Comparison of vaginal microbiota between women with inflammatory bowel disease and healthy controls.

BACKGROUND: The gut microbiota in patients with inflammatory bowel disease are perturbed in both composition and function. The vaginal microbiome and its role in the reproductive health of women with inflammatory bowel disease is less well described. OBJECTIVE: We aim to compare the vaginal microbiota of women with inflammatory bowel disease to healthy controls. METHODS: Women with inflammatory bowel disease enrolled in a longitudinal cohort study provided self-collected vaginal swabs. Healthy controls underwent provider-collected vaginal swabs at routine gynecologic exams. All participants completed surveys on health history, vulvovaginal symptoms and gastrointestinal symptoms, if applicable. Microbiota were characterized by sequencing the V4 region of the 16S rRNA gene. Associations between patient characteristics and microbial community composition were evaluated by PERMANOVA and Principal Components Analysis. Lactobacillus dominance of the microbial community was compared between groups using chi-square and Poisson regression. RESULTS: The cohort included 54 women with inflammatory bowel disease (25 Ulcerative colitis, 25 Crohn's Disease) and 26 controls. A majority, 72 (90%) were White; 17 (31%) with inflammatory bowel disease and 7 (27%) controls were postmenopausal. The composition of the vaginal microbiota did not vary significantly by diagnosis or severity of inflammatory bowel disease but did vary by menopausal status (p = 0.042). There were no significant differences in Shannon Diversity Index between healthy controls and women with IBD in premenopausal participants. There was no difference in proportion of Lactobacillus dominance according to diagnosis in premenopausal participants. A subgroup of postmenopausal women with Ulcerative colitis showed a significant higher alpha diversity and a lack of Lactobacillus dominance in the vaginal microbiome. CONCLUSIONS: Menopausal status had a larger impact on vaginal microbial communities than inflammatory bowel disease diagnosis or severity.

Antepartum depressive symptoms are associated with significant postpartum opioid use.

BACKGROUND: Antepartum depression is common, and outside of childbirth preoperative anxiety and depression have been associated with heightened postoperative pain. In light of the national opioid epidemic, the relationship between antepartum depressive symptoms and postpartum opioid use is particularly relevant. OBJECTIVE: This study evaluated the association between antepartum depressive symptoms and significant postpartum opioid use during birth hospitalization. STUDY DESIGN: This retrospective cohort study at an urban academic medical center from 2017 to 2019 included patients who received prenatal care at the medical center and linked pharmacy and billing data with electronic medical records. The exposure was antepartum depressive symptoms, defined as Edinburgh Postnatal Depression Scale ≥10 during the antepartum period. The outcome was significant opioid use, defined as: (1) any opioid use following vaginal birth and (2) the top quartile of total opioid use following cesarean delivery. Postpartum opioid use was quantified using standard conversions for opioids dispensed on postpartum days 1 to 4 to calculate morphine milligram equivalents. Poisson regression was used to calculate risk ratios and 95% confidence intervals, stratified by mode of delivery and adjusted for suspected confounders. Mean postpartum pain score was a secondary outcome. RESULTS: The cohort included 6094 births; 2351 births (38.6%) had an antepartum Edinburgh Postnatal Depression Scale score. Of these, 11.5% had a maximum score ≥10. Significant opioid use was observed in 10.6% of births. We found that individuals with antepartum depressive symptoms were more likely to have significant postpartum opioid use, with an adjusted risk ratio of 1.5 (95% confidence interval, 1.1-2.0). When stratified by mode of delivery, this association was more pronounced for cesarean births, with an adjusted risk ratio of 1.8 (95% confidence interval, 1.1-2.7), and was no longer significant for vaginal births. Mean pain scores after cesarean delivery were significantly higher in parturients with antepartum depressive symptoms. CONCLUSION: Antepartum depressive symptoms were associated with significant postpartum inpatient opioid use, especially following cesarean delivery. Whether identifying and treating depressive symptoms in pregnancy may impact the pain experience and opioid use postpartum warrants further investigation.

A novel approach to joint prediction of preeclampsia and delivery timing using semicompeting risks.

BACKGROUND: Preeclampsia is a pregnancy complication that contributes substantially to perinatal morbidity and mortality worldwide. Existing approaches to modeling and prediction of preeclampsia typically focus either on predicting preeclampsia risk alone, or on the timing of delivery following a diagnosis of preeclampsia. As such, they are misaligned with typical healthcare interactions during which the 2 events are generally considered simultaneously. OBJECTIVE: This study aimed to describe the "semicompeting risks" framework as an innovative approach for jointly modeling the risk and timing of preeclampsia and the timing of delivery simultaneously. Through this approach, one can obtain, at any point during the pregnancy, clinically relevant summaries of an individual's predicted outcome trajectories in 4 risk categories: not developing preeclampsia and not having delivered, not developing preeclampsia but having delivered because of other causes, developing preeclampsia but not having delivered, and developing preeclampsia and having delivered. STUDY DESIGN: To illustrate the semicompeting risks methodology, we presented an example analysis of a pregnancy cohort from the electronic health record of an urban, academic medical center in Boston, Massachusetts (n=9161 pregnancies). We fit an illness-death model with proportional-hazards regression specifications describing 3 hazards for timings of preeclampsia, delivery in the absence of preeclampsia, and delivery following preeclampsia diagnosis. RESULTS: The results indicated nuanced relationships between a variety of risk factors and the timings of preeclampsia diagnosis and delivery, including maternal age, race/ethnicity, parity, body mass index, diabetes mellitus, chronic hypertension, cigarette use, and proteinuria at 20 weeks' gestation. Sample predictions for a diverse set of individuals highlighted differences in projected outcome trajectories with regard to preeclampsia risk and timing, and timing of delivery either before or after preeclampsia diagnosis. CONCLUSION: The semicompeting risks framework enables characterization of the joint risk and timing of preeclampsia and delivery, providing enhanced, meaningful information regarding clinical decision-making throughout the pregnancy.

Tranexamic acid in the routine treatment of postpartum hemorrhage in the United States: a cost-effectiveness analysis.

BACKGROUND: The World Maternal Antifibrinolytic trial demonstrated that tranexamic acid administered during postpartum hemorrhage reduces hemorrhage-related mortality and laparotomies. The World Health Organization has thus recommended early use of tranexamic acid in the treatment of postpartum hemorrhage. This recommendation has not been universally adopted in the United States, in part because of concerns about cost-effectiveness. OBJECTIVE: We aim to demonstrate the cost-effectiveness of routine tranexamic acid administration in the treatment of postpartum hemorrhage in the United States, where the rate of hemorrhage-related mortality is lower than that described in the World Maternal Antifibrinolytic trial. STUDY DESIGN: We constructed a decision tree comparing 3 strategies in women with a clinical diagnosis of postpartum hemorrhage: no tranexamic acid, tranexamic acid given at any time, and ideal use of tranexamic acid given within 3 hours of delivery. The study was performed from a health care institution perspective with a time horizon of delivery until 6 weeks postpartum. We included interventions that differed by arm in the World Maternal Antifibrinolytic trial (hemorrhage-related mortality, laparotomies, and brace or compression sutures) and incorporated probabilities and costs based on available data for a population of women with postpartum hemorrhage in the United States. In our base case, the rate of postpartum hemorrhage-related mortality was 0.0388%, and the cost of tranexamic acid was $37.80. We assumed that the relative risk reduction in death and laparotomy with tranexamic acid would be similar to the World Maternal Antifibrinolytic trial (19% and 36%, respectively). The primary outcome was incremental cost per hemorrhage-related death averted, and a main secondary outcome was incremental cost per laparotomy avoided under each strategy. Another planned secondary outcome was cost per quality-adjusted life-year. We anticipated that the risk reduction (benefit) because of tranexamic acid in the United States may be less than in the World Maternal Antifibrinolytic trial; thus, we performed 1-way and 2-way sensitivity analyses to explore the parameter uncertainty across a wide range of data-supported estimates. Probabilistic sensitivity analyses with Monte Carlo simulation were performed. RESULTS: Tranexamic acid strategies were dominant (more effective and cost saving) compared with no tranexamic acid for patients with postpartum hemorrhage in the United States. One-way analyses showed that tranexamic acid is cost saving as long as the relative risk reduction of death with tranexamic acid is greater than 4.7%; the model was not sensitive to any other variables. Threshold analyses outside the bounds defined in the model showed that tranexamic acid is cost saving as long as the relative risk reduction of laparotomy with tranexamic acid is greater than 7% or the cost of tranexamic acid is less than $194. A 2-way sensitivity analysis of the risk reduction of death because of tranexamic acid and the baseline risk of postpartum hemorrhage-related death confirmed that tranexamic acid is cost saving across a wide range of plausible estimates. Furthermore, probabilistic sensitivity analysis demonstrated that the tranexamic acid strategies are cost saving in >99.9% of 10,000 Monte Carlo simulations. Despite the initial cost of administration, the annual net cost savings expected from routine use of tranexamic acid for the treatment of postpartum hemorrhage in the United States is $11.3 million, and we estimate that 9 maternal deaths would be averted in 1 year with this strategy. Giving tranexamic acid within 3 hours would almost triple the cost savings and improve maternal outcomes much further. CONCLUSION: A policy of routine tranexamic acid early in the treatment of postpartum hemorrhage is likely to be cost saving in the United States. This conclusion holds true even when the relative risk reduction with tranexamic acid is significantly less than reported in the World Maternal Antifibrinolytic trial and when tranexamic acid is significantly more expensive than currently reported.

Choice of Trial of Labor after Cesarean and Association with Likelihood of Success.

OBJECTIVE: To investigate whether the predicted chance of success is associated with the choice to undergo trial of labor after cesarean (TOLAC). STUDY DESIGN: Retrospective cohort study of women with a single prior nonelective cesarean delivering a term singleton in 2012 at a tertiary care hospital. A vaginal birth after cesarean (VBAC) score (likelihood of success) was estimated for each patient. The primary outcome was percentage of women choosing TOLAC among women with favorable (> 70% likelihood) and unfavorable VBAC scores. Other factors such as desired sterilization, provider type, and spontaneous labor were included in the analysis. RESULTS: In 2012, 434 women were eligible: 73 with VBAC score >70%, and 361 with score ≤70%. Of those with score >70%, 63% chose TOLAC, compared with 21% with score ≤70% (p < 0.01). In a multivariable analysis, spontaneous labor onset was highly associated with choosing TOLAC: adjusted odds ratio 26.7 (95% confidence interval 13.86-51.29). The choice of TOLAC was also positively associated with resident provider and desired fertility. CONCLUSION: Almost four in ten women with a history of nonelective primary cesarean and a very high predicted likelihood of VBAC choose elective repeat cesarean. Spontaneous labor was strongly associated with the choice to undergo TOLAC.