Effect of a model based on education and teleassistance for the management of obstetric emergencies in 10 rural populations from Colombia.

Introduction: Pregnant women and health providers in rural areas of low-income and middle-income countries face multiple problems concerning high-quality obstetric care. This study was performed to identify changes in maternal and perinatal indicators after implementing a model based on education and telecare between a high-complexity hospital in 10 low-complexity hospitals in a southwestern region of Colombia. Methods: A quasiexperimental study with a historic control group and without a pretest was conducted between 2017 and 2019 to make comparisons before and after obstetric emergency care through the use of teleassistance from 10 primary care centers to the referral center (Fundación Valle del Lili, FVL). Results: A total of 470 patients were treated before teleassistance implementation and 154 patients were treated after teleassistance implementation. After program implementation, the maternal clinical indicators showed a 65% reduction in the number of obstetric patients who were referred with obstetric emergencies. The severity of maternal disease that was measured at the time of admission to level IV through the Modified Early Obstetric Warning System score was observed to decrease. Conclusion: The implementation of a model based on education and teleassistance between low-complexity hospitals and tertiary care centers generated changes in indicators that reflect greater access to rural areas, lower morbidity at the time of admission, and a decrease in the total number of emergency events.

Toward a new taxonomy of obstetrical disease: improved performance of maternal blood biomarkers for the great obstetrical syndromes when classified according to placental pathology.

BACKGROUND: The major challenge for obstetrics is the prediction and prevention of the great obstetrical syndromes. We propose that defining obstetrical diseases by the combination of clinical presentation and disease mechanisms as inferred by placental pathology will aid in the discovery of biomarkers and add specificity to those already known. OBJECTIVE: To describe the longitudinal profile of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and the PlGF/sFlt-1 ratio throughout gestation, and to determine whether the association between abnormal biomarker profiles and obstetrical syndromes is strengthened by information derived from placental examination, eg, the presence or absence of placental lesions of maternal vascular malperfusion. STUDY DESIGN: This retrospective case cohort study was based on a parent cohort of 4006 pregnant women enrolled prospectively. The case cohort of 1499 pregnant women included 1000 randomly selected patients from the parent cohort and all additional patients with obstetrical syndromes from the parent cohort. Pregnant women were classified into six groups: 1) term delivery without pregnancy complications (n=540; control); 2) preterm labor and delivery (n=203); 3) preterm premature rupture of the membranes (n=112); 4) preeclampsia (n=230); 5) small-for-gestational-age neonate (n=334); and 6) other pregnancy complications (n=182). Maternal plasma concentrations of PlGF and sFlt-1 were determined by enzyme-linked immunosorbent assays in 7560 longitudinal samples. Placental pathologists, masked to clinical outcomes, diagnosed the presence or absence of placental lesions of maternal vascular malperfusion. Comparisons between mean biomarker concentrations in cases and controls were performed by utilizing longitudinal generalized additive models. Comparisons were made between controls and each obstetrical syndrome with and without subclassifying cases according to the presence or absence of placental lesions of maternal vascular malperfusion. RESULTS: 1) When obstetrical syndromes are classified based on the presence or absence of placental lesions of maternal vascular malperfusion, significant differences in the mean plasma concentrations of PlGF, sFlt-1, and the PlGF/sFlt-1 ratio between cases and controls emerge earlier in gestation; 2) the strength of association between an abnormal PlGF/sFlt-1 ratio and the occurrence of obstetrical syndromes increases when placental lesions of maternal vascular malperfusion are present (adjusted odds ratio [aOR], 13.6 vs 6.7 for preeclampsia; aOR, 8.1 vs 4.4 for small-for-gestational-age neonates; aOR, 5.5 vs 2.1 for preterm premature rupture of the membranes; and aOR, 3.3 vs 2.1 for preterm labor (all P<0.05); and 3) the PlGF/sFlt-1 ratio at 28 to 32 weeks of gestation is abnormal in patients who subsequently delivered due to preterm labor with intact membranes and in those with preterm premature rupture of the membranes if both groups have placental lesions of maternal vascular malperfusion. Such association is not significant in patients with these obstetrical syndromes who do not have placental lesions. CONCLUSION: Classification of obstetrical syndromes according to the presence or absence of placental lesions of maternal vascular malperfusion allows biomarkers to be informative earlier in gestation and enhances the strength of association between biomarkers and clinical outcomes. We propose that a new taxonomy of obstetrical disorders informed by placental pathology will facilitate the discovery and implementation of biomarkers as well as the prediction and prevention of such disorders.

Experience of a telehealth and education program with maternal and perinatal outcomes in a low-resource region in Colombia.

INTRODUCTION: Maternal morbidity and mortality rates associated with perinatal care remain a significant public health concern. Rural populations from low and middle-income countries have multiple barriers to access that contribute to a lack of adherence to prenatal care, and high rates of maternal mortality and morbidity. An intervention model based on telehealth and education was implemented between a tertiary high complex care hospital and a second-level hospital from a limited source region. OBJECTIVES: We sought to identify an association in maternal and perinatal care quality indicators after implementing a model based on telehealth and education for patients with obstetric emergencies between two hospitals in a southwestern region of Colombia. METHODS: We conducted an ecological study between 2017 and 2019 to compare before and after obstetric emergency care through telemedicine from a secondary care center (Hospital Francisco de Paula Santander-HFPS) to the referral center (Fundación Valle del Lili-FVL). The intervention included verification visits to determine the installed capacity of care, a concerted improvement plan, and on-site educational training modules in obstetric and perinatal care. RESULTS: There were 102 and 148 patients treated before and after telemedicine implementation respectively. Clinical indicators after model implementation showed a reduction in perinatal mortality of 29%. In addition, a reduction in the need for transfusion of blood products due to postpartum hemorrhage was observed as well as the rate of eclampsia. CONCLUSIONS: Implementing a model based on telehealth and education between secondary and tertiary care centers allowed the strengthening of the security of care in obstetric emergencies and had a positive effect on perinatal mortality.

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.

Impact of the change of the Atalah standard cut-off point to classify underweight nutritional status during pregnancy

ABSTRACT Chile, and several Latin American countries, use the Atalah standard to assess nutritional status during pregnancy. However, this standard (underweight: pre-pregnancy body mass index (BMI)<20 kg/m2 and normal weight: pre-pregnancy BMI= 20-24.9 kg/m2) differ from those recommended by the US Institute of Medicine (IOM2009) (underweight: BMI<18.5 kg/m2 and normal weight: 18.5-24.9 kg/m2). Using a large population database from a Chilean public hospital, we compared the prevalence of underweight and normal weight at the beginning of pregnancy with Atalah and IOM2009 standards. Additionally, we evaluated the performance of both standards in detecting adverse neonatal outcomes and gestational weight gain. Methods: Data from clinical records of single birth pregnancies (n= 59,476) at the Sótero del Río Hospital, between 2003-2012 were collected. We compared 1. nutritional status, 2. proportion of excessive gestational weight gain, 3. association between nutritional status and neonatal outcomes (large/small for gestational age, low birth weight, preterm birth and macrosomia), using logistic regression models, and 4. Sensitivity, specificity, and predictive values to predict adverse neonatal outcomes per nutritional status. Results: Pre-pregnancy underweight decreased from 8.6% to 2.5% and women with BMI between 18.5-19.9kg/m2, who exceeded the recommended gestational weight gain increased from 32.7% to 49.2% when using IOM2009 instead of Atalah. Both standards showed low sensitivity, but the IOM2009 cut-off points showed better specificity for identifying healthy newborns. Conclusion: The cut-off points recommended by the IOM2009 better identify the prevalence of underweight and normal weight during pregnancy without increasing neonatal risk. This study supports the recent change of the Ministry of Health in adopting the WHO cut-off points during pregnancy.

RESUMEN Chile y diversos países Latinoaméricanos utilizan el estándar de Atalah para evaluar el estado nutricional (EN) durante el embarazo. Sin embargo, los puntos de corte de este estándar (bajo peso, BP: índice de masa corporal pre-gestacional (IMC)<20 kg/m2 y normal, NP: IMC pregestacional= 20-24,9 kg/m2) difieren de los recomendados por el Instituto de Medicina de EE.UU. (IOM2009) (BP: BMI<18.5kg/m2 and NP: 18,5-24,9 kg/m2). Con datos obtenidos desde el Hospital Sótero del Río, nosotros evaluamos la prevalencia de BP y NP al comienzo del embarazo con los estándares de Atalah e IOM2009. Adicionalmente, nosotros comparamos el comportamiento de ambos estándares en detectar resultados neonatales (RN) adversos y en la clasificación de la ganancia de peso gestacional (GPG). Métodos: Se obtuvieron datos de embarazos simples entre 2003-2012, (n= 59.476). Nosotros comparamos: 1. Prevalencia de EN, 2. Proporción de excesiva GPG, 3. Asociación entre EN y RN, usando modelos de regresión logística, y 4. Sensibilidad, especificidad y valores predictivos para predecir RN según EN. Resultados: La prevalencia de BP pregestacional disminuyó de 8,6% a 2,5% y las mujeres con IMC entre 18,5-19,9 kg/m2 que excedieron la GPG recomendada, incrementaron desde 33% a 50% cuando se utilizó el estándar IOM2009 en vez de Atalah. Ambos estándares mostraron baja sensibilidad, pero IOM2009 mostró mejor especificidad para identificar recién nacidos saludables. Conclusión: Estandar IOM2009 identifica con mayor precisión la prevalencia de BP y NP durante la gestación sin incrementar el riesgo neonatal. Este estudio respalda el reciente cambio del MINSAL al adoptar los puntos de corte de la OMS durante el embarazo.

Gingival Crevicular Placental Alkaline Phosphatase Is an Early Pregnancy Biomarker for Pre-Eclampsia.

Early and innovative diagnostic strategies are required to predict the risk of developing pre-eclampsia (PE). The purpose of this study was to evaluate the performance of gingival crevicular fluid (GCF) placental alkaline phosphatase (PLAP) concentrations to correctly classify women at risk of PE. A prospectively collected, retrospectively stratified cohort study was conducted, with 412 pregnant women recruited at 11-14 weeks of gestation. Physical, obstetrical, and periodontal data were recorded. GCF and blood samples were collected for PLAP determination by ELISA assay. A multiple logistic regression classification model was developed, and the classification efficiency of the model was established. Within the study cohort, 4.3% of pregnancies developed PE. GCF-PLAP concentration was 3- to 6-fold higher than in plasma samples. GCF-PLAP concentrations and systolic blood pressure were greater in women who developed PE (p = 0.015 and p < 0.001, respectively). The performance of the multiparametric model that combines GCF-PLAP concentration and the levels of systolic blood pressure (at 11-14 weeks gestation) showed an association of systolic blood pressure and GCF-PLAP concentrations with the likelihood of developing PE (OR:1.07; 95% CI 1.01-1.11; p = 0.004 and OR:1.008, 95% CI 1.000-1.015; p = 0.034, respectively). The model had a sensitivity of 83%, a specificity of 72%, and positive and negative predictive values of 12% and 99%, respectively. The area under the receiver operating characteristic (AUC-ROC) curve was 0.77 and correctly classified 72% of PE pregnancies. In conclusion, the multivariate classification model developed may be of utility as an aid in identifying pre-symptomatic women who subsequently develop PE.

Clinical chorioamnionitis at term X: microbiology, clinical signs, placental pathology, and neonatal bacteremia - implications for clinical care.

OBJECTIVES: Clinical chorioamnionitis at term is considered the most common infection-related diagnosis in labor and delivery units worldwide. The syndrome affects 5-12% of all term pregnancies and is a leading cause of maternal morbidity and mortality as well as neonatal death and sepsis. The objectives of this study were to determine the (1) amniotic fluid microbiology using cultivation and molecular microbiologic techniques; (2) diagnostic accuracy of the clinical criteria used to identify patients with intra-amniotic infection; (3) relationship between acute inflammatory lesions of the placenta (maternal and fetal inflammatory responses) and amniotic fluid microbiology and inflammatory markers; and (4) frequency of neonatal bacteremia. METHODS: This retrospective cross-sectional study included 43 women with the diagnosis of clinical chorioamnionitis at term. The presence of microorganisms in the amniotic cavity was determined through the analysis of amniotic fluid samples by cultivation for aerobes, anaerobes, and genital mycoplasmas. A broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry was also used to detect bacteria, select viruses, and fungi. Intra-amniotic inflammation was defined as an elevated amniotic fluid interleukin-6 (IL-6) concentration ≥2.6 ng/mL. RESULTS: (1) Intra-amniotic infection (defined as the combination of microorganisms detected in amniotic fluid and an elevated IL-6 concentration) was present in 63% (27/43) of cases; (2) the most common microorganisms found in the amniotic fluid samples were Ureaplasma species, followed by Gardnerella vaginalis; (3) sterile intra-amniotic inflammation (elevated IL-6 in amniotic fluid but without detectable microorganisms) was present in 5% (2/43) of cases; (4) 26% of patients with the diagnosis of clinical chorioamnionitis had no evidence of intra-amniotic infection or intra-amniotic inflammation; (5) intra-amniotic infection was more common when the membranes were ruptured than when they were intact (78% [21/27] vs. 38% [6/16]; p=0.01); (6) the traditional criteria for the diagnosis of clinical chorioamnionitis had poor diagnostic performance in identifying proven intra-amniotic infection (overall accuracy, 40-58%); (7) neonatal bacteremia was diagnosed in 4.9% (2/41) of cases; and (8) a fetal inflammatory response defined as the presence of severe acute funisitis was observed in 33% (9/27) of cases. CONCLUSIONS: Clinical chorioamnionitis at term, a syndrome that can result from intra-amniotic infection, was diagnosed in approximately 63% of cases and sterile intra-amniotic inflammation in 5% of cases. However, a substantial number of patients had no evidence of intra-amniotic infection or intra-amniotic inflammation. Evidence of the fetal inflammatory response syndrome was frequently present, but microorganisms were detected in only 4.9% of cases based on cultures of aerobic and anaerobic bacteria in neonatal blood.

Early pregnancy levels of gingival crevicular fluid matrix metalloproteinases-8 and -9 are associated with the severity of periodontitis and the development of gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is increasing worldwide and women with a history of GDM are at risk of developing type 2 diabetes which is a risk factor for periodontitis. The aim of this study was to explore the association between the concentrations of matrix metalloproteinase (MMP)-8 and -9 in gingival crevicular fluid (GCF) during early pregnancy with the periodontal diagnosis and the risk of GDM development. METHODS: A prospective cohort study, including 314 women, enrolled at 11 to 14 weeks of pregnancy was conducted. A complete maternal/obstetric and periodontal exam was performed, and GCF samples were obtained for the MMP-8 and -9 determination by Multiplex Elisa Assays. Mann-Whitney test; Spearman's correlation and log-binomial regression model estimated the association between MMPs concentration in GCF and GDM. RESULTS: Fourteen percent of the pregnancies were diagnosed with GDM. An increase in the concentration of MMP-8 and -9 in women with periodontitis stage III and IV compared to periodontitis stage I was observed (99.31 ng/mL [IQR: 85.32] versus 71.95 ng/mL [IQR: 54.04], and 262.4 ng/mL [IQR: 312.55] versus 114.1 ng/mL [IQR: 184.94], respectively). Women who developed GDM showed increased concentrations of MMP-8 and -9 in GCF since the beginning of pregnancy (P = 0.0381; P = 0.0302, respectively). MMP-8 concentration in GCF was associated with GDM (RR: 1.19; P = 0.045; CI 95% 1.00 to 1.40; and RR: 1.20; P = 0.063; CI 95% 0.99 to 1.45 in the adjusted model). CONCLUSION(S): GCF concentrations of MMP-8 and -9 at early of pregnancy are increased in women with severe periodontitis and associated with the GDM development.

Personalized assessment of cervical length improves prediction of spontaneous preterm birth: a standard and a percentile calculator.

BACKGROUND: A sonographic short cervix (length <25 mm during midgestation) is the most powerful predictor of preterm birth. Current clinical practice assumes that the same cervical length cutoff value should apply to all women when screening for spontaneous preterm birth, yet this approach may be suboptimal. OBJECTIVE: This study aimed to (1) create a customized cervical length standard that considers relevant maternal characteristics and gestational age at sonographic examination and (2) assess whether the customization of cervical length evaluation improves the prediction of spontaneous preterm birth. STUDY DESIGN: This retrospective analysis comprises a cohort of 7826 pregnant women enrolled in a longitudinal protocol between January 2006 and April 2017 at the Detroit Medical Center. Study participants met the following inclusion criteria: singleton pregnancy, ≥1 transvaginal sonographic measurements of the cervix, delivery after 20 weeks of gestation, and available relevant demographics and obstetrical history information. Data from women without a history of preterm birth or cervical surgery who delivered at term without progesterone treatment (N=5188) were used to create a customized standard of cervical length. The prediction of the primary outcome, spontaneous preterm birth at <37 weeks of gestation, was assessed in a subset of pregnancies (N=7336) that excluded cases with induced labor before 37 weeks of gestation. Area under the receiver operating characteristic curve and sensitivity at a fixed false-positive rate were calculated for screening at 20 to 23 6/7, 24 to 27 6/7, 28 to 31 6/7, and 32 to 35 6/7 weeks of gestation in asymptomatic patients. Survival analysis was used to determine which method is better at predicting imminent delivery among symptomatic women. RESULTS: The median cervical length remained fundamentally unchanged until 20 weeks of gestation and subsequently decreased nonlinearly with advancing gestational age among women who delivered at term. The effects of parity and maternal weight and height on the cervical length were dependent on the gestational age at ultrasound examination (interaction, P<.05 for all). Parous women had a longer cervix than nulliparous women, and the difference increased with advancing gestation after adjusting for maternal weight and height. Similarly, maternal weight was nonlinearly associated with a longer cervix, and the effect was greater later in gestation. The sensitivity at a 10% false-positive rate for prediction of spontaneous preterm birth at <37 weeks of gestation by a short cervix ranged from 29% to 40% throughout pregnancy, yet it increased to 50%, 50%, 53%, and 54% at 20 to 23 6/7, 24 to 27 6/7, 28 to 31 6/7, and 32 to 35 6/7 weeks of gestation, respectively, for a low, customized percentile (McNemar test, P<.001 for all). When a cervical length <25 mm was compared to the customized screening at 20 to 23 6/7 weeks of gestation by using a customized percentile cutoff value that ensured the same negative likelihood ratio for both screening methods, the customized approach had a significantly higher (about double) positive likelihood ratio in predicting spontaneous preterm birth at <33, <34, <35, <36, and <37 weeks of gestation. Among symptomatic women, the difference in survival between women with a customized cervical length percentile of ≥10th and those with a customized cervical length percentile of <10th was greater than the difference in survival between women with a cervical length ≥25 mm and those with a cervical length <25 mm. CONCLUSION: Compared to the use of a cervical length <25 mm, a customized cervical length assessment (1) identifies more women at risk of spontaneous preterm birth and (2) improves the distinction between patients at risk for impending preterm birth in those who have an episode of preterm labor.

Maternal sepsis.

Maternal sepsis is "a life-threatening condition defined as an organ dysfunction caused by an infection during pregnancy, delivery, puerperium, or after an abortion," with the potential to save millions of lives if a proper approximation is made. Undetected or poorly managed maternal infections can lead to sepsis, death, or disability for the mother, and an increased likelihood of early neonatal infection and other adverse outcomes. Physiological, immunologic, and mechanical changes that occur in pregnancy make pregnant women more susceptible to infections than nonpregnant women and may obscure signs and symptoms of infection and sepsis, resulting in a delay in the recognition and treatment of sepsis. Prioritization of the creation and validation of tools that allow the development of clear and standardized diagnostic criteria of maternal sepsis and septic shock, according to the changes inherent to pregnancy, correspond to highly effective strategies to reduce the impact of these conditions on maternal health worldwide. After an adequate diagnostic approach, the next goal is achieving stabilization, trying to stop the progression from sepsis to septic shock, and improving tissue perfusion to limit cell dysfunction. Management protocol implementation during the first hour of treatment will be the most important determinant for the reduction of maternal mortality associated with sepsis and septic shock.

Diagnóstico prenatal de malformaciones congénitas y alteraciones cromosómicas: resultado de la experiencia CIMAF - Hospital Dr. Sótero Del Río / Prenatal Diagnosis of Congenital Malformations and Chromosomal Abnormalities: Single Center Experience - Hospital Dr. Sótero Del Río, Chile

INTRODUCCIÓN: El diagnóstico prenatal de anomalías congénitas tiene como objetivo ofrecer consejería apropiada, identificar aquellas patologías que se benefician de terapia fetal y coordinar la derivación de estas pacientes a centros terciarios para un óptimo manejo perinatal. Para el diagnóstico y manejo de las anomalías congénitas en el Hospital Dr. Sótero Del Río contamos con un equipo multidisciplinario. El objetivo de este estudio es describir nuestra experiencia como centro de referencia en Santiago de Chile en relación al diagnostico prenatal de malformaciones congénitas, estudio genético prenatal y resultados perinatales. MÉTODOS: Estudio retrospectivo y descriptivo. Se incluyó a las pacientes registradas en las bases de datos ecográficas entre 2010 y 2019 del Hospital Dr. Sotero del Rio. Se revisaron fichas clínicas para evaluación y seguimiento postnatal. RESULTADOS: Se evaluaron 404 pacientes con sospecha de malformaciones congénitas o marcadores de aneuploidías. La edad gestacional media de la evaluación fue 29 semanas (14-38 semanas). La mediana de la edad gestacional al parto fue 37.6 semanas (20-41 semanas). Se obtuvo un 78% de recién nacidos vivos, 12% óbitos fetales y 10% mortineonatos. Las malformaciones más frecuentes fueron cardiovasculares, sistema nervioso central, hidrops, extremidades, abdomen y genitourinario. Se realizo el estudio genético en 232 pacientes; 61% resultado normal, 12.5% trisomía 21, 8% trisomía 18, 4% trisomía 13, 4% XO, 4% otras. Se analizaron las pacientes que se acogieron a la ley de interrupción voluntaria del embarazo. CONCLUSIÓN: Destacamos la importancia de derivación a centros de referencia de pacientes con sospecha de malformaciones congénitas para un adecuado diagnostico prenatal, ofrecer un manejo con equipo multidisciplinario y así mejorar los resultados neonatales.

INTRODUCTION: The objectives of prenatal diagnosis of fetal malformations are to offer the patient and her family the proper counseling, identify those conditions that benefits of prenatal therapy and to coordinate the referral to tertiary centers to improve neonatal survival. Our hospital counts with a multidisciplinary team who evaluate the patients together. The objective of this study is to describe our experience as a referral center in prenatal diagnosis, management and neonatal outcomes in Santiago de Chile. METHODS: Retrospective and descriptive study. Patients registered in our prenatal diagnosis database between September 2010 and July 2019 were included. Clinical files were reviewed for neonatal outcomes. OUTCOMES: 404 patients with congenital malformations or aneuploidy markers were evaluated. The average gestational age of the evaluation was 29 weeks. Median gestational age to delivery was 37 weeks plus 6 days. 78% of livebirth, 12% fetal demise and 10% of neonatal death were obtained. The most frequent fetal malformations were cardiovascular, central nervous system, fetal hydrops, extremities, abdominal wall defects and urinary system. Fetal karyotype was performed in 232 patients; 61% normal karyotype, 12.5% trisomy 21, 8% trisomy 18, 4% trisomy 13, 4% monosomy X, 4% others. We also analyze the patients who agreed to termination of pregnancy according to Chilean legislation. CONCLUSION: We highlight the importance of referral of patients with suspected fetal malformations to tertiary centers for an adequate evaluation by a multidisciplinary team of specialists, to improve the survival and neonatal outcome.

Effectiveness of a normative nutrition intervention in Chilean pregnant women on maternal and neonatal outcomes: the CHiMINCs study.

BACKGROUND: Some nutritional interventions have shown their efficacy in reducing gestational weight gain (GWG); however, their applicability in routine care is limited. OBJECTIVE: We assessed the effectiveness of a low-intensity and high-coverage nutritional intervention on maternal and offspring outcomes; the intervention enhanced existing nutritional health care standards and practices at the primary health care level in Chile. METHODS: This study was a cluster-randomized controlled trial of 12 primary health care centers (PHCCs) from Santiago, Chile. PHCCs were randomly allocated to either nutritional intervention [intervention group (IG), n = 5] or routine care [control group (CG), n = 7]. A total of 4631 pregnant women were recruited (IG, n = 2565; and CG, n = 2066). Primary outcomes were adequate GWG and glycemic control in mothers and birth weight, birth length, macrosomia, and large for gestational age in neonates. The intervention consisted of 4 key actions: training of health care professionals on nutritional recommendations, counseling of pregnant women on diet and physical activity recommendations, offering a physical activity program implemented in the participating PHCCs, and adequate referral to dietitians. Women randomly assigned to the CG received routine antenatal care. RESULTS: At baseline, the mean age was 26.1 y; 45% of women were primipara and 24% were obese. No differences were found in the percentage of women achieving adequate GWG (IG: 30.3%, compared with CG: 31.3%; OR: 0.94; 95% CI: 0.81, 1.09), but women in the IG had lower GWG than those in the CG (11.3 compared with 11.9 kg; mean difference: -0.63 kg; 95% CI: -1.19, -0.08). Effects of the intervention were significantly higher in women with obesity at the begining of pregnancy (mean difference: -1.24 kg; 95% CI: -2.18, -0.30; P for interaction < 0.05). No differences were found between groups regarding maternal glycemic control or neonatal outcomes. CONCLUSIONS: Our findings demonstrate that a low-intensity, high-coverage intervention delivered through the Chilean public health care system under standard operating conditions reduces GWG and has the potential for successful scale-up. This trial was registered at clinicaltrials.gov as NCT01916603.

Comparison of two identification and susceptibility test kits for Ureaplasma spp and Mycoplasma hominis in amniotic fluid of patients at high risk for intra-amniotic infection.

Objective: Ureaplasma urealyticum and Mycoplasma hominis are the most common microorganisms found in the amniotic fluid of patients at risk for preterm delivery. However, culture techniques for genital mycoplasms require special conditions, are barely considered as part of the evaluation of suspected intra-amniotic infection (IAI) and the results are available within 2 and 7 days. The objectives of this study are to validate the use of two commercially available kits (Mycoplasma IES y MYCOFAST® RevolutioN) for the identification of Ureaplasma spp. and Mycoplasma hominis in amniotic fluid, to compare the results of these kits with those obtained by culture and real-time polymerase chain reaction (qPCR) and to report the antibiotic sensitivity profile of the genital mycoplasms identified.Methods: This is a prospective cohort study including women with singleton and twin gestations between 16 and 36 weeks. Patients were admitted to perform an amniocentesis due to pregnancy complications considered at high risk for IAI (e.g. preterm labor with intact membranes, preterm prelabour rupture of membranes, short cervix, etc.), treatment of polyhydramnios, and for the assessment of fetal death and fever without a focus.Results: Overall, 93 patients underwent amniocentesis and 63 had results available for all tests. The prevalence of a positive culture was 6% (4/63). There were four cases of Ureaplasma spp. and none of Mycoplasma hominis. The qPCR identified one case as Ureaplasma spp., one case as Ureaplasma parvum and two cases as Ureaplasma urealyticum. For all tests, the diagnostic performance was as follows: sensitivity 100% [95% CI (39.8-100%)], specificity 100% [95% CI (93.9-100%)], positive predictive value 100% [95% CI (39.8-100%)] and negative predictive value 100% [95% CI (93.9-100%)]. In this cohort, Ureaplasma spp. showed low resistance to erythromycin, but a high resistance to clindamycin and clarithromycin that may change according to the antibiotic concentration.Conclusions: To our knowledge, this is the first study that validates the use of the Mycoplasma IES and MYCOFAST® RevolutioN kits for the identification of genital mycoplasmas in amniotic fluid. The results of these kits are mostly available within 24 hours, have an excellent correlation with those from broth cultures and qPCR and characterize the antibiotic sensitivity profile of the genital mycoplasms identified, providing an opportunity for specific treatment in cases of IAI. Further validation studies in other populations are needed.

The diagnostic performance of the beta-glucan assay in the detection of intra-amniotic infection with Candida species.

INTRODUCTION: A bioassay based on the detection of beta-glucan, a constituent of the cell wall of fungi, has been successfully used to diagnose fungal infections in a variety of biological fluids but not yet in the amniotic fluid. OBJECTIVE: To determine the diagnostic performance of a beta-glucan bioassay in the detection of Candida species in the amniotic fluid of women who either did or did not have an intrauterine contraceptive device (IUD) in place during an episode of spontaneous preterm parturition. METHODS: The study population comprised women who had a singleton pregnancy without congenital or chromosomal abnormalities, who experienced preterm labor or preterm prelabor rupture of the fetal membranes, and who underwent a transabdominal amniocentesis for clinical indications. Samples of amniotic fluid were cultured for aerobic and anaerobic bacteria, genital mycoplasmas, and Candida species, and assayed for beta-glucan, using the (1→3)-beta-d-glucan-specific Limulus amebocyte lysate test (beta-glucan assay) in all cases. Amniotic fluid interleukin (IL)-6 assay results were also available for all cases. The beta-glucan assay takes about 1 hour to run: a concentration >80 pg/mL was considered positive for fungi. Sterile intra-amniotic inflammation of the amniotic cavity was defined by the presence of an amniotic fluid IL-6 concentration ≥2.6 ng/mL and a negative amniotic fluid culture. RESULTS: (1) One hundred ninety-seven (197) women met the study criteria, of whom 58 (29.4%) had an IUD in place; (2) 20 (10.2%) women had a culture of proven intra-amniotic Candida species-related infection, 19 of whom had a positive beta-glucan assay [sensitivity, 95% (19/20; 95% confidence interval (CI): 75.1-99.9%)]; and (3) the specificity of the beta-glucan assay was 75.1% [133/177; 95% CI: 68.1-99.9%]. It was affected by the presence of nonfungal intra-amniotic infections and an IUD, but not by the presence of sterile intra-amniotic inflammation, and there was a significant interaction between the presence of an IUD and nonfungal intra-amniotic infections (estimated for the interaction effect = 2.1923, p value =.026). The assay's specificity was reduced when nonfungal intra-amniotic infections were diagnosed but only in women who did not have an IUD. Among women without an IUD, the assay's specificity was 91.4% (117/128); it was 93% (106/114) for those without intra-amniotic infection, and 78.6% (11/14) for those with a nonfungal intra-amniotic infection; the difference was not significant (p = .09). Among women with an IUD, the assay's specificity was 32.7% (16/49); 42.9% (9/21) for those with a nonfungal intra-amniotic infection; and 25% (7/28) for those without intra-amniotic infection; and the difference was significant (p = .03). CONCLUSIONS: The beta-glucan assay is a sensitive, rapid, point-of-care test used to diagnose intra-amniotic Candida species-related infection, and it has a high specificity in pregnant women who did not have an IUD in place.

Clinical chorioamnionitis at term IX: in vivo evidence of intra-amniotic inflammasome activation.

Background The inflammasome has been implicated in the mechanisms that lead to spontaneous labor at term. However, whether the inflammasome is activated in the amniotic cavity of women with clinical chorioamnionitis at term is unknown. Herein, by measuring extracellular ASC [apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (CARD)], we investigated whether there is in vivo inflammasome activation in amniotic fluid of patients with clinical chorioamnionitis at term with sterile intra-amniotic inflammation and in those with intra-amniotic infection. Methods This was a retrospective cross-sectional study that included amniotic fluid samples collected from 76 women who delivered after spontaneous term labor with diagnosed clinical chorioamnionitis. Intra-amniotic inflammation was defined as an elevated amniotic fluid interleukin (IL)-6 concentration ≥2.6 ng/mL, and intra-amniotic infection was diagnosed by the presence of microbial invasion of the amniotic cavity (MIAC) accompanied by intra-amniotic inflammation. Patients were classified into the following groups: (1) women without intra-amniotic inflammation or infection (n=16); (2) women with MIAC but without intra-amniotic inflammation (n=5); (3) women with sterile intra-amniotic inflammation (n=15); and (4) women with intra-amniotic infection (n=40). As a readout of in vivo inflammasome activation, extracellular ASC was measured in amniotic fluid by enzyme-linked immunosorbent assay. Acute inflammatory responses in the amniotic fluid and placenta were also evaluated. Results In clinical chorioamnionitis at term: (1) amniotic fluid concentrations of ASC (extracellular ASC is indicative of in vivo inflammasome activation) and IL-6 were greater in women with intra-amniotic infection than in those without intra-amniotic inflammation, regardless of the presence of MIAC; (2) amniotic fluid concentrations of ASC and IL-6 were also higher in women with sterile intra-amniotic inflammation than in those without intra-amniotic inflammation, regardless of the presence of MIAC; (3) amniotic fluid concentrations of IL-6, but not ASC, were more elevated in women with intra-amniotic infection than in those with sterile intra-amniotic inflammation; (4) a positive and significant correlation was observed between amniotic fluid concentrations of ASC and IL-6; (5) no differences were observed in amniotic fluid ASC and IL-6 concentrations between women with and without MIAC in the absence of intra-amniotic inflammation; (6) women with intra-amniotic infection had elevated white blood cell counts and reduced glucose levels in amniotic fluid compared to the other three study groups; and (7) women with intra-amniotic infection presented higher frequencies of acute maternal and fetal inflammatory responses in the placenta than those with sterile intra-amniotic inflammation. Conclusion The intra-amniotic inflammatory response, either induced by alarmins or microbes, is characterized by the activation of the inflammasome - as evidenced by elevated amniotic fluid concentrations of extracellular ASC - in women with clinical chorioamnionitis at term. These findings provide insight into the intra-amniotic inflammatory response in women with clinical chorioamnionitis at term.

The Cellular Transcriptome in the Maternal Circulation During Normal Pregnancy: A Longitudinal Study.

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.

Clinical Chorioamnionitis at Term: New Insights into the Etiology, Microbiology, and the Fetal, Maternal and Amniotic Cavity Inflammatory Responses.

Clinical chorioamnionitis is the most common infection related diagnosis made in labor and delivery units worldwide. It is traditionally believed to be due to microbial invasion of the amniotic cavity, which elicits a maternal inflammatory response characterized by maternal fever, uterine tenderness, maternal tachycardia and leukocytosis. The condition is often associated with fetal tachycardia and a foul smelling amniotic fluid. Recent studies in which amniocentesis has been used to characterize the microbiologic state of the amniotic cavity and the inflammatory response show that only 60% of patients with the diagnosis of clinical chorioamnionitis have proven infection using culture or molecular microbiologic techniques. The remainder of the patients have intra-amniotic inflammation without demonstrable microorganisms or a maternal systemic inflammatory response (fever) in the absence of intra-amniotic inflammation. The latter cases often represent a systemic inflammatory response after epidural anesthesia/analgesia has been administered. The most common microorganisms are Ureaplasma species and Gardnerella vaginalis. In the presence of ruptured membranes, the frequency of infection is 70%, which is substantially higher than patients who have intact membranes (25%). The amniotic fluid inflammatory response is characterized by an infiltration of neutrophils and monocytes. Both cell types are activated in the presence of infection and can produce inflammatory cytokines. The white blood cells in the amniotic fluid can be of fetal or maternal origin. The maternal inflammatory response is characterized by an elevation in the concentration of pyrogenic cytokines. The cytokine plasma concentrations in the fetal circulation are elevated even if there is no evidence of an intra-amniotic inflammatory response suggesting that maternal plasma cytokines may cross the placental barrier and induce a mild fetal inflammatory response. Placental pathology is of limited value in the diagnosis of proven intra-amniotic infection. The clinical criteria traditionally used in clinical medicine have accuracy around 50% and therefore, they cannot distinguish between patients with a proven intra-amniotic infection and those with intra-amniotic inflammation alone. Analysis of amniotic fluid with a bedside test for MMP-8 can allow the rapid identification of the patient at risk for infection and may decrease the need for antibiotic administration to neonates. An important consideration is whether antibiotics effective against Ureaplasma species should be administered to patients with clinical chorioamnionitis, given that these genital mycoplasmas are the most common organisms found in the amniotic fluid. The emergent picture is that clinical chorioamnionitis is a heterogeneous syndrome, which requires further study to optimize maternal and neonatal outcomes.

Periodontitis and placental growth factor in oral fluids are early pregnancy predictors of gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) affects around 7% to 10% of all pregnancies. Early detection of predisposition to GDM is the first step in developing efficacious preventive treatment. The objective of the present study was to establish the utility of placental proteins presents in oral fluids (gingival crevicular fluid [GCF] and saliva), and periodontal disease status as early pregnancy predictors of GDM. METHODS: A nested case control within a prospective cohort was conducted. Pregnant systemically healthy women, aged between 18 and 40 years at 11 to 14 weeks gestation were included. Samples of oral fluids were collected and a complete maternal/obstetric and periodontal history was obtained. The concentration of placental growth factor (PlGF) and soluble Fms-like tyrosine kinase 1 (sFlt-1) were measured by enzyme-linked immunosorbent assay in a nested case control sample of the prospective cohort. Multiple logistic regression models assessed the association. The evaluation of the diagnostic accuracy of the biomarkers was performed through receiver operating characteristic (ROC) curves by calculating the area under the curve (AUC). RESULTS: There were recruited 212 pregnant women at 11 to 14 weeks of pregnancy, of these, 14 women (i.e., 6.6%) developed GDM, and displayed significant greater bleeding on probing (BOP) [P = 0.0003]; periodontal probing depth (PD) [P = 0.0028]; clinical attachment level (AL) [P = 0.0008] and periodontal inflamed surface area (PISA) [P = 0.0001]. Similarly, initial glycemia and GCF-PlGF concentrations were significantly greater in women with GDM [P = 0.0012, and P = 0.0019, respectively]. When data were subjected to ROC curve analysis, the combination of initial glycemia and GCF-PlGF concentration delivered an area under the ROC curve of 0.897. Multiple logistic regression analyses demonstrate an association between glycemia (OR 1.21, 95% confidence interval [CI] 1.06 to 1.38; P = 0.005) and GCF-PlGF concentrations in women who developed GDM (OR 1.68, CI 1.05 to 2.68 P = 0.03). CONCLUSIONS: Within the limitations of the present study, the results support that first trimester maternal glycemia combined with GCF-PlGF concentrations could be a surrogate biomarker for the future development of GDM in pre-symptomatic women.