Tandem mass tag-based quantitative proteomic profiling of the serum of patients with abnormal uterine bleeding associated with copper intrauterine device.

OBJECTIVE: To investigate changes in the level of protein in serum and uncover the underlying pathogenesis of abnormal uterine bleeding (AUB) associated with copper intrauterine devices (Cu IUD). METHODS: Protein profiles were investigated via tandem mass tag (TMT)-based quantitative proteomics and bioinformatics technology. Quantification and characterization of candidate proteins were further performed in 33 controls and 45 cases by Luminex assay and enzyme-linked immunosorbent assay. RESULTS: In total, 842 proteins were identified via TMT coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the serum of individuals with IUDs. Among them, 25 differentially expressed proteins (p < 0.05) were observed, including eight upregulated proteins and 17 downregulated proteins. Ten proteins were verified, and Alpha-1-Antitrypsin (a1AT) had a significantly elevated expression in women with AUB associated with the Cu IUD compared with healthy controls (p = 0.026) and a high area under the curve value (0.656), as well as sensitivity (64.9%) and specificity (71.9%). CONCLUSION: This is the first study to explore changes in serum protein and the underlying mechanisms of AUB associated with the Cu IUD via TMT technology. a1AT with biomarker potential was validated. These findings might provide an experimental basis for the early diagnosis or treatment of AUB associated with the Cu IUD.

Exacerbated mini-puberty of infancy in an ex-extreme preterm girl.

Vaginal bleeding can occur shortly after delivery in 3%-5% of newborns as a consequence of placental hormone withdrawal . Although usually benign, its differential diagnosis includes central precocious puberty, tumours and other pathological conditions. A girl born at 26 weeks of gestation presented with five episodes of vaginal bleeding, each lasting less than a week, initiated at 4 months of age. Luteinising hormone and oestradiol levels were in the pubertal range. Later, she exhibited breast development, with no other pubertal signs. An ultrasonography test revealed an impregnated endometrium and a right ovarian cyst with 43 mm of diameter. A cranioencephalic MRI was unremarkable. Clinicians adopted expectant management and there was clinical, hormonal and radiological resolution in 3 months. The spontaneous resolution suggested mini-puberty of infancy. This is usually an asymptomatic condition, but to date, four cases of an exacerbated form in extremepremature infants have been reported. Long-term follow-up data are missing.A girl born at 26 weeks of gestation presented with five episodes of vaginal bleeding, each lasting less than a week, initiated at 4 months of age. Luteinising hormone and oestradiol levels were in the pubertal range. Later, she exhibited breast development, with no other pubertal signs. An ultrasonography test revealed an impregnated endometrium and a right ovarian cyst with 43 mm of diameter. A cranioencephalic MRI was unremarkable. Clinicians adopted expectant management and there was clinical, hormonal and radiological resolution in 3 months. The spontaneous resolution suggested mini-puberty of infancy. This is usually an asymptomatic condition, but to date, four cases of an exacerbated form in extremepremature infants have been reported. Long-term follow-up data are missing.

Congenital dysfibrinogenaemia presented with preterm premature rupture of the membranes and vaginal bleeding.

A 26-year-old woman was found to have congenital dysfibrinogenaemia after presenting to our hospital with premature rupture of the membranes and vaginal bleeding. Given the absence of clear guidelines for the management of pregnancy complicated by dysfibrinogenaemia, we followed expert consensus that exists among published works, with some modifications. This case was managed by a multidisciplinary team of obstetrics-gynaecology, haematology and paediatric haematology. Here we review how the patient presented, the investigations that led to the diagnosis and the treatment options.

The role of viscoelastic testing in the management of the parturient.

Viscoelastic testing is the measurement of how the viscoelastic properties of blood change as blood clots. In pregnancy, unique changes in clotting function occur overall to make the pregnant woman hypercoagulable. Viscoelastic testing may be able to play a role in guiding placement of epidural and spinal anesthetics by demonstrating enhanced coagulation function, even when there are individual parts of the coagulation system that are abnormal, for example, thrombocytopenia. These tools may also play a role in addressing the management of maternal hemorrhage, which in the United States is on the rise. This review discusses the opportunity to use viscoelastic testing in the parturient.

Haematological features, transfusion management and outcomes of massive obstetric haemorrhage: findings from the Australian and New Zealand Massive Transfusion Registry.

Massive obstetric haemorrhage (MOH) is a leading cause of maternal morbidity and mortality world-wide. Using the Australian and New Zealand Massive Transfusion Registry, we performed a bi-national cohort study of MOH defined as bleeding at ≥20 weeks' gestation or postpartum requiring ≥5 red blood cells (RBC) units within 4 h. Between 2008 and 2015, we identified 249 cases of MOH cases from 19 sites. Predominant causes of MOH were uterine atony (22%), placenta praevia (20%) and obstetric trauma (19%). Intensive care unit admission and/or hysterectomy occurred in 44% and 29% of cases, respectively. There were three deaths. Hypofibrinogenaemia (<2 g/l) occurred in 52% of cases in the first 24 h after massive transfusion commenced; of these cases, 74% received cryoprecipitate. Median values of other haemostatic tests were within accepted limits. Plasma, platelets or cryoprecipitate were transfused in 88%, 66% and 57% of cases, respectively. By multivariate regression, transfusion of ≥6 RBC units before the first cryoprecipitate (odds ratio [OR] 3·5, 95% CI: 1·7-7·2), placenta praevia (OR 7·2, 95% CI: 2·0-26·4) and emergency caesarean section (OR 4·9, 95% CI: 2·0-11·7) were independently associated with increased risk of hysterectomy. These findings confirm MOH as a major cause of maternal morbidity and mortality and indicate areas for practice improvement.

Deciphering the intervention mechanism of Taohong Siwu Decoction following the abnormal uterine bleeding rats based on serum metabolic profiles.

Abnormal uterine bleeding (AUB), one of the most significant characters of incomplete abortion, is a widespread phenomenon in gynecological that put a woman into a terrible physiological and psychological state. Taohong Siwu Decoction (TSD) is a traditional Chinese medicine (TCM) prescriptions which have treated AUB in China for decades. Our previous study elucidated that TSD reduced the volume of uterine bleedings as well as repaired the endometrium. The present study aims to investigate the mechanisms of TSD on AUB based on serum metabolomics. In this study, serum metabolic profile data was collected using ultra high-performance liquid chromatography with ion trap/time-of-flight mass spectrometry and gas chromatography-mass spectrometry. 23 potential biomarkers (urea, serine, L-proline, L-glutamic acid, palmitic acid, l-acetylcarnitine, LysoPC(16:0), LysoPC(20:4), l-proline, linoleic acid, stearic acid, l-isoleucine, phenylalanine, l-tyrosine, Oleic acid, et al) were eventually identified using multivariate statistical analysis (PCA and OPLS-DA) with VIP > 1, P < 0.05. Correlation analysis, fold-change (FC), area under receiver characteristic (ROC), false discovery rate (FDR) were used for data confirmation to ensure the authenticity of the data. The related-metabolic pathway mainly included amino acid metabolism (Phenylalanine, tyrosine, and tryptophan metabolism; Valine, leucine and isoleucine biosynthesis; Arginine and proline metabolism; Glycine, serine and threonine metabolism) and lipid metabolism (linoleic acid metabolism, glycerophospholipid metabolism). The results show that TSD has a favorable therapeutic effect on AUB by adjusting the metabolic disorders, which could provide dietary guidance for the clinic.

Nexplanon Subdermal Implant: Assessment of Sexual Profile, Metabolism, and Bleeding in a Cohort of Italian Women.

OBJECTIVES: To evaluate the impact on metabolism, bleeding, and sexual function of Nexplanon, a subdermal implant. STUDY DESIGN: We recruited women (n=101) receiving the Nexplanon implant at two university centers in Italy between 2011 and 2016 into this prospective, observational, multicenter research trial. Participants completed the Interview for Ratings of Sexual Function (IRSF) and the Female Sexual Function Index (FSFI) questionnaires before and 3 and 6 months after the implant was inserted. In addition, all blood parameters were assessed at these visits. All women were given a menstrual diary card and a pictorial blood assessment chart to record daily any vaginal bleeding. RESULTS: The studied metabolic parameters remained in the normal range, showing no alarming modifications: minimal statistical reductions (in aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglycerides, and activated partial thromboplastin time) and increases (in glucose and prothrombin activity) were observed. Changes in IRSF score over 6 months showed a significant increase in pleasure, personal initiative, orgasm, intensity of orgasm, and satisfaction, and a significant decrease in anxiety and discomfort. Mean Body Mass Index decreased, and the weekly frequency of sexual intercourse increased. CONCLUSIONS: Nexplanon showed not only a lower metabolic and bleeding impact, but also important positive effects on sexual function. It expands the range of possibilities for women, 38 and couples, in the modern concepts of sexual and reproductive wellbeing.

Fibrinogen for the management of critical obstetric hemorrhage.

AIM: In cases of critical obstetric hemorrhage leading to extreme hypofibrinogenemia, fibrinogen is the marker that indicates the critical severity, and early fibrinogen supplementation centering on hemostatic resuscitation is a vital treatment to stabilize a catastrophic condition. In this review, we investigated the effect of fibrinogen level on hemostasis and what we can do to treat hypofibrinogenemia efficiently and improve patients' outcome. METHODS: We reviewed numerous articles related to hypofibrinogenemia in critical obstetric hemorrhage. Especially, we performed a systematic review on target value of fibrinogen for hemostasis and effectiveness of fibrinogen concentrate. We also reviewed the articles about the methods for early normalization of fibrinogen level such as tranexamic acid, massive transfusion protocol, and point-of-care testing. RESULTS: The target value of fibrinogen calculated by needs for massive transfusion was 200 mg/dL or 10 mm of A5FIBTEM . Although fibrinogen concentrate worked poorly on fibrinogen levels within the normal range, it improved the blood fibrinogen levels rapidly when it was administered to critical obstetric hemorrhage patients with serious hypofibrinogenemia. Hence, the volume of FFP transfused could be reduced along with a reduction in the frequency of pulmonary edema due to volume overload. CONCLUSION: The patient group for which fibrinogen concentrate works most effectively is cases with severe hypofibrinogenemia. Further research is required in the light of evidence. The essence of the transfusion algorithm in critical obstetric hemorrhage is to approach the target value for obtaining hemostasis, ensure an accurate and prompt grasp of the severity using point-of-care testing, introduce a massive transfusion protocol and use tranexamic acid.

Same-day confirmation of intrauterine pregnancy failure in women with first- and early second-trimester bleeding.

OBJECTIVE: To determine if alpha-fetoprotein (AFP) concentration in vaginal blood, in the setting of dissolved fetal tissue, is significantly higher than its concentration in the maternal serum. DESIGN: A prospective cohort study. SETTING: Medical center. PATIENT(S): Four groups of women were evaluated: 1) with missed/incomplete miscarriage with vaginal bleeding; 2) with threatened miscarriage; 3) with vaginal bleeding during cerclage placement; and 4) undergoing dilation and curettage (D&C). INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): In each patient, AFP concentration in the vaginal blood or in the liquid component of the evacuated products of conception (POC; D&C group) was compared with the AFP concentration in the maternal serum. RESULT(S): The median (range) concentration ratios of AFP in vaginal blood (or POC) to AFP in maternal serum were 24.5 (5.1-8,620) and 957 (4.6-24,216) for the missed/incomplete (n = 30) and the D&C (n = 22) groups, respectively, whereas they were only 1.2 (0.4-13.4) and 1.01 (0.7-1.5) for the threatened miscarriage (n = 15) and cerclage (n = 9) groups, respectively. Receiver operating characteristic (ROC) analysis demonstrated 100% sensitivity and 86.7% specificity for the detection of the passage of fetal tissue (ratio 4.3, area under the ROC curve 0.96). CONCLUSION(S): Higher concentrations of AFP in vaginal blood than in maternal serum may indicate the presence of dissolved fetal tissue (i.e., confirming a failed pregnancy).

Expression of matrix metalloproteinase enzymes in endometrium of women with abnormal uterine bleeding.

OBJECTIVES: Abnormal uterine bleeding (AUB) is caused by derangement of physiological processes of tissue growth, shedding and regeneration. It is known that interplay between metalloproteinases (MMP's) and tissue inhibitors of metalloproteinases (TIMP's) may play a crucial role in its occurrence. AIM: To define if expression of proMMP-2, MMP-2 and TIMP-1 in endometrium of women with AUB is dependent on steroid sex hormone concentration and histopathological picture. MATERIALS AND METHODS: Endometrial scraps were taken from 21 women with AUB and 19 controls. Samples were evaluated in light microscopy by a certified pathologist. Activity of proMMP-2 and MMP-2 proteins levels were evaluated by gelatin zymography and TIMP-1 by reversed zymography. The results has been correlated with serum estradiol and progesterone concentrations in linear regression model. RESULTS: Expression: of proMMP-2 in endometrium of women with AUB is correlated with estradiol concentration and inversely correlated with progesterone levels. It was significantly higher in women with dysfunctional endometrium (p<0.001). Expression of MMP-2 was highest in women with endometrial polyps and longer bleeding (p<0.01), while expression of TIMP-1 was independent from hormone concentration. CONCLUSION: Lack of correlation between proMMP-2 and MMP-2 levels suggest different pathway of their activation in AUB. ProMMP-2 is up regulated by estradiol and down regulated by progesterone while MMP-2 levels increase with the length of bleeding.

CA 125 is a better marker to differentiate endometrial cancer and abnormal uterine bleeding.

BACKGROUND: Incidence of endometrial cancer in India is increasing due to lifestyle changes and obesity. As 5 year survival rate of cancer confined to uterus is good, there is need for serum tumor marker for early diagnosis. This study was designed to identify a tumor marker which differentiate endometrial carcinoma and abnormal uterine bleeding (AUB) because common presentation of endometrial carcinoma is AUB. OBJECTIVES: To estimate and compare serum prolactin, Cancer Antigen 125 (CA-125), Cancer Antigen 15-3 (CA15-3), and Carcino embryonic antigen (CEA) levels in patients with endometrial cancer and abnormal uterine bleeding; To evaluate the role of these markers in diagnosing endometrial cancer. METHODOLOGY: Thirty eight patients with endometrial cancer and 40 patients with AUB were recruited in this study. Serum prolactin, CA 125, CEA, and CA 15-3 levels were estimated in both groups. RESULTS: The levels of CA 15-3, CA 125, CEA, and prolactin were increased in endometrial carcinoma patients, on comparison with AUB patients. CA 125 alone was found to be a better marker to detect endometrial cancer with 52.63% sensitivity, 80.00% specificity. CONCLUSION: As individual tumor marker, serum CA 125 has the ability to detect endometrial cancer in patients with abnormal uterine bleeding.

Predictive value of some hematological parameters for non-invasive and invasive mole pregnancies.

AIM: The aim of this study was to discriminate mole pregnancies and invasive forms among cases with first trimester vaginal bleeding by the utilization of some complete blood count parameters conjunct to sonographic findings and beta human chorionic gonadotropin concentration. MATERIALS AND METHODS: Consecutive 257 cases with histopathologically confirmed mole pregnancies and 199 women without mole pregnancy presented with first trimester vaginal bleeding who admitted to Zeynep Kamil Women and Children's Health Training Hospital between January 2012 and January 2016 were included in this cross-sectional study. The serum beta HCG level at presentation, and beta hCG levels at 1st, 2nd and 3rd weeks of postevacuation with some parameters of complete blood count were utilized to discriminate cases with molar pregnancy and cases with invasive mole among first trimester pregnants presented with vaginal bleeding and abnormal sonographic findings. RESULTS: Levels of beta hCG at baseline (AUC = 0.700, p < 0.05) and 1st (AUC = 0.704, p < 0.05), 2nd (AUC = 0.870, p < 0.001) and 3rd (AUC = 0.916, p < 0.001) weeks of postevacuation period were significant predictors for the cases with persistent disease. While area under curve for mean platelet volume is 0.715, it means that mean platelet volume has 21.5% additional diagnostic value for predicting persistency in molar patients. For 8.55 cut-off point for mean platelet volume, sensitivity is 84.6% and specificity is 51.6%. Area under curve for platelet/lymphocyte ratio is 0.683 means that platelet/lymphocyte ratio has additional 18.3% diagnostic value. For 102.25 cut-off point sensitivity is 86.6% and specificity is 46.2. CONCLUSIONS: Simple, widely available complete blood count parameters may be used as an adjunct to other risk factors to diagnose molar pregnancies and predict postevacuation trophoblastic disease.

Abnormal uterine bleeding in women receiving direct oral anticoagulants for the treatment of venous thromboembolism.

Abnormal uterine bleeding (AUB) is a common complication of anticoagulant therapy in premenopausal women affected with acute venous thromboembolism. AUB impacts quality of life, and can lead to premature cessation of anticoagulation. There is increasing data to suggest that the direct oral anticoagulants when used for the treatment of venous thromboembolism differ in their menstrual bleeding profile. This article aims to review the existing literature regarding the association between AUB and the direct oral anticoagulants and make practical recommendations.

The effect of blood staining on cervicovaginal quantitative fetal fibronectin concentration and prediction of spontaneous preterm birth.

OBJECTIVE: Spontaneous preterm birth is the leading cause of neonatal morbidity and mortality. Cervicovaginal fetal fibronectin (fFN) has enhanced prediction of preterm birth and, more recently, quantified results have become available so that management can planned more effectively and targeted to individual women. Manufacture guidelines stipulate that fetal fibronectin (fFN) samples should be discarded in the presence of moderate to heavy vaginal bleeding but there hasn't yet been any formal investigation into the effect of blood staining on fetal fibronectin concentration and subsequent preterm birth prediction. The objective for this study was to determine the impact of blood stained swabs on quantitative fetal fibronectin (qfFN) concentration and prediction of spontaneous preterm birth (sPTB) in asymptomatic high-risk women. STUDY DESIGN: Predefined blinded sub-analysis of a larger prospective study of qfFN in asymptomatic women at high-risk of preterm labour. Women with and without blood stained swabs were matched for gestational age at testing and delivery, risk factors and cervical length measurement. RESULTS: Median fFN concentration in blood stained swabs (n=58) was 66ng/ml vs. 7.5ng/ml in the controls (n=58) (p<0.0001). At ≥50ng/ml threshold the false positive ratio (FPR) in blood stained was 25/33 (75.8%) vs. 8/15 (53%) in controls, (risk difference 22.4; -6.8 to 51.6, p=0.18). At ≥50ng/ml threshold the false-negative ratio (FNR) in blood stained was 2/25 (8.0%) vs. 1/43 (2.3%) in controls (risk difference -5.7; -17.2 to 5.9, p=0.55). At each threshold 10, 50 and 200ng/ml blood stained swabs had higher sensitivity but lower specificity for predicting preterm birth. Receiver Operating Characteristic (ROC) curve, the strongest global measure of test performance, for prediction of delivery at <34 weeks gestation was similar in blood stained vs. control groups. (0.78 vs. 0.84) in blood stained vs. control groups respectively. CONCLUSION: Blood stained swabs have elevated qfFN concentrations but may still have predictive value, and clinical utility. Very low fFN values (<10ng/ml) are especially reassuring and indicate lower risk of delivery than non-blood stained swabs. The higher false positive rate must be noted and explained to the patient.

Anemia grave secundaria a sangrado vaginal en niña de 13 años que rechaza transfusión sanguínea / Severe anemia secondary to vaginal bleeding in a 13-year old girl who rejects blood transfusion

Introducción: El sangrado vaginal como causa de anemia grave no es frecuente en la edad pediátrica, pero cuando aparece suele ser secundario a una hemorragia uterina disfuncional. El tratamiento del mismo tiene como objetivo el establecimiento y/o mantenimiento de la estabilidad hemodinámica del paciente. La situación actual en España establece que toda actuación en el ámbito de la salud de un paciente necesita el consentimiento libre y voluntario del afectado, siendo necesario el consentimiento por representación por varias razones, de las que destacamos que el paciente sea menor de edad y no sea capaz intelectual ni emocionalmente de comprender el alcance de la intervención. El consentimiento informado por representación debe adoptarse atendiendo siempre al mayor beneficio para la vida o salud del paciente. Caso clínico. Presentamos un caso de sangrado vaginal con una hemoglobina de 5 g/L, en una niña de 13 años que rechaza la transfusión sanguínea por creencias religiosas. Ante la anemia grave y la negativa de la paciente y de los padres a administrar la transfusión, se decide como primera medida la administración de líquidos intravenosos y aporte de hierro intravenoso, solicitando autorización judicial para, en caso de fracaso del tratamiento inicial, poder trasfundir concentrado de hematíes, situación que no se produce dada su repuesta favorable. Conclusiones. La buena evolución de la paciente nos permite concluir que ante una causa que imposibilite la transfusión sanguínea se puede administrar hierro intravenoso con buena repuesta

Introduction: Vaginal bleeding as a cause of severe anemia is not frequent in the pediatric age. However when it appears, it is generally secondary to dysfunction uterine bleeding. The objective of its treatment is to establish and/ or maintain the hemodynamic stability of the patient. The current situation in Spain establishes that all action within the health care setting of a patient requires free and voluntary consent of the patient, consent by representation being necessary for several reasons, standing out among them that the patient is a minor and is not intellectually or emotional capable of understanding the scope of the intervention. Informed consent by representation should always be adopted considering the best benefit for the patient's life or health. Clinical case. We present a case of vaginal bleeding with 5 g/L hemoglobin in a 13-year old girl who rejected blood transfusion due to religious beliefs. In view of the severe anemia and rejection by the patient and her parents to administer the transfusion, it was decided as a first step to administer intravenous fluids and intravenous iron supply and to request court authorization in case of initial treatment failure to be able to make a concentration red blood cell transfusion, a situation which did not occur given her favorable response. Conclusions. The good evolution of the patient allowed us to conclude that when it is not possible to perform a blood transfusion, intravenous iron can be administered with good response

Single-dose intravenous iron for iron deficiency: a new paradigm.

Iron-deficiency anemia is the most common hematologic problem in the world. Although oral iron is often viewed as front-line therapy, extensive published evidence has accumulated that IV iron is superior, in both efficacy and safety, to oral iron in many clinical situations and should be introduced much sooner in the treatment paradigm of iron-deficient patients. In this chapter, we will review the formulations of IV iron that allow total complete replacement doses in 1 or 2 sessions including practical tips for administration. We realize safety concerns abound and therefore will analyze evidence based overstated concerns regarding serious adverse events highlighting unnecessary interventions for minor, self-limiting infusion reactions, which infrequently occur with intravenous iron administration. Recent data for the use of IV iron in a variety of clinic situations will be reviewed including women with heavy uterine bleeding, pregnancy, bariatric surgery, inflammatory bowel disease, and restless legs syndrome. Briefly discussed is the new frontier of IV iron's use in the prevention of acute (high altitude) mountain sickness. It is clear that in many clinical situations IV iron is a new and improved standard of care offering advantages over oral iron in efficacy, toxicity, and convenience to patients and health care providers.

Effects of delayed cord clamping on the third stage of labour, maternal haematological parameters and acid-base status in fetuses at term.

OBJECTIVE: To compare the time in the third stage of labour, differences in maternal hematologic parameters 48h after birth and acid-base status in the umbilical cord between the early cord clamping (ECC) and delayed cord clamping (DCC). STUDY DESIGN: 97 healthy pregnancies at term and a spontaneous vertex delivery at Clinic University Hospital "Virgen de la Arrixaca" (Murcia, Spain), were randomized to ECC group (<10s post-delivery) or to DCC group (2min post-delivery). Duration of the third stage of labour was measured. Samples for acid-base status were taken both from the umbilical artery and vein. Blood samples were taken from the mothers 48h after birth. RESULTS: No statistical differences were found in the time of the third stage of labour (p=0.35). No statiscally significant differences were found between the number of red cells (p=0.25), hemoglobin (p=0.08) or hematocrit (p=0.15) in mothers. Umbilical acid-base status or gas analysis did not show any differences between the two groups CONCLUSIONS: Delayed cord clamping does not affect significantly the time of the third stage of labour. It does not show either any effect on the hematological parameters in the mother 48h after birth.

Interferon beta-1b-induced postmenopausal bleeding in a patient with multiple sclerosis.

OBJECTIVE: Postmenopausal bleeding must always be evaluated to rule out endometrial carcinoma, although there are many benign etiologies. There have been rare reports of premenopausal bleeding with interferon beta-1b, used to treat multiple sclerosis, but no prior reports in postmenopausal women. METHODS: Literature searches were performed using PubMed and Medline for articles with content related to premenopausal and postmenopausal bleeding while taking interferon beta-1b. The searches were restricted to the English language. Search terms included interferon beta-1b and/or uterine hemorrhage and/or vaginal bleeding and/or postmenopausal and/or menopause. RESULTS: The literature review found no related articles for postmenopausal bleeding while taking interferon beta-1b. We present a case of a patient with postmenopausal bleeding attributed to elevation of serum estradiol in association with interferon beta-1b therapy. CONCLUSION: It is important for patients and providers to be aware of the association between postmenopausal bleeding with the use of interferon beta-1b therapy which could be due to elevated serum estradiol levels.

Differences in Serum Human Chorionic Gonadotropin Rise in Early Pregnancy by Race and Value at Presentation.

OBJECTIVE: To assess whether variation in serum human chorionic gonadotropin (hCG) measures, used to assess early gestation viability, are associated with differences in clinical presentation and patient factors. METHOD: This retrospective cohort study included 285 women with first-trimester pain and bleeding and a pregnancy of unknown location for whom a normal intrauterine pregnancy was ultimately confirmed. Serial samples were collected at three U.S. sites and hCG changes were analyzed for differences by race, ethnicity, and clinical factors. A nonlinear, mixed-effects regression model was used assuming a random subject shift in the time axis. RESULTS: The hCG rise in symptomatic women with ongoing intrauterine pregnancy differs by patient factors and level at presentation. The 2-day minimum (first percentile) rise in hCG was faster when presenting hCG values were low and slower when presenting hCG value was high. African American women had a faster hCG rise (P<.001) compared with non-African American women. Variation in hCG curves was associated with prior miscarriage (P=.014), presentation of bleeding (P<.001), and pain (P=.002). For initial hCG values of less than 1,500, 1,500-3,000 and greater than 3,000 milli-international units/mL, the predicted 2-day minimal (first percentile) rise was 49%, 40%, and 33%, respectively. CONCLUSION: The rise of hCG levels in women with viable intrauterine pregnancies and symptoms of potential pregnancy failure varies significantly by initial value. Changes in hCG rise related to race should not affect clinical care. To limit interruption of a potential desired intrauterine pregnancy, a more conservative "cutoff" (slower rise) is needed when hCG values are high. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00194168.

Maternal Early Pregnancy Serum Metabolomics Profile and Abnormal Vaginal Bleeding as Predictors of Placental Abruption: A Prospective Study.

BACKGROUND & OBJECTIVE: Placental abruption, an ischemic placental disorder, complicates about 1 in 100 pregnancies, and is an important cause of maternal and perinatal morbidity and mortality worldwide. Metabolomics holds promise for improving the phenotyping, prediction and understanding of pathophysiologic mechanisms of complex clinical disorders including abruption. We sought to evaluate maternal early pregnancy pre-diagnostic serum metabolic profiles and abnormal vaginal bleeding as predictors of abruption later in pregnancy. METHODS: Maternal serum was collected in early pregnancy (mean 16 weeks, range 15 to 22 weeks) from 51 abruption cases and 51 controls. Quantitative targeted metabolic profiles of serum were acquired using electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and the Absolute IDQ® p180 kit. Maternal sociodemographic characteristics and reproductive history were abstracted from medical records. Stepwise logistic regression models were developed to evaluate the extent to which metabolites aid in the prediction of abruption. We evaluated the predictive performance of the set of selected metabolites using a receiver operating characteristics (ROC) curve analysis and area under the curve (AUC). RESULTS: Early pregnancy vaginal bleeding, dodecanoylcarnitine/dodecenoylcarnitine (C12 / C12:1), and phosphatidylcholine acyl-alkyl C 38:1 (PC ae C38:1) strongly predict abruption risk. The AUC for these metabolites alone was 0.68, for early pregnancy vaginal bleeding alone was 0.65, and combined the AUC improved to 0.75 with the addition of quantitative metabolite data (P = 0.003). CONCLUSION: Metabolomic profiles of early pregnancy maternal serum samples in addition to the clinical symptom, vaginal bleeding, may serve as important markers for the prediction of abruption. Larger studies are necessary to corroborate and validate these findings in other cohorts.