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Catalin S Buhimschi

Publications and source records attributed to Catalin S Buhimschi.

At least 19 recordsLinked to original sources
PubMed2007

Proteomic profiling of the amniotic fluid to detect inflammation, infection, and neonatal sepsis.

BACKGROUND: Proteomic analysis of amniotic fluid shows the presence of biomarkers characteristic of intrauterine inflammation. We sought to validate prospectively the clinical utility of one such proteomic profile, the Mass Restricted (MR) score. METHODS AND FINDINGS: We enrolled 169 consecutive women with singleton pregnancies admitted with preterm labor or preterm premature rupture of membranes. All women had a clinically indicated amniocentesis to rule out intra-amniotic infection. A proteomic fingerprint (MR score) was generated from fresh samples of amniotic fluid using surface-enhanced laser desorption ionization (SELDI) mass spectrometry. Presence or absence of the biomarkers of the MR score was interpreted in relationship to the amniocentesis-to-delivery interval, placental inflammation, and early-onset neonatal sepsis for all neonates admitted to the Newborn Special Care Unit (n = 104). Women with "severe" amniotic fluid inflammation (MR score of 3 or 4) had shorter amniocentesis-to-delivery intervals than women with "no" (MR score of 0) inflammation or even "minimal" (MR score of 1 or 2) inflammation (median [range] MR 3-4: 0.4 d [0.0-49.6 d] versus MR 1-2: 3.8 d [0.0-151.2 d] versus MR 0: 17.0 d [0.1-94.3 d], p < 0.001). Nonetheless, a "minimal" degree of inflammation was also associated with preterm birth regardless of membrane status. There was a significant association between the MR score and severity of histological chorioamnionitis (r = 0.599, p < 0.001). Furthermore, neonatal hematological indices and early-onset sepsis significantly correlated with the MR score even after adjusting for gestational age at birth (OR for MR 3-4: 3.3 [95% CI, 1.1 to 9.2], p = 0.03). When compared with other laboratory tests routinely used to diagnose amniotic fluid inflammation and infection, the MR score had the highest accuracy to detect inflammation (white blood cell count > 100 cells/mm3), whereas the combination of Gram stain and MR score was best for rapid prediction of intra-amniotic infection (positive amniotic fluid culture). CONCLUSIONS: High MR scores are associated with preterm delivery, histological chorioamnionitis, and early-onset neonatal sepsis. In this study, proteomic analysis of amniotic fluid was shown to be the most accurate test for diagnosis of intra-amniotic inflammation, whereas addition of the MR score to the Gram stain provides the best combination of tests to rapidly predict infection.

Adolescent↗
PubMed2006

Serum and urine inhibin A but not free activin A are endocrine biomarkers of severe pre-eclampsia.

OBJECTIVE: Elevation of total serum inhibin A and activin A has been interpreted as evidence of placental dysfunction in women who develop pre-eclampsia. We sought to evaluate serum and urine levels of inhibin A and free activin A in normal and hypertensive pregnancies. STUDY DESIGN: Inhibin A and free activin A were measured by immunoassay in simultaneously collected serum and urine samples from 75 women: (1) severe pre-eclampsia (n = 30); (2) mild pre-eclampsia (n = 11); (3) chronic hypertension (n = 9); (4) pregnant control women (n = 16); and (5) nonpregnant control women (n = 9). Urine levels were normalized to milligrams urine creatinine, and fractional excretions were calculated. RESULTS: Serum and urine inhibin A were increased and fractional excretion was decreased in pregnancy. Serum, urine, and fractional excretion of inhibin A were increased in severe pre-eclampsia, compared with other gravidas. The only difference observed in free activin A was a decrease in serum free activin A in chronic hypertension, compared with severe pre-eclampsia and pregnant control women. Urine inhibin A showed the greatest discrimination between severe pre-eclampsia and pregnant control women: a cut-off of 45 pg/mg urine creatinine had 96.8% sensitivity, 87.5% specificity, and 93.6% accuracy. Women with urine inhibin A greater than 90 pg/mg urine creatinine had a 17-fold relative risk (95% confidence interval 9.7-459.5) of a clinically indicated delivery due to pre-eclampsia. CONCLUSION: Serum and urine levels of inhibin A are altered in severe pre-eclampsia. Urine inhibin A may have application in the diagnosis and management of pre-eclampsia. Those with chronic hypertension have lower serum but not urine free activin A levels, compared with severe pre-eclampsia and mild pre-eclampsia.

Activins↗
PubMed2006

Lactate dehydrogenase isoform activity mapping in patients with intra-amniotic infection.

OBJECTIVE: Five distinct lactate dehydrogenase isoenzymes have been described. We sought to illustrate the specific amniotic fluid lactate dehydrogenase isoenzyme activity profiles in women with intra-amniotic infection. STUDY DESIGN: Amniotic fluid was retrieved from 82 women who were stratified in the following groups: (1) positive amniotic fluid cultures (n = 23 women; gestational age, 26 weeks [range, 21-32 weeks]); (2) negative amniotic fluid cultures (n = 22 women; gestational age, 30 weeks [range, 16-36 weeks]); (3) second trimester control (normal genetic karyotype; n = 17 women; gestational age, 18 weeks [range, 16-22 weeks]); and (4) third trimester control (fetal lung maturity testing; n = 20 women; gestational age, 36 weeks [range, 31-38 weeks]). The optical density of each isoform was determined relative to a standard with 5 known lactate dehydrogenase isoenzyme activities. Total lactate dehydrogenase activity was measured by the clinical laboratory immediately after retrieval and by a kinetic UV spectrophotometric assay at the time of the isoelectric focusing. RESULTS: Infection increased total lactate dehydrogenase activity: positive amniotic fluid cultures (median, 762.4 [range, 169.3-3374.8]) vs negative amniotic fluid cultures (median, 203.7 [range, 57.8-1939.3]; U/L; P < .001]). Lactate dehydrogenase isoform profiling identified significant and specific increases in lactate dehydrogenase isoforms 3, 4 (P < .01), and 5 (P < .05) in positive amniotic fluid cultures compared to the negative amniotic fluid cultures group. A selective up-regulation in lactate dehydrogenase isoform 5 was identified at term in healthy subjects. CONCLUSION: Intra-amniotic infection is characterized by an increase in the activities of lactate dehydrogenase isoforms 3, 4, and 5; advancing gestational age demonstrates an up-regulation of isoform 5 only.

Adult↗
PubMed2006

A low vaginal "pool" amniotic fluid glucose measurement is a predictive but not a sensitive marker for infection in women with preterm premature rupture of membranes.

OBJECTIVE: We sought to identify the use of vaginal amniotic fluid (vAF) glucose measurements in predicting infection of the amniotic fluid retrieved by transabdominal amniocentesis (aAF) in women with preterm premature rupture of the membranes (PPROM). STUDY DESIGN: Fluid was retrieved by aAF was retreived from 35 consecutive women with PPROM on whom an amniocentesis was clinically indicated to rule out intra-amniotic infection/inflammation and successfully completed. aAF was cultured for aerobic, anaerobic bacteria, Ureaplasma and Mycoplasma species. Clinical laboratory analysis for aAF included glucose concentration, Gram stain, lactate dehydrogenase, and white and red blood cell count. vAF was analyzed only for glucose concentration. Glucose concentration for the paired abdominal-vaginal AF samples (aAF-vAF) was determined by using well-established clinical and research laboratory methods. At the end of enrollment we stratified our patients into 2 groups: (1) positive microbial cultures (+)AFC (n = 17, gestational age [GA]: 27.3 +/- 0.7 weeks) or (2) negative microbial cultures (-)AFC (n = 18, GA: 31.3 +/- 0.5 weeks). Cohen kappa measure of concordance and receiver operating characteristic (ROC) curve analysis were used to test the ability of the vaginal "pool" glucose measurements to discriminate between women with positive or negative AF cultures. RESULTS: Women with (+)AFC ruptured and delivered at an earlier GA compared with the (-)AFC group (p < .001). The latency period was similar (P = .35). There was a significant linear correlation between aAF and vAF glucose concentrations (r = 0.783, P < .001). Women with intra-amniotic infection (IAI) had significantly lower aAF [mean +/- SEM (+)AFC: 11.4 +/- 3.2 vs (-)AFC 23.0 +/- 2.8 mg/dL, P = .01] and vAF glucose levels [(+)AFC: 10.1 +/- 2.8 vs (-)AFC: 19.8 +/- 2.9 mg/dL, P = .02] compared with the noninfected group. Cohen kappa measure of concordance indicated "substantial" agreement between aAF and vAF glucose measurements (kappa = 0.719, 95% CI = 0.491-0.947). The sensitivity of the vAF glucose level to detect IAI ranged from 82% to 47%, whereas specificity ranged from 100% to 56% depending on the threshold we used. A vaginal "pool" (vAF) glucose measurement less than 5 mg/dL had 47.1% sensitivity, 100% specificity, 100% positive predictive value, 66.7% negative predictive value, and 74.2% accuracy in identifying women with (+)AFC. CONCLUSION: Vaginal glucose determination is a readily available, inexpensive, rapid AF marker that can be measured practically in any clinical laboratory. vAF glucose measurements less than 5 mg/dL have predictive value, but low sensitivity for detection of IAI.

Adult↗
PubMed2006

The effect of dystocia and previous cesarean uterine scar on the tensile properties of the lower uterine segment.

OBJECTIVE: The remodeling of uterine connective tissue during labor can lead to the reorganization of the extracellular matrix that, in turn, may influence the biomechanical properties of the myometrial wall. We hypothesized that the stretching of the lower uterine segment in laboring women with dystocia changes the viscoelastic properties of the uterine wall. STUDY DESIGN: We tested the tensile strength of lower uterine segment myometrium in 68 pregnant women at term. The biomechanical, structural, and biochemical properties were compared among 3 groups: (1) 39 laboring women who underwent primary low-transverse cesarean delivery for labor dystocia, (2) 12 nonlaboring women who underwent primary elective low-transverse cesarean delivery and (3) 17 women who underwent an elective repeat low-transverse cesarean delivery at term. The tensile properties were quantitated with a stretching regimen that was designed to mimic the conditions of labor. Parameters such as slope, yield point, and break point were recorded, analyzed, and interpreted. Biochemical properties were determined by the measurement of the sulfated glycosaminoglycans, hydroxyproline, and pyridinoline-deoxypyridinoline. Histologic properties of the connective tissue were assessed by collagen birefringence. Lastly, the association between these properties and biomechanical responses were compared among groups. RESULTS: Lower uterine segment myometrium specimens obtained from laboring women were stiffer compared with specimens from women who were not in labor (P = .013) or had scarred myometrium (P < .001). The force that was required to reach the yield point was similar between labor and nonlabor groups (P = .216). Likewise, a previous lower uterine segment scar did not alter the yield point. The break point was similar among all groups (P = .317). Sulfated glycosaminoglycan levels were unaffected by labor or scarring (P = .354). Scarred lower uterine segment myometrium had a higher collagen content compared with unscarred myometrium specimens that were obtained during labor (P = .025). Although there were similar degrees of collagen cross-linking among groups (P = .212), there was lower collagen birefringence in myometrium from laboring women compared with nonlaboring women (P < .001). CONCLUSION: Labor alters the viscoelastic properties of myometrium. Lower uterine segment myometrium is stiffest in women with dysfunctional labor compared with nonlabor control subjects. Labor and scarring also alter the pattern of collagen birefringence. Similar collagen cross-linking among the study groups may explain the reason that the breaking strength of the tissue is not altered by the state of labor and the reason that the rupture of the uterine scar is a rare event.

Adult↗
PubMed2006

Burkitt's lymphoma of the ovary in pregnancy.

BACKGROUND: Burkitt's lymphoma is a rapidly growing and, if untreated, rapidly fatal tumor derived from B-lymphocytes. The occurrence of Burkitt's lymphoma during pregnancy is rare. CASE: A patient with Burkitt's lymphoma presented at 12 weeks of gestation with abdominal and tooth pain. An 11 x 11 x 15 cm mass was seen on abdominal/pelvic ultrasonogram. She underwent a left salpingo-oophorectomy with removal of the mass, as well as a tooth extraction. The pathology examination confirmed lymphoma in the left ovary and in the tissue surrounding the extracted tooth. After surgical resection, she was treated with multiagent chemotherapy beginning at 13 4/7 weeks of gestation. At 39 weeks, she delivered a viable female infant weighing 2,270 g. CONCLUSION: The finding of an adnexal mass in conjunction with head and neck symptoms led to consideration of Burkitt's lymphoma. Prompt treatment with multiagent chemotherapy should be considered for pregnant patients with Burkitt's lymphoma.

Adult↗
PubMed2006

Fractional excretion of angiogenic factors in women with severe preeclampsia.

OBJECTIVE: We estimated the fractional excretions of soluble fms-like tyrosine kinase 1 (sFlt-1), vascular endothelial growth factor, and placental growth factor of severely preeclamptic women at the time of disease clinical manifestation. METHODS: Levels of free sFlt-1, vascular endothelial growth factor, and placental growth factor were measured by immunoassay from time-matched serum-urine samples from 64 women in the following groups: nonpregnant reproductive aged (n = 9), healthy pregnant controls (n = 13), mildly preeclamptic women (n = 15), and women with severe preeclampsia (n = 27). Urinary concentrations of angiogenic factors were normalized to creatinine and fractional excretions calculated. Correlations were estimated between fractional excretions of angiogenic factors, albuminuria, nonspecific proteinuria and urine protein-to-creatinine ratio. RESULTS: Severely preeclamptic women had more than double urinary vascular endothelial growth factor (P = .01) and fractional excretion of vascular endothelial growth factor compared with mildly preeclamptic women (P = .007) or pregnant controls (P < .001). Serum, urine and fractional excretion levels of sFlt-1 were much higher among severely preeclamptic women compared with all the other pregnant groups (P < .001). Conversely, severely preeclamptic women had lower serum placental growth factor levels compared with healthy pregnant women (P < .05) and mildly preeclamptic groups (P < .05). Severely preeclamptic women had increased fractional excretions of placental growth factor, albumin, proteinuria, and random urine total protein/creatinine ratio. Among severely preeclamptic women there was no correlation between proteinuria and fractional excretion of vascular endothelial growth factor (r = 0.30, P = .127) or sFlt-1 (r = 0.35, P = .07). There was a significant correlation between fractional excretion for placental growth factor, random urine total protein/creatinine ratio (r = 0.60, P = .002), and nonspecific proteinuria (r = 0.50, P = .01). CONCLUSION: Severe preeclampsia is characterized by increased fractional excretion of angiogenic factors and especially of vascular endothelial growth factor, likely reflecting 2 separate phenomena that may have additive effects: "endogenous" renal production and glomerular "leakage."

Adult↗
PubMed2006

Clinical proteomics: a novel diagnostic tool for the new biology of preterm labor, part I: proteomics tools.

The molecular mechanisms regulating myometrial contractility and preterm premature rupture of the membranes leading to preterm birth are poorly understood. The completion of the human genome sequence led to the development of functional genomics and gene array technology to simultaneously identify candidate genes potentially involved in regulation of human parturition. However, the study of living systems can now be expanded past genomics based on the rationale that it is the protein products of the genes, not simply gene expression, that have effects and cause disturbances at the cellular level. Therefore, identification of disease biomarkers, followed by a description of their functional networks, has the potential to significantly aid the development of new strategies for the prediction, diagnosis, and prevention of preterm birth. Interest in mass spectrometry and its use as a new clinical diagnostic tool has grown rapidly and is poised to become an important medical field for the next century.

Biomarkers↗
PubMed2006

Proteomics, part II: the emerging role of proteomics over genomics in spontaneous preterm labor/birth.

UNLABELLED: Conventional wisdom holds that complications of immature organ systems such as respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia are the primary causes of the high neonatal morbidity and mortality attendant preterm delivery. However, recent evidence suggests that a major cause of prematurity-associated neonatal pathology is the fetal and neonatal response to inflammation/infection. Although functional genomics offered the promise of providing answers to many of these questions, the identification of the genes intrinsic to human parturition proved to be a difficult task. Proteomic profiling of the amniotic fluid (AF) provides a precise means for detection of inflammation by revealing the presence of 4 biomarkers (defensins-2 and -1, calgranulin-C, and calgranulin-A) that are highly predictive of intrauterine inflammation (MR score). The MR score is especially useful as it presents a gradient of disease activity progressing from "absent" to "mild" to "severe" inflammation. Thus, it provides the ability to identify patients who may benefit from interventions in utero in a modern diagnostic-therapeutic framework. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to explain that the cause or causes of preterm delivery are still unknown, recall that functional genomics has not given the answer to these causes, and state that proteomic profiling of amniotic fluid, through mass-restricted (MR) scoring, may be predictive of intrauterine inflammation and allow for potential diagnosis and potential therapy.

Animals↗
PubMed2006

Alterations in syncytiotrophoblast cytokine expression following treatment with lipopolysaccharide.

PROBLEM: The placental syncytium is a differentiated cell type on the surface of the villus that has the potential to release cytokines directly to maternal blood. Responsiveness of this cell type to inflammatory compounds remains largely unelucidated. METHOD OF STUDY: Response to a pro-inflammatory (lipopolysaccharide, LPS) and an anti-inflammatory (dexamethasone, DEX) compound was studied in primary cultures of syncytiotrophoblasts (SCTs). Cells were incubated with and without LPS and DEX. Cytokine levels in conditioned media were determined by enzyme-linked immunosorbent assay and proteome arrays. RESULTS: LPS treatment induced a fourfold increase in interleukin-8 (IL-8) levels in SCTs. LPS enhanced the expression of both pro- and anti-inflammatory cytokines in SCTs. DEX treatment reduced IL-8 levels in control and LPS-treated cultures by 70-90%. CONCLUSION: Cytokine expression in SCTs was enhanced by LPS treatment and this effect was suppressed by glucocorticoid treatment. This suggests that inflammatory compounds may alter cytokine expression in the syncytium throughout gestation.

Anti-Inflammatory Agents↗
PubMed2005

Proteomic biomarkers that predict the clinical success of rescue cerclage.

OBJECTIVE: The origin of incompetent cervix is multifactorial, and the success of rescue cerclage is unpredictable. We tested amniotic fluid from women who were preparing to undergo rescue cerclage for proteomic biomarkers and correlated their presence with clinical outcome. STUDY DESIGN: Amniocentesis was performed to facilitate rescue cerclage in 37 consecutive women with painless dilation (> 2 cm) and no detectable uterine activity for 4 hours (range, 1-24 hours) before cerclage. Thirty-nine consecutive women with a sonographically normal pregnancy and cervix who underwent amniocentesis for chromosomal testing during the same study interval at the same clinical site provided the control samples. A proteomic fingerprint was generated with the discarded sample and the Mass-Restricted score (MR score) for inflammation calculated. Peaks corresponding to free hemoglobin chains were sought as evidence of decidual hemorrhage or intra-amniotic bleeding. RESULTS: Amniocentesis was performed at 23.5 weeks in cerclage (mean dilation, 4 cm) versus 19.5 weeks in control subjects. Cerclage subjects were delivered at 28.8 weeks; control subjects were delivered at 39.2 weeks. Thirty-two of 37 of cerclage subjects (86%) were delivered prematurely. Ten of 37 of cerclage subjects (27%), but no control subject, had a MR score that was indicative of inflammation (P < .001). Hemoglobin peaks were present in 12 of 37 of cerclage subject (32%), but no control subjects. Among cerclage subjects, those with a MR score of 3 to 4 were delivered earlier than those with a MR score of 0 to 2 (P < .001). Women with a MR score of 3 to 4 had a shorter latency period (days from amniocentesis to delivery; 3 days) and a shorter percentage of prolongation (1.8%) than women with a MR score of 0 to 2 (35 days; P < .05; 17.9%; P < .05). Women with hemoglobin had a shorter latency period (6 days) and a shorter percentage of prolongation (3.8%) than women without hemoglobin (38 days; P < .05; 21.8%; P < .05). Hemoglobin was present in 7 of 10 of the cerclage subjects (70%) with a MR score of 3 to 4. Women with both a MR score of 3 to 4 and hemoglobin had the shortest intervals to delivery. CONCLUSION: These findings illustrate 2 pathologic mechanisms that are associated with preterm delivery are also associated with incompetent cervix. Either an intrauterine inflammatory response or decidual hemorrhage predates surgery in one half the women whose condition requires rescue cerclage. The activation of either mechanism predicts cerclage failure.

Adult↗
PubMed2005

Urinary angiogenic factors cluster hypertensive disorders and identify women with severe preeclampsia.

OBJECTIVE: Serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) are altered in women with clinical preeclampsia. We sought to identify whether similar alterations in urinary levels of these proteins cluster hypertensive disorders in pregnancy, and identify women with severe preeclampsia (sPE). STUDY DESIGN: Free urinary levels of sFlt-1, VEGF, and PlGF were measured by immunoassay in 68 women enrolled prospectively in the following groups: nonpregnant reproductive age (NP-CTR n = 14), healthy pregnant control (P-CTR n = 16), pregnant hypertensive and proteinuric women who did not meet criteria for severe preeclampsia (pHTN n = 21), and women with sPE (n = 17). RESULTS: There was no difference in gestational age at the time of enrollment among groups (median [range]: sPE: 31 [24-40], pHTN: 34 [16-40], P-CTR: 28 [7-39] wks). Urinary excretion of VEGF was significantly increased in sPE women compared with NP-CTR (P = .023), but did not differ among pregnant groups. Urinary PlGF levels were significantly increased in pregnant compared with nonpregnant women, but were decreased in all hypertensive women compared with healthy P-CTR (P < .001). Urinary sFlt-1 concentrations were significantly increased in women with sPE relative to all other groups (P < .001). pHTN women had higher sFlt-1 urinary output compared with P-CTR group (P = .001). A cutoff >2.1 in the ratio log [sFlt-1/PlGF] had 88.2% sensitivity and 100% specificity in differentiating women with sPE from normotensive controls. We also described that the log[sFlt-1/PlGF] ratio identified women with sPE better than proteinuria alone (P = .03). Our regression model revealed that uric acid correlated best with log[sFlt-1/PlGF] ratio (r = 0.628; P = .005). CONCLUSION: sPE is associated with increased urinary output of the antiangiogenic factor sFlt-1 and a decreased output of PlGF at the time of clinical manifestation, providing a rapid noninvasive screening of hypertensive women based on a sFlt/PlGF ratio. This ratio may be used as representation for severity of the disease, and appears to be superior to random urinary protein measurements.

Adult↗
PubMed2005

Sonographic myometrial thickness predicts the latency interval of women with preterm premature rupture of the membranes and oligohydramnios.

OBJECTIVE: Term labor is associated with global thinning of the myometrium. We hypothesized that a thickened myometrium at the time of preterm premature rupture of membranes (PPROM) predicts less myometrial wall stress and, consequently, a longer latency interval. STUDY DESIGN: Myometrial thickness was measured prospectively in 76 pregnant women enrolled in the following groups: PPROM (n=28, mean [range], gestational age [GA]: 29.5 weeks [w] [21.0 w-33.0 w]), preterm nonlabor control group (P-CTR), (n=21, GA: 27.5 w [23.0 w-32.0 w]) and term nonlabor control (T-CTR) (n=27, GA: 38.6 w [37.0 w-41.6 w]). All PPROM women had oligohydramnios (AFI: 1.4 cm [0.0 cm-5.1 cm]). MT was measured ultrasonographically at the midanterior, fundal, posterior, and lower uterine segment wall in cases and controls with an intraoperator variability <10%. RESULTS: Women in the PPROM group displayed uniform thickness of the uterine body (mean +/- SEM, anterior: 10.6 +/- 0.6 mm, fundal: 10.7 +/- 0.7 mm, posterior: 8.9 +/- 0.5 mm, P=.078). At midanterior site the myometrium of the PPROM group was thicker compared to both P-CTR (P < .001) and T-CTR (P=.025) groups. This difference was preserved at the fundus (PPROM vs P-CTR, P < .001; PPROM vs T-CTR, P=.015). There was a positive correlation between fundal MT and latency period (r=0.43, P=0.02) that persisted after adjusting for GA (P=.04). A fundal MT less than 12.1 mm was 93.7% sensitive and 63.6% specific for the identification of women whose latency period was less than 120 hours. CONCLUSION: Significant thickening of the anterior and fundal walls of the uterus follows PPROM. A thick myometrium in nonlaboring patients with PPROM is associated with longer latency interval. Sonographic evaluation of MT may represent an alternative clinical tool for the prediction of a short latency interval in women with PPROM.

Adult↗
PubMed2005

Discriminatory proteomic biomarker analysis identifies free hemoglobin in the cerebrospinal fluid of women with severe preeclampsia.

OBJECTIVE: Preeclampsia is an idiopathic multisystem disorder specific to human pregnancy. This study used proteomic analysis of cerebrospinal fluid (CSF) to identify protein biomarkers characteristic of preeclampsia and related to its severity. STUDY DESIGN: CSF was collected from women diagnosed clinically with severe preeclampsia (sPE: n = 7), mild preeclampsia (mPE: n = 8), and normotensive controls (CRL: n = 8). Samples were subjected to proteomic analysis using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectroscopy. A discriminative proteomic biomarker profile was extracted by applying Mass Restricted analysis, and a Preeclampsia Proteomic Biomarker (PPB) score developed based on the presence or absence of four discriminatory protein peaks in individual CSF SELDI tracings. In-gel tryptic digests, Western blot analysis, on-chip immunoassays, ELISA, and spectral analysis were used to identify the biomarkers composing the PPB score. RESULTS: PPB score distinguished patients with a clinical diagnosis of sPE from mPE and CRLs. (PPB median [range]: sPE: 4 [0-4] vs mPE: 1 [0-1] vs CRL: 0 [0-0]; P < 0.001). PPB scores were unaffected by parity, magnesium seizure prophylaxis, CSF leukocyte counts, and total protein content. Proteomic identification techniques matched the discriminatory protein peaks to the alpha- and beta-hemoglobin chains. ELISA confirmed that women diagnosed clinically with sPE had significantly higher CSF hemoglobin concentrations than women with mPE or CRL (median [range]: sPE: 6.6 [0.0-10.3] microg/mL vs mPE: 0 [0-1.3] microg/mL vs CRL: 0 [0-0] microg/mL; P < 0.001). CONCLUSION: Proteomic analysis of CSF can accurately distinguish sPE from both mPE and CRL. Patients with sPE have nanomolar amounts of free hemoglobin in their CSF. Further studies are needed to confirm these observations and determine their physiologic implications.

Biomarkers↗
PubMed2005

Normal labor: mechanism and duration.

Labor is refers to the chain of physiologic events that allows a fetus to undertake its journey from the uterus to the outside world. The mean duration of a singleton preganancy is 40.0 weeks (280 days), which is dated from the first day of the last normal menstrual period. The period from 37.0 weeks (259 days) to 42.0 weeks (294 days) of gestation is regarded as "term". This article focuses on the onset progress, and mechanics of normal labor term. Topics such as preterm labor (labor before 37 weeks), postterm labor (labor after 42 weeks), and abnormal labor and delivery have not been addressed and are discussed in detail elsewhere in this issue.

Female↗
PubMed2005

Rupture of the uterine scar during term labour: contractility or biochemistry?

OBJECTIVE: Vaginal birth after a prior low transverse caesarean section (VBAC) is advocated as a safe and effective method to reduce the total caesarean section rate. However, the risk of uterine rupture has dampened the enthusiasm of practising clinicians for VBAC. Uterine rupture occurs more frequently in women receiving prostaglandins in preparation for the induction of labour. We hypothesised that similar to the cervix, prostaglandins induces biochemical changes in the uterine scar favouring dissolution, predisposing the uterus to rupture at the scar of the lower segment as opposed to elsewhere. DESIGN: We tested aspects of this hypothesis by investigating the location of uterine rupture associated with prostaglandins and compared it with the sites of rupture in the absence of prostaglandins. SETTINGS: Two North American University Hospitals. POPULATION: Twenty-six women with a prior caesarean section, experiencing uterine rupture in active labour. METHODS: Retrospective review of all pregnancies complicated by uterine rupture at two North American teaching hospitals from 1991 to 2000. MAIN OUTCOME MEASURE: Site of the uterine rupture. RESULTS: Thirty-four women experienced rupture after a previous caesarean section with low transverse uterine incision. Ten of the women who ruptured (29%) received prostaglandins for cervical ripening (dinoprostone: n= 8 or misoprostol: n= 2) followed by either spontaneous contractions (n= 3) or oxytocin augmentation during labour (n= 7). In 16 women (47%), oxytocin alone was sufficient for the induction/augmentation of labour. Eight (23%) women ruptured at term before reaching the active phase of labour in the absence of pro-contractile agents or attempted VBAC. There were no differences among the groups in terms of age, body mass index, parity, gestational age, fetal weight or umbilical cord pH measurements. Women treated with prostaglandins experienced rupture at the site of their old scar more frequently than women in the oxytocin-alone group whose rupture tended to occur remote from their old scar (prostaglandins 90%vs oxytocin 44%; OR: 11.6, 95% CI: 1.2-114.3). CONCLUSION: Women in active labour treated with prostaglandins for cervical ripening appear more likely to rupture at the site of their old scar than women augmented without prostaglandins. We propose that prostaglandins induce local, biochemical modifications that weaken the scar, predisposing it to rupture.

Adult↗
PubMed2005

Proteomic biomarker analysis of amniotic fluid for identification of intra-amniotic inflammation.

BACKGROUND: Intra-amniotic inflammation is associated with poor neonatal outcome independent of prematurity. We applied proteomic technology (SELDI: surface-enhanced laser desorption ionisation) to identify the proteomic profile of intra-amniotic inflammation. DESIGN: One hundred and four samples of amniotic fluid were analysed. In stage 1, samples from patients with symptoms of preterm labour and known outcomes were tested to identify the characteristic profile for inflammation. We extracted the profile using a novel, stepwise logical approach comparing SELDI tracings from patients who delivered preterm and had intra-amniotic inflammation in response to infection to the tracings of patients who had symptoms of preterm labour but delivered at term. In stage 2, we applied the algorithm to samples from pregnancies whose outcomes were unknown to the investigators. SETTING: North-American university in collaboration with Ciphergen field demonstration laboratory. SAMPLE: One hundred and four samples of human amniotic fluid from transabdominal amniocentesis. METHODS: SELDI (surface-enhanced laser desorption ionisation) and Mass Restricted analysis, a novel algorithm for extraction of clinical and biological relevant biomarkers from proteomic SELDI tracings. MAIN OUTCOME MEASURE: Presence of intra-amniotic inflammation and/or infection leading to preterm birth. RESULTS: Patients with intra-amniotic inflammation that deliver preterm have a distinctive amniotic fluid proteomic profile of three or four of the following proteins: neutrophil defensins-1 and -2, and calgranulins A and C. Based on the presence or absence of these biomarkers, we devised the mass restricted (MR) score ranging from 0 (all biomarker peaks absent) to 4 (all biomarker peaks present). In stage 1, MR score > 2 had 92.9% sensitivity (95% CI 76.5-98.9) and 91.8% specificity (95% CI 80.4-97.7) for detection of intra-amniotic inflammation. In blind testing (stage 2), MR score > 2 provided 100% specificity and sensitivity (95% CI 100-100). A MR score > 2 was associated with imminent preterm delivery. CONCLUSION: Proteomic analysis of amniotic fluid reveals the presence of biomarkers characteristic of intrauterine inflammation. This methodology may identify the subgroup of patients that might benefit most from interventions to prevent fetal damage in utero.

Adult↗