Betty Thames

Oxytocin exposure during labor among women with postpartum hemorrhage secondary to uterine atony

OBJECTIVE We sought to determine if women with severe postpartum hemorrhage (PPH) secondary to uterine atony received greater amounts of oxytocin during labor compared to women without PPH. STUDY DESIGN Subjects with severe PPH secondary to uterine atony, who received a blood transfusion, were compared to matched controls. Total oxytocin exposure was calculated as the area under the concentration curve (mU/min*min). Variables were compared using paired t test, χ², and logistic regression. RESULTS Women with severe PPH had a mean oxytocin area under the curve of 10,054 mU compared to 3762 mU in controls (P < .001). After controlling for race, body mass index, admission hematocrit, induction status, magnesium therapy, and chorioamnionitis using logistic regression, oxytocin area under the curve continued to predict severe PPH. CONCLUSION Women with severe PPH secondary to uterine atony were exposed to significantly more oxytocin during labor compared to matched controls.

Transcriptional profiling of human placentas from pregnancies complicated by preeclampsia reveals disregulation of sialic acid acetylesterase and immune signalling pathways.

The placenta plays an important role as a regulator of fetal nutrition and growth throughout development and placental factors contribute to gestational abnormalities such as preeclampsia. This study describes the genome-wide gene expression profiles of a large (n = 60) set of human placentas in order to uncover gene expression patterns associated with preeclampsia. In addition to confirming changes in expression of soluble factors associated with preeclampsia such as sFLT1 (soluble fms-like tyrosine kinase-1), sENG (soluble endoglin), and INHA (inhibin alpha), we also find changes in immune-associated signaling pathways, offering a potential upstream explanation for the shallow trophoblast invasion and inadequate uterine remodeling typically observed in pathogenesis of preeclampsia. Notably, we also find evidence of preeclampsia-associated placental upregulation of sialic acid acetylesterase (SIAE), a gene functionally associated with autoimmune diseases.

Blood component therapy in postpartum hemorrhage

BACKGROUND: The purpose of this study was to examine blood component therapy in the treatment of postpartum hemorrhage.

Differentially expressed microRNAs and affected biological pathways revealed by modulated modularity clustering (MMC) analysis of human preeclamptic and IUGR placentas

INTRODUCTION This study focuses on the implementation of modulated modularity clustering (MMC) a new cluster algorithm for the identification of molecular signatures of preeclampsia and intrauterine growth restriction (IUGR), and the identification of affected microRNAs METHODS Eighty-six human placentas from normal (40), growth-restricted (27), and preeclamptic (19) term pregnancies were profiled using Illumina Human-6 Beadarrays. MMC was utilized to generate modules based on similarities in placental transcriptome. Gene Set Enrichment Analysis (GSEA) was used to predict affected microRNAs. Expression levels of these candidate microRNAs were investigated in seventy-one human term placentas as follows: control (29); IUGR (26); and preeclampsia (16). RESULTS MMC identified two modules, one representing IUGR placentas and one representing preeclamptic placentas. 326 differentially expressed genes in the module representing IUGR and 889 differentially expressed genes in a module representing preeclampsia were identified. Functional analysis of molecular signatures associated with IUGR identified P13K/AKT, mTOR, p70S6K, apoptosis and IGF-1 signaling as being affected. Analysis of variance of GSEA-predicted microRNAs indicated that miR-194 was significantly down-regulated both in preeclampsia (p = 0.0001) and IUGR (p = 0.0304), and miR-149 was significantly down-regulated in preeclampsia (p = 0.0168). DISCUSSION Implementation of MMC, allowed identification of genes disregulated in IUGR and preeclampsia. The reliability of MMC was validated by comparing to previous linear modeling analysis of preeclamptic placentas. CONCLUSION MMC allowed the elucidation of a molecular signature associated with preeclampsia and a subset of IUGR samples. This allowed the identification of genes, pathways, and microRNAs affected in these diseases.

Postpartum von Willebrand factor levels in women with and without von Willebrand disease and implications for prophylaxis

The aim of this study was to elucidate the fall in von Willebrand factor (VWF) and factor VIII activity (FVIII) after childbirth in women with and without von Willebrand disease (VWD). VWF:RCo, VWF:Ag, and FVIII were obtained in the third trimester of pregnancy, on admission for childbirth, and 10 times postpartum. Specimens were processed within 4 h and analysed centrally. Means were calculated at each time point. Forty women (40 pregnancies) without VWD and 32 women (35 pregnancies) with VWD were enrolled. 15/32 with VWD were treated (30% of those with type 1 and all of those with type 2) in 17 pregnancies. Treatments prior to delivery consisted of desmopressin (2/17), VWF concentrate (15/17) and after delivery VWF concentrate (16/17). Duration of treatment was 0–21 days (median 6). VWF levels peaked at 250% of baseline – 4 h postpartum in women with VWD and 12 h postpartum in women without VWD. Thereafter, VWF levels fell rapidly, approached baseline at 1 week and reached baseline at 3 weeks. Except immediately postpartum, when the levels among treated cases were higher, levels among women with VWD appeared to parallel, but were lower than those among women without VWD. Levels were lowest among those who received treatment. VWF levels fall rapidly after childbirth. Except immediately postpartum, current treatment strategies do not raise VWF levels to the levels of women without VWD or even to the levels of women with milder, untreated VWD. Consequently, women with VWD may be at risk of postpartum haemorrhage despite treatment.

Near-miss maternal mortality: cardiac dysfunction as the principal cause of obstetric intensive care unit admissions.

OBJECTIVE: Evaluation of “near-miss” maternal mortality is a robust surveillance method to assess the quality of obstetric care and determinants of poor maternal outcome. To evaluate near-miss maternal mortality, we examined patient characteristics and maternal and neonatal outcomes for an obstetric population admitted to intensive care units (ICUs) in a tertiary care center. METHODS: Pregnant and postpartum patients admitted to Duke University Medical Center ICUs from January 2005 to April 2011 were enrolled. Demographic, diagnostic, and outcome data were abstracted from the medical records for analysis. RESULTS: A total of 86 women were included in the study. No participants were included more than once. The mean maternal age (±standard deviation) was 29.8±7.2 years. When racial and ethnic differences were examined, African American women were more likely to be admitted to the ICU. Significant ethnic differences in body mass index (BMI) were noted with African American women (mean BMI 35) and Hispanic women (mean BMI 36) having significantly higher BMIs than white women (mean BMI 28). The majority of patients (87%) were admitted postpartum. The mean length of stay was 10 days. The leading reason for admission to the ICUs was maternal cardiac disease (36%) followed by complications from hemorrhage (29%), sepsis (9%), and hypertensive disorders (9%). No significant racial or ethnic differences in maternal medical comorbidities or neonatal outcome were noted. CONCLUSION: In this obstetric population, the leading reason for ICU admissions was cardiac disease. The increasing prevalence of advanced maternal age, congenital heart disease, obesity, diabetes, and hypertension among women who are of childbearing age may be contributing factors. LEVEL OF EVIDENCE: III

Body Mass Index and Severe Postpartum Hemorrhage

Background/Aims: The purpose of this study was to determine the relationship between maternal characteristics and severe postpartum hemorrhage (PPH). Methods: Medical records of women who delivered at Duke University Hospital between 2001 and 2004 with an ICD-9 code for PPH were reviewed. Women with PPH who received blood component therapy (severe PPH) were selected as cases and compared with controls matched for age, parity and mode of delivery. Results: Among 12,476 deliveries, there were 109 women with severe PPH. Hispanic women had an almost fourfold increase in the odds of severe PPH [OR 3.9 (1.8, 8.7)] that persisted when controlling for other significant predictors of PPH. Women with PPH were almost two times more likely [OR 1.8 (1.1, 3.1)] to have a BMI <30 when controlling for Hispanic ethnicity, oxytocin exposure, labor induction, treatment with magnesium and chorioamnionitis. Conclusion: Systemic factors as well as obstetrical factors modify the risk of severe PPH. Hispanic women and women with a BMI <30 are more likely to have severe PPH. When mode of delivery is controlled for, BMI ≧30 is associated with a reduced risk of severe PPH.

Characterization of antithrombin levels in pregnancy

OBJECTIVE To characterize antithrombin (AT) levels in normal pregnancy. METHODS We performed secondary analyses with data from 3 studies. Using a single measurement from each subject in the first analysis (cross-sectional), we correlated AT levels with gestational age from the middle of the second trimester throughout the third trimester of pregnancy. Using serial measurements in a second analysis (cohort), we compared AT levels between the late first and second trimesters of pregnancy and baseline (the level at 6 weeks postpartum). Using serial measurements in a third analysis (cohort), we analyzed the pattern of change in AT levels in the immediate postpartum period. Assays of AT activity were performed using the Dade Behring (Siemens) Berichrom Antithrombin III Chromogenic Assay. AT levels were correlated with gestational age using the Pearson correlation coefficient and compared between the different time points using one-way ANOVA. RESULTS Overall, AT levels were 20% lower than baseline during pregnancy (p<0.01). There was no significant difference between AT levels obtained between late first trimester and late second trimester. From midtrimester to term, however, AT levels were negatively correlated with gestational age with a 13% drop during this period of time (r=-0.26 [-0.39, -0.11]; p<0.01). Immediately after childbirth, AT levels fell precipitously to 30% below baseline (p<0.05) and reached a nadir 12 hours postpartum before rising and returning to baseline by 72 hours postpartum. CONCLUSION It appears that antithrombin (AT) is consumed at the time of delivery. Our findings have implications for AT replacement or even anticoagulation at the time of delivery.

Obesity-related coagulation changes in pregnancy.

Obesity, a health concern of increasing importance in developed countries, is associated with a fourto five-fold increased risk of venous thromboembolism (VTE) in pregnancy [1,2]. In one study, obese pregnant womenwere three times more likely to suffer a pulmonary embolism (PE) than a deep vein thrombosis (DVT), placing them at greater risk for mortality than non-obese gravidas [2]. Obesity is also associated with poor pregnancy outcomes, including a 40 percent increased risk for stillbirth compared to non-obese gravidas [3]. A respectable body of literature has documented many of the changes in clotting and fibrinolysis during normal pregnancy, but little has been reported on the effect of obesity on these processes [4–8]. We hypothesize that the increased risk of VTE in pregnancy associated with obesity, while likely multifactorial, is partly explained by changes in coagulation proteins. We compared clotting factor levels in obese and non-obese pregnant women with the purpose of identifying specific changes in obese gravidas that might place them at higher risk for VTE than non-obese gravidas.

Screening for underlying bleeding disorders in women with menorrhagia

Objective: Menorrhagia, excessive menstrual bleeding, affects up to 20% of reproductive-aged women. Underlying bleeding disorders, such as von Willebrand’s disease (vWD) and platelet abnormalities, may present as menorrhagia. Gynecologists do not routinely screen women with menorrhagia for bleeding disorders. The purpose of this preliminary study was to detect underlying bleeding disorders in women with menorrhagia using a new screening test. Methods: Reproductive-aged women with a diagnosis of menorrhagia were identified. Participants were screened using the PFA-100 (Dade Behring, Inc., Miami, FL), an in vitro platelet function analyzer found to be both sensitive (95%) and specific (88%) in the detection of vWD and platelet disorders. A positive test result was defined as prolonged time until clot formation. Results were confirmed with additional testing. Results: During the first 8 months of the study, 43 women were enrolled. The median age was 40 years. Twenty-one (49%) were white, 21 (49%) were African American, and 1 (2%) was Asian. Sixteen of the 43 women had a positive PFA-100 test result. Eleven had positive results suggestive of aspirin use. Five (12%) were found to have an underlying bleeding disorder: two with vWD and three with platelet abnormalities. Conclusions: Our preliminary findings suggest that the PFA-100 is useful in the evaluation of women with menorrhagia. A significant number of these women appear to have underlying bleeding disorders.