Maternal outcomes following postpartum autotransfusion of blood lost during vaginal obstetric hemorrhage.

BACKGROUND: Autotransfusion following vaginal delivery has not been as widely adopted and existing data on this topic are limited to small case series. METHODS: This is a single-center retrospective matched cohort study. Deliveries exposed to autotransfusion during obstetric hemorrhage were matched to unexposed controls with obstetric hemorrhage who did not receive autotransfusion. The primary outcome was allogeneic transfusion of packed red blood cells. Planned secondary analyses included change in hemoglobin following delivery, composite maternal safety outcomes, and unplanned postpartum health care utilization. RESULTS: Thirty-six deliveries exposed to autotransfusion were matched to 144 unexposed controls. There was no significant difference in allogenic transfusion of packed red blood cells in the patients exposed to autotransfusion red with unexposed controls (adjusted OR 1.1; 95% CI 0.5-2.4). Deliveries that received autotransfusion had a less severe pre- to post-delivery decline in hemoglobin compared with unexposed controls across all values of QBL (p = .003). There were no significant differences in maternal morbidity outcomes evaluated in exposed versus unexposed deliveries. CONCLUSION: Autotransfusion in cases of vaginal obstetric hemorrhage did not attenuate rates of allogenic packed red blood cell transfusion but did result in a less severe pre- to postdelivery decline in hemoglobin at discharge. Autotransfusion cases did not have any markers of increased maternal morbidity when compared with a control group. These findings support emerging evidence indicating that autotransfusion of blood lost during vaginal obstetric hemorrhage is a safe and potentially effective tool for use in the management of obstetric hemorrhage.

The Contribution of Neighborhood Context to the Association of Race with Severe Maternal Morbidity.

OBJECTIVE: Severe maternal morbidity (SMM) has disproportionate frequencies among racial minorities and those of socioeconomic disadvantage, with people of Black race consistently having the highest proportion. Neighborhood level deprivation has been associated with maternal morbidity and mortality, including adverse pregnancy outcomes. We sought to explore the relationship between neighborhood socioeconomic disadvantage and SMM and describe how neighborhood context impacts the relationship between race and SMM. STUDY DESIGN: We performed a retrospective cohort analysis of all delivery admissions in a single health care network from 2015 to 2019. Area deprivation index (ADI) was used to represent neighborhood socioeconomic disadvantage and is a composite index of neighborhood that spans income, education, household characteristics, and housing. The index ranges from 1 to 100 with higher values indicating higher disadvantage. Logistic regression assessed the relationship between ADI and SMM and estimated the effect that ADI has on the relationship between race and SMM. RESULTS: Of the 63,208 birthing persons in our cohort, the unadjusted incidence of SMM was 2.2%. ADI was significantly associated with SMM, with higher values conferring higher risk for SMM (p < 0.001). The absolute risk of SMM increased roughly by 1.0% from the lowest to highest ADI value. Those of Black race had the highest unadjusted incidence of SMM compared with the referent group (3.4 vs. 2.0%) and highest median ADI (92; interquartile range [IQR]: 20). In the multivariable model, in which the primary exposure was race and ADI was adjusted for, Black race had a 1.7 times odds SMM when compared with White race (95% confidence interval [CI]: 1.5-1.9). This association was attenuated to 1.5 adjusted odds when controlling for ADI (95% CI: 1.3-1.7). Risk attenuation for SMM was not seen in other race categories. CONCLUSION: Neighborhood context contributes to SMM but does not explain the majority of racial disparities. KEY POINTS: · Neighborhood context is associated with SMM, with higher disadvantage conferring higher risk.. · Compared with White race, all other races had higher rates of SMM, with Black race having the highest.. · Accounting for neighborhood modestly attenuates the magnitude of association of Black race with SMM.. · Neighborhood context contributes to health outcomes but does not explain the majority of disparities..

Association between gestational age at delivery and indicator-specific severe maternal morbidity.

OBJECTIVE: Individuals who deliver preterm are disproportionately affected by severe maternal morbidity. Limited data suggest that indicator-specific maternal morbidity varies by gestational age at delivery. We sought to evaluate the relationship between gestational age at delivery and the incidence of severe maternal morbidity and indicator-specific severe maternal morbidity. METHODS: We used a hospital administrative delivery database to identify all singleton deliveries between 16 and 42 weeks gestation from 2002 to 2018. We defined severe maternal morbidity as the presence of any International Classification of Disease diagnosis or procedure codes outlined by the Centers for Disease Control and Prevention, intensive care unit admission, and/or prolonged postpartum hospital length of stay. Indicator-specific severe maternal morbidity was based on the diagnosis and procedure codes and was characterized across gestational age epochs. We categorized gestational age into three epochs to capture extremely preterm birth (less than 28 weeks gestation), preterm birth (28-36 weeks gestation) and term birth (37 weeks gestation and above). Multivariable binomial regression was used to assess the association between categories of gestational age at delivery and severe maternal morbidity adjusting for confounders including age, race, body mass index (BMI), insurance status, and preexisting hypertension or diabetes. RESULTS: Severe maternal morbidity occurred in 2.5% of all deliveries. The unadjusted incidence of severe maternal morbidity by gestational age epoch was 12% at less than 28 weeks gestation, 8.4% at 28 to 36 weeks of gestation, and 1.7% at greater than or equal to 37 weeks gestation. After controlling for potential confounders the predicted probability of severe maternal morbidity was 16% (95% CI 14,17%) at 24 weeks compared to 2.2% (95% CI 2.1,2.3%) at 38 weeks. Sepsis, acute respiratory distress syndrome, mechanical ventilation, and shock were the most common diagnostic codes in deliveries less than 28 weeks gestation. Heart failure and cardiac arrhythmias were more common in patients with severe maternal morbidity delivering at term. CONCLUSION: A high proportion of severe maternal morbidity occurred in preterm patients, with the highest rates occurring at less than 28 weeks gestation. Individuals with severe maternal morbidity who deliver preterm had distinct indicators of morbidity compared to those who deliver at term.

Comparative Analysis of Obstetric Hemorrhage Risk Prediction Tools.

OBJECTIVE: Hemorrhage risk prediction tools were developed in response to rising rates of obstetric hemorrhage (OBH). The California Maternal Quality Care Collaborative (CMQCC) risk prediction tool classifies patients as low, medium, and high risk for OBH based on individual risk factors. At our institution, Magee-Womens Hospital (MWH), a unique OBH risk prediction tool was derived from the CMQCC tool that differs through its use of weighted risk factors and distinctive laboratory value cutoffs. Our objective is to compare this enhanced institution-specific tool to the CMQCC tool. STUDY DESIGN: This study was a retrospective cohort analysis of delivery admissions from a single health care network. Admission OBH risk scores were assigned to each patient using both the MWH and CMQCC scores. Cohen's kappa estimated agreement. Scoring systems and maternal outcomes were compared using chi-square test. Composite morbidity included transfusion, hysterectomy, uterine artery embolization, and intensive care unit admission. RESULTS: A total of 21,843 delivery admissions were included. A moderate association was observed between scoring systems (kappa = 0.41, p < 0.001). The CMQCC tool categorized 16,184 (74%) patients as low risk, 4,664 (21%) as medium risk, and 995 (5%) as high risk. The MWH tool categorized 13,137 (60%) patients as low risk, 8,113 (37%) as medium risk, and 593 (3%) as high risk. The MWH score recategorized CMQCC low-risk patients to a higher stratum 26% of the time. CMQCC high-risk patients were recategorized to a lower stratum 82% of the time. Both the MWH and CMQCC tools were able to differentiate OBH-related morbidity across risk strata. The MWH tool independently predicted risk of composite morbidity within each stratum of the CMQCC score. CONCLUSION: Both the MWH and CMQCC tools independently distinguish risk of composite morbidity. Adding weighted values to individual risk factors further discriminates risk of morbidity. This suggests it may be reasonable to adapt the CMQCC tool to reflect institutional populations and resources. KEY POINTS: · The nationally adopted CMQCC risk prediction tool identifies women at risk for obstetric hemorrhage.. · Our institution (MWH) developed a unique tool that weights individual risk factors to better capture risk.. · The CMQCC and MWH tools both differentiate risk; though similar to other tools, categorize a proportion of women who hemorrhage as low risk..

Traditional uterine tamponade and vacuum-induced uterine tamponade devices in obstetrical hemorrhage management.

Obstetrical hemorrhage is the leading cause of maternal morbidity and mortality worldwide, and the rates of severe hemorrhage are increasing. There is a crucial need to expand treatment options for hemorrhage to address this global crisis. Over the last decade, the evolution of hemorrhage control devices has contributed to advancements in obstetrical hemorrhage management. The number of existing hemorrhage control devices and techniques has increased markedly in recent years, and new devices are in development. The current evidence for established and investigational hemorrhage control devices has been summarized in this review. Of note, 2 main categories of devices exist: traditional uterine tamponade and vacuum-induced uterine tamponade. Although traditional intrauterine balloon tamponade devices are currently used widely in postpartum hemorrhage management, novel hemorrhage control devices and techniques have been developed. These include the minisponge tamponade device, the Jada System, a modified Bakri balloon technique, and a suction tube uterine tamponade technique. Reassuring safety data and preliminary efficacy data from pilot studies of these novel techniques support the powerful role intrauterine devices can play in obstetrical hemorrhage management. This review aimed to improve awareness of device options so that continued efforts can be made to integrate new technology into hemorrhage management protocols. Well-designed studies inclusive of new hemorrhage control devices are essential to understanding where new technology fits into preexisting obstetrical hemorrhage algorithms. In addition, access to new tamponade technology remains limited on a global scale. Programs aimed at both increasing access to devices and expanding educational initiatives are essential to make new technology a standard component for hemorrhage management.

How do I perform cell salvage during vaginal obstetric hemorrhage?

BACKGROUND: Obstetric hemorrhage is a leading cause of preventable maternal mortality. To combat this, obstetric organizations worldwide recommend consideration of autotransfusion during severe peripartum bleeding to minimize allogenic transfusion. Current guidelines for autotransfusion in obstetrics are limited to patients undergoing cesarean birth. At present, women experiencing vaginal obstetric hemorrhage are excluded from many obstetric autotransfusion protocols. However, emerging data suggest that autotransfusion of vaginally shed blood is both safe and feasible in the obstetric patient population. METHODS AND MATERIALS: In this review, we will provide an overview of the current literature surrounding cell salvage of vaginally send blood and a detailed outline of our institution's blood collection protocol. RESULTS: Recent data suggests autotransfusion of vaginally shed blood is both safe and effective. DISCUSSION: Implementation of autotransfusion technology into the delivery room is a critical next step for the advancement of transfusion medicine in obstetrics. This review provides an overview of the data surrounding autotransfusion of vaginally shed blood during maternal hemorrhage and describes practical suggestions for how it can be effectively implemented into routine practice.

Autotransfusion of vaginally shed blood as a novel therapy in obstetric hemorrhage: A case series.

OBJECTIVE: To report maternal outcomes in a cohort of women who received autotransfusion of vaginally shed blood and to describe the feasibility of blood collection and cell salvage processing at the time of vaginal hemorrhage. STUDY DESIGN AND METHODS: We conducted a retrospective case series of patients who received autotransfusion of vaginally shed blood at the time of obstetric hemorrhage from January 2014 to August 2020. Maternal data and cell salvage utilization characteristics were abstracted from the electronic medical record. RESULTS: Sixty-four cases were identified in which autotransfusion of vaginally shed blood occurred during an obstetric hemorrhage. Median quantitative blood loss was 2175 ml (interquartile range 1500-2250 ml) with 89% of cases having a blood loss greater than 1000 ml. Patients on average received approximately 1.3 units of autologous blood product (384 ml, interquartile range 244-520 ml) and no direct adverse events were observed during transfusion. We observed heterogeneity in autologous blood volume across all values of quantitative blood loss. The need for allogenic blood transfusion was common and occurred in 72% of all cases (N = 46). There were no documented cases of maternal sepsis or severe infectious morbidity. CONCLUSION: In 64 cases where autotransfusion of vaginally shed blood occurred, autotransfusion was well tolerated. Heterogeneity in autologous blood volume collection likely represents the lack of standardized protocols for blood collection in the delivery room. Autotransfusion of vaginally shed blood is a feasible and reasonable technique to employ during severe obstetric hemorrhage.

Prolonged second stage effect on pelvic floor dysfunction: a follow up survey to a randomized controlled trial.

BACKGROUND: Pelvic floor dysfunction is a group of disorders that can significantly impact quality of life due to persistent urinary and anal incontinence. Data evaluating the effect of prolonged second stage of labor and postpartum pelvic floor dysfunction is heterogenous and limited. OBJECTIVE: To evaluate whether extending the length of labor in nulliparous women with prolonged second stage affects the presence of self-reported pelvic floor dysfunction after a randomized controlled trial of prolonged second stage. STUDY DESIGN: We conducted a planned follow up survey to our randomized controlled trial of prolonged second stage of labor using the Pelvic Floor Distress Inventory-20 (PFDI-20). The primary outcome was the PFDI-20 summary score. Secondary outcomes included urinary and fecal incontinence, prolapse, and patient satisfaction. Women surveyed were nulliparous patients with epidural anesthesia, previously enrolled in a randomized controlled trial that assigned them to extended labor, at least 1 additional hour in the second stage if they were undelivered after three hours, or to usual labor, defined as expedited delivery after three hours in the second stage. Women were surveyed at 12 - 36 months postpartum. RESULTS: Thirty-four of the seventy-eight women responded to the survey (43.6%). 17 women (50.0%) were from the extended labor group and 17 from the usual labor group (50.0%). Maternal demographic data were not significantly different between groups. The PFDI-20 summary score was 13.8 ± 23.3 in the extended labor group and 13.1 ± 20.9 in the usual labor group (p = 0.9). The Pelvic Organ Prolapse Distress Inventory-6 was 1.2 ± 2.9 in the extended labor group and 2.7 ± 6.4 in the usual labor group (p = 0.4). The Colorectal-Anal Distress Inventory-8 was 0.8 ± 2.8 in the extended labor group and 2.1 ± 4.0 in the usual labor group (p = 0.6). The Urinary Distress Inventory-6 was 11.8 ± 21.1 in the extended labor group and 8.3 ± 14.5 in the usual labor group (p = 0.6). Maternal and neonatal outcomes, as well as patient satisfaction, were not statistically significantly different between groups. CONCLUSION: Extending the length of labor in nulliparas with singleton gestations, epidural anesthesia, and prolonged second stage did not have an impact on PFDI-20 scores at 12-36 months postpartum. However, our study was underpowered to detect small, but potentially clinically important, differences. CLINICAL TRIAL NUMBER: NCT02101515 (Study Registration Date March 28, 2014) https://clinicaltrials.gov/ct2/show/NCT02101515.

Obstetric hemorrhage risk assessment tool predicts composite maternal morbidity.

Obstetric hemorrhage is one of the leading preventable causes of maternal mortality in the United States. Although hemorrhage risk-prediction models exist, there remains a gap in literature describing if these risk-prediction tools can identify composite maternal morbidity. We investigate how well an established obstetric hemorrhage risk-assessment tool predicts composite hemorrhage-associated morbidity. We conducted a retrospective cohort analysis of a multicenter database including women admitted to Labor and Delivery from 2016 to 2018, at centers implementing the Association of Women's Health, Obstetric, and Neonatal Nurses risk assessment tool on admission. A composite morbidity score incorporated factors including obstetric hemorrhage (estimated blood loss ≥ 1000 mL), blood transfusion, or ICU admission. Out of 56,903 women, 14,803 (26%) were categorized as low-risk, 26,163 (46%) as medium-risk and 15,937 (28%) as high-risk for obstetric hemorrhage. Composite morbidity occurred at a rate of 2.2%, 8.0% and 11.9% within these groups, respectively. Medium- and high-risk groups had an increased combined risk of composite morbidity (diagnostic OR 4.58; 4.09-5.13) compared to the low-risk group. This established hemorrhage risk-assessment tool predicts clinically-relevant composite morbidity. Future randomized trials in obstetric hemorrhage can incorporate these tools for screening patients at highest risk for composite morbidity.

Correlation between hemorrhage risk prediction score and severe maternal morbidity.

BACKGROUND: Obstetrical hemorrhage is a leading cause of severe maternal morbidity, a key indicator of a nation's healthcare delivery system and often associated with a high rate of preventability. Limited data suggest that a patient's hemorrhage risk score may be associated with risk for maternal morbidity such as severe hemorrhage, intensive care unit admission, or transfusion. Little is known regarding the relationship between hemorrhage risk score and nontransfusion-related morbidity. OBJECTIVE: We sought to evaluate the association between a patient's California Maternal Quality Care Collaborative admission hemorrhage risk score and severe maternal morbidity. STUDY DESIGN: This was a retrospective cohort of delivery admissions from 2018 to 2019 in a single healthcare network. Admission risk scores were assigned to each patient using the California Maternal Quality Care Collaborative criteria. Rates of transfusion- and nontransfusion-associated severe maternal morbidity were compared across low-, medium-, and high-risk strata. We defined severe maternal morbidity as the presence of any International Classification of Diseases diagnosis or procedure codes outlined by the Centers for Disease Control and Prevention, need for intensive care unit admission, or prolonged postpartum hospital length of stay. A multivariable logistic regression was used to assess the association between hemorrhage risk score and severe maternal morbidity. RESULTS: In the overall cohort, severe maternal morbidity occurred in 2.4% (n=517) of all deliveries. Excluding cases requiring transfusion, 0.6% (n=131) of cases still had a severe maternal morbidity event. The incidence of severe maternal morbidity was 1.6% (n=264) in patients categorized as low risk for hemorrhage compared with 2.5% (n=118) and 13.6% (n=135) in patients who were categorized as medium or high risk for hemorrhage, respectively (P<.001). Patients classified as high risk had a significant association with both severe maternal morbidity (adjusted odds ratio, 8.8; 95% confidence interval, 7.0-11) and nontransfusion-associated severe maternal morbidity (adjusted odds ratio, 3.6; 95% confidence interval, 2.2-5.9). CONCLUSION: In addition to predicting the risk for obstetrical hemorrhage and transfusion, our findings indicate that the California Maternal Quality Care Collaborative admission hemorrhage risk tool predicts risk for transfusion- and nontransfusion-associated severe maternal morbidity. Our findings imply that despite awareness and the identification of patients at high risk for obstetrical hemorrhage on admission, significant hemorrhage-associated morbidity persisted. Our data indicate that the identification of risk alone may be insufficient to reduce morbidity and imply that further work is needed to investigate and implement new practices in response to a patient's score stratum.

Hemorrhage Risk Assessment on Admission: Utility for Prediction of Maternal Morbidity.

OBJECTIVE: Hemorrhage is a major cause of maternal morbidity and mortality prompting creation of innovative risk assessment tools to identify patients at highest risk. We aimed to investigate the association of hemorrhage risk assessment with maternal morbidity and to evaluate maternal outcomes after implementation of the risk assessment across hospital sites. STUDY DESIGN: We conducted a retrospective cohort analysis of a multicenter database including women admitted to labor and delivery from January 2015 to June 2018. The Association of Women's Health, Obstetric and Neonatal Nurses risk assessment tool was used to categorize patients as low, medium, or high risk for hemorrhage. Multivariate logistic regression was used to describe the association between hemorrhage risk score and markers of maternal morbidity and evaluate maternal outcomes before and after standardized implementations of the risk assessment tool. RESULTS: In this study, 14,861 women were categorized as low risk (26%), 26,080 (46%) moderate risk, and 15,730 (28%) high risk (N = 56,671 births). For women with high-risk scores, the relative risk (RR) ratio compared with low-risk women was 4.9 (RR: 95% confidence interval [CI]: 3.2-7.4) for blood transfusion and 5.2 (RR: 95% CI: 4.6-5.9) for estimated blood loss (EBL) ≥ 1,000 mL. For the second objective, 110,633 women were available for pre- and postimplementation analyses (39,027 and 71,606, respectively). A 20% reduction in rates of blood transfusion (0.5-0.4%, p = 0.02) and EBL ≥ 1,000 mL (6.3-5.9%, p = 0.014) was observed between pre- and postimplementations of the admission hemorrhage risk assessment tool. CONCLUSION: Women who were deemed high risk for hemorrhage using a hemorrhage risk assessment tool had five times higher risk for blood transfusion and EBL ≥ 1,000 mL compared with low-risk women. Given the low incidence of the outcomes explored, the hemorrhage risk assessment works moderately well to identify patients at risk for peripartum morbidity. KEY POINTS: · This study aimed to understand the utility of the AWOHNN hemorrhage risk assessment tool for predicting hemorrhage-related morbidity and to evaluate maternal outcomes before and after tool implementations.. · A high score using a hemorrhage risk assessment tool on admission is associated with five times higher risk for blood transfusion and/or estimated blood loss ≥ 1,000 mL, compared with a low score.. · Use of a hemorrhage risk assessment tool works moderately well to identify patients at highest risk for hemorrhage-related morbidity..

Next Generation Medical Management of Postpartum Hemorrhage.

BACKGROUND: Postpartum hemorrhage remains a significant contributor to morbidity and mortality of women of childbearing age worldwide. Trends in both incidence and severity of postpartum hemorrhage are increasing which makes it imperative to identify drugs that could target prevention and/or treatment of these postpartum hemorrhages for women living in high, middle and low-income countries. METHODS: We have reviewed current advances in the medical management of postpartum hemorrhage focusing on non-uterotonic therapy. We specifically describe the use and mechanism of action of tranexamic acid (TXA) and fibrinogen concentrate. Furthermore, we address the existing data for using these medications in postpartum hemorrhage, highlighting both strengths and limitations. RESULTS: This review describes a new generation of medications that are promising for the prevention and/or treatment of postpartum hemorrhage. For patients at risk for significant hemorrhage, TXA has been shown to reduce intraoperative blood loss and can be given as a prophylactic agent. For the treatment of postpartum hemorrhage, early use of TXA has the potential to reduce mortality. In addition, some data exists supporting the use of fibrinogen concentrate, though more studies are required to help formulate guidelines for its use. CONCLUSION: A promising new approach for the management of severe postpartum hemorrhage is using medications that alter coagulation. More data are needed to describe ideal patient populations, dosing, the time of administration, and infusion rate.

Correction: Predicting peripartum blood transfusion in women undergoing cesarean delivery: A risk prediction model.

[This corrects the article DOI: 10.1371/journal.pone.0208417.].

Predicting peripartum blood transfusion in women undergoing cesarean delivery: A risk prediction model.

OBJECTIVE: There has been an appreciable rise in postpartum hemorrhage requiring blood transfusions in the United States. Our objective is to better define patients at greatest risk for peripartum transfusion at the time of cesarean in order to identify cases for early intervention and monitoring. METHODS: Our study is a secondary analysis of a retrospective cohort study. Cases of intraoperative and immediate postpartum blood transfusion among women undergoing cesarean delivery were identified. Multivariable logistic regression models were used to identify antepartum and intrapartum risk factors that were independently associated with blood transfusion. A risk calculator was then developed to predict the need for transfusion. RESULTS: Of 56,967 women, 1488 (2.6%) required any blood transfusion. The strongest risk factors for peripartum blood transfusion included anemia (odds ratio [OR] 3.7, 95% CI 3.3-4.3), abruption on presentation (OR 3.3, CI 2.6-4.1), general anesthesia (OR 5.2, CI 4.4-6.1) and abnormal placentation (OR 92.0, CI 57.4-147.6). An antepartum (model 1) and combined antepartum plus intrapartum risk model (model 2) were developed (model 1 AUC = 0.77, model 2 AUC = 0.83) and internally validated. CONCLUSIONS: Among women who required cesarean delivery, we were able to identify risk factors which predispose women to peripartum blood transfusion and developed a prediction model with good discrimination.

Tranexamic Acid for Prevention and Treatment of Postpartum Hemorrhage: An Update on Management and Clinical Outcomes.

IMPORTANCE: Postpartum hemorrhage (PPH) remains a major cause of maternal mortality worldwide, occurring in both vaginal and cesarean deliveries. We have witnessed improvements in both prevention and treatment of PPH. Tranexamic acid (TXA) has been investigated as a potential adjunct therapy to uterotonics within this setting. OBJECTIVE: The aim of this article is to summarize existing recommendations on the use of TXA in obstetrics and review current data on clinical outcomes after TXA use. EVIDENCE ACQUISITION: We reviewed guidelines from a number of professional societies and performed an extensive literature search reviewing relevant and current data in this area. RESULTS AND CONCLUSIONS: In the prevention of PPH, TXA use before both vaginal and cesarean deliveries reduces the amount of postpartum blood loss and should be considered in patients at higher risk for hemorrhage. In the treatment of PPH, TXA should be initiated early for maximal survival benefit from hemorrhage, and it provides no additional benefit if administered more than 3 hours from delivery. Overall, current evidence assessing the risks of TXA use in an obstetric population is reassuring.

Use of transcriptional profiling to delineate the initial response of mice to intravaginal herpes simplex virus type 2 infection.

Intravaginal (ivag) infection of mice with herpes simplex virus type 2 (HSV-2) causes genital tissue damage, quickly followed by development of fatal encephalopathy. To delineate initial host responses generated by HSV-2 infection, here oligonucleotide microarrays compared gene expression in vaginal tissue from uninfected mice and mice 1, 2, 3, 4, 5, 6, or 7 days after ivag infection with 10(4) pfu HSV-2. While comparison of mRNA expression in uninfected and HSV-infected vaginal tissue detected few changes during the first 2 days post infection (dpi), there were 156 genes whose expression was first significantly altered 3 dpi that remained significantly modified at all later time points examined. These 156 genes were significantly enriched in canonical pathways associated with interferon (IFN) signaling, activation of IFN elements by intracellular pattern recognition receptors, and antiviral immunity induced by cytosolic RIG-like receptors. Evaluation of this gene set with the National Center for Biotechnology Information Gene and INTERFEROME databases corroborated pathway analysis, as function of most (53%) were linked to IFN-mediated host immunity. In the final set of experiments, ivag administration of the Toll-like receptor 3 agonist polyinosinic: polycytidylic acid (poly I:C) 24 h before ivag HSV-2 infection reduced the incidence of genital pathology and encephalopathy, while these poly I:C-treated mice were subsequently protected from ocular HSV-2 challenge lethal to uninfected controls. The latter results imply that the exuberant antiviral immunity produced in our experimental model is simply formed too late to prevent viral replication and dissemination, and that poly I:C-induced formation of an antiviral state protecting against primary ivag infection also permits development of HSV-specific protective immunity.

Limitations of the criteria used to diagnose histologic endometritis in epidemiologic pelvic inflammatory disease research.

While endometrial neutrophils and plasma cells are criteria used to diagnose histologic endometritis in epidemiologic pelvic inflammatory disease (PID) research, plasma cell misidentification and nonspecificity may limit the accuracy of these criteria. Herein, we examined: (1) the identification of endometrial plasma cells with conventional methyl green pyronin-based methodology versus plasma cell-specific (CD138) immunostaining, (2) the prevalence of endometrial plasma cells among women at low risk for PID, and (3) endometrial leukocyte subpopulations among women diagnosed with acute or chronic histologic endometritis by conventional criteria. We observed an absence of CD138+ cells in 25% of endometrial biopsies in which plasma cells had been identified by conventional methodology, while additional immunohistochemical analyses revealed indistinguishable inflammatory infiltrates among women diagnosed with acute or chronic endometritis by conventional criteria. Among women considered at lower risk for PID development, flow cytometric analyses detected plasma cells in 30% of endometrial biopsy specimens, suggesting that these cells, even when accurately identified, only nonspecifically identify upper genital tract inflammatory processes. Combined, our findings underscore the limitations of the criteria used to diagnose histologic endometritis in PID-related research and suggest that satisfactory understanding of PID pathogenesis, treatment, and prevention is hindered by continued use of these criteria.