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Small bowel obstruction (SBO) in pregnancy is exceedingly rare. Management of SBO in the third trimester may pose particular challenges, as clinicians must determine whether or not the delivery of the fetus is indicated. In this report, we review the case of a patient in her mid-20's with no prior surgical history who presented with nausea and vomiting at 34 weeks of gestation and was ultimately diagnosed with an SBO. Following expectant management during the initial 4 days of inpatient admission, the patient subsequently underwent an exploratory laparotomy at 35 weeks without concurrent delivery. She was monitored for the remainder of her pregnancy with non-stress tests to evaluate fetal status and eventually underwent induction of labour at 39 weeks, resulting in a successful vaginal delivery. Herein, we review the challenges related to the diagnosis and management of SBO in pregnancy, as well as the maternal-fetal outcomes in the setting of SBO in the third trimester.
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Parto Obstétrico , Obstrucción Intestinal , Femenino , Humanos , Embarazo , Feto , Hospitalización , Pacientes Internos , Obstrucción Intestinal/diagnóstico por imagen , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Tercer Trimestre del Embarazo , AdultoRESUMEN
OBJECTIVE: Placental cytosine (CpG) methylation was measured to predict new-onset postpartum preeclampsia (NOPP) and interrogate its molecular pathogenesis. METHODS: NOPP was defined as patients with a new diagnosis of postpartum preeclampsia developing ≥48 h to ≤6 weeks after delivery with no prior hypertensive disorders. Placental tissue was obtained from 12 NOPP cases and 12 normotensive controls. Genome-wide individual cytosine (CpG) methylation level was measured with the Infinium MethylationEPIC BeadChip array. Significant differential methylation (NOPP vs. controls) for individual CpG loci was defined as false discovery rate (FDR) p value <.05. Gene functional enrichment using Qiagen's ingenuity pathway analysis (IPA) was performed to help elucidate the molecular pathogenesis of NOPP. A logistic regression model for NOPP prediction based on the methylation level in a combination of CpG loci was generated. The area under the receiver operating characteristic curves (AUC [95% CI]) sensitivity, and specificity for NOPP prediction based on the CpG methylation level was calculated for each locus. RESULTS: There were 537 (in 540 separate genes) significantly (FDR p<.05 with a ≥ 2.0-fold methylation difference) differentially methylated CpG loci between the groups. A total of 143 individual CpG markers had excellent individual predictive accuracy for NOPP prediction (AUC ≥0.80), of which 14 markers had outstanding accuracy (AUC ≥0.90). A logistic regression model based on five CpG markers yielded an AUC (95% CI)=0.99 (0.95-0.99) with sensitivity 95% and specificity 93% for NOPP prediction. IPA revealed dysregulation of critical pathways (e.g., angiogenesis, chronic inflammation, and epithelial-mesenchymal transition) known to be linked to classic preeclampsia, in addition to other previously undescribed genes/pathways. CONCLUSIONS: There was significant placental epigenetic dysregulation in NOPP. NOPP shared both common and unique molecular pathways with classic preeclampsia. Finally, we have identified novel potential biomarkers for the early post-partum prediction of NOPP.
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Preeclampsia , Humanos , Femenino , Embarazo , Islas de CpG , Preeclampsia/diagnóstico , Preeclampsia/genética , Preeclampsia/metabolismo , Metilación de ADN , Placenta/metabolismo , Epigénesis Genética , Periodo Posparto/genética , Biomarcadores/metabolismo , Citosina/metabolismoRESUMEN
Cerebral palsy (CP), defined as a group of nonprogressive disorders of movement and posture, is the most common cause of severe neurodisability in children. The prevalence of CP is the same across the globe, affecting approximately 17 million people worldwide. Cerebral Palsy is an umbrella term used to describe the disease due to its inherent heterogeneity. For instance, CP has multiple (1) causes; (2) clinical types; (3) patterns of neuropathology on brain imaging and (4) it's associated with several developmental pathologies such as intellectual disability, autism, epilepsy, and visual impairment. Understanding its physiopathology is crucial to developing protective strategies. Despite its importance, there is still insufficient progress in the areas of CP prediction, early diagnosis, treatment, and prevention. Herein we describe the current risk factors and biomarkers used for the diagnosis and prediction of CP. With the advancement in biomarker discovery, we predict that our understanding of the etiopathophysiology of CP will also increase, lending to more opportunities for developing novel treatments and prognosis.
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Parálisis Cerebral/diagnóstico , Animales , Biomarcadores/análisis , Parálisis Cerebral/epidemiología , Parálisis Cerebral/etiología , HumanosRESUMEN
The Joint Commission recommends that severe maternal morbidity (SMM) cases involving peripartum ICU admissions and blood transfusion > 4 units undergo systematic reviews to determine opportunities for improvement in care. This article describes a retrospective study of an SMM multidisciplinary committee review using a published template. METHODS: Residents attend a patient safety and quality improvement (PSQI) course at orientation, learn in serial PSQI educational sessions, and receive individual training on the SMM review. The multidisciplinary SMM review process determines contributory factors, identifies best practices, recognizes care improvement opportunities, and facilitates adoption of appropriate interventions. How the process educated residents on the Clinical Learning Environment Review (CLER) focus areas was explored. RESULTS: From January 2015 to June 2017, 45 SMM cases were reviewed. Reviewers were primarily residents/fellows (64.4% of cases), nurses (11.1%), and maternal-fetal medicine faculty (24.4%). Transfusion > 4 units occurred in 44.4% of cases, and ICU admission in 68.9%. Causes of SMM included obstetric bleeding (57.8%), hypertensive crisis (42.2%), and cardiac disease (24.4%). Preterm delivery occurred in 60.0% of cases; 71.1% were postpartum, and 80.0% had cesarean deliveries. Contributory provider factors included diagnostic delays (55.6%) and treatment delays or errors (44.4%). Contributory patient factors included psychiatric/behavioral health (20.0%) and health care barriers (22.2%). Morbidity could have been prevented by provider factors in 53.3% of cases and by patient factors in 37.8%. Interventions initiated included recruiting a safety nurse, TeamSTEPPS® training, and adoption of hypertension and postpartum hemorrhage safety bundles. CONCLUSION: SMM reviews can be successfully implemented and provide training on safety and quality.
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Internado y Residencia , Obstetricia/educación , Seguridad del Paciente , Complicaciones del Embarazo/prevención & control , Mejoramiento de la Calidad , Femenino , Humanos , Modelos Educacionales , Embarazo , Estudios RetrospectivosRESUMEN
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 small for gestational age (SGA) neonate differ from that of normal pregnant women 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 < .0001 and p = .4, respectively); (2) patients with PE had a higher median maternal plasma TF activity than women with normal pregnancies (p < .0001) and mothers with SGA fetuses (p = .002); (3) among patients with PE, those with distal villous hypoplasia had a higher median maternal TF activity than those without these placental lesions (p = .018); and (4) following adjustment for confounding variables, maternal plasma TF and TFPI activity were not associated with an SGA neonate. CONCLUSIONS: Plasma TF activity is higher in women with PE than in those with SGA or normal pregnancies. We propose that these changes may be responsible, at least in part, for the increased in-vivo thrombin generation observed in this obstetrical syndrome.
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Lipoproteínas/sangre , Preeclampsia/sangre , Trombina/metabolismo , Tromboplastina/metabolismo , Adulto , Estudios Transversales , Femenino , Humanos , Recién Nacido Pequeño para la Edad Gestacional , Placenta/patología , Preeclampsia/patología , Embarazo , Adulto JovenRESUMEN
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 = .001, p = .006, p < .0001); 2) the median ETP was higher in the PE than in the NP (p < .0001) and SGA (p = .02) groups; 3) patients with SGA had a shorter median TPTC and a higher median VI than the NP (p = .002, p = .012) and PE (p < .0001, p = .006) groups. CONCLUSIONS: (1) Patients with PE had higher in vivo thrombin generation than women with NP and those with an SGA fetus; (2) the difference in TGA patterns between PE and SGA suggests that the latter group had faster TGA, while patients with PE had a longer reaction, generating more thrombin. This observation is important for the identification of a subset of patients who might benefit from low molecular-weight heparin.
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Preeclampsia/sangre , Trombina/biosíntesis , Adulto , Estudios de Casos y Controles , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional/sangre , Lipoproteínas/sangre , Embarazo , Trombina/análisis , Adulto JovenRESUMEN
Ultrasound (US)-based thermal imaging is very sensitive to tissue motion, which is a major obstacle to apply US temperature monitoring to noninvasive thermal therapies of in vivo subjects. In this study, we aim to develop a motion compensation method for stable US thermal imaging in in vivo subjects. Based on the assumption that the major tissue motion is approximately periodic caused by respiration, we propose a motion compensation method for change in backscattered energy (CBE) with multiple reference frames. Among the reference frames, the most similar reference to the current frame is selected to subtract the respiratory-induced motions. Since exhaustive reference searching in all stored reference frames can impede real-time thermal imaging, we improve the reference searching by using a motion-mapped reference model. We tested our method in six tumor-bearing mice with high intensity focused ultrasound (HIFU) sonication in the tumor volume until the temperature had increased by 7°C. The proposed motion compensation was evaluated by root-mean-square-error (RMSE) analysis between the estimated temperature by CBE and the measured temperature by thermocouple. As a result, the mean ±SD RMSE in the heating range was 1.1±0.1°C with the proposed method, while the corresponding result without motion compensation was 4.3±2.6°C. In addition, with the idea of motion-mapped reference frame, total processing time to produce a frame of thermal image was reduced in comparison with the exhaustive reference searching, which enabled the motion-compensated thermal imaging in 15 frames per second with 150 reference frames under 50% HIFU duty ratio.
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Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Movimiento/fisiología , Termografía/métodos , Animales , Ratones , Ratones Desnudos , Neoplasias Experimentales , RespiraciónRESUMEN
We present a method to enhance depth quality of a time-of-flight (ToF) camera without additional devices or hardware modifications. By controlling the turn-off patterns of the LEDs of the camera, we obtain depth and normal maps simultaneously. Sixteen subphase images are acquired with variations in gate-pulse timing and light emission pattern of the camera. The subphase images allow us to obtain a normal map, which are combined with depth maps for improved depth details. These details typically cannot be captured by conventional ToF cameras. By the proposed method, the average of absolute differences between the measured and laser-scanned depth maps has decreased from 4.57 to 3.77 mm.
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BACKGROUND: To compare the diagnostic ability of optic disc rim area (RA), retinal nerve fiber layer thickness (RNFLT), and their combination on sector-based analysis of spectral domain optical coherence tomography (Cirrus OCT) in discriminating subjects with early-stage open angle glaucoma (OAG) from normal subjects. METHODS: RA and RNFLT of 78 early OAG and 80 normal subjects were measured on Cirrus OCT at the global area, 4 quadrants, 12 clock hours, and 7 + 11 o'clock (a sector that includes 7 and 11 o'clock). A new parameter, RR (a multiplication of the RA and RNFLT) was derived to identify the best combination of the two parameters. Areas under the receiver operating characteristics curves (AUCs) of RA, RNFLT, and RR were compared. RESULTS: AUCs of RA were larger than those of RNFLT at nasal quadrant, at 1-5 o'clock on Cirrus OCT (all P values < 0.05). At the remaining areas, the two parameters were not significantly different on both devices (all P values > 0.05). RR had significantly larger AUCs than those of both RA and RNFLT at 7 + 11 o'clock (0.931 for RA, 0.933 for RNFLT, and 0.968 for RR) and global area (0.914 for RA, 0.905 for RNFLT, and 0.935 for RR), which were the two areas with largest AUCs. CONCLUSIONS: RR outperformed both RA and RNFLT of the Cirrus OCT, especially at areas with diagnostic importance. This suggests that combinations of RA and RNFLT by sector-based analysis of Cirrus OCT would be promising to determine early glaucoma.
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Fibras Nerviosas/patología , Disco Óptico/patología , Enfermedades del Nervio Óptico/diagnóstico , Células Ganglionares de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Área Bajo la Curva , Estudios de Casos y Controles , Femenino , Glaucoma de Ángulo Abierto/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Pruebas del Campo Visual , Campos VisualesRESUMEN
Listeria is commonly found in processed and prepared foods and listeriosis is associated with high morbidity and mortality. Preventative measures are well prescribed and monitoring and voluntary recall of contaminated products has resulted in a 44% reduction in the prevalence of perinatal listeriosis in the USA. Pregnant women are at high risk for listeriosis, but symptoms are non-specific and diagnosis is difficult. The intracellular life-cycle of Listeria protects the bacterium from host innate and adaptive immune responses. Antibiotic treatment requires agents able to penetrate, distribute, and remain stable within host cells. Prolonged use of high-dose ampicillin can significantly improve neonatal outcome.
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Listeriosis , Complicaciones Infecciosas del Embarazo , Antibacterianos/uso terapéutico , Femenino , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/microbiología , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Listeria monocytogenes/crecimiento & desarrollo , Listeriosis/diagnóstico , Listeriosis/tratamiento farmacológico , Listeriosis/prevención & control , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/prevención & control , Factores de Riesgo , Estaciones del AñoRESUMEN
To measure the retinal arteriole and venule oxygen saturation (SO(2)) using a conventional fundus camera, retinal oximetry based on nonsimultaneous image acquisition was developed and evaluated. Two retinal images were sequentially acquired using a conventional fundus camera with two bandpass filters (568 nm: isobestic, 600 nm: nonisobestic wavelength), one after another, instead of a built-in green filter. The images were registered to compensate for the differences caused by eye movements during the image acquisition. Retinal SO(2) was measured using two wavelength oximetry. To evaluate sensitivity of the proposed method, SO(2) in the arterioles and venules before and after inhalation of 100% O(2) were compared, respectively, in 11 healthy subjects. After inhalation of 100% O(2), SO(2) increased from 96.0 ±6.0% to 98.8% ±7.1% in the arterioles (p=0.002) and from 54.0 ±8.0% to 66.7% ±7.2% in the venules (p=0.005) (paired t-test, n=11). Reproducibility of the method was 2.6% and 5.2% in the arterioles and venules, respectively (average standard deviation of five measurements, n=11).
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Técnicas de Diagnóstico Oftalmológico , Fondo de Ojo , Oximetría/métodos , Oxígeno/sangre , Vasos Retinianos/fisiología , Arteriolas/anatomía & histología , Arteriolas/fisiología , Humanos , Oximetría/instrumentación , Reproducibilidad de los Resultados , Vasos Retinianos/anatomía & histología , Vénulas/anatomía & histología , Vénulas/fisiologíaRESUMEN
OBJECTIVE: The aim of this study was to examine if maternal plasma concentrations of soluble vascular endothelial growth factor receptor (sVEGFR)-2 change prior to the diagnosis of preeclampsia. STUDY DESIGN: A longitudinal study was conducted in normal pregnant women (n = 160) and patients with preeclampsia (n = 40). Blood samples were collected at 7 gestational age intervals from 6 weeks to term. Plasma concentrations of sVEGFR-2 were determined by enzyme-linked immunosorbent assay. Analysis was performed with cross-sectional and longitudinal (mixed effects model) approaches. RESULTS: Mothers destined to develop preeclampsia have lower plasma sVEGFR-2 concentrations than those who will have a normal pregnancy (longitudinal approach; P < .05). Cross-sectional analysis suggested that the median plasma sVEGFR-2 concentration in women destined to develop preeclampsia was significantly lower than that in normal pregnant women from 28-31 weeks of gestation (P = .001) or 6-10 weeks prior to the diagnosis (P < .001). CONCLUSION: A lower maternal plasma sVEGFR-2 concentration precedes the development of preeclampsia, both term and preterm.
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Preeclampsia/sangre , Preeclampsia/diagnóstico , Receptor 2 de Factores de Crecimiento Endotelial Vascular/sangre , Adolescente , Adulto , Biomarcadores/sangre , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Edad Gestacional , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Selección de Paciente , Embarazo , Estadísticas no ParamétricasRESUMEN
OBJECTIVE: Women with a fetal death at the time of diagnosis have higher maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, than women with a normal pregnancy. An important question is whether these changes are the cause or consequence of fetal death. To address this issue, we conducted a longitudinal study and measured the maternal plasma concentrations of selective angiogenic and anti-angiogenic factors before the diagnosis of a fetal death. The anti-angiogenic factors studied were sVEGFR-1 and soluble endoglin (sEng), and the angiogenic factor, placental growth factor (PlGF). METHODS: This retrospective longitudinal nested case-control study included 143 singleton pregnancies in the following groups: (1) patients with uncomplicated pregnancies who delivered a term infant with an appropriate weight for gestational age (n=124); and (2) patients who had a fetal death (n=19). Blood samples were collected at each prenatal visit, scheduled at 4-week intervals from the first trimester until delivery. Plasma concentrations of sVEGFR-1, sEng, and PlGF were determined by specific and sensitive ELISA. A linear mixed-effects model was used for analysis. RESULTS: (1) The average profiles of analyte concentrations as a function of gestational age for sVEGFR-1, sEng and PlGF were different between women destined to have a fetal death and those with a normal pregnancy after adjusting for covariates (p<0.05); (2) Plasma sVEGFR-1 concentrations in patients destined to have a fetal death were significantly lower between 7 and 11 weeks of gestation and became significantly higher than those of women with a normal pregnancy between 20 and 37 weeks of gestation (p<0.05); (3) Similarly, plasma sEng concentrations of women destined to have a fetal death were lower at 7 weeks of gestation (p=0.04) and became higher than those of controls between 20 and 40 weeks of gestation (p<0.05); (4) In contrast, plasma PlGF concentrations were higher among patients destined to develop a fetal death between 7 and 14 weeks of gestation and became significantly lower than those in the control group between 22 and 39 weeks of gestation (p<0.05); (5) The ratio of PlGF/(sVEGFR-1 × sEng) was significantly higher in women destined to have a fetal death between 7 and 13 weeks of gestation (94-781%) and significantly lower (44-75%) than those in normal pregnant women between 20 and 40 weeks of gestation (p<0.05); (6) Similar results were obtained when patients with a fetal death were stratified into those who were diagnosed before or after 37 weeks of gestation. CONCLUSIONS: Fetal death is characterised by higher maternal plasma concentrations of PlGF during the first trimester compared to normal pregnancy. This profile changes into an anti-angiogenic one during the second and third trimesters.
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Antígenos CD/sangre , Muerte Fetal/sangre , Proteínas Gestacionales/sangre , Receptores de Superficie Celular/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Adolescente , Adulto , Endoglina , Femenino , Edad Gestacional , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Neovascularización Fisiológica , Factor de Crecimiento Placentario , Embarazo , Estudios RetrospectivosRESUMEN
OBJECTIVE: Angiogenic factors have been implicated in the pathophysiology of sepsis. In experimental models of sepsis (endotoxemia and/or cecal ligation puncture), there is increased expression of vascular endothelial growth factors (VEGF) and the administration of exogenous soluble VEGF receptor (sVEGFR)-1, an antagonist to VEGF, reduces morbidity and mortality. Moreover, a dramatic elevation in sVEGFR-1 has been demonstrated in human sepsis. Although a balance between angiogenic and anti-angiogenic factors is essential for feto-placental development, the changes of angiogenic factors during pregnancy in the context of infection have never been explored. Angiogenic factors also play crucial roles in the pathophysiology of preeclampsia (PE). This study was conducted to determine if maternal plasma concentrations of placental growth factor (PlGF), sVEGFR-2, and soluble endoglin (sEng) change in pregnancies complicated by acute pyelonephritis (AP) compared with normal pregnancy and PE. STUDY DESIGN: A case-control study was conducted in patients with AP, normal pregnant (NP) women, and patients with PE (n=36 for each group) matched for gestational age. AP was diagnosed in the presence of fever (temperature >or=38 degrees C), clinical signs of infection, and a positive urine culture for microorganisms. Plasma concentrations of PlGF, sVEGFR-2, and sEng were determined by ELISA. The results of plasma sVEGFR-1 concentrations have previously been reported, but were included in this study to provide a complete picture of the angiogenic/anti-angiogenic profiles. Serum concentrations of interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, interferon (IFN)-gamma, granulocyte macrophage colony stimulating factor, and tumor necrosis factor (TNF) were also determined using high sensitivity multiplexed immunoassays in patients with AP and NP. RESULTS: AP was associated with a lower median plasma concentration of PlGF and sVEGFR-2 than NP (both p<0.001). There were no significant differences in the median plasma concentrations of sEng and sVEGFR-1 between AP and NP (p=0.7 and 0.5, respectively). In contrast, there was a 5-fold decrease of the median plasma concentration of PlGF, and an 8-10-fold increase of the median plasma concentrations of sVEGFR-1 and sEng in PE compared with those in AP (all p<0.001). No significant difference in the median plasma concentration of sVEGFR-2 was observed between patients with PE and AP (p=0.5). Pregnant women with AP had median plasma concentrations of IL-6, IL-7, IL-8, IL-10, IFN-gamma, and TNF-alpha significantly higher than those in NP women (all p<0.001, except IL-7 p=0.004). CONCLUSION: AP is associated with changes in the profile of angiogenic and anti-angiogenic factors. Although some of these changes resemble those in PE (decreased PlGF and sVEGFR-2), the magnitude of the changes of PlGF is much higher in PE. We conclude that despite high plasma inflammatory cytokine concentrations, acute systemic inflammation in pregnancy has a different angiogenic/anti-angiogenic profile than that of PE.
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Inductores de la Angiogénesis/sangre , Inhibidores de la Angiogénesis/sangre , Complicaciones del Embarazo/sangre , Pielonefritis/complicaciones , Enfermedad Aguda , Adulto , Antígenos CD/sangre , Estudios de Casos y Controles , Endoglina , Femenino , Humanos , Recién Nacido , Interferón gamma/sangre , Interleucinas/sangre , Factor de Crecimiento Placentario , Preeclampsia/sangre , Embarazo , Resultado del Embarazo , Proteínas Gestacionales/sangre , Pielonefritis/sangre , Pielonefritis/diagnóstico , Receptores de Superficie Celular/sangre , Factor de Necrosis Tumoral alfa/sangre , Receptor 2 de Factores de Crecimiento Endotelial Vascular/sangreRESUMEN
OBJECTIVE: Angiogenesis is critical for successful pregnancy. An anti-angiogenic state has been implicated in preeclampsia, fetal growth restriction and fetal death. Increased maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, have been reported in women with preeclampsia and in those with fetal death. Recent observations indicate that an excess of sVEGFR-1 and soluble endoglin (sEng) is also present in the amniotic fluid of patients with preeclampsia. The aim of this study was to determine whether fetal death is associated with changes in amniotic fluid concentrations of sVEGFR-1 and sEng, two powerful anti-angiogenic factors. Study design. This cross-sectional study included patients with fetal death (n = 35) and controls (n = 129). Fetal death was subdivided according to clinical circumstances into: (1) unexplained (n = 25); (2) preeclampsia and/or placental abruption (n = 5); and (3) chromosomal/congenital anomalies (n = 5). The control group consisted of patients with preterm labor (PTL) who delivered at term (n = 92) and women at term not in labor (n = 37). AF concentrations of sVEGFR-1 and sEng were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Patients with a fetal death had higher median amniotic fluid concentrations of sVEGFR-1 and sEng than women in the control group (p < 0.001 for each); (2) these results remained significant among different subgroups of stillbirth (p < 0.05 for each); and (3) amniotic fluid concentrations of sVEGFR-1 and those of sEng above the third quartile were associated with a significant risk of unexplained preterm fetal death (adjusted OR = 10.8; 95%CI 1.3-89.2 and adjusted OR 87; 95% CI 2.3-3323, respectively). Conclusion. Patients with an unexplained fetal death at diagnosis are characterized by an increase in the amniotic fluid concentrations of sVEGFR-1 and sEng. These observations indicate that an excess of anti-angiogenic factors in the amniotic cavity is associated with unexplained fetal death especially in preterm gestations.
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Líquido Amniótico/metabolismo , Antígenos CD/metabolismo , Muerte Fetal/metabolismo , Receptores de Superficie Celular/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adolescente , Adulto , Estudios Transversales , Endoglina , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Adulto JovenRESUMEN
OBJECTIVE: Adipokines have been implicated in metabolic regulation and the immune response thus providing a molecular mechanism for the interaction between these two systems. Retinol binding protein 4 (RBP4) is a novel adipokine that plays a role in the pathophysiology of obesity-induced insulin resistance, as well as in the modulation of inflammation. The aim of this study was to determine whether there are changes in maternal plasma concentrations of RBP4 in pregnant women with acute pyelonephritis. STUDY DESIGN: This cross-sectional study included pregnant women in the following groups: 1) normal pregnancy (n=80); 2) pyelonephritis (n=39). Maternal plasma RBP4 concentrations were determined by enzyme-linked immunoassays. Non-parametric statistics were used for analyses. RESULTS: 1) The median maternal plasma RBP4 concentration was lower in patients with acute pyelonephritis than in those with a normal pregnancy (3709.6 ng/mL, interquartile range (IQR) 2917.7-5484.2 vs. 9167.6 ng/mL, IQR 7496.1- 10,384.1, P<0.001; 2) the median maternal plasma RBP4 concentration did not differ significantly between patients with acute pyelonephritis who had a positive blood culture and those with a negative culture (3285.3 ng/mL, IQR 2274.1-4741.1 vs. 3922.6 ng/mL, IQR 3126.8-5547.1, respectively, P=0.2); and 3) lower maternal plasma RBP4 concentrations were independently associated with pyelonephritis after adjustment for confounding factors. CONCLUSIONS: In contrast to what has been reported in preeclampsia, acute pyelonephritis during pregnancy is associated with lower maternal plasma RBP4 concentrations than in normal pregnancy. This finding suggests that the acute maternal inflammatory process associated with pyelonephritis is fundamentally different from that of the chronic systemic inflammatory process suggested in preeclampsia, in which RBP4 concentrations were found to be elevated.
Asunto(s)
Complicaciones Infecciosas del Embarazo/sangre , Pielonefritis/sangre , Pielonefritis/complicaciones , Proteínas Plasmáticas de Unión al Retinol/metabolismo , Enfermedad Aguda , Adulto , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Mediadores de Inflamación/sangre , Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
PROBLEM: Plasma concentrations of fragment Bb (FBb) are a marker for activation of the alternative pathway of the complement system. High concentrations of FBb in maternal blood, as early as the first trimester, are associated with subsequent spontaneous pre-term delivery <34 weeks of gestation. The aim of this study was to determine whether spontaneous pre-term labor (PTL) with intact membranes, intra-amniotic infection/inflammation (IAI) or labor at term are associated with alterations in circulating maternal FBb concentrations. METHOD OF STUDY: This cross-sectional study included women in the following groups: (i) non-pregnant (n = 40); (ii) normal pregnancy (gestational age range 20-36, 6/7 weeks, n = 63); (iii) women at term not in labor (n = 70); (iv) women at term in spontaneous labor (n = 59); (v) patients with an episode of PTL who delivered at term (n = 62); (vi) PTL without IAI who delivered pre-term (n = 30); and (vii) PTL with IAI who delivered pre-term (n = 67). Maternal plasma FBb concentrations were determined by ELISA. RESULTS: (i) Among patients with PTL, those who had a pre-term delivery either with IAI (1.21 microg/mL, IQR 0.77-2.16) or without IAI (1.13 microg/mL, IQR 0.92-2.08) had a higher median maternal plasma FBb concentration than those who delivered at term (0.86 microg/mL, IQR 0.64-1.57; P = 0.007 and P = 0.026, respectively); (ii) there was no difference in the median plasma FBb concentration between patients with and without IAI who delivered pre-term (P = 0.9); (iii) in contrast, spontaneous labor at term was not associated with a significant change in the maternal plasma FBb concentration (P = 0.8); (iv) maternal plasma concentration of FBb did not differ significantly between normal pregnant women and the non-pregnant controls (P = 0.8) and were not correlated with advancing gestational age (r = -0.28, P = 0.8). CONCLUSION: (i) Pre-term parturition is associated with activation of the alternative complement pathway in maternal circulation; (ii) such activation is not detectable in spontaneous labor at term; (iii) IAI does not explain the activation of the alternative pathway of complement in PTL. Collectively, these observations suggest that pre-term and term labors have fundamental differences in the regulation of innate immunity.
Asunto(s)
Vía Alternativa del Complemento/inmunología , Proteínas del Sistema Complemento/inmunología , Parto , Nacimiento Prematuro/inmunología , Adulto , Estudios Transversales , Femenino , Humanos , Trabajo de Parto/inmunología , Embarazo , Complicaciones Infecciosas del Embarazo/inmunología , Nacimiento a Término/inmunología , Adulto JovenRESUMEN
OBJECTIVE: Vaginal bleeding, placental abruption, and defective placentation are frequently observed in patients with preterm prelabor rupture of membranes (PROM). Recently, a role of vascular endothelial growth factor (VEGF) and its receptor, VEGF receptor (VEGFR)- 1 has been implicated in the mechanisms of membrane rupture. The purpose of this study was to determine whether the soluble form of VEGFR-1 and -2 concentrations in amniotic fluid (AF) change with preterm PROM, intra-amniotic infection/inflammation (IAI), or parturition. STUDY DESIGN: This cross-sectional study included 544 patients in the following groups: (1) midtrimester (MT) (n = 48); (2) preterm labor (PTL) leading to term delivery (n = 143); (3) PTL resulting in preterm delivery with (n = 72) and without IAI (n = 100); (4) preterm PROM with (n = 46) and without IAI (n = 42); (5) term in labor (n = 48); and (6) term not in labor (n = 45). The concentrations of sVEGFR-1 and sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. RESULTS: (1) Preterm PROM (with and without IAI) had a lower median AF concentration of sVEGFR-1 than patients with PTL who delivered at term (p < 0.001 for each comparison); (2) A decrease in AFsVEGFR-1 concentrations per each quartile was associated with PROM after adjusting for confounders (OR 1.8; 95%CI 1.4-2.3); (3) IAI, regardless of the membrane status, was not associated with a change in the median AF concentrations of sVEGFR-1 and sVEGFR-2 (p > 0.05 for each comparison); and (4) Spontaneous term and PTL did not change the median sVEGFR-1 and sVEGFR-2 concentrations (p > 0.05 for each comparison). CONCLUSION: (1) This is the first evidence that preterm PROM is associated with a lower AF concentration of sVEGFR-1 than patients with PTL intact membranes. These findings cannot be attributed to gestational age, labor, or IAI; and (2) AF concentrations of sVEGFR-2 did not change with preterm PROM, IAI, or labor at term and preterm.
Asunto(s)
Líquido Amniótico/metabolismo , Rotura Prematura de Membranas Fetales/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adolescente , Adulto , Estudios Transversales , Femenino , Edad Gestacional , Humanos , Embarazo , Nacimiento Prematuro/metabolismo , Nacimiento a Término/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: An anti-angiogenic state has been implicated in the pathophysiology of preeclampsia, fetal growth restriction and fetal death. Vascular endothelial growth factor (VEGF), an indispensible angiogenic factor for embryonic and placental development exerts its angiogenic properties through the VEGF receptor (VEGFR)-2. A soluble form of this protein (sVEGFR-2) has been recently detected in maternal blood. The aim of this study was to determine if fetal death was associated with changes in the concentrations of sVEGFR-2 in maternal plasma and amniotic fluid. STUDY DESIGN: Maternal plasma was obtained from patients with fetal death (n = 59) and normal pregnant women (n = 134). Amniotic fluid was collected from 36 patients with fetal death and the control group consisting of patients who had an amniocentesis and delivered at term (n = 160). Patients with fetal death were classified according to the clinical circumstances into the following groups: (1) unexplained; (2) preeclampsia and/or placental abruption; (3) chromosomal and/or congenital anomalies. Plasma and amniotic fluid concentrations of sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. RESULTS: (1) Patients with a fetal death had a significantly lower median plasma concentration of sVEGFR-2 than normal pregnant women (p < 0.001). The median plasma concentration of sVEGFR-2 in patients with unexplained fetal death and in those with preeclampsia/abruption, but not that of those with congenital anomalies, was lower than that of normal pregnant women (p = 0.006, p < 0.001 and p = 0.2, respectively); (2) the association between plasma sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 3.2; 95% CI: 1.4-7.3 per each quartile decrease in plasma sVEGFR-2 concentrations); (3) each subgroup of fetal death had a higher median amniotic fluid concentration of sVEGFR-2 than the control group (p < 0.001 for each); (4) the association between amniotic fluid sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 15.6; 95% CI: 1.5-164.2 per each quartile increase in amniotic fluid sVEGFR-2 concentrations); (5) among women with fetal death, there was no relationship between maternal plasma and amniotic fluid concentrations of sVEGFR-2 (Spearman Rho: 0.02; p = 0.9). CONCLUSION: Pregnancies with a fetal death, at the time of diagnosis, are characterized by a decrease in the maternal plasma concentration of sVEGFR-2, but an increase in the amniotic fluid concentration of this protein. Although a decrease in sVEGFR-2 concentration in maternal circulation depends upon the clinical circumstances of fetal death, an increase in sVEGFR-2 concentration in amniotic fluid seems to be a common feature of fetal death. It remains to be determined if the perturbation in sVEGFR-2 concentrations in maternal and fetal compartments observed herein preceded the death of a fetus.
Asunto(s)
Muerte Fetal/sangre , Muerte Fetal/etiología , Circulación Placentaria , Receptor 2 de Factores de Crecimiento Endotelial Vascular/sangre , Desprendimiento Prematuro de la Placenta/sangre , Desprendimiento Prematuro de la Placenta/epidemiología , Desprendimiento Prematuro de la Placenta/metabolismo , Adolescente , Adulto , Líquido Amniótico/química , Líquido Amniótico/metabolismo , Estudios de Casos y Controles , Estudios Transversales , Femenino , Muerte Fetal/diagnóstico , Muerte Fetal/epidemiología , Humanos , Intercambio Materno-Fetal/fisiología , Concentración Osmolar , Circulación Placentaria/fisiología , Preeclampsia/sangre , Preeclampsia/epidemiología , Preeclampsia/metabolismo , Embarazo , Solubilidad , Receptor 2 de Factores de Crecimiento Endotelial Vascular/análisis , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/fisiología , Adulto JovenRESUMEN
OBJECTIVE: Maternal circulating visfatin concentrations are higher in patients with a small-for-gestational-age (SGA) neonate than in those who delivered an appropriate-for-gestational age (AGA) neonate or in those with pre-eclampsia. It has been proposed that enhanced transfer of visfatin from the foetal to maternal circulation may account for the high concentrations of maternal visfatin observed in patients with an SGA neonate. The aims of this study were: (1) to determine whether cord blood visfatin concentrations differ between normal neonates, SGA neonates and newborns of pre-eclamptic mothers; and (2) to assess the relationship between maternal and foetal circulating visfatin concentrations in patients with an SGA neonate and those with pre-eclampsia. STUDY DESIGN: This cross-sectional study included 88 pregnant women and their neonates, as well as 22 preterm neonates in the following groups: (1) 44 normal pregnant women at term and their AGA neonates; (2) 22 normotensive pregnant women and their SGA neonates; (3) 22 women with pre-eclampsia and their neonates; and (4) 22 preterm neonates delivered following spontaneous preterm labour without funisitis or histologic chorioamnionitis, matched for gestational age with infants of pre-eclamptic mothers. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses. RESULTS: (1) The median visfatin concentration was lower in umbilical cord blood than in maternal circulation, in normal pregnancy, SGA and pre-eclampsia groups (p<0.001 for all comparisons); (2) the median cord blood visfatin concentrations did not differ significantly between term AGA or SGA neonates, infants of mothers with pre-eclampsia and their gestational-age-matched preterm AGA neonates; (3) maternal and cord blood visfatin concentrations correlated only in the normal term group (r=0.48, p=0.04). CONCLUSION: Circulating visfatin concentrations are lower in the foetal than in the maternal circulation and did not significantly differ between the study groups. Thus, it is unlikely that the foetal circulation is the source of the high maternal visfatin concentrations reported in patients with an SGA neonate.