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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)

To describe the characteristics of amniotic fluid sludge obtained from patients in term and preterm gestations.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.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 (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.

Background: Rural populations are commonly characterized by poverty, low educational level, and poor access to health services, and pregnant women often lack adherence to prenatal care. Referral of obstetric patients in critical conditions from these areas is associated with high maternal morbidity/mortality. We thought to identify changes in maternal/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: An ecological study was conducted between 2017 to 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 project included verification visits to determine the installed capacity of care, a concerted improvement plan, an on-site education project supported by simulation in eight obstetric and perinatal care modules, and the strengthening of non-technical competencies. The communication platform between institutions was a technological development of the FVL, and the telecalls were made through licensed platforms.Findings: 102 patients were treated before, and 148 after telemedicine implementation. The clinical indicators after model implementation showed a significant reduction in perinatal mortality of 29%. An effect statistically significant for outcome maternal did not found, however, was observed a reduction in the need for transfusion of blood products due to postpartum hemorrhage (PPH), as well as the rate of eclampsia.Interpretation: 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 significantly impacted perinatal mortality.Funding: Fundación Valle del Lili

RESUMEN 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.

Severe obstetric hemorrhage is a catastrophic event and represents the main cause of maternal morbidity and mortality worldwide. The elevated mortality rate due to hemorrhage is associated with metabolic complications and organ hypoperfusion that may trigger a state of irreversible coagulopathy. Thus, the use of conventional measures to control bleeding frequently generates a vicious cycle in which the patient continues bleeding (prolonging surgical times). Damage-control surgery has proven to be feasible and effective in the context of obstetric hemorrhage. It combines surgical and resuscitative measures that generate successful results in the control of refractory bleeding, ultimately decreasing mortality in patients being in critical condition.

Objective To examine the temporal trends in gestational diabetes mellitus (GDM) prevalence in Chile, and to determine the main predictors of GDM. Methods A secondary analysis was conducted of all birth records at Hospital Dr. Sotero del Rio, Chile, from January 1, 2002, to December 31, 2015. We excluded those women with pre-existing type 2 diabetes, those with missing data, and those with unlikely data. GDM was defined as fasting glucose levels >5.55 mmol/L [>100 mg/dL] or >7.77 mmol/L [>140 mg/dL] 2 hours after glucose load in the oral glucose tolerance test. Potential predictors were selected based on prior research and ease of evaluation. Results From the original database of 100 758 records, 86 362 women were included in the final cohort. The mean GDM prevalence was 7.6% (95% CI [confidence interval] 7.5%-7.8%), increasing from 4.4% (95% CI 4.0%-4.9%) in 2002 to 13.0% (95% CI 12.0%-13.9%) in 2015. Age, education, marital status, parity, family history of type 2 diabetes, personal history of GDM, hypertension and pre-eclampsia, alcohol consumption, smoking, and pre-gestational nutritional status performed well in the prediction of GDM. Conclusion One out of eight Chilean pregnant women of medium- to low socio-economic status were found to develop GDM. We identified a set of easy-to-capture predictors in the primary health care system that may allow for the early identification of women at high-risk for the development of GDM.

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.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.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.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 P0.05); 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.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.

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 gen...

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 &lt, 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.

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.

Background Lifestyle interventions have shown limited effectiveness in the prevention of gestational diabetes mellitus. The combination of lifestyle interventions with omega-3 polyunsaturated fatty acid supplementation could have a synergetic effect on maternal and offspring outcomes. Objective We evaluated the effects of docosahexaenoic acid supplementation among obese and overweight pregnant women (independently or combined with a dietary counseling intervention) on metabolic control in mothers and their offspring. Study Design This study was a randomized controlled trial with a 2×2 factorial design. The following inclusion criteria were used: 4000 g); and neonatal insulin resistance (cord blood Homeostasis Model Assessment for Insulin Resistance ≥2.60), which was assessed in a subsample of 226 newborns. The analysis was by intention to treat and by efficacy. The trial was registered on ClinicalTrials.gov ( NCT02574767 ). Results The overall incidence of gestational diabetes mellitus was 20.2% (Group 1, 21.0%; Group 2, 20.1%; Group 3, 18.9%; and Group 4, 20.9%). Mean birthweight was 3403.0 g (standard deviation, 575.3), and the incidence of macrosomia was 11.9% (Group 1, 13.2%; Group 2, 10.8%; Group 3, 11.5%; and Group 4, 12.1%). Median cord blood Homeostasis Model Assessment for Insulin Resistance was 0.9 (interquartile range, 0.6–1.7), and 10.2% showed cord blood insulin resistance (Group 1, 12.0%; Group 2, 12.0%; Group 3, 9.7%; and Group 4, 5.1%). No significant differences were found among groups regarding primary outcomes (P Conclusion For women who were overweight or obese at the beginning of pregnancy, this combined intervention did not reduce the risk of gestational diabetes in mothers or macrosomia and insulin resistance in neonates.

BACKGROUND: A sonographic short cervix length (

Preeclampsia is a pregnancy-specific disorder defined by new onset of hypertension and proteinuria after 20 weeks of gestation. The early detection of patients at risk of developing preeclampsia is crucial, however, predictive models are still controversial. We aim to evaluate the diagnostic performance of a predictive algorithm in the first trimester of pregnancy, in order to identify patients that will subsequently develop preeclampsia, and to study the effect of aspirin on reducing the rate of this complication in patients classified as high risk by this algorithm. A retrospective cohort including 1132 patients attending prenatal care at Cl&iacute, nica D&aacute, vila in Santiago, Chile, was conceived. The risk of developing preeclampsia (early and late onset) was calculated using algorithms previously described by Plasencia et al. Patients classified as high risk, in the first trimester of pregnancy, by these algorithms, were candidates to receive 100 mg/daily aspirin as prophylaxis at the discretion of the attending physician. The overall incidence of preeclampsia in this cohort was 3.5% (40/1132), and the model for early onset preeclampsia prediction detected 33% of patients with early onset preeclampsia. Among the 105 patients considered at high risk of developing preeclampsia, 56 received aspirin and 49 patients did not. Among those who received aspirin, 12% (7/56) developed preeclampsia, which is equal to the rate of preeclampsia (12% (6/49)) of those who did not receive this medication. Therefore, the diagnostic performance of an algorithm combining uterine artery Doppler and maternal factors in the first trimester predicted only one third of patients that developed preeclampsia. Among those considered at high risk for developing the disease using this algorithm, aspirin did not change the incidence of preeclampsia, however, this could be due either to the small study sample size or the type of the study, a retrospective, non-interventional cohort study.

Some nutritional interventions have shown their efficacy in reducing gestational weight gain (GWG); however, their applicability in routine care is limited.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.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.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.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.

Objectives We examined if the guidelines for gestational weight gain (GWG) proposed by the Institute of Medicine (IOM) are the most suitable for Chilean women. Study design Secondary analysis of records of single full-term births at the Dr. Sotero del Rio Hospital, Santiago, Chile, during 2003–2012 (n = 62,579). Methods From clinical records, we obtained data regarding maternal age, height, prepregnancy and at delivery weights, pathologies during pregnancy such as gestational diabetes (GDM) and pre-eclampsia, gestational age at delivery, and number of infants born small for gestational age (SGA) and large for gestational age (LGA). We formulated a mathematical model (MM) to determine the GWG range that maximizes the likelihood of a healthy pregnancy (HP) if the recommendation is followed. We defined an HP as one where the mother has no complications such as pre-eclampsia, GDM, SGA, or LGA. Results Forty-six percent of women had prepregnancy overweight or obesity. The prevalence of GDM, pre-eclampsia, SGA, and LGA were 3%, 1.2%, 9%, and 12%, respectively. An HP was present in 76% of pregnancies, 79% in the underweight group, 79% in normal weight group, 74% in the overweight group, and 67% in obese women. The GWG recommendations given by the MM (14–20 kg for underweight, 6–20 kg for normal weight, 9–11 kg for overweight, and 6–7 kg for obese) led to higher probabilities of achieving an HP than the ones obtained with the IOM recommendations. Conclusion The adoption of GWG recommendations based on characteristics of the Chilean population might lead to better short- and long-term health results for pregnant women.

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.

IntroducciA³n: La rotura prematura ovular (RPO) antes de la viabilidad fetal consiste en una complicaciA³n obstA©trica de baja incidencia, pero de alta morbimortalidad perinatal asociada. Estudios sugieren que el volumen de lA­quido amniA³tico (LA) es un factor importante a considerar. El objetivo de este trabajo es evaluar si en RPO ≤24 semanas, un bolsillo vertical mAiximo (BVM)

OBJECTIVE: We aimed to determine the differences in the pattern and magnitude of thrombin generation between patients with preeclampsia (PE) and those with a small-for-gestational-age (SGA) fetus. METHODS: This cross-sectional study included women in the following groups: 1) normal pregnancy (NP) (n=49); 2) PE (n=56); and 3) SGA (n=28). Maternal plasma thrombin generation (TGA) was measured, calculating: a) lag time (LT); b) velocity index (VI); c) peak thrombin concentration (PTC); d) time-to-peak thrombin concentration (TPTC); and e) endogenous thrombin potential (ETP). RESULTS: 1) The median TPTC, VI, and ETP differed among the groups (p=0.001, p=0.006, p

A G3P2 patient who conceived while using an intrauterine contraceptive device (IUD) presented at 20 weeks of gestation with mild irregular uterine contractions and vaginal bleeding. Sonographic examination at admission showed the presence of dense amniotic fluid "sludge" and a long sonographic uterine cervix (42 mm). To assess the microbiologic significance of amniotic fluid "sludge", we performed a transabdominal amniocentesis. The procedure was performed under real-time ultrasound, and fluid resembling pus at gross examination was noted. Rapid amniotic fluid analysis showed the presence of a high white blood cell count and structures resembling hyphae. Amniotic fluid cultures were positive for Candida albicans. Treatment was begun with broad-spectrum antibiotics, including Fluconazole, upon the visualization of pus in the "sludge" material because of the presence of hyphae in the Gram stain. Despite treatment, the patient went into spontaneous preterm labor and delivered five days after admission. Placental examination revealed acute fungal histologic chorioamnionitis and funisitis. This represents the first report of transabdominal collection and analysis of amniotic fluid "sludge" and the microbiologic detection of Candida albicans in this material. This report provides evidence that transabdominal retrieval of "sludge" is possible and may be of significant value for patient management and selection of antimicrobial agents.

Objective Pregestational maternal obesity (PGMO) associates with foetoplacental vascular endothelial dysfunction and higher risk for insulin resistance in the neonate. We characterised the PGMO consequences on the insulin response of the human foetoplacental vasculature. Methods Umbilical veins were from pregnancies where the mother was with PGMO (body mass index 30–42.3 kg/m2, n = 33) or normal pregestational weight (PGMN) (body mass index 19.5–24.4 kg/m2, n = 21) with total gestational weight gain within the physiological range. Umbilical vein ring segments were mounted in a myograph for isometric force measurements. Primary cultures of human umbilical vein endothelial cells were used in passage 3. Vessel rings and cells were exposed to 1 nmol/L insulin (20 min) in the absence or presence of 100 μmol/L NG-nitro- l -arginine methyl ester (inhibitor of nitric oxide synthase, NOS). Results Vessel rings from PGMO showed reduced nitric oxide synthase-activity dependent dilation to insulin or calcitonin-gene related peptide compared with PGMN. PGMO associated with higher inhibitor phosphorylation of the insulin receptor substrate 1 (IRS-1) and lower activator phosphorylation of protein kinase B/Akt (Akt). Cells from PGMO also showed lower nitric oxide level and reduced activator serine1177 but increased inhibitor threonine495 phosphorylation of endothelial nitric oxide synthase (eNOS) and saturable transport of l -arginine. HUVECs from PGMO were not responsive to insulin. Conclusion The lack of response to insulin by the foetoplacental endothelium may result from reduced IRS-1/Akt/eNOS signalling in PGMO. These findings may result in higher risk of insulin resistance in neonates to PGMO pregnancies.

Background The frequency of intra-amniotic infection/inflammation (IAI/I) in patients with midtrimester cervical insufficiency is up to 50%. Our purpose was to determine the perinatal outcomes of cervical cerclage in patients with acute cervical insufficiency with bulging membranes, and to compare the admission-to-delivery interval and pregnancy outcomes according to the results of amniotic fluid (AF) analysis and cerclage placement. Methods This was a retrospective cohort study including singleton pregnancies with cervical insufficiency between 15 and 26.9 weeks in two tertiary health centers. IAI/I was defined when at least one of the following criteria was present in AF: (a) a white blood cell (WBC) count >50 cells/mm3; (b) glucose concentration Results Seventy patients underwent an amniocentesis to rule out IAI/I. The prevalence of IAI/I was 19%. Forty-seven patients underwent a cerclage. Patients with a cerclage had a longer median admission-to-delivery interval (33 vs. 2 days; P Conclusion The pregnancy outcomes of patients with midtrimester cervical insufficiency and bulging membranes are poor as they have a high prevalence of IAI/I. Therefore, a pre-operative amniocentesis is key to identify the best candidates for the subsequent placement of a cerclage.

Clinical chorioamnionitis at term (TCC) is the most common obstetrical infliction diagnosed in labor and delivery units worldwide and is associated with a substantial increase in maternal and neonatal morbidity and mortality. This obstetrical complication is a heterogeneous condition, as only half of patients have detectable microorganisms in the amniotic cavity. Because bioactive lipids play a key role in the initiation and resolution of an inflammatory response, we aimed to characterize the amniotic fluid lipidome in patients with TCC. We studied the amniotic fluid of patients in the following groups: 1) spontaneous labor at term without clinical chorioamnionitis (TLB) and 2) spontaneous labor at term with clinical chorioamnionitis (TCC). The TCC group was subdivided into a) those with microbial invasion of the amniotic cavity (TCC-MIAC) and b) those without microbial invasion of the amniotic cavity (TCC-noMIAC). The amniotic fluid concentration of proinflammatory lipid mediators did not differ between patients in TLB with TCC. In contrast, concentration of lipids with anti-inflammatory/proresolution properties was significantly lower in all patients with TCC than in those with TLB. These results suggest that while proinflammatory lipid mediators are involved in infection-driven intra-amniotic inflammation, a relative deficiency of anti-inflammatory/proresolution lipid mediator biosynthesis is a characteristic of TCC.

Objectives: The objectives of this study are to explore the feasibility of measuring endothelial and placental biomarkers in saliva and gingival crevicular fluid (GCF) and to determine if patients with preeclampsia (PE) have a different profile of these biomarkers in oral fluids. Method: A case-control study was conducted, including patients with PE (n=10) and a control group with normal pregnancies randomly selected (n=20) admitted at the Sotero del Rio Hospital in Santiago, Chile. A complete periodontal and obstetric history that involved the collection of oral fluids was performed at the same gestational age. Levels of Cd63 extracellular vesicles, placental alkaline phosphatase (PLAP), placental growth factor (PlGF), and sFlt-1 levels were determined by ELISA assays. Data analysis was performed with chi-square or Fisher's exact test, and Mann-Whitney U-test for continuous variables. The association was assessed using a multiple logistic regression model. Results: sFlt-1 concentrations in saliva and GCF were significantly higher in patients with PE (p=0.045 and p=0.033 respectively). Concentrations of PLAP were elevated in GCF of patients with PE (p=0.049). The PLAP/CD63 ratio in GCF of patients with PE was significantly higher (p=0.0008). No differences in PlGF levels were observed. Conclusion(s): GCF of patients with PE concentrates higher levels of biomarkers related with the PE development.

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.

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.

For hypertensive women in CHIPS (Control of Hypertension in Pregnancy Study), we assessed whether the maternal benefits of tight control could be achieved, while minimizing any potentially negative effect on fetal growth, by delaying initiation of antihypertensive therapy until later in pregnancy. For the 981 women with nonsevere, chronic or gestational hypertension randomized to less-tight (target diastolic blood pressure, 100 mm Hg), or tight (target, 85 mm Hg) control, we used mixed-effects logistic regression to examine whether the effect of less-tight (versus tight) control on major outcomes was dependent on gestational age at randomization, adjusting for baseline factors as in the primary analysis and including an interaction term between gestational age at randomization and treatment allocation. Gestational age was considered categorically (quartiles) and continuously (linear or quadratic form), and the optimal functional form selected to provide the best fit to the data based on the Akaike information criterion. Randomization before (but not after) 24 weeks to less-tight (versus tight) control was associated with fewer babies with birth weight P interaction =0.005), but more preterm birth ( P interaction =0.043), and no effect on perinatal death or high-level neonatal care >48 hours ( P interaction =0.354). For the mother, less-tight (versus tight) control was associated with more severe hypertension at all gestational ages but particularly so before 28 weeks ( P interaction =0.076). In women with nonsevere, chronic, or gestational hypertension, there seems to be no gestational age at which less-tight (versus tight) control is the preferred management strategy to optimize maternal or perinatal outcomes. Clinical Trial Registration— URL: https://www.isrctn.com . Unique identifier: ISRCTN71416914.

Background Lifestyle interventions are the primary prevention strategy for gestational diabetes (GDM) in obese/overweight women; however, these interventions have shown limited effectiveness. Omega-3 polyunsaturated fatty acids (PUFAs) intake has shown beneficial effects on glucose metabolism, lipid fractions and inflammatory factors in women who already have GDM. Combining PUFAs supplementation with a lifestyle intervention could achieve lower increase of glucose levels by improving insulin sensitivity. Our aim is to assess two prenatal nutritional interventions (home-based dietary counseling and/or docosahexaenoic acid (DHA) supplementation) delivered to obese/overweight women during pregnancy for them and their offspring to achieve better metabolic control. Methods/design Randomized controlled trial, 2 × 2 factorial design. Eligible pregnant women will be randomly allocated to one of the four parallel arms: 1) Home-based dietary counseling +800 mg/day DHA supplementation (n = 250); 2) 800 mg/day DHA (n = 250); 3) Home-based dietary counseling +200 mg/day DHA (n = 250); 4) 200 mg/day DHA (n = 250). Primary outcomes are: GDM; macrosomia; and neonatal insulin resistance. Data analyses will be done on an intention-to-treat basis. Discussion We expect the present study to contribute to the understanding of the potential effectiveness of an omega-3 supplementation on the risk of developing GDM in overweight/obese pregnant women. We will also test if the combination of having better dietary habits alongside with omega 3 supplementation will improve insulin sensitivity and as consequence, a lower elevation of glucose levels could be achieved. Trial Registration: NCT02574767

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.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.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 concentration80 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.(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).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.

OBJECTIVE: The aim of this study was to determine whether the activity of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the plasma of women with preeclampsia (PE) and a small-for-gestational-age (SGA) neonate differs from that of women with normal pregnancy and whether they are related to specific placental lesions.. METHODS: This cross-sectional study included the following groups: 1) normal pregnancy (n=68); 2) PE (n= 128); and 3) SGA (n=56). Maternal plasma TF and TFPI activity was determined with chromogenic assays. RESULTS: 1) The median maternal plasma TF activity, but not TFPI activity, differed among the study groups (p

Objective Clinical chorioamnionitis is the most common infection/inflammatory process diagnosed in labor and delivery units worldwide. The condition is a syndrome that can be caused by (1) intra-amniotic infection, (2) intra-amniotic inflammation without demonstrable microorganisms (i.e. sterile intra-amniotic inflammation), and (3) maternal systemic inflammation that is not associated with intra-amniotic inflammation. The presence of intra-amniotic inflammation is a risk factor for adverse maternal and neonatal outcomes in a broad range of obstetrical syndromes that includes clinical chorioamnionitis at term. Although the diagnosis of intra-amniotic infection has relied on culture results, such information is not immediately available for patient management. Therefore, the diagnosis of intra-amniotic inflammation could be helpful as a proxy for intra-amniotic infection, while results of microbiologic studies are pending. A rapid test is now available for the diagnosis of intra-amniotic inflammation, based on the determination of neutrophil collagenase or matrix metalloproteinase-8 (MMP-8). The objectives of this study were (1) to evaluate the diagnostic indices of a rapid MMP-8 test for the identification of intra-amniotic inflammation/infection in patients with the diagnosis of clinical chorioamnionitis at term, and (2) to compare the diagnostic performance of a rapid MMP-8 test to that of a conventional enzyme-linked immunosorbent assay (ELISA) interleukin (IL)-6 test for patients with clinical chorioamnionitis at term. Materials and methods A retrospective cohort study was conducted. A transabdominal amniocentesis was performed in patients with clinical chorioamnionitis at term (n=44). Amniotic fluid was analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital Mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). Amniotic fluid IL-6 concentrations were determined by ELISA, and rapid MMP-8 results were determined by Yoon's MMP-8 Check®. Intra-amniotic inflammation was defined as an elevated amniotic fluid IL-6 concentration ≥2.6 ng/mL, and intra-amniotic infection was diagnosed by the presence of microorganisms in the amniotic fluid accompanied by intra-amniotic inflammation. The diagnostic indices of Yoon's MMP-8 Check® for the identification of intra-amniotic inflammation were calculated. In order to objectively compare Yoon's MMP-8 Check® with the ELISA IL-6 test for the identification of intra-amniotic inflammation, we used an amniotic fluid white blood cell (WBC) count ≥50 cells/mm3 to define intra-amniotic inflammation. Results (1) A positive rapid MMP-8 test had a sensitivity of 82.4% (28/34), specificity of 90% (9/10), positive predictive value of 96.6% (28/29), negative predictive value of 60% (9/15), positive likelihood ratio 8.2 (95% CI 1.3-53.2), and negative likelihood ratio 0.2 (95% CI 0.1-0.4) for the identification of intra-amniotic inflammation (prevalence 77.3%); (2) a positive rapid MMP-8 test had a sensitivity of 91.7% (22/24), specificity of 65% (13/20), positive predictive value of 75.9% (22/29), negative predictive value of 86.7% (13/15), positive likelihood ratio of 2.6 (95% CI 1.4-4.8), and negative likelihood ratio of 0.1 (95% CI 0.03-0.5) for the identification of intra-amniotic infection; (3) the rapid MMP-8 test had a significantly higher specificity than the ELISA IL-6 test in the identification of intra-amniotic inflammation as determined by an amniotic fluid WBC count ≥50 cells/mm3. The sensitivity and accuracy of the rapid MMP-8 test were comparable to those of the ELISA IL-6 test; and (4) importantly, the rapid MMP-8 test had 100% sensitivity and 100% negative predictive value in the identification of neonates affected with fetal inflammatory response syndrome (FIRS). Conclusion The rapid diagnosis of intra-amniotic inflammation is possible by analysis of amniotic fluid using a point-of-care test for MMP-8. Patients with a positive test are at risk of delivering a neonate affected with systemic inflammation, a risk factor for adverse neonatal outcome.

Lipid mediators play an important role in reproductive biology, especially, in parturition. Enhanced biosynthesis of eicosanoids, such as prostaglandin E2 (PGE2) and PGF2α, precedes the onset of labor as a result of increased expression of inducible cyclooxygenase 2 (COX-2) in placental tissues. Metabolism of arachidonic acid results in bioactive lipid mediators beyond prostaglandins that could significantly influence myometrial activity. Therefore, an unbiased lipidomic approach was used to profile the arachidonic acid metabolome of amniotic fluid. In this study, liquid chromatography–mass spectrometry was used for the first time to quantitate these metabolites in human amniotic fluid by comparing patients at midtrimester, at term but not in labor, and at term and in spontaneous labor. In addition to exposing novel aspects of COX pathway metabolism, this lipidomic study revealed a dramatic increase in epoxygenase- and lipoxygenase-pathway-derived lipid mediators in spontaneous labor with remarkable product selectivity. Despite their recognition as anti-inflammatory lipid mediators and regulators of ion channels, little is known about the epoxygenase pathway in labor. Epoxygenase pathway metabolites are established regulators of vascular homeostasis in cardiovascular and renal physiology. Their presence as the dominant lipid mediators in spontaneous labor at term portends a yet undiscovered physiological function in parturition.—Maddipati, K. R., Romero, R., Chaiworapongsa, T., Zhou, S.-L., Xu, Z., Tarca, A. L., Kusanovic, J. P., Munoz, H., Honn, K. V. Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor.