Pharmacological Interventions in Labor and Delivery.

While there is not a wide range of pregnancy-specific drugs, there are some very specific high-risk areas of obstetric care for which unique pharmacological approaches have been established. In preterm birth, labor induction and augmentation, and the management of postpartum hemorrhage, these pharmacological approaches have become the bedrock in managing some of the most common and problematic areas of antenatal and intrapartum care. In this review, we summarize the existing established and emerging evidence that supports and broadens these pharmacological approaches to obstetric management and its impact on clinical practice. It is clear that existing therapeutics are limited. They have largely been developed from our knowledge of the physiology of the myometrium and act on hormonal receptors and their signaling pathways or on ion channels influencing excitability. Newer drugs in development are mostly refinements of these two approaches, but novel agents from plants and improved formulations are also discussed.

Oxytocin is not associated with postpartum hemorrhage in labor augmentation in a retrospective cohort study in the United States.

BACKGROUND: Previous studies reported conflicting results on the relationship between oxytocin use for labor augmentation and the risk of postpartum hemorrhage, probably because it is rather challenging to disentangle oxytocin use from labor dystocia. OBJECTIVE: This study aimed to investigate the independent association between oxytocin use for augmentation and the risk of postpartum hemorrhage by using advanced statistical modeling to control for labor patterns and other covariates. STUDY DESIGN: We used data from 20,899 term, cephalic, singleton pregnancies of patients with spontaneous onset of labor and no previous cesarean delivery from Intermountain Healthcare in Utah in the Consortium on Safe Labor. Presence of postpartum hemorrhage was identified on the basis of a clinical diagnosis. Propensity scores were calculated using a generalized linear mixed model for oxytocin use for augmentation, and covariate balancing generalized propensity score was applied to obtain propensity scores for the duration and total dosage of oxytocin augmentation. A weighted generalized additive mixed model was used to depict dose-response curves between the duration and total dosage of oxytocin augmentation and the outcomes. The average treatment effects of oxytocin use for augmentation on postpartum hemorrhage and estimated blood loss (mL) were assessed by inverse probability weighting of propensity scores. RESULTS: The odds of both postpartum hemorrhage and estimated blood loss increased modestly when the duration and/or total dosage of oxytocin used for augmentation increased. However, in comparison with women for whom oxytocin was not used, oxytocin augmentation was not clinically or statistically significantly associated with estimated blood loss (6.5 mL; 95% confidence interval, 2.5-10.3) or postpartum hemorrhage (adjusted odds ratio, 1.02; 95% confidence interval, 0.82-1.24) when rigorously controlling for labor pattern and potential confounders. The results remained consistent regardless of inclusion of women with an intrapartum cesarean delivery. CONCLUSION: The odds of postpartum hemorrhage and estimated blood loss increased modestly with increasing duration and total dosage of oxytocin augmentation. However, in comparison with women for whom oxytocin was not used and after controlling for potential confounders, there was no clinically significant association between oxytocin use for augmentation and estimated blood loss or the risk of postpartum hemorrhage.

Agnostic identification of plasma biomarkers for postpartum hemorrhage risk.

BACKGROUND: Postpartum hemorrhage is difficult to predict, is associated with significant maternal morbidity, and is the leading cause of maternal mortality worldwide. The identification of maternal biomarkers that can predict increased postpartum hemorrhage risk would enhance clinical care and may uncover mechanisms that lead to postpartum hemorrhage. OBJECTIVE: This retrospective case-control study employed agnostic proteomic profiling of maternal plasma samples to identify differentially abundant proteins in controls and postpartum hemorrhage cases. STUDY DESIGN: Maternal plasma samples were procured from a cohort of >60,000 participants in a single institution's perinatal repository. Postpartum hemorrhage was defined as a decrease in hematocrit of ≥10% or receipt of transfusion within 24 hours after delivery. Postpartum hemorrhage cases (n=30) were matched by maternal age and delivery mode (vaginal or cesarean) with controls (n=56). Mass spectrometry was used to identify differentially abundant proteins using integrated peptide peak areas. Statistically significant differences between groups were defined as P<.05 after controlling for multiple comparisons. RESULTS: By study design, cases and controls did not differ in race, ethnicity, gestational age at delivery, blood type, or predelivery platelet count. Cases had slightly but significantly lower predelivery and postdelivery hematocrit and hemoglobin. Mass spectrometry detected 1140 proteins, including 77 proteins for which relative abundance differed significantly between cases and controls (fold change >1.15, P<.05). Of these differentially abundant plasma proteins, most had likely liver or placental origins. Gene ontology term analysis mapped to protein clusters involved in responses to wound healing, stress response, and host immune defense. Significantly differentially abundant proteins with the highest fold change (prostaglandin D2 synthase, periostin, and several serine protease inhibitors) did not correlate with predelivery hematocrit or hemoglobin but identified postpartum hemorrhage cases with logistic regression modeling revealing good-to-excellent area under the operator receiver characteristic curves (0.802-0.874). Incorporating predelivery hemoglobin with these candidate proteins further improved the identification of postpartum hemorrhage cases. CONCLUSION: Agnostic analysis of maternal plasma samples identified differentially abundant proteins in controls and postpartum hemorrhage cases. Several of these proteins are known to participate in biologically plausible pathways for postpartum hemorrhage risk and have potential value for predicting postpartum hemorrhage. These findings identify candidate protein biomarkers for future validation and mechanistic studies.

Uterine packing with chitosan-covered tamponade to treat postpartum hemorrhage.

Postpartum hemorrhage remains a major cause of maternal mortality and morbidity worldwide with higher rates found in resource-challenged countries. Conventional use of uterotonics such as oxytocin, prostaglandins, and medications to support coagulation, such as fibrinogen and tranexamic acid, are helpful but may not be sufficient to arrest life-threatening postpartum hemorrhage. Severe postpartum hemorrhage leads to an increased need for blood transfusions and the use of invasive techniques, such as intrauterine balloon tamponade, compression sutures, and arterial ligation, as advanced steps in the management cascade. In extreme cases where hemorrhage is resistant to these therapies, a hysterectomy may be necessary to avoid possible maternal death. Uterine packing with a chitosan-covered tamponade is an emerging tool in the armamentarium of the obstetrical team, especially when resources for advance surgical and other invasive options may be limited. Modified chitosan-impregnated gauze was originally described in the management of acute hemorrhage in the field of military medicine, combining the physiological antihemorrhaging effect of modified chitosan with a compression tamponade for the acute treatment of wound bleeding. The first described use in obstetrics was in 2012, showing that the chitosan-covered tamponade is an effective intervention to arrest ongoing therapy-resistant postpartum hemorrhage. Further studies showed a reduction in hysterectomies and blood transfusions. The method is, however, underreported and is not yet an established method used worldwide. To demonstrate the step-by-step application of the intrauterine chitosan-covered tamponade in the management of therapy-resistant postpartum hemorrhage, we have produced a teaching video to illustrate the important steps and techniques to optimize the effectiveness and safety of this novel intervention.

Time to redefine prolonged third stage of labor? A systematic review and meta-analysis of the length of the third stage of labor and adverse maternal outcome after vaginal birth.

OBJECTIVES: (1) To assess the association between the duration of the third stage of labor and adverse maternal outcome after vaginal birth and (2) evaluate whether earlier manual placenta removal reduces this risk of adverse outcome. DATA SOURCES: PubMed/MEDLINE, EMBASE, ClinicalTrials.gov, Cochrane Library, Journals@Ovid and the WHO International Clinical Trials Registry from January 1st 2000-June 13th 2023. STUDY ELIGIBILITY CRITERIA: All studies that assessed adverse maternal outcome, defined as any maternal complication after vaginal birth, in relation to duration of the third stage of labor and timing of manual placenta removal. STUDY APPRAISAL AND SYNTHESIS METHODS: Included studies were evaluated according the COSMOS-E (Conducting Systematic Reviews and Meta-Analyses of Observational Studies of Etiology) methodology. Pooled odds ratios with 95% confidence intervals were calculated. We assessed heterogeneity (I2 test); performed subgroup analyses; and calculated 95% prediction intervals. RESULTS: To answer the first objective, 18 cohort studies were included. Assessed cut-offs of third stage were: 15, 30 and 60 minutes. Women with a third stage ≥15 minutes had an increased risk of postpartum hemorrhage compared to <15 minutes (Odds Ratio [OR] 5.55; 95%CI 1.74,17.72). For women without risk factors for postpartum hemorrhage, the OR was 2.20; 95%CI 0.75,6.49. Among women with a third stage ≥60 minutes versus <60 minutes, the OR was 3.72; 95%CI 2.36-5.89. Incidence of red blood cell transfusion was increased for a third stage ≥30 minutes versus <30 minutes (OR 3.23; 95%CI 2.26-4.61). Three studies assessed the timing of placenta removal and risk of adverse maternal outcome yet could not be pooled due to different outcome measures. One randomized controlled trial reported a significantly higher incidence of hemodynamic compromise in women with manual placenta removal at 15 versus 10 minutes (19.2%,30/156 6.4%,10/156) while two observational studies reported a lower risk of bleeding among women without manual placenta removal. CONCLUSION: Although the risk of adverse maternal outcome after vaginal birth increases when the third stage of labor exceeds 15 minutes, there is no convincing evidence supporting a reduction of the third stage of labor by earlier manual removal of the placenta to reduce the incidence of adverse maternal outcome.

Early vs delayed amniotomy following transcervical Foley balloon in the induction of labor: a randomized clinical trial.

BACKGROUND: The optimal timing of amniotomy during labor induction is a topic of ongoing debate due to the potential risks associated with both amniotomy and prolonged labor. As such, individuals in the field of obstetrics and gynecology must carefully evaluate the associated benefits and drawbacks of this procedure. While amniotomy can expedite the labor process, it may also lead to complications such as umbilical cord prolapse, fetal distress, and infection. Therefore, a careful and thorough examination of the risks and benefits of amniotomy during labor induction is essential in making an informed decision regarding the optimal timing of this procedure. OBJECTIVE: This study aimed to determine if an amniotomy within 2 hours after Foley balloon removal reduced the duration of active labor and time taken to achieve vaginal delivery when compared with an amniotomy ≥4 hours after balloon removal among term pregnant women who underwent labor induction. STUDY DESIGN: This was an open-label, randomized controlled trial that was conducted at a single academic center from October 2020 to March 2023. Term participants who were eligible for preinduction cervical ripening with a Foley balloon were randomized into 2 groups, namely the early amniotomy (rupture of membranes within 2 hours after Foley balloon removal) and delayed amniotomy (rupture of membranes performed more than 4 hours after Foley balloon removal) groups. Randomization was stratified by parity. The primary outcome was time from Foley balloon insertion to active phase of labor. Secondary outcomes, including time to delivery, cesarean delivery rates, and maternal and neonatal complications, were analyzed using intention-to-treat and per-protocol analyses. RESULTS: Of the 150 participants who consented and were enrolled, 149 were included in the analysis. In the intention-to-treat population, an early amniotomy did not significantly shorten the time between Foley balloon insertion and active labor when compared with a delayed amniotomy (885 vs 975 minutes; P=.08). An early amniotomy was associated with a significantly shorter time from Foley balloon placement to active labor in nulliparous individuals (1211; 584-2340 vs 1585; 683-2760; P=.02). When evaluating the secondary outcomes, an early amniotomy was associated with a significantly shorter time to active labor onset (312.5 vs 442.5 minutes; P=.02) and delivery (484 vs 587 minutes; P=.03) from Foley balloon removal with a higher rate of delivery within 36 hours (96% vs 85%; P=.03). Individuals in the early amniotomy group reached active labor 1.5 times faster after Foley balloon insertion than those in the delayed group (hazard ratio, 1.5; 95% confidence interval, 1.1-2.2; P=.02). Those with an early amniotomy also reached vaginal delivery 1.5 times faster after Foley balloon removal than those in the delayed group (hazard ratio, 1.5; 95% confidence interval, 1-2.2; P=.03). A delayed amniotomy was associated with a higher rate of postpartum hemorrhage (0% vs 9.5%; P=.01). No significant differences were observed in the cesarean delivery rates, length of hospital stay, maternal infection, or neonatal outcomes. CONCLUSION: Although an early amniotomy does not shorten the time from Foley balloon insertion to active labor, it shortens time from Foley balloon removal to active labor and delivery without increasing complications. The increased postpartum hemorrhage rate in the delayed amniotomy group suggests increased risks with delayed amniotomy.

Closed- or open-glottis pushing for vaginal delivery: a planned secondary analysis of the TRAnexamic Acid for Preventing postpartum hemorrhage after vaginal delivery study.

BACKGROUND: The effect on obstetrical outcomes of closed- or open-glottis pushing is uncertain among both nulliparous and parous women. OBJECTIVE: This study aimed to assess the association between open- or closed-glottis pushing and mode of delivery after an attempted singleton vaginal birth at or near term. STUDY DESIGN: This was an ancillary planned cohort study of the TRAAP (TRAnexamic Acid for Preventing postpartum hemorrhage after vaginal delivery) randomized controlled trial, conducted in 15 French maternity units from 2015 to 2016 that enrolled women with an attempted singleton vaginal delivery after 35 weeks' gestation. After randomization, characteristics of labor and delivery were prospectively collected, with special attention to active second-stage pushing and a specific planned questionnaire completed immediately after birth by the attending care provider. The exposure was the mode of pushing, classified into 2 groups: closed- or open-glottis. The main endpoint was operative vaginal delivery. Secondary endpoints were items of maternal morbidity, including severe perineal laceration, episiotomy, postpartum hemorrhage, duration of the second stage of labor, and a composite severe neonatal morbidity outcome. We also assessed immediate maternal satisfaction, experience of delivery, and psychological status 2 months after delivery. The associations between mode of pushing and outcome were analyzed by multivariate logistic regression to control for confounding bias, with multilevel mixed-effects analysis, and a random intercept for center. RESULTS: Among 3041 women included in our main analysis, 2463 (81.0%) used closed-glottis pushing and 578 (19.0%) open-glottis pushing; their respective operative vaginal delivery rates were 19.1% (n=471; 95% confidence interval, 17.6-20.7) and 12.5% (n=72; 95% confidence interval, 9.9-15.4; P<.001). In an analysis stratified according to parity and after controlling for available confounders, the rate of operative vaginal delivery did not differ between the groups among nulliparous women: 28.7% (n=399) for the closed-glottis and 27.5% (n=64) for the open-glottis group (adjusted odds ratio, 0.93; 95% confidence interval, 0.65-1.33; P=.7). The operative vaginal delivery rate was significantly lower for women using open- compared with closed-glottis pushing in the parous population: 2.3% (n=8) for the open- and 6.7% (n=72) for the closed-glottis groups (adjusted odds ratio, 0.43; 95% confidence interval, 0.19-0.90; P=.03). Other maternal and neonatal outcomes did not differ between the 2 modes of pushing among either the nulliparous or parous groups. CONCLUSION: Among nulliparous women with singleton pregnancies at term, the risk of operative vaginal birth did not differ according to mode of pushing. These results will inform shared decision-making about the mode of pushing during the second stage of labor.

Society for Maternal-Fetal Medicine Special Statement: Emergency checklist, planning worksheet, and system preparedness bundle for placenta accreta spectrum.

Placenta accreta spectrum is a life-threatening complication of pregnancy that is underdiagnosed and can result in massive hemorrhage, disseminated intravascular coagulation, massive transfusion, surgical injury, multisystem organ failure, and even death. Given the rarity and complexity, most obstetrical hospitals and providers do not have comprehensive expertise in the diagnosis and management of placenta accreta spectrum. Emergency management, antenatal interdisciplinary planning, and system preparedness are key pillars of care for this life-threatening disorder. We present an updated sample checklist for emergent and unplanned cases, an antenatal planning worksheet for known or suspected cases, and a bundle of activities to improve system and team preparedness for placenta accreta spectrum.

Oxytocin: physiology, pharmacology, and clinical application for labor management.

Oxytocin is a peptide hormone that plays a key role in regulating the female reproductive system, including during labor and lactation. It is produced primarily in the hypothalamus and secreted by the posterior pituitary gland. Oxytocin can also be administered as a medication to initiate or augment uterine contractions. To study the effectiveness and safety of oxytocin, previous studies have randomized patients to low- and high-dose oxytocin infusion protocols either alone or as part of an active management of labor strategy along with other interventions. These randomized trials demonstrated that active management of labor and high-dose oxytocin regimens can shorten the length of labor and reduce the incidence of clinical chorioamnionitis. The safety of high-dose oxytocin regimens is also supported by no associated differences in fetal heart rate abnormalities, postpartum hemorrhage, low Apgar scores, neonatal intensive care unit admissions, and umbilical artery acidemia. Most studies reported no differences in the cesarean delivery rates with active management of labor or high-dose oxytocin regimens, thereby further validating its safety. Oxytocin does not have a predictable dose response, thus the pharmacologic effects and the amplitude and frequency of uterine contractions are used as physiological parameters for oxytocin infusion titration to achieve adequate contractions at appropriate intervals. Used in error, oxytocin can cause patient harm, highlighting the importance of precise administration using infusion pumps, institutional safety checklists, and trained nursing staff to closely monitor uterine activity and fetal heart rate changes. In this review, we summarize the physiology, pharmacology, infusion regimens, and associated risks of oxytocin.

Implementing a Bundle for Evidence-based Cesarean Delivery May Not Be As Beneficial as Expected: A Multi-center, Pre- and Post- Study.

BACKGROUND: Standardization of procedures improves outcomes. Though systematic reviews have summarized the evidence-based steps (EBS) of cesarean delivery (CD), their bundled implementation has not been investigated. OBJECTIVE: In this pre- and post-implementation trial, we sought to ascertain if bundled EBS of CD, compared to surgeon's preference, improves outcomes. STUDY DESIGN: A StaRI (Standards for Reporting Implementation Studies) compliant, multi-center pre- and post-implementation trial at 4 teaching hospitals was conducted. The pre-implementation period consisted of CD done based on the physicians' preferences for 3 months; educational intervention (e.g., didactics, badge cards, posters, video) occurred at the 4th month. CDs in post-implementation period employed the bundled EBS. A pre-planned 10% randomized audit of both groups assessed adherence and uptake of EBS. The primary outcome was a composite maternal morbidity (CMM), which included estimated blood loss > 1,000 mL, blood transfusion, endometritis, post-partum fever, wound complications, sepsis, thrombosis, ICU admission, hysterectomy, or death. The secondary outcome was a composite neonatal morbidity (CNM) and some of its components were 5-min Apgar score < 7, positive pressure oxygen use, hypoglycemia, or sepsis. A priori Bayesian sample size calculation indicated 700 CD in each group was needed to demonstrate 20% relative reduction (from 15% to 12%) of CMM with 75% certainty. Bayesian logistic regression with neutral priors was used to calculate likelihood of net-improvement in adjusted relative risk (aRR) with 95% credible intervals (CrI). RESULTS: A total of 1,425 consecutive CD (721 in pre- and 704 in post-implementation group) were examined. Audited data indicated that the baseline EBS utilization rate during the pre-implementation period was 79%; after the implementation bundled EBS of CD the audited adherence was 89%-an uptake of 10.0% of the EBS. In four aspects, the maternal characteristics differed significantly in the pre- and post-implementation periods: race/ethnicity, hypertensive disorder, and the relative contribution of the 4 centers to the cohorts and the gestational age at delivery, but the indications for CD and whether its duration was < versus > 60 min did not. The rates of CMM in the pre- and post-implementation groups were 26% and 22%, respectively (aRR, 0.88; 95% CrI, 0.73-1.04), with a 94 % Bayesian probability of a reduction in CMM. The CNM occurred in 37% of the pre- and in 41% of the post-implementation group (aRR, 1.12; 95% CrI 0.98-1.39), with a 95% Bayesian probability of worsening in CNM. When CMM were segregated by preterm (<37 wks) and term (> 37 weeks) CD, the improvement in maternal outcomes persisted; when CNM were segregated by gestational age subgroupsthe potential for worsening neonatal outcomes persisted as well. CONCLUSIONS: Standardization of the evidence-based bundled steps of cesarean delivery resulted in a modest reduction of the composite maternal outcome; however, a paradoxical increase in neonatal composite morbidity was noted. Although individual evidence-based steps may be of value, while awaiting additional intervention trials a formal bundling of such steps is currently not recommended.

Posttraumatic stress disorder 2 months after cesarean delivery: a multicenter prospective study.

BACKGROUND: The prevalence and risk factors of posttraumatic stress disorder after cesarean delivery, outside high-risk contexts, remain unclear. OBJECTIVE: This study aimed to assess posttraumatic stress disorder prevalence and risk factors at 2 months postpartum among a general population of women with cesarean delivery. STUDY DESIGN: This was a prospective ancillary cohort study of the Tranexamic Acid for Preventing Postpartum Hemorrhage after Cesarean Delivery (TRAAP2) trial, conducted in 27 French hospitals from 2018 to 2020, enrolling women expected to undergo cesarean delivery before or during labor at ≥34 weeks of gestation. After randomization, characteristics of the cesarean delivery and postpartum blood loss were prospectively collected. Two months after childbirth, posttraumatic stress disorder profile (presence of posttraumatic stress disorder symptoms) and provisional diagnosis (positive screening for diagnosis consistent with a posttraumatic stress disorder) were assessed by 2 self-administered questionnaires (Impact of Event Scale - Revised and Traumatic Event Scale). The corrected posttraumatic stress disorder prevalence was estimated with inverse probability weighting to take nonresponse into account. Associations between potential risk factors and posttraumatic stress disorder were analyzed by multivariate logistic or linear regression modeling according to the type of dependent variable. RESULTS: In total, 2785 of 4431 women returned the Impact of Event Scale - Revised questionnaire and 2792 the Traumatic Event Scale (response rates of 62.9% and 63.0%). The prevalence of posttraumatic stress disorder profile was 9.0% (95% confidence interval, 7.8%-10.3%) and of provisional diagnosis 1.7% (95% confidence interval, 1.2%-2.4%). Characteristics associated with a higher risk of posttraumatic stress disorder profile were prepregnancy vulnerability factors (young age, high body mass index, and African-born migrant) and cesarean delivery-related obstetrical factors (cesarean delivery after induced labor [adjusted odds ratio, 1.81; 95% confidence interval, 1.14-2.87], postpartum hemorrhage [adjusted odds ratio, 1.61; 95% confidence interval, 1.04-2.46] and high-intensity pain during the postpartum stay [adjusted odds ratio, 1.90; 95% confidence interval, 1.17-3.11]). Women who had immediate skin-to-skin contact with their newborn were at lower risk of posttraumatic stress disorder (adjusted odds ratio, 0.66; 95% confidence interval, 0.46-0.98), and women with bad memories of delivery on day 2 postpartum were at higher risk (adjusted odds ratio, 3.20; 95% confidence interval, 1.97-5.12). The Impact of Event Scale - Revised and the Traumatic Event Scale yielded consistent results. CONCLUSION: Approximately 1 in 11 women with cesarean deliveries had posttraumatic stress disorder symptoms at 2 months postpartum. Some obstetrical interventions and components of cesarean delivery management may influence this risk.

Prevalence and risk factors for postpartum depression 2 months after a vaginal delivery: a prospective multicenter study.

BACKGROUND: Very little is known about the prevalence and risk factors of postpartum depression among women with vaginal births without major pregnancy complications. OBJECTIVE: This study aimed to assess the prevalence of postpartum depression and identify its characteristics 2 months after singleton vaginal delivery at or near term. STUDY DESIGN: This was an ancillary cohort study of the TRanexamic Acid for Preventing Postpartum Hemorrhage After Vaginal Delivery randomized controlled trial, which was conducted in 15 French hospitals in 2015-2016 and enrolled women with singleton vaginal deliveries after 35 weeks of gestation. After randomization, the characteristics of labor, delivery, and the immediate postpartum experience, including the experience of childbirth, were prospectively collected. Medical records provided women's other characteristics, particularly any psychiatric history. Of note, 2 months after childbirth, provisional postpartum depression diagnosis was defined as a score of ≥13 on the Edinburgh Postnatal Depression Scale, a validated self-administered questionnaire. The corrected prevalence of postpartum depression was calculated with the inverse probability weighting method to take nonrespondents into account. Associations between potential risk factors and postpartum depression were analyzed by multivariate logistic regression. Moreover, an Edinburgh Postnatal Depression Scale cutoff value of ≥11 was selected to perform a sensitivity analysis. RESULTS: The questionnaire was returned by 2811 of 3891 women (72.2% response rate). The prevalence rates of the provisional diagnosis were 9.9% (95% confidence interval, 8.6%-11.3%) defined by an Edinburgh Postnatal Depression Scale score of ≥13 and 15.5% (95% confidence interval, 14.0%-17.1%) with a cutoff value of ≥11. The characteristics associated with higher risks of postpartum depression in multivariate analysis were mostly related to prepregnancy characteristics, specifically age of <25 years (adjusted odds ratio, 1.8; 95% confidence interval, 1.1-2.9) and advanced age (adjusted odds ratio, 1.8; 95% confidence interval, 1.2-2.6), migration from North Africa (adjusted odds ratio, 2.9; 95% confidence interval, 1.9-4.4), previous abortion (adjusted odds ratio, 1.4; 95% confidence interval, 1.0-2.0), and psychiatric history (adjusted odds ratio, 2.9; 95% confidence interval, 1.8-4.8). Some characteristics of labor and delivery, such as induced labor (adjusted odds ratio, 1.5; 95% confidence interval, 1.1-2.0) and operative vaginal delivery (adjusted odds ratio, 1.4; 95% confidence interval, 1.0-2.0), seemed to be associated with postpartum depression. In addition, bad memories of childbirth in the immediate postpartum were strongly associated with postpartum depression symptoms at 2 months after giving birth (adjusted odds ratio, 2.4; 95% confidence interval, 1.3-4.2). CONCLUSION: Approximately 10% of women with vaginal deliveries have postpartum depression symptoms, assessed by a score of ≥13 on the depression scale that was used at 2 months. Prepregnancy vulnerability factors; obstetrical characteristics, such as induced labor and operative vaginal delivery; and bad memories of childbirth 2 days after delivery were the main factors associated with this provisional diagnosis. A screening approach that targets risk factors may help to identify women at risk of postpartum depression who could benefit from early intervention.

Intrauterine devices in the management of postpartum hemorrhage.

Obstetrical hemorrhage is a relatively frequent obstetrical complication and a common cause of maternal morbidity and mortality worldwide. The majority of maternal deaths attributable to hemorrhage are preventable, thus, developing rapid and effective means of treating postpartum hemorrhage is of critical public health importance. Intrauterine devices are one option for managing refractory hemorrhage, with rapid expansion of available devices in recent years. Intrauterine packing was historically used for this purpose, with historical cohorts documenting high rates of success. Modern packing materials, including chitosan-covered gauze, have recently been explored with success rates comparable to uterine balloon tamponade in small trials. There are a variety of balloon tamponade devices, both commercial and improvised, available for use. Efficacy of 85.9% was cited in a recent meta-analysis in resolution of hemorrhage with the use of uterine balloon devices, with greatest success in the setting of atony. However, recent randomized trials have demonstrated potential harm associated with improvised balloon tamponade use In low resource settings and the World Health Organization recommends use be restricted to settings where monitoring is available and care escalation is possible. Recently, intrauterine vacuum devices have been introduced, which offer a new mechanism for achieving hemorrhage control by mechanically restoring uterine tone via vacuum suction. The Jada device, which is is FDA-cleared and commercially available in the US, found successful bleeding control in 94% of cases in an initial single-arm trial, with recent post marketing registry study described treatment success following hemorrhage in 95.8% of vaginal and 88.2% of cesarean births. Successful use of improvised vacuum devices has been described in several studies, including suction tube uterine tamponade via Levin tubing, and use of a modified Bakri balloon. Further research is needed with head-to-head comparisons of efficacy of devices and assessment of cost within the context of both device pricing and overall healthcare resource utilization.

Third stage of labor: evidence-based practice for prevention of adverse maternal and neonatal outcomes.

The third stage of labor is defined as the time period between delivery of the fetus through delivery of the placenta. During a normal third stage, uterine contractions lead to separation and expulsion of the placenta from the uterus. Postpartum hemorrhage is a relatively common complication of the third stage of labor. Strategies have been studied to mitigate the risk of postpartum hemorrhage, leading to the widespread implementation of active management of the third stage of labor. Initially, active management of the third stage of labor consisted of a bundle of interventions including administration of a uterotonic agent, early cord clamping, controlled cord traction, and external uterine massage. However, the effectiveness of these interventions as a bundle has been questioned, leading to abandonment of some components in recent years. Despite this, upon review of selected international guidelines, we found that the term "active management of the third stage of labor" was still used, but recommendations for and against individual interventions were variable and not necessarily supported by current evidence. In this review, we: (1) examine the physiology of the third stage of labor, (2) present evidence related to interventions that prevent postpartum hemorrhage and promote maternal and neonatal health, (3) review current global guidelines and recommendations for practice, and (4) propose future areas of investigation. The interventions in this review include pharmacologic agents to prevent postpartum hemorrhage, cord clamping, cord milking, cord traction, cord drainage, early skin-to-skin contact, and nipple stimulation. Treatment of complications of the third stage of labor is outside of the scope of this review. We conclude that current evidence supports the use of effective pharmacologic postpartum hemorrhage prophylaxis, delayed cord clamping, early skin-to-skin contact, and controlled cord traction at delivery when feasible. The most effective uterotonic regimens for preventing postpartum hemorrhage after vaginal delivery include oxytocin plus ergometrine; oxytocin plus misoprostol; or carbetocin. After cesarean delivery, carbetocin or oxytocin as a bolus are the most effective regimens. There is inconsistent evidence regarding the use of tranexamic acid in addition to a uterotonic compared with a uterotonic alone for postpartum hemorrhage prevention after all deliveries. Because of differences in patient comorbidities, costs, and availability of resources and staff, decisions to use specific prevention strategies are dependent on patient- and system-level factors. We recommend that the term "active management of the third stage of labor" as a combined intervention no longer be used. Instead, we recommend that "third stage care" be adopted, which promotes the implementation of evidence-based interventions that incorporate practices that are safe and beneficial for both the woman and neonate.

Water birth: a systematic review and meta-analysis of maternal and neonatal outcomes.

OBJECTIVE: This systematic review and meta-analysis aimed to conduct a thorough and contemporary assessment of maternal and neonatal outcomes associated with water birth in comparison with land-based birth. DATA SOURCES: We conducted a comprehensive search of PubMed, EMBASE, CINAHL, and gray literature sources, from inception to February 28, 2023. STUDY ELIGIBILITY CRITERIA: We included randomized and nonrandomized studies that assessed maternal and neonatal outcomes in patients who delivered either conventionally or while submerged in water. METHODS: Pooled unadjusted odds ratios with 95% confidence intervals were calculated using a random-effects model (restricted maximum likelihood method). We assessed the 95% prediction intervals to estimate the likely range of future study results. To evaluate the robustness of the results, we calculated fragility indices. Maternal infection was designated as the primary outcome, whereas postpartum hemorrhage, perineal lacerations, obstetrical anal sphincter injury, umbilical cord avulsion, low Apgar scores, neonatal aspiration requiring resuscitation, neonatal infection, neonatal mortality within 30 days of birth, and neonatal intensive care unit admission were considered secondary outcomes. RESULTS: Of the 20,642 articles identified, 52 were included in the meta-analyses. Based on data from observational studies, water birth was not associated with increased probability of maternal infection compared with land birth (10 articles, 113,395 pregnancies; odds ratio, 0.93; 95% confidence interval, 0.76-1.14). Patients undergoing water birth had decreased odds of postpartum hemorrhage (21 articles, 149,732 pregnancies; odds ratio, 0.80; 95% confidence interval, 0.68-0.94). Neonates delivered while submerged in water had increased odds of cord avulsion (10 articles, 91,504 pregnancies; odds ratio, 1.75; 95% confidence interval, 1.38-2.24) and decreased odds of low Apgar scores (21 articles, 165,917 pregnancies; odds ratio, 0.69; 95% confidence interval, 0.58-0.82), neonatal infection (15 articles, 53,635 pregnancies; odds ratio, 0.64; 95% confidence interval, 0.42-0.97), neonatal aspiration requiring resuscitation (19 articles, 181,001 pregnancies; odds ratio, 0.60; 95% confidence interval, 0.43-0.84), and neonatal intensive care unit admission (30 articles, 287,698 pregnancies; odds ratio, 0.56; 95% confidence interval, 0.45-0.70). CONCLUSION: When compared with land birth, water birth does not appear to increase the risk of most maternal and neonatal complications. Like any other delivery method, water birth has its unique considerations and potential risks, which health care providers and expectant parents should evaluate thoroughly. However, with proper precautions in place, water birth can be a reasonable choice for mothers and newborns, in facilities equipped to conduct water births safely.

Clinical chorioamnionitis at term: definition, pathogenesis, microbiology, diagnosis, and treatment.

Clinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration.

Uterine Artery Embolization Versus Hysterectomy in Postpartum Hemorrhage: A Systematic Review With Meta-Analysis.

PURPOSE: The objective of this study is to perform a meta-analysis comparing the effectiveness of uterine artery embolization (UAE) versus peripartum hysterectomy for acute refractory postpartum hemorrhage (PPH) control. MATERIALS AND METHODS: We systematically searched 6 medical databases for studies comparing UAE and hysterectomy in PPH. Outcomes examined were mortality, hospitalization duration (HD) in days, and red blood cells (RBC) units utilization. Statistical analysis used RevMan 5.1.7 and random-effects models. Odds ratios (OR) and mean differences (MDs) with 95% confidence intervals (CIs) were used for dichotomous and continuous outcomes, respectively. RESULTS: We included 833 patients from 4 cohort studies, with 583 (70%) undergoing UAE. The UAE population required fewer RBC units (MD: -7.39; 95% CI: -14.73 to -0.04; p=0.05) and had shorter HD (MD: -3.22; 95% CI: -5.42 to -1.02; p=0.004). Lower mortality rates were noted for UAE in the pooled analysis, but no statistical significance. Uterine artery embolization demonstrated lower procedural complications (16.45% vs. 28.8%), in which UAE had less ureter and bladder lesions (OR: 0.05; 95% CI: 0.01-0.38; p=0.004 and OR: 0.02; 95% CI: 0.00-0.15; p<0.001, respectively). Only 35 (6%) required conversion to hysterectomy, while 27 (4.6%) underwent re-embolization with 100% bleeding control. Uterine artery embolization did not hinder fertility, with normal menstruation restored in 19 patients with postoligomenorrhea. CONCLUSION: Uterine artery embolization for the control of PPH is associated with lower use of RBC units and HD, but similar rates of mortality are noted when compared to hysterectomy. These results associated with uterine preservation could support its importance for refractory PPH management. CLINICAL IMPACT: Uterine Artery Embolization is associated with a shorter hospitalization duration and reduced use of red blood cell units when compared with hysterectomy in refractory postpartum hemorrhage. Although demonstrating similar mortality rates, these findings, together with fertility preservation, support the method incorporation as a valuable option in obstetric services.

Propensity score analysis of low-dose aspirin and bleeding complications in pregnancy.

OBJECTIVE: Low-dose aspirin (LDA) has been shown to reduce the risk of preterm pre-eclampsia and it has been suggested that it should be recommended for all pregnancies. However, some studies have reported an association between LDA and an increased risk of bleeding complications in pregnancy. Our aim was to evaluate the risk of placental abruption and postpartum hemorrhage (PPH) in patients for whom their healthcare provider had recommended prophylactic aspirin. METHODS: This multicenter cohort study included 72 598 singleton births at 19 hospitals in the USA, between January 2019 and December 2021. Pregnancies complicated by placenta previa/accreta, birth occurring at less than 24 weeks' gestation, multiple pregnancy or those with data missing for aspirin recommendation were excluded. Propensity scores were calculated using 20 features spanning sociodemographic factors, medical history, year and hospital providing care. The association between LDA recommendation and placental abruption or PPH was estimated by inverse-probability treatment weighting using the propensity scores. RESULTS: We included 71 627 pregnancies in the final analysis. Aspirin was recommended to 6677 (9.3%) and was more likely to be recommended for pregnant individuals who were 35 years or older (P < 0.001), had a body mass index of 30 kg/m2 or higher (P < 0.001), had prepregnancy hypertension (P < 0.001) and who had a Cesarean delivery (P < 0.001). Overall, 1.7% of the study cohort (1205 pregnancies) developed preterm pre-eclampsia: 1.3% in the no-aspirin and 5.8% in the aspirin group. After inverse-probability weighting with propensity scores, aspirin was associated with increased risk of placental abruption (adjusted odds ratio (aOR), 1.44 (95% CI, 1.04-2.00)) and PPH (aOR, 1.21 (95% CI, 1.05-1.39)). The aOR translated to a number needed to harm with LDA of 79 (95% CI, 43-330) for PPH and 287 (95% CI, 127-3151) for placental abruption. CONCLUSIONS: LDA recommendation in pregnancy was associated with increased risk for placental abruption and for PPH. Our results support the need for more research into aspirin use and bleeding complications in pregnancy before recommending it beyond the highest-risk pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Impact of cell salvage on hematocrit and post-partum anemia in low hemorrhage risk elective cesarean delivery.

BACKGROUND: Postpartum anemia is a significant contributor to peripartum morbidity. The utilization of cell salvage in low risk cases and its impact on postpartum anemia has not been investigated. We therefore aimed to examine the impact of autologous blood transfusion/cell salvage in routine cesarean delivery on postoperative hematocrit and anemia. STUDY DESIGN AND METHODS: Retrospective cohort study from a perfusion database from a large academic center where cell salvage is performed at the discretion of the obstetrical team. Data from 99 patients was obtained. All patients were scheduled elective cesarean deliveries that took place on the labor and delivery floor. Thirty patients in the cohort had access to cell salvage where autologous blood was transfused after surgery. Pre-procedural hemoglobin/hematocrit measurements were obtained along will postpartum samples that were collected on post-partum day one. RESULTS: The median amount of blood returned to cell salvage patients was 250 mL [206-250]. Hematocrit changes in cell salvage patients was significantly smaller than controls (-1.85 [-3.87, -0.925] vs -6.4 [-8.3, -4.75]; p < 0.001). The odds of developing new anemia following surgery were cut by 74% for the cell salvage treatment group, compared to the odds for the control group (OR = 0.26 (0.07-0.78); p = 0.028) DISCUSSION: Despite losing more blood on average, patients with access to cell salvage had higher postoperative HCT, less postpartum anemia, and no difference in complications related to transfusion. The utilization of cell salvage for routine cesarean delivery warrants further research.

The association between maternal vitamin D deficiency and postpartum hemorrhage and uterine atony.

INTRODUCTION: Postpartum hemorrhage is the leading cause of maternal morbidity and mortality worldwide. There are several known risk factors for postpartum hemorrhage related to pregnancy and delivery, but less evidence of predisposing factors. Recent research has shown that vitamin D deficiency may increase the risk of cesarean section due to dystocia, based on its effect on striated muscle as well as possible effect on the myometrium. Whether vitamin D deficiency increases the risk for postpartum hemorrhage and especially atonic hemorrhage is unknown. MATERIAL AND METHODS: This was a retrospective translational study. The study population included 1367 women in Sweden and the main exposure was the serum concentration of 25-hydroxylated vitamin D at time of delivery. The LIASON® 25 OH vitamin D total assay method was used for analyzing 25-hydroxylated vitamin D. Vitamin D insufficiency was defined as serum concentration <50 nmol/L and vitamin D deficiency as serum concentrations <25 nmol/L. Primary outcomes were postpartum hemorrhage and severe postpartum hemorrhage defined as bleeding ≥500 mL and ≥ 1000 mL, respectively 2 h after delivery. Secondary outcome was atonic postpartum hemorrhage. Crude and adjusted odds ratios were calculated with 95% confidence intervals using univariable and multivariable logistic regression. Three different adjustment methods were used, adjusting for maternal, obstetrical and neonatal confounders. RESULTS: Postpartum hemorrhage and severe postpartum hemorrhage afflicted 31.3% and 6.4% of the women, respectively. Rate of atonic postpartum hemorrhage was 21% in the whole population. Rate of vitamin D insufficiency and deficiency was 57%. Vitamin D insufficiency or deficiency was neither found to be associated with postpartum hemorrhage, nor with atonic postpartum hemorrhage. CONCLUSIONS: In this study, the vitamin D status of women at the time of delivery was not a predictor of postpartum hemorrhage overall or atonic postpartum hemorrhage.