preterm birth.

Introduction: Malnutrition in hemodialysis patients is a consequence of various deficiency andhypercatabolic factors and constitutes a risk factor for morbidity and mortality. Objective: Determinethe association between hypoalbuminemia and hypophosphatemia with the Subjective globalassessment (SGA) C in patients with chronic renal disease on hemodialysis. Methods: Analytical cross-sectional study. Patients from the hemodialysis service of the Hospital Guillermo Almenara werestudied. The Kruskal-Wallis test and multiple comparisons test were used for the association betweencontinuous variables of malnutrition and the types of SGA. The square-chi test was used for thecategorical variables hypoalbuminemia (≤3.5 g/dL) and hypophosphatemia (

Pregnancy represents a unique immunological state in which the mother adapts to tolerate the semi-allogenic conceptus; yet, the cellular dynamics in the maternal circulation are poorly understood. Using exon-level expression profiling of up to six longitudinal whole blood samples from 49 pregnant women, we undertook a systems biology analysis of the cellular transcriptome dynamics and its correlation with the plasma proteome. We found that: (1) chromosome 14 was the most enriched in transcripts differentially expressed throughout normal pregnancy; (2) the strongest expression changes followed three distinct longitudinal patterns, with genes related to host immune response (e.g., MMP8, DEFA1B, DEFA4, and LTF) showing a steady increase in expression from 10 to 40 weeks of gestation; (3) multiple biological processes and pathways related to immunity and inflammation were modulated during gestation; (4) genes changing with gestation were among those specific to T cells, B cells, CD71+ erythroid cells, natural killer cells, and endothelial cells, as defined based on the GNF Gene Expression Atlas; (5) the average expression of mRNA signatures of T cells, B cells, and erythroid cells followed unique patterns during gestation; (6) the correlation between mRNA and protein abundance was higher for mRNAs that were differentially expressed throughout gestation than for those that were not, and significant mRNA-protein correlations were observed for genes part of the T-cell signature. In summary, unique changes in immune-related genes were discovered by longitudinally assessing the cellular transcriptome in the maternal circulation throughout normal pregnancy, and positive correlations were noted between the cellular transcriptome and plasma proteome for specific genes/proteins. These findings provide insights into the immunobiology of normal pregnancy.

Abstract Background Gestational diabetes mellitus (GDM) is a global public health concern with potential implications for the health of a mother and her offspring. However, data on the prevalence and risk factors of GDM in Latin America are scarce. The study was designed to estimate the prevalence of GDM and identify maternal risk factors among Peruvian women. Methods A cross-sectional study was conducted among 1300 pregnant women attending a prenatal clinic in Lima, Peru. GDM was diagnosed using an Oral Glucose Tolerance Test (OGTT) performed between 24 and 28 gestational weeks using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Depression status was assessed using the Patient Health Questionnaire-9. Multivariate logistic regression models were used to identify risk factors of GDM. Results Approximately 16% of pregnant women were diagnosed with GDM. The prevalence of obesity and depression were 24.4 and 10.6%, respectively. After adjusting for confounders, mid-pregnancy obesity was associated with a 1.64-fold increased odds of GDM (OR: 1.64; 95% CI: 1.03–2.61). Participants with a family history of diabetes had a 1.5-fold increased odds of developing GDM (OR: 1.51, 95% CI: 1.10–2.07) as compared to women without this family history. Depression was associated with a 1.54-fold increased odds of GDM (OR: 1.54; 95% CI:1.09–2.17). Conclusions GDM is highly prevalent and was associated with maternal obesity, family history of diabetes and antepartum depression among Peruvian women. Intervention programs aimed at early diagnoses and management of GDM need to take maternal obesity, family history of diabetes and antepartum depression into account.

Introducción: La depresión posparto y la violencia basada en género son patologías muy frecuentes en la mujer; la importancia de un diagnóstico y tratamiento oportuno radica en evitar las consecuencias a futuro en la mujer, el recién nacido y la familia en general. Objetivos: Determinar la asociación entre depresión posparto y la violencia basada en género. Diseño: Exploratorio, de corte transversal. Lugar: Hospital Nacional Docente Madre Niño San Bartolomé, Lima, Perú. Participantes: Mujeres puérperas. Intervenciones: Se aplicó una ficha de datos sociodemográficos y del parto, la escala de Edimburgo, el inventario revisado de factores predictores de depresión posparto y el instrumento de detección de violencia basada en género a 100 mujeres, de 1 a 12 meses de tiempo puerperal. Principales medidas de resultados: Asociación entre depresión posparto y violencia basada en género. Resultados: La tasa de depresión posparto fue 17%, encontrando diferencias estadísticas al compararla con autoestima, depresión previa al embarazo, ansiedad durante la gestación, satisfacción marital y eventos estresantes durante la gestación. El 51% fue víctima de violencia basada en género, siendo la más frecuente la forma psicológica. Se halló diferencias estadísticas entre depresión posparto y violencia basada en género (p=0,001), así como, diferencias estadísticas entre depresión posparto y violencia durante la gestación, encontrando un OR de 5,5 (IC: < 5,5; 16,7>). Conclusiones: Las mujeres víctimas de violencia tienen riesgo elevado de sufrir depresión posparto.

Objetivo: Demostrar que la privación social y afectiva en la madre se asocia a restricción del crecimiento fetal, muerte fetal, parto pretérmino, alteraciones anatómicas y funcionales en el feto y recién nacido. Materiales y Métodos: Estudio retrospectivo en el que se analizó la base de datos materno-perinatal del Hospital San Bartolomé. Se examinó tres grupos de gestantes con privación social y afectiva: 1) madres solteras (n=6561), 2) gestantes adolescentes con ausencia de control prenatal (n=2131) y 3) primigestas con talla menor de 160 cm (n=35722). Se comparó las complicaciones maternas y perinatales con las gestantes : 1) madres con unión estable (n=40629), 2) gestantes adolescentes con control prenatal (n=7644) y 3) primigestas con talla mayor de 159 cm (n=5264). Se empleó el odds ratio (OR) y el intervalo de confianza al 95% (IC). Resultados: Las madres solteras presentaron mayor riesgo de falla en la función placentaria (OR 1,92, IC95% 1,51-2,44), restricción del crecimiento fetal (OR 2,02, IC95% 1,45-2,82), rotura prematura de membranas fetales (OR 1,28, IC95% 1,00-1,63) comparadas con las madres con unión de pareja estable. Las gestantes adolescentes con ausencia de control prenatal presentaron mayor riesgo de muerte fetal (OR 2,89, CI95% 1,85-4,50), rotura prematura de membranas fetales (OR 1,38, CI95% 1,18-1,62), parto pretérmino (OR 1,63, CI95% 1,39-1,91), neonato pequeño para la edad (OR 1,25, IC95% 1,08-1,44), morbilidad neonatal (OR 1,23, IC95% 1,07-1,41), asfixia perinatal (OR 2,73, IC95% 1,33-5,58), neonato con Ápgar bajo en minuto 1 (OR 1,26, IC95% 1,05-1,52), dificultad respiratoria (OR 1,51, IC95% 1,10-2,06), sepsis neonatal (OR 1,54, IC95% 1,19-1,99), prematuridad (OR 1,50, IC95% 1,27-1,78), muerte neonatal (OR 2,56, IC95% 1,88-3,48) y muerte perinatal (OR 3,02, IC95% 2,24-4,07) comparadas con las gestantes adolescentes con control prenatal. Las primigestas con talla menor de 160 cm presentaron mayor riesgo de ausencia de control prenatal (OR 1,22, IC95% 1,13-1,32), parto pretérmino (OR 1,12, IC95% 1,00-1,26), desproporción fetopélvica (OR 1,49, IC95% 1,11-2,02), parto por cesárea (OR 1,28, IC95% 1,19-1,38), Ápgar bajo en minuto 1 (OR 1,20, IC95% 1,07-1,35), recién nacido pequeño para la edad (OR 1,29, IC95% 1,17-1,42) y recién nacido prematuro (OR 1,12, IC95% 1,00-1,26) comparadas con la primigesta con talla mayor de 159 cm. Conclusiones: Las mujeres con falta de apoyo social y afectivo, como son las madres solteras, las mujeres adolescentes sin cuidado prenatal y las mujeres de talla baja, presentan riesgo aumentado en la salud materna y perinatal. Estos resultados sugieren que la privación social y/o afectiva en la madre repercute negativamente en el resultado perinatal, generando alteraciones anatómicas y funcionales en el feto y recién nacido.

Objetivo: Establecer los valores del peso al nacer de un grupo de recién nacidos sanos hijos de mujeres residentes en Lima que tuvieron embarazos simples sin complicaciones obstétricas ni neonatales. Materiales y Métodos: Se realizó un estudio retrospectivo, analítico y transversal, en el cual se revisó la base de datos maternas y perinatales del Departamento de Obstetricia y Pediatría del Hospital Nacional Docente Madre-Niño San Bartolomé entre el 1 de enero 1991 y el 31 de diciembre de 1999 (SIP). Se seleccionó los embarazos simples de mujeres entre 20 y 30 años, con IMC entre 20 y 25 kg/mt², sin patología materna previa y sin complicaciones obstétricas, con variación ± 2 semanas entre FUR y examen físico del neonato vivo y sano. Resultados: El peso al nacer de 5 443 recién nacidos sanos en Lima [percentil 50 [percentil 10-percentil 90]) a las 35, 36, 37, 38, 39, 40, 41 y 42 semanas fueron 2640 (2346-3356), 2850 (2430-3344), 3100 (2688-3632), 3200 (2770-3700), 3300 (2850-3770), 3370 (2950-3850), 3450 (3030-3980) , 3512 (3102 - 4000) gramos. Los fetos varones a término sanos pesaron en promedio 108 gramos más que los femeninos (p

Objetivo: Establecer los valores del índice ponderal (IP) de un grupo de recién nacidos sanos hijos de mujeres peruanas residentes en Lima, que tuvieron embarazos simples sanos. Materiales y Métodos: Estudio retrospectivo, analítico y transversal, en el cual se revisó la base de datos maternas y perinatales SIP del Departamento de Obstetricia y Pediatría del Hospital Nacional Docente Madre-Niño "San Bartolomé", entre el 1 de enero de 1991 y el 31 de diciembre de 1999. Se seleccionó los embarazos simples de mujeres sanas entre 20 y 30 años, con IMC entre 20 y 25, sin complicaciones obstétricas, con diferencia ± 2 semanas entre la fecha de última regla y edad gestacional por examen físico del neonato vivo y sano. Se definió IP como peso al nacer en gramos x 100/[talla en cm]³. Resultados: El índice ponderal [percentil 50 (percentil 10-percentil 90)] de 5,443 recién nacidos sanos en Lima para gestaciones de 35,36, 37,38, 39, 40, 41 y 42 semanas fueron 2,55 (2,22-2,84), 2,59 (2,36-3,04), 2,71 (2,42-3,03), 2,73 (2,44-3,05), 2,72 (2,44-3,05), 2,74 (2,44-3,06), 2,79 (2,45-3,03) y 2,79 (2,42-3,03) g/cm³ , respectivamente. El IP en fetos a término fue mayor en las multíparas que en las nulíparas (p

OBJETIVOS: 1) Conocer las características maternas y la asociación de la flora microbiana vaginal (FMV) en gestantes con riesgo alto de prematuridad (GAP); y, 2) Determinar la asociación de la FMV y el resultado materno-perinatal en dichas gestantes. DISEÑO: Estudio caso-control, desde enero 1994 hasta diciembre 1995. MATERIAL Y MÉTODOS: El grupo de casos incluyó 238 madres con gestaciones simples, internadas por amenaza de parto pretérmino, fluido vaginal aumentado, pielonefritis aguda e hipertensión arterial, a quienes se realizó estudio directo en lámina de la FMV. El grupo control consistió en 3 850 gestantes con feto único que tuvieron parto a término en el mismo período. Las gestantes del grupo de casos fueron separadas en aquellas que presentaron vaginitis bacteriana (n=136), vaginosis bacteriana (VB, n=57) y trichomonas vaginalis (TV, n=45). RESULTADOS: Las gestantes con TV y aquellas con VB tenían una pareja sexual. Los casos presentaron mayor riesgo de malnutrición materna, peso materno bajo, un familiar diabético/hipertenso crónico, prediabetes, anemia crónica, amenaza de aborto, cicatriz uterina, fiebre puerperal y endometritis. Los neonatos de los casos presentaron mayor riesgo de hiperbilirrubinemia, sepsis neonatal, prematuridad, dificultad respiratoria, morbilidad neonatal, infante pequeño y grande para la edad de gestación. CONCLUSIONES: La herencia y el medio ambiente determinan el estado de nutrición, el tipo de flora microbiana vaginal y la respuesta inflamatoria del huésped (madre/feto). La respuesta del huésped a varios factores estresores sería la responsable del síndrome del parto pretérmino, la prematuridad y la morbilidad neonatal.

Objective: To predict spontaneous preterm birth among pregnant women in an African American population using first trimester peripheral blood maternal immune cell microRNA., Study Design: This was a retrospective nested case-control study in pregnant patients enrolled between March 2006 and October 2016. For initial study inclusion, samples were selected that met the following criteria: 1) singleton pregnancy; 2) maternal body mass index (BMI) <30 kg/m2; 3) blood sample drawn between 6 weeks to 12 weeks 6 days gestation; 4) live born neonate with no detectable birth defects. Using these entry criteria, 486 samples were selected for study inclusion. After sample quality was confirmed, 139 term deliveries (38-42 weeks) and 18 spontaneous preterm deliveries (<35 weeks) were selected for analysis. Samples were divided into training and validation sets. Real time reverse transcription quantitative polymerase chain reaction (rt-qPCR) was performed on each sample for 45 microRNAs. MicroRNA Risk Scores were calculated on the training set and area-under-the-curve receiver-operating-characteristic (AUC-ROC) curves were derived from the validation set., Results: The AUC-ROC for the validation set delivering preterm was 0.80 (95% CI: 0.69 to 0.88; p = 0.0001), sensitivity 0.89, specificity of 0.71 and a mean gestational age of 10.0 ±1.8 weeks (range: 6.6-12.9 weeks). When the validation population was divided by gestational age at the time of venipuncture into early first trimester (mean 8.4 ±1.0 weeks; range 6.6-9.7 weeks) and late first trimester (mean 11.5±0.8 weeks; range 10.0-12.9 weeks), the AUC-ROC scores for early and late first trimester were 0.79 (95% CI: 0.63 to 0.91) and 0.81 (95% CI: 0.66 to 0.92), respectively., Conclusion: Quantification of first trimester peripheral blood MicroRNA identifies risk of spontaneous preterm birth in samples obtained early and late first trimester of pregnancy in an African American population., Competing Interests: E.E.W and J.L.R. are co-inventors on US Patent #20130245135 entitled: “Methods and compositions for assessing patients with preeclampsia-related conditions using microRNA”. X.J., N.G, P.P. and R.R. have no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The amniotic fluid (AF) cell-free transcriptome is modulated by physiologic and pathologic processes during pregnancy. AF gene expression changes with advancing gestation reflect fetal development and organ maturation; yet, defining normal expression and splicing patterns for biomarker discovery in obstetrics requires larger heterogeneous cohorts, evaluation of potential confounding factors, and novel analytical approaches., Methods: Women with a normal pregnancy who had an AF sample collected during midtrimester (n = 30) or at term gestation (n = 68) were included. Expression profiling at exon level resolution was performed using Human Transcriptome Arrays. Differential expression was based on moderated t-test adjusted p < 0.05 and fold change > 1.25; for differential splicing, a splicing index > 2 and adjusted p < 0.05 were required. Functional profiling was used to interpret differentially expressed or spliced genes. The expression of tissue-specific and cell-type specific signatures defined by single-cell genomics was quantified and correlated with covariates. In-silico validation studies were performed using publicly available datasets., Results: 1) 64,071 genes were detected in AF, with 11% of the coding and 6% of the non-coding genes being differentially expressed between midtrimester and term gestation. Expression changes were highly correlated with those previously reported (R > 0.79, p < 0.001) and featured increased expression of genes specific to the trachea, salivary glands, and lung and decreased expression of genes specific to the cardiac myocytes, uterus, and fetal liver, among others. 2) Single-cell RNA-seq signatures of the cytotrophoblast, Hofbauer cells, erythrocytes, monocytes, T and B cells, among others, showed complex patterns of modulation with gestation (adjusted p < 0.05). 3) In 17% of the genes detected, we found differential splicing with advancing gestation in genes related to brain development processes and immunity pathways, including some that were missed based on differential expression analysis alone., Conclusions: This represents the largest AF transcriptomics study in normal pregnancy, reporting for the first time that single-cell genomic signatures can be tracked in the AF and display complex patterns of expression during gestation. We also demonstrate a role for alternative splicing in tissue-identity acquisition, organ development, and immune processes. The results herein may have implications for the development of fetal testing to assess placental function and fetal organ maturity.

Objective: Amniotic fluid cytokines have been implicated in the mechanisms of preterm labor and birth. Cytokines can be packaged within or on the surface of extracellular vesicles. The main aim of this study was to test whether the protein abundance internal to and on the surface of extracellular vesicles changes in the presence of sterile intra-amniotic inflammation and proven intra-amniotic infection in women with preterm labor as compared to the women with preterm labor without either intra-amniotic inflammation or proven intra-amniotic infection., Study Design: Women who had an episode of preterm labor and underwent an amniocentesis for the diagnosis of intra-amniotic infection or intra-amniotic inflammation were classified into three groups: 1) preterm labor without either intra-amniotic inflammation or proven intra-amniotic infection, 2) preterm labor with sterile intra-amniotic inflammation, and 3) preterm labor with intra-amniotic infection. The concentrations of 38 proteins were determined on the extracellular vesicle surface, within the vesicles, and in the soluble fraction of amniotic fluid., Results: 1) Intra-amniotic inflammation, regardless of detected microbes, was associated with an increased abundance of amniotic fluid cytokines on the extracellular vesicle surface, within vesicles, and in the soluble fraction. These changes were most prominent in women with proven intra-amniotic infection. 2) Cytokine changes on the surface of extracellular vesicles were correlated with those determined in the soluble fraction; yet the magnitude of the increase was significantly different between these compartments. 3) The performance of prediction models of early preterm delivery based on measurements on the extracellular vesicle surface was equivalent to those based on the soluble fraction., Conclusions: Differential packaging of amniotic fluid cytokines in extracellular vesicles during preterm labor with sterile intra-amniotic inflammation or proven intra-amniotic infection is reported herein for the first time. The current study provides insights into the biology of the intra-amniotic fluid ad may aid in the development of biomarkers for obstetrical disease., Competing Interests: The authors have declared that no competing interests exist.

Pregnancy represents a unique immunological state in which the mother adapts to tolerate the semi-allogenic conceptus; yet, the cellular dynamics in the maternal circulation are poorly understood. Using exon-level expression profiling of up to six longitudinal whole blood samples from 49 pregnant women, we undertook a systems biology analysis of the cellular transcriptome dynamics and its correlation with the plasma proteome. We found that: (1) chromosome 14 was the most enriched in transcripts differentially expressed throughout normal pregnancy; (2) the strongest expression changes followed three distinct longitudinal patterns, with genes related to host immune response (e.g., MMP8, DEFA1B, DEFA4 , and LTF ) showing a steady increase in expression from 10 to 40 weeks of gestation; (3) multiple biological processes and pathways related to immunity and inflammation were modulated during gestation; (4) genes changing with gestation were among those specific to T cells, B cells, CD71+ erythroid cells, natural killer cells, and endothelial cells, as defined based on the GNF Gene Expression Atlas; (5) the average expression of mRNA signatures of T cells, B cells, and erythroid cells followed unique patterns during gestation; (6) the correlation between mRNA and protein abundance was higher for mRNAs that were differentially expressed throughout gestation than for those that were not, and significant mRNA-protein correlations were observed for genes part of the T-cell signature. In summary, unique changes in immune-related genes were discovered by longitudinally assessing the cellular transcriptome in the maternal circulation throughout normal pregnancy, and positive correlations were noted between the cellular transcriptome and plasma proteome for specific genes/proteins. These findings provide insights into the immunobiology of normal pregnancy., (Copyright © 2019 Gomez-Lopez, Romero, Hassan, Bhatti, Berry, Kusanovic, Pacora and Tarca.)

Background: In comparison to the non-pregnant state, the first trimester of pregnancy is characterized by systemic adaptation of the mother. The extent to which these adaptive processes are reflected in the maternal blood metabolome is not well characterized., Objective: To determine the differences between the plasma metabolome of non-pregnant and pregnant women before 16 weeks gestation., Study Design: This study included plasma samples from 21 non-pregnant women and 50 women with a normal pregnancy (8-16 weeks of gestation). Combined measurements by ultrahigh performance liquid chromatography/tandem mass spectrometry and by gas chromatography/mass spectrometry generated molecular abundance measurements for each sample. Molecular species detected in at least 10 samples were included in the analysis. Differential abundance was inferred based on false discovery adjusted p-values (FDR) from Mann-Whitney-Wilcoxon U tests <0.1 and a minimum median abundance ratio (fold change) of 1.5. Alternatively, metabolic data were quantile normalized to remove sample-to-sample differences in the overall metabolite abundance (adjusted analysis)., Results: Overall, 637 small molecules met the inclusion criteria and were tested for association with pregnancy; 44% (281/637) of small molecules had significantly different abundance, of which 81% (229/281) were less abundant in pregnant than in non-pregnant women. Eight percent (14/169) of the metabolites that remained significant in the adjusted analysis also changed as a function of gestational age. A pathway analysis revealed enrichment in steroid metabolites related to sex hormones, caffeine metabolites, lysolipids, dipeptides, and polypeptide bradykinin derivatives (all, FDR < 0.1)., Conclusions: This high-throughput mass spectrometry study identified: 1) differences between pregnant vs. non-pregnant women in the abundance of 44% of the profiled plasma metabolites, including known and novel molecules and pathways; and 2) specific metabolites that changed with gestational age., Competing Interests: BI is employed by Metabolon Inc., who provided the metabolomics profiling on a pay for service basis. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: To identify maternal plasma protein markers for early preeclampsia (delivery <34 weeks of gestation) and to determine whether the prediction performance is affected by disease severity and presence of placental lesions consistent with maternal vascular malperfusion (MVM) among cases., Study Design: This longitudinal case-control study included 90 patients with a normal pregnancy and 33 patients with early preeclampsia. Two to six maternal plasma samples were collected throughout gestation from each woman. The abundance of 1,125 proteins was measured using high-affinity aptamer-based proteomic assays, and data were modeled using linear mixed-effects models. After data transformation into multiples of the mean values for gestational age, parsimonious linear discriminant analysis risk models were fit for each gestational-age interval (8-16, 16.1-22, 22.1-28, 28.1-32 weeks). Proteomic profiles of early preeclampsia cases were also compared to those of a combined set of controls and late preeclampsia cases (n = 76) reported previously. Prediction performance was estimated via bootstrap., Results: We found that 1) multi-protein models at 16.1-22 weeks of gestation predicted early preeclampsia with a sensitivity of 71% at a false-positive rate (FPR) of 10%. High abundance of matrix metalloproteinase-7 and glycoprotein IIbIIIa complex were the most reliable predictors at this gestational age; 2) at 22.1-28 weeks of gestation, lower abundance of placental growth factor (PlGF) and vascular endothelial growth factor A, isoform 121 (VEGF-121), as well as elevated sialic acid binding immunoglobulin-like lectin 6 (siglec-6) and activin-A, were the best predictors of the subsequent development of early preeclampsia (81% sensitivity, FPR = 10%); 3) at 28.1-32 weeks of gestation, the sensitivity of multi-protein models was 85% (FPR = 10%) with the best predictors being activated leukocyte cell adhesion molecule, siglec-6, and VEGF-121; 4) the increase in siglec-6, activin-A, and VEGF-121 at 22.1-28 weeks of gestation differentiated women who subsequently developed early preeclampsia from those who had a normal pregnancy or developed late preeclampsia (sensitivity 77%, FPR = 10%); 5) the sensitivity of risk models was higher for early preeclampsia with placental MVM lesions than for the entire early preeclampsia group (90% versus 71% at 16.1-22 weeks; 87% versus 81% at 22.1-28 weeks; and 90% versus 85% at 28.1-32 weeks, all FPR = 10%); and 6) the sensitivity of prediction models was higher for severe early preeclampsia than for the entire early preeclampsia group (84% versus 71% at 16.1-22 weeks)., Conclusion: We have presented herein a catalogue of proteome changes in maternal plasma proteome that precede the diagnosis of preeclampsia and can distinguish among early and late phenotypes. The sensitivity of maternal plasma protein models for early preeclampsia is higher in women with underlying vascular placental disease and in those with a severe phenotype., Competing Interests: The authors have declared that no competing interests exist. ALT, TC, SSH, and RR are co-authors of an invention disclosure based on results from this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

While there is consistent evidence that episodes of physical exertion are associated with an immediately higher risk of acute ischemic vascular events, the risk of placental abruption immediately following episodes of physical exertion has not been studied. In a multicenter case-crossover study, we interviewed 663 women with placental abruption at 7 Peruvian hospitals between January 2013 and August 2015. We asked women about physical exertion in the hour before symptom onset and compared this with their frequency of physical exertion over the prior week. Compared with times with light or no exertion, the risk of placental abruption was 7.8 (95% confidence interval (CI): 5.5, 11.0) times greater in the hour following moderate or heavy physical exertion. The instantaneous incidence rate ratio of placental abruption within an hour of moderate or heavy physical exertion was lower for women who habitually engaged in moderate or heavy physical activity more than 3 times per week in the year before pregnancy (rate ratio (RR) = 3.0, 95% CI: 1.6, 5.9) compared with more sedentary women (RR = 17.3, 95% CI: 11.3, 26.7; P for homogeneity < 0.001), and the rate ratio was higher among women with preeclampsia/eclampsia (RR = 13.6, 95% CI: 7.0, 26.2) than among women without (RR = 6.7, 95% CI: 4.4, 10.0; P for homogeneity = 0.07).

Background: Late-onset preeclampsia is the most prevalent phenotype of this syndrome; nevertheless, only a few biomarkers for its early diagnosis have been reported. We sought to correct this deficiency using a high through-put proteomic platform., Methods: A case-control longitudinal study was conducted, including 90 patients with normal pregnancies and 76 patients with late-onset preeclampsia (diagnosed at ≥34 weeks of gestation). Maternal plasma samples were collected throughout gestation (normal pregnancy: 2-6 samples per patient, median of 2; late-onset preeclampsia: 2-6, median of 5). The abundance of 1,125 proteins was measured using an aptamers-based proteomics technique. Protein abundance in normal pregnancies was modeled using linear mixed-effects models to estimate mean abundance as a function of gestational age. Data was then expressed as multiples of-the-mean (MoM) values in normal pregnancies. Multi-marker prediction models were built using data from one of five gestational age intervals (8-16, 16.1-22, 22.1-28, 28.1-32, 32.1-36 weeks of gestation). The predictive performance of the best combination of proteins was compared to placental growth factor (PIGF) using bootstrap., Results: 1) At 8-16 weeks of gestation, the best prediction model included only one protein, matrix metalloproteinase 7 (MMP-7), that had a sensitivity of 69% at a false positive rate (FPR) of 20% (AUC = 0.76); 2) at 16.1-22 weeks of gestation, MMP-7 was the single best predictor of late-onset preeclampsia with a sensitivity of 70% at a FPR of 20% (AUC = 0.82); 3) after 22 weeks of gestation, PlGF was the best predictor of late-onset preeclampsia, identifying 1/3 to 1/2 of the patients destined to develop this syndrome (FPR = 20%); 4) 36 proteins were associated with late-onset preeclampsia in at least one interval of gestation (after adjustment for covariates); 5) several biological processes, such as positive regulation of vascular endothelial growth factor receptor signaling pathway, were perturbed; and 6) from 22.1 weeks of gestation onward, the set of proteins most predictive of severe preeclampsia was different from the set most predictive of the mild form of this syndrome., Conclusions: Elevated MMP-7 early in gestation (8-22 weeks) and low PlGF later in gestation (after 22 weeks) are the strongest predictors for the subsequent development of late-onset preeclampsia, suggesting that the optimal identification of patients at risk may involve a two-step diagnostic process.