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.

The physiology and pharmacology of oxytocin in labor and in the peripartum period.

Oxytocin is a reproductive hormone implicated in the process of parturition and widely used during labor. Oxytocin is produced within the supraoptic nucleus and paraventricular nucleus of the hypothalamus and released from the posterior pituitary lobe into the circulation. Oxytocin is released in pulses with increasing frequency and amplitude in the first and second stages of labor, with a few pulses released in the third stage of labor. During labor, the fetus exerts pressure on the cervix of the uterus, which activates a feedforward reflex-the Ferguson reflex-which releases oxytocin. When myometrial contractions activate sympathetic nerves, it decreases oxytocin release. When oxytocin binds to specific myometrial oxytocin receptors, it induces myometrial contractions. High levels of circulating estrogen at term make the receptors more sensitive. In addition, oxytocin stimulates prostaglandin synthesis and release in the decidua and chorioamniotic membranes by activating a specific type of oxytocin receptor. Prostaglandins contribute to cervical ripening and uterine contractility in labor. The oxytocin system in the brain has been implicated in decreasing maternal levels of fear, pain, and stress, and oxytocin release and function during labor are stimulated by a social support. Moreover, studies suggest, but have not yet proven, that labor may be associated with long-term, behavioral and physiological adaptations in the mother and infant, possibly involving epigenetic modulation of oxytocin production and release and the oxytocin receptor. In addition, infusions of synthetic oxytocin are used to induce and augment labor. Oxytocin may be administered according to different dose regimens at increasing rates from 1 to 3 mIU/min to a maximal rate of 36 mIU/min at 15- to 40-minute intervals. The total amount of synthetic oxytocin given during labor can be 5 to 10 IU, but lower and higher amounts of oxytocin may also be given. High-dose infusions of oxytocin may shorten the duration of labor by up to 2 hours compared with no infusion of oxytocin; however, it does not lower the frequency of cesarean delivery. When synthetic oxytocin is administered, the plasma concentration of oxytocin increases in a dose-dependent way: at infusion rates of 20 to 30 mIU/min, plasma oxytocin concentration increases approximately 2- to 3-fold above the basal level. Synthetic oxytocin administered at recommended dose levels is not likely to cross the placenta or maternal blood-brain barrier. Synthetic oxytocin should be administered with caution as high levels may induce tachystole and uterine overstimulation, with potentially negative consequences for the fetus and possibly the mother. Of note, 5 to 10 IU of synthetic oxytocin is often routinely given as an intravenous or intramuscular bolus administration after delivery to induce uterine contractility, which, in turn, induces uterine separation of the placenta and prevents postpartum hemorrhage. Furthermore, it promotes the expulsion of the placenta.

Optimal misoprostol dosing among patients with a body mass index greater than 30: a randomized controlled trial.

BACKGROUND: Patients with obesity experience an increased duration of labor with an increased risk for perinatal morbidity. When compared with parturients without obesity, they also experience fewer uterine contractions after administration of misoprostol. It is unclear if the same dose of misoprostol should be used for induction of labor in patients with obesity compared to non-obese patients. Therefore, we sought to investigate if a higher dose of misoprostol for patients with obesity is more effective. OBJECTIVE: This study aimed to determine if 50 µg compared with 25 µg of vaginal misoprostol reduced the time from induction start to delivery among patients with obesity. STUDY DESIGN: We performed a double-blinded, pragmatic randomized controlled trial, between June 1, 2022, and July 17, 2023. Patients with a body mass index ≥30 kg/m2 who underwent labor induction at ≥ 36 weeks' gestation, had a singleton gestation, and a cervical dilation ≤3 cm at admission were included. Patients were excluded if they had a contraindication to vaginal delivery or misoprostol administration. Patients were randomized to 25 or 50 µg of vaginal misoprostol, stratified by parity, body mass index <40 kg/m2 or ≥40 kg/m2, and provider intent to use mechanical dilation at the onset of labor induction. Usual labor management was followed at the discretion of the provider. The primary outcome was time from induction to delivery. A priori, we estimated that 90 subjects per group (N=180) were needed for an 85% power to detect a 3-hour difference between groups with a type I error of 5%. Analysis was by intention-to-treat. A 2-sample t test was used for the primary outcome, Cohen's d was used as a measure of effect, and P values were reported. RESULTS: Of the 180 patients randomized, 88 were assigned to the 25 µg group and 92 were assigned to the 50 µg group. Of those, 96.1% of patients received the designated intervention. The baseline characteristics were similar between groups. No difference was found in the primary outcome of time to delivery (21.6 hours vs 18.6 hours; d=.28; 95% confidence interval, -0.02 to 0.57). In a planned subgroup analysis, multiparous patients delivered faster in the 50 µg group (15.2 hours vs 12.0 hours; d=.51; 95% confidence interval, 0.04-0.97). The risk for tachysystole associated with fetal heart tracing changes was rare overall (2.2%) and not significantly different between groups. No differences in maternal or neonatal adverse effects were observed. CONCLUSION: Patients with obesity who underwent cervical ripening with 50 µg of vaginal misoprostol experienced a similar time to delivery when compared with those who received 25 µg of misoprostol. However, multiparous patients had a significantly reduced time to delivery when 50 µg was used. A higher dose of misoprostol may be a promising intervention for reducing time in labor, which warrants further study.

Single-balloon catheter with concomitant vaginal misoprostol is the most effective strategy for labor induction: a meta-review with network meta-analysis.

OBJECTIVE: Several systematic reviews and meta-analyses have been conducted to summarize the evidence for the efficacy of various labor induction agents. However, the most effective agents or strategies have not been conclusively determined. We aimed to perform a meta-review and network meta-analysis of published systematic reviews to determine the efficacy and safety of currently employed pharmacologic, mechanical, and combined methods of labor induction. DATA SOURCES: With the assistance of an experienced medical librarian, we performed a systematic search of the literature using PubMed, EMBASE, and the Cochrane Central Register of Control Trials. We systematically searched electronic databases from inception to May 31, 2021. STUDY ELIGIBILITY CRITERIA: We considered systematic reviews and meta-analyses of randomized controlled trials comparing different agents or methods for inpatient labor induction. METHODS: We conducted a frequentist random-effects network meta-analysis employing data from randomized controlled trials of published systematic reviews. We performed direct pairwise meta-analyses to compare the efficacy of the various labor induction agents and placebo or no treatment. We performed ranking to determine the best treatment using the surface under the cumulative ranking curve. The main outcomes assessed were cesarean delivery, vaginal delivery within 24 hours, operative vaginal delivery, hyperstimulation, neonatal intensive care unit admissions, and Apgar scores of <7 at 5 minutes of birth. RESULTS: We included 11 systematic reviews and extracted data from 207 randomized controlled trials with a total of 40,854 participants. When assessing the efficacy of all agents and methods, the combination of a single-balloon catheter with misoprostol was the most effective in reducing the odds of cesarean delivery and vaginal birth >24 hours (surface under the cumulative ranking curve of 0.9 for each). Among the pharmacologic agents, low-dose vaginal misoprostol was the most effective in reducing the odds of cesarean delivery, whereas high-dose vaginal misoprostol was the most effective in achieving vaginal delivery within 24 hours (surface under the cumulative ranking curve of 0.9 for each). Single-balloon catheter (surface under the cumulative ranking curve of 0.8) and double-balloon catheter (surface under the cumulative ranking curve of 0.9) were the most effective in reducing the odds of operative vaginal delivery and hyperstimulation. Buccal or sublingual misoprostol (surface under the cumulative ranking curve of 0.9) and the combination of single-balloon catheter and misoprostol (surface under the cumulative ranking curve of 0.9) most effectively reduced the odds of abnormal Apgar scores and neonatal intensive care unit admissions. CONCLUSION: The combination of a single-balloon catheter with misoprostol was the most effective method in reducing the odds for cesarean delivery and prolonged time to vaginal delivery. This method was associated with a reduction in admissions to the neonatal intensive care unit.

Outpatient cervical ripening and labor induction with low-dose vaginal misoprostol reduces the interval to delivery: a systematic review and network meta-analysis.

OBJECTIVE: Several systematic reviews and meta-analyses have summarized the evidence on the efficacy and safety of various outpatient cervical ripening methods. However, the method with the highest efficacy and safety profile has not been determined conclusively. We performed a systematic review and network meta-analysis of published randomized controlled trials to assess the efficacy and safety of cervical ripening methods currently employed in the outpatient setting. DATA SOURCES: With the assistance of an experienced medical librarian, we performed a systematic search of the literature using MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov. We systematically searched electronic databases from inception to January 14, 2020. STUDY ELIGIBILITY CRITERIA: We considered randomized controlled trials comparing a variety of methods for outpatient cervical ripening. METHODS: We conducted a frequentist random effects network meta-analysis employing data from randomized controlled trials. We performed a direct, pairwise meta-analysis to compare the efficacy of various outpatient cervical ripening methods, including placebo. We employed ranking strategies to determine the most efficacious method using the surface under the cumulative ranking curve; a higher surface under the cumulative ranking curve value implied a more efficacious method. We assessed the following outcomes: time from intervention to delivery, cesarean delivery rates, changes in the Bishop score, need for additional ripening methods, incidence of Apgar scores <7 at 5 minutes, and uterine hyperstimulation. RESULTS: We included data from 42 randomized controlled trials including 6093 participants. When assessing the efficacy of all methods, 25 µg vaginal misoprostol was the most efficacious in reducing the time from intervention to delivery (surface under the cumulative ranking curve of 1.0) without increasing the odds of cesarean delivery, the need for additional ripening methods, the incidence of a low Apgar score, or uterine hyperstimulation. Acupressure (surface under the cumulative ranking curve of 0.3) and primrose oil (surface under the cumulative ranking curve of 0.2) were the least effective methods in reducing the time to delivery interval. Among effective methods, 50 mg oral mifepristone was associated with the lowest odds of cesarean delivery (surface under the cumulative ranking curve of 0.9). CONCLUSION: When balancing efficacy and safety, vaginal misoprostol 25 µg represents the best method for outpatient cervical ripening.

Tafoxiparin, a novel drug candidate for cervical ripening and labor augmentation: results from 2 randomized, placebo-controlled studies.

BACKGROUND: Slow progression of labor is a common obstetrical problem with multiple associated complications. Tafoxiparin is a depolymerized form of heparin with a molecular structure that eliminates the anticoagulant effects of heparin. We report on 2 phase II clinical studies of tafoxiparin in primiparas. Study 1 was an exploratory, first-in-pregnant-women study and study 2 was a dose-finding study. OBJECTIVE: Study 1 was performed to explore the effects on labor time of subcutaneous administration of tafoxiparin before onset of labor. Study 2 was performed to test the hypothesis that intravenous treatment with tafoxiparin reduces the risk for prolonged labor after spontaneous labor onset in situations requiring oxytocin stimulation because of dystocia. STUDY DESIGN: Both studies were randomized, double-blind, and placebo-controlled. Participants were healthy, nulliparous females aged 18 to 45 years with a normal singleton pregnancy and gestational age confirmed by ultrasound. The primary endpoints were time from onset of established labor (cervical dilation of 4 cm) until delivery (study 1) and time from start of study treatment infusion until delivery (study 2). In study 1, patients at 38 to 40 weeks of gestation received 60 mg tafoxiparin or placebo daily as 0.4 mL subcutaneous injections until labor onset (maximum 28 days). In study 2, patients experiencing slow progression of labor, a prolonged latent phase, or labor arrest received a placebo or 1 of 3 short-term tafoxiparin regimens (initial bolus 7, 21, or 35 mg followed by continuous infusion at 5, 15, or 25 mg/hour until delivery; maximum duration, 36 hours) in conjunction with oxytocin. RESULTS: The number of participants randomized in study 1 was 263, and 361 were randomized in study 2. There were no statistically significant differences in the primary endpoints between those receiving tafoxiparin and those receiving the placebo in both studies. However, in study 1, the risk for having a labor time exceeding 12 hours was significantly reduced by tafoxiparin (tafoxiparin 6/114 [5%] vs placebo 18/101 [18%]; P=.0045). Post hoc analyses showed that women who underwent labor induction had a median (range) labor time of 4.44 (1.2-8.5) hours with tafoxiparin and 7.03 (1.5-14.3) hours with the placebo (P=.0041) and that co-administration of tafoxiparin potentiates the effect of oxytocin and facilitates a shorter labor time among women with a labor time exceeding 6 to 8 hours (P=.016). Among women induced into labor, tafoxiparin had a positive effect on cervical ripening in 11 of 13 cases (85%) compared with 3 of 13 participants (23%) who received the placebo (P=.004). For women requiring oxytocin because of slow progression of labor, the corresponding results were 34 of 51 participants (66%) vs 16 of 40 participants (40%) (P=.004). In study 2, tafoxiparin had no positive effects on the secondary endpoints when compared with the placebo. Except for injection-site reactions in study 1, adverse events were no more common for tafoxiparin than for the placebo among either mothers or infants. There were few serious or treatment-related adverse events. CONCLUSION: Subcutaneous treatment with tafoxiparin before labor onset (study 1) may be effective in reducing the labor time among women undergoing labor induction and among those requiring oxytocin for slow progression of labor. Moreover, tafoxiparin may have a positive effect on cervical ripening. Short-term, intravenous treatment with tafoxiparin as an adjunct to oxytocin in patients with labor arrest (study 2) did not affect labor time or other endpoints. Both studies suggest that tafoxiparin has a favorable safety profile in mothers and their infants.

Trial of labor after cesarean, vaginal birth after cesarean, and the risk of uterine rupture: an expert review.

The decision to pursue a trial of labor after cesarean delivery is complex and depends on patient preference, the likelihood of successful vaginal birth after cesarean delivery, assessment of the risks vs benefits of trial of labor after cesarean delivery, and available resources to support safe trial of labor after cesarean delivery at the planned birthing center. The most feared complication of trial of labor after cesarean delivery is uterine rupture, which can have catastrophic consequences, including substantial maternal and perinatal morbidity and mortality. Although the absolute risk of uterine rupture is low, several clinical, historical, obstetrical, and intrapartum factors have been associated with increased risk. It is therefore critical for clinicians managing patients during trial of labor after cesarean delivery to be aware of these risk factors to appropriately select candidates for trial of labor after cesarean delivery and maximize the safety and benefits while minimizing the risks. Caution is advised when considering labor augmentation and induction in patients with a previous cesarean delivery. With established hospital safety protocols that dictate close maternal and fetal monitoring, avoidance of prostaglandins, and careful titration of oxytocin infusion when induction agents are needed, spontaneous and induced trial of labor after cesarean delivery are safe and should be offered to most patients with 1 previous low transverse, low vertical, or unknown uterine incision after appropriate evaluation, counseling, planning, and shared decision-making. Future research should focus on clarifying true risk factors and identifying the optimal approach to intrapartum and induction management, tools for antenatal prediction, and strategies for prevention of uterine rupture during trial of labor after cesarean delivery. A better understanding will facilitate patient counseling, support efforts to improve trial of labor after cesarean delivery and vaginal birth after cesarean delivery rates, and reduce the morbidity and mortality associated with uterine rupture during trial of labor after cesarean delivery.

Methods for the induction of labor: efficacy and safety.

This review assessed the efficacy and safety of pharmacologic agents (prostaglandins, oxytocin, mifepristone, hyaluronidase, and nitric oxide donors) and mechanical methods (single- and double-balloon catheters, laminaria, membrane stripping, and amniotomy) and those generally considered under the rubric of complementary medicine (castor oil, nipple stimulation, sexual intercourse, herbal medicine, and acupuncture). A substantial body of published reports, including 2 large network meta-analyses, support the safety and efficacy of misoprostol (PGE1) when used for cervical ripening and labor induction. Misoprostol administered vaginally at doses of 50 µg has the highest probability of achieving vaginal delivery within 24 hours. Regardless of dosing, route, and schedule of administration, when used for cervical ripening and labor induction, prostaglandin E2 seems to have similar efficacy in decreasing cesarean delivery rates. Globally, although oxytocin represents the most widely used pharmacologic agent for labor induction, its effectiveness is highly dependent on parity and cervical status. Oxytocin is more effective than expectant management in inducing labor, and the efficacy of oxytocin is enhanced when combined with amniotomy. However, prostaglandins administered vaginally or intracervically are more effective in inducing labor than oxytocin. A single 200-mg oral tablet of mifepristone seems to represent the lowest effective dose for cervical ripening. The bulk of the literature assessing relaxin suggests this agent has limited benefit when used for this indication. Although intracervical injection of hyaluronidase may cause cervical ripening, the need for intracervical administration has limited the use of this agent. Concerning the vaginal administration of nitric oxide donors, including isosorbide mononitrate, isosorbide, nitroglycerin, and sodium nitroprusside, the higher incidence of side effects with these agents has limited their use. A synthetic hygroscopic cervical dilator has been found to be effective for preinduction cervical ripening. Although a pharmacologic agent may be administered after the use of the synthetic hygroscopic dilator, in an attempt to reduce the interval to vaginal delivery, concomitant use of mechanical and pharmacologic methods is being explored. Combining the use of a single-balloon catheter with dinoprostone, misoprostol, or oxytocin enhances the efficacy of these pharmacologic agents in cervical ripening and labor induction. The efficacy of single- and double-balloon catheters in cervical ripening and labor induction seems similar. To date, the combination of misoprostol with an intracervical catheter seems to be the best approach when balancing delivery times with safety. Although complementary methods are occasionally used by patients, given the lack of data documenting their efficacy and safety, these methods are rarely used in hospital settings.

Vaginal misoprostol versus vaginal dinoprostone for cervical ripening and induction of labour: An individual participant data meta-analysis of randomised controlled trials.

BACKGROUND: Induction of labour (IOL) is common practice and different methods carry different effectiveness and safety profiles. OBJECTIVES: To compare the effectiveness, and maternal and perinatal safety outcomes of IOL with vaginal misoprostol versus vaginal dinoprostone using individual participant data from randomised clinical trials. SEARCH STRATEGY: The following databases were searched from inception to March 2023: CINAHL Plus, ClinicalTrials.gov, Cochrane Pregnancy and Childbirth Group Trial Register, Ovid Embase, Ovid Emcare, Ovid MEDLINE, Scopus and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: Randomised controlled trials (RCTs), with viable singleton gestation, no language restrictions, and all published and unpublished data. DATA COLLECTION AND ANALYSIS: An individual participant data meta-analysis was carried out. MAIN RESULTS: Ten of 52 eligible trials provided individual participant data, of which two were excluded after checking data integrity. The remaining eight trials compared low-dose vaginal misoprostol versus dinoprostone, including 4180 women undergoing IOL, which represents 32.8% of all participants in the published RCTs. Of these, 2077 were assigned to low-dose vaginal misoprostol and 2103 were assigned to vaginal dinoprostone. Compared with vaginal dinoprostone, low-dose vaginal misoprostol had a comparable rate of vaginal birth. Composite adverse perinatal outcomes did not differ between the groups. Compared with vaginal dinoprostone, composite adverse maternal outcomes were significantly lower with low-dose vaginal misoprostol (aOR 0.80, 95% CI 0.65-0.98, P = 0.03, I2 = 0%). CONCLUSIONS: Low-dose vaginal misoprostol and vaginal dinoprostone for IOL are comparable in terms of effectiveness and perinatal safety. However, low-dose vaginal misoprostol is likely to lead to a lower rate of composite adverse maternal outcomes than vaginal dinoprostone.

Impact of combined propranolol and oxytocin on the process and outcomes of labor: a meta-analysis of randomized controlled trials.

PURPOSE: To systematically review the impact of propranolol combined with oxytocin on the process and outcomes of labor. METHODS: A comprehensive literature search was performed across multiple databases, including China National Knowledge Infrastructure (CNKI), VIP, Wanfang, China Biomedical Literature Database, PubMed, Embase, and the Cochrane Library. All publicly published randomized controlled trials (RCTs) of propranolol combined with oxytocin compared to the use of oxytocin alone in labor were collected. After screening the literature and extracting data, the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 recommended bias risk assessment tool was used to assess the quality of the included studies. A meta-analysis was conducted using RevMan 5.3 software, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to rate the quality of evidence for outcome measures. RESULTS: Meta-analysis results showed that the group receiving propranolol combined with oxytocin was more capable of reducing the cesarean section rate (eight studies, 815 women, RR = 0.67, 95% CI (0.53, 0.86), P = 0.001) and shortening the duration of the latent phase (two studies, 206 women, MD = - 1.20, 95% CI (- 1.97, - 0.43), P = 0.002) and the duration of the active phase on day 1 (two studies, 296 women, MD = - 0.69, 95% CI (- 0.83, - 0.54), P < 0.00001), compared to the oxytocin monotherapy group. No significant difference was found between the two groups in terms of the 5-min Apgar score (five studies, 609 women, MD = - 0.05, 95% CI (- 0.14, 0.04), P = 0.32) and the rate of admissions to the Neonatal Intensive Care Unit (NICU) (three studies, 359 women, RR = 0.82, 95% CI (0.38, 1.79), P = 0.62). CONCLUSION: The combined use of propranolol and oxytocin can significantly reduce the cesarean section rate, shorten the duration of the latent phase and the duration of the active phase on day 1, and is safe. However, due to the limitations, the conclusions of this article still need to be verified by large-sample, multicenter, rigorously designed high-quality clinical RCTs. TRIAL REGISTRATION: Registration number is INPLASY202390107.

Continued versus discontinued oxytocin stimulation in the active phase of labour (CONDISOX): individual management based on artificial intelligence - a secondary analysis.

BACKGROUND: Current guidelines regarding oxytocin stimulation are not tailored to individuals as they are based on randomised controlled trials. The objective of the study was to develop an artificial intelligence (AI) model for individual prediction of the risk of caesarean delivery (CD) in women with a cervical dilatation of 6 cm after oxytocin stimulation for induced labour. The model included not only variables known when labour induction was initiated but also variables describing the course of the labour induction. METHODS: Secondary analysis of data from the CONDISOX randomised controlled trial of discontinued vs. continued oxytocin infusion in the active phase of induced labour. Extreme gradient boosting (XGBoost) software was used to build the prediction model. To explain the impact of the predictors, we calculated Shapley additive explanation (SHAP) values and present a summary SHAP plot. A force plot was used to explain specifics about an individual's predictors that result in a change of the individual's risk output value from the population-based risk. RESULTS: Among 1060 included women, 160 (15.1%) were delivered by CD. The XGBoost model found women who delivered vaginally were more likely to be parous, taller, to have a lower estimated birth weight, and to be stimulated with a lower amount of oxytocin. In 108 women (10% of 1060) the model favoured either continuation or discontinuation of oxytocin. For the remaining 90% of the women, the model found that continuation or discontinuation of oxytocin stimulation affected the risk difference of CD by less than 5% points. CONCLUSION: In women undergoing labour induction, this AI model based on a secondary analysis of data from the CONDISOX trial may help predict the risk of CD and assist the mother and clinician in individual tailored management of oxytocin stimulation after reaching 6 cm of cervical dilation.

Outpatient labor induction-Exploring future potential by assessing eligibility in a historical cohort.

INTRODUCTION: Labor induction rates have increased over the last decades, and in many high-income countries, more than one in four labors are induced. Outpatient management of labor induction has been suggested in low-risk pregnancies to improve women's birth experiences while also promoting a more efficient use of healthcare resources. The primary aim of this paper was to assess the proportion of women in a historical cohort that would have been eligible for outpatient labor induction with oral misoprostol. Second, we wanted to report safety outcomes and assess efficacy outcomes for mothers and infants in pregnancies that met the criteria for outpatient care. MATERIAL AND METHODS: Criteria for outpatient labor induction with oral misoprostol were applied to a historical cohort of women with induction of labor at two Norwegian tertiary hospitals in the period January 1, through July 31, 2021. The criteria included low-risk women with an unscarred uterus expecting a healthy, singleton baby in cephalic position at term. The primary outcome was the proportion of women eligible for outpatient labor induction. Secondary outcomes included reasons for ineligibility and, for eligible women, safety and efficacy outcomes. RESULTS: Overall, 29.7% of the 1320 women who underwent labor induction in a singleton term pregnancy met the criteria for outpatient labor induction. We identified two serious adverse events that potentially could have occurred outside the hospital if the women had received outpatient care. The mean duration from initiation of labor induction to administration of the last misoprostol was 22.4 h. One in 14 multiparous women gave birth within 3 h after the last misoprostol dose. CONCLUSIONS: In this historical cohort, three in ten women met the criteria for outpatient management of labor induction with oral misoprostol. Serious adverse events were rare. The average time span from the initiation of labor induction to the last misoprostol was nearly 24 h. This suggests a potential for low-risk women with an induced labor to spend a substantial period of time at home before labor onset. However, larger studies testing or evaluating labor induction with oral misoprostol as an outpatient procedure are needed to draw conclusions.

Intramyometrial and intravenous oxytocin compared to intravenous carbetocin for prevention of postpartum hemorrhage in elective cesarean section-A quasi-randomized controlled phase IV non-inferiority interventional trial.

INTRODUCTION: Our objective was to assess non-inferiority of the unique approach used in our institution of combined 10 IU IM (intramyometrial) and 10 IU IV (intravenous) oxytocin to carbetocin IV in preventing severe postpartum blood loss in elective cesarean sections. The design was a prospective controlled phase IV non-inferiority interventional trial. The setting was a tertiary center at University Hospital, Zurich, Switzerland. MATERIAL AND METHODS: The population consisted of 550 women undergoing elective cesarean section after 36 completed weeks of gestation at low risk for postpartum hemorrhage (PPH). Participants were assigned to either combined oxytocin regimen (10 IU IM and 10 IU IV) or carbetocin (100 µg IV). Non-inferiority for oxytocin for severe PPH was assessed with a 0.05 margin using the Newcombe-Wilson score method. The main outcome measures were severe postpartum blood loss defined as delta hemoglobin (∆Hb, Hb prepartum-Hb postpartum) ≥30 g/L. RESULTS: Non-inferiority of combined oxytocin (IM/IV) in preventing severe postpartum blood loss was not shown (17 women in the oxytocin group vs. 7 in the carbetocin group). The number needed to treat when using carbetocin was 28. The risk difference for ∆Hb ≥30 g/L was 0.04 (oxytocin 0.06 vs. 0.03), 95% confidence interval (CI) (0.00-0.08). No significant difference was observed for ∆Hb (median 12 [IQR 7.0-19.0] vs. 11 [5.0-17.0], p = 0.07), estimated blood loss (median 500 [IQR 400-600] vs. 500 [400-575], p = 0.38), or the PPH rate defined as estimated blood loss ≥1000 mL (12[4.5] vs. 5 [2.0], risk difference 0.03, 95% CI (-0.01 to 0.06), p = 0.16). More additional uterotonics were administered in the oxytocin group compared to the carbetocin group (15.2% vs. 5.9%, p = 0.001). Total case costs were non-significantly different in the oxytocin group (US $ 10 146 vs. 9621, mean difference 471.4, CI (-476.5 to 1419.3), p = 0.33). CONCLUSIONS: Combined (IM/IV) oxytocin is not non-inferior to carbetocin regarding severe postpartum blood loss defined as postpartum Hb decrease ≥30 g/L in elective cesarean sections. We recommend carbetocin for use in clinical practice for elective cesarean sections.

Short stature and vaginal dinoprostone as independent predictors of composite maternal-newborn adverse outcomes in induction of labor after one previous cesarean: a retrospective cohort study.

BACKGROUND: The rates of labor induction and cesarean delivery is rising worldwide. With the confluence of these trends, the labor induction rate in trials of labor after cesarean can be as high as 27-32.7%. Induction of labor after one previous cesarean (IOLAC) is a high-risk procedure mainly due to the higher risk of uterine rupture. Nevertheless, the American College of Obstetricians and Gynecologists considers IOLAC as an option in motivated and informed women in the appropriate care setting. We sought to identify predictors of a composite of maternal and newborn adverse outcomes following IOLAC. METHODS: The electronic medical records of women who delivered between January 2018 to September 2022 in a Malaysian university hospital were screened to identify cases of IOLAC. A case is classified as a composite adverse outcome if at least one of these 11 adverse outcomes of delivery blood loss ≥ 1000 ml, uterine scar complications, cord prolapse or presentation, placenta abruption, maternal fever (≥ 38 0C), chorioamnionitis, intensive care unit (ICU) admission, Apgar score < 7 at 5 min, umbilical artery cord artery blood pH < 7.1 or base excess ≤-12 mmol/l, and neonatal ICU admission was present. An unplanned cesarean delivery was not considered an adverse outcome as the practical management alternative for a clinically indicated IOLAC was a planned cesarean. Bivariate analysis of participants' characteristics was performed to identify predictors of their association with composite adverse outcome. Characteristics with crude p < 0.10 on bivariate analysis were incorporated into a multivariable binary logistic regression analysis model. RESULTS: Electronic medical records of 19,064 women were screened. 819 IOLAC cases and 98 cases with composite adverse outcomes were identified. Maternal height, ethnicity, previous vaginal delivery, indication of previous cesarean, indication for IOLAC, and method of IOLAC had p < 0.10 on bivariate analysis and were incorporated into a multivariable binary logistic regression analysis. After adjustment, only maternal height and IOLAC by vaginal dinoprostone compared to Foley balloon remained significant at p < 0.05. Post hoc adjusted analysis that included all unplanned cesarean as an added qualifier for composite adverse outcome showed higher body mass index, short stature (< 157 cm), not of Chinese ethnicity, no prior vaginal delivery, prior cesarean indicated by labor dystocia, and less favorable Bishop score (< 6) were independent predictors of the expanded composite adverse outcome. CONCLUSION: Shorter women and IOLAC by vaginal dinoprostone compared to Foley balloon were independently predictive of composite of adverse outcome.

Shorter stature and dinoprostone labor induction are independent predictors of a composite maternal-newborn adverse outcome excluding unplanned cesarean delivery.

Patterns of oxytocin use for induction and augmentation of labour among healthcare providers in Nigeria.

BACKGROUND: The practice of intrapartum use of oxytocin for induction and augmentation of labour is increasing worldwide with documented wide variations in clinical use, especially dose administrations. There is also evidence of intrapartum use by unauthorized cadre of staff. AIM: This study assessed the patterns - frequency of intrapartum use of oxytocin, the doses and routes of administration for induction and augmentation of labour, and identified the predictors of oxytocin use for induction and augmentation of labour by healthcare providers in Nigeria. METHODS: This was a cross-sectional study conducted among healthcare providers - doctors, nurses/midwives and community health workers (CHWs) in public and private healthcare facilities across the country's six geopolitical zones. A multistage sampling technique was used to select 6,299 eligible healthcare providers who use oxytocin for pregnant women during labour and delivery. A self-administered questionnaire was used to collect relevant data and analysed using STATA 17 statistical software. Summary and inferential statistics were done and further analyses using multivariable regression models were performed to ascertain independent predictor variables of correct patterns of intrapartum oxytocin usage. The p-value was set at < 0.05. RESULTS: Of the 6299 respondents who participated in the study, 1179 (18.7%), 3362 (53.4%), and 1758 (27.9%) were doctors, nurses/midwives and CHWs, respectively. Among the respondents, 4200 (66.7%) use oxytocin for augmentation of labour while 3314 (52.6%) use it for induction of labour. Of the 1758 CHWs, 37.8% and 49% use oxytocin for induction and augmentation of labour, respectively. About 10% of the respondents who use oxytocin for the induction or augmentation of labour incorrectly use the intramuscular route of administration and about 8% incorrectly use intravenous push. Being a doctor, and a healthcare provider from government health facilities were independent positive predictors of the administration of correct dose oxytocin for induction and augmentation of labour. The CHWs were most likely to use the wrong route and dose administration of oxytocin for the induction and augmentation of labour. CONCLUSION: Our study unveiled a concerning clinical practice of intrapartum oxytocin use by healthcare providers in Nigeria - prevalence of intrapartum use of oxytocin, inappropriate routes of administration for induction and augmentation of labour, varied and inappropriately high start dose of administration including unauthorized and high intrapartum use of oxytocin among CHWs.

Methods of induction of labor in women with obesity: A secondary analysis of two multicenter randomized controlled trials.

INTRODUCTION: Obesity is an increasing public health concern worldwide and can lead to more complications in pregnancy and childbirth. Women with obesity more often require induction of labor for various indications. The aim of this study is to assess which method of induction of labor is safest and most effective in women with obesity. MATERIAL AND METHODS: This is a secondary analysis of two randomized controlled trials about induction of labor. Women with a term singleton pregnancy in cephalic presentation, an unfavorable cervix, intact membranes and without a previous cesarean section were randomly allocated to cervical priming with a Foley catheter or vaginal prostaglandin-E2-gel (PROBAAT-I) or a Foley catheter or oral misoprostol (PROBAAT-II). The inclusion and exclusion criteria for the studies were identical. Induction methods were compared in women with obesity (body mass index ≥30.0). Main outcomes were cesarean section and postpartum hemorrhage (blood loss >1000 mL). RESULTS: A total of 2664 women, were included in the trials, 517 of whom were obese: 254 women with obesity received a Foley catheter, 176 oral misoprostol and 87 prostaglandin E2 (PGE2). A cesarean section was performed in 29.1% of women allocated to Foley vs 22.2% in the misoprostol and 23.0% in the PGE2 groups. Comparisons between groups revealed no statistically significant differences: the relative risk [RR] was 1.31 (95% confidence interval [CI] 0.94-1.84) in the Foley vs misoprostol group and 1.27 (95% CI 0.83-1.95) in the Foley vs PGE2 group. The rates of postpartum hemorrhage were comparable (10.6%, 11.4% and 6.9%, respectively; P = 0.512). In women with obesity, more often a switch to another method occurred in the Foley group, (20.1% vs 6.3% in misoprostol vs 1.1% in the PGE2 group; P < 0.001). The risk of a failed Foley placement was higher in women with obesity than in women without obesity (8.3% vs 3.2%; adjusted odds ratio 3.12, 95% CI 1.65-5.90). CONCLUSIONS: In women with obesity we found a nonsignificant trend towards an increased rate of cesarean sections in the group induced with a Foley catheter compared to oral misoprostol; however, the study lacked power for this subgroup analysis. The finding of a higher risk of failed placement of a Foley catheter in women with obesity can be used in shared decision making.

Use of vaginal dinoprostone for women with term prelabor rupture of membranes and an unfavorable cervix within 6 h versus within 6-24 h.

BACKGROUND: Most guidelines propose inducing labor within 24 h following term (37 or more weeks of gestation) prelabor rupture of membranes (PROM). However, the exact timing for initiating induction within the 24 h period remains unknown. This study aims to comparatively assess the efficacy and safety of the use of vaginal dinoprostone within 6 h versus within 6-24 h for singleton pregnancies with PROM and an unfavorable cervix (Bishop score < 6). METHODS: This was a retrospective cohort study including singleton pregnancies with PROM and an unfavorable cervix (Bishop score < 6) in which labor was induced using vaginal dinoprostone. Women were divided into two groups according to the timing of the use of induction (within 6 h versus within 6-24 h after PROM). Baseline maternal data, maternal and neonatal outcomes were recorded for statistical analysis. RESULTS: 450 women were included, 146 (32.4%) of whom were induced within 6 h of PROM and 304 (67.6%) were induced within 6-24 h. Cesarean delivery rate (15.8% versus 29.3%, p = 0.002) and nonreassuring fetal heart rate tracing (4.8% versus 10.5%, p = 0.043) in group with vaginal dinoprostone within 6 h were significantly lower than those in group with vaginal dinoprostone within 6-24 h. There was no significant differences in terms of duration from IOL to vaginal delivery. CONCLUSION: Induction of labor within 6 h with vaginal dinoprostone after PROM for singleton pregnancies with an unfavorable cervix (Bishop score < 6) significantly associated with less cesarean section, less nonreassuring fetal heart rate tracing, compared to induction of labor within 6-24 h after PROM.

Impact of different obstetric interventions and types of delivery on breastfeeding: a nationwide cross-sectional survey of Hungarian women.

BACKGROUND: We assessed the effect of different obstetric interventions and types of delivery on breastfeeding. METHODS: A quantitative, cross-sectional study was carried out using an online questionnaire. Data collection was performed in 2021 in Hungary. We included biological mothers who had raised their at least 5-year-old child(ren) at home (N = 2,008). The questionnaire was completed anonymously and voluntarily. In addition to sociodemographic data (age, residence, marital status, education, occupation, income status, number of biological children, and anthropometric questions about the child and the mother), we asked about the interventions used during childbirth, and the different ways of infant feeding used. Statistical analysis was carried out using Microsoft Excel 365 and SPSS 25.0. Descriptive statistics, two-sample t tests, χ2 tests and ANOVA were used to analyse the relationship or differences between the variables (p < 0,05). RESULTS: We found that in deliveries where synthetic oxytocin was used for both induction and acceleration, there was a higher incidence of emergency cesarean section. However, the occurrence of vaginal deliveries was significantly higher in cases where oxytocin administration was solely for the purpose of accelerating labour (p < 0.001).Mothers who received synthetic oxytocin also received analgesics (p < 0.001). Women giving birth naturally who used oxytocin had a lower success of breastfeeding their newborn in the delivery room (p < 0.001). Children of mothers who received obstetric analgesia had a higher rate of complementary formula feeding (p < 0.001). Newborns born naturally had a higher rate of breastfeeding in the delivery room (p < 0.001) and less formula feeding in the hospital (p < 0.001). Infants who were breastfed in the delivery room were breastfed for longer periods (p < 0.001). Exclusive breastfeeding up to six months was longer for infants born naturally (p = 0.005), but there was no difference in the length of breastfeeding (p = 0.081). CONCLUSIONS: Obstetric interventions may increase the need for further interventions and have a negative impact on early or successful breastfeeding. TRIAL REGISTRATION: Not relevant.

Effect of Maternal Age and Body Mass Index on Induction of Labor Using Oral Misoprostol in Late-Term Pregnancies: A Retrospective Cross-Sectional Study.

INTRODUCTION: Several studies have shown that late- and post-term pregnancies are associated with an increased risk of perinatal morbidity and mortality. In this case, induction of labor is the recommended approach. For full-term pregnancies, various methods exist to prepare the cervix and/or commence labor. Prostaglandins serve the dual purpose of cervical ripening and labor induction, blurring the distinction between the two processes. The aim of this research was to evaluate the effect of maternal age and body mass index (BMI) on oral misoprostol induction of labor for late-term pregnancies. METHODS: This was a retrospective cross-sectional study (ClinicalTrial ID: NCT06184139), including only late-term pregnancies in healthy nulliparous women carrying a single cephalic fetus with normal birthweight who underwent induction of labor with oral misoprostol. We used the oral misoprostol regimen proposed by the World Health Organization (WHO) for induction of labor in term singleton pregnancies in women who have not had a previous cesarean delivery and a Bishop score <7. The regimen was oral misoprostol in aqueous solution at the low dose of 25 µg every 2 h until a Bishop score ≥7, labor, or for a maximum of 8 doses. RESULTS: One hundred and four pregnant women underwent induction of labor with oral misoprostol for late-term pregnancy on the 290th day of gestation. Study population was divided in two groups based on age (<35 and ≥35 years) and obesity (BMI <30 and ≥30). No statistically significant differences were recorded between younger and older women. Obese women reported a longer time between the last dose of misoprostol and cervical dilation of 6 cm (p = 0.01), a longer time between the last dose of misoprostol and delivery (p = 0.04), and a higher rate of grade II vaginal lacerations (p = 0.02). CONCLUSIONS: Maternal BMI is a factor negatively influencing the efficacy of oral misoprostol for induction of labor in late-term pregnancy.

Effect of administration routes of oxytocin on hemoglobin in neonates with delayed umbilical cord clamping: a multi-centre randomized controlled clinical trial.

PURPOSE: To evaluate the effect of intravenous infusion versus intramyometrial injection of oxytocin on hemoglobin levels in neonates with delayed umbilical cord clamping during cesarean section. METHODS: The multi-centre randomized controlled trial was performed at three hospitals from February to June 2023. Women with term singleton gestations scheduled for cesarean delivery were allocated to receive an intravenous infusion of 10 units of oxytocin or a myometrial injection of 10 units of oxytocin during the surgery. The primary outcome was neonatal hemoglobin at 48 to 96 h after birth. Secondary outcomes were side-effects of oxytocin, postpartum haemorrhage, phototherapy for jaundice, feeding at 1 month, maternal and neonatal morbidity and re-admissions. RESULTS: A total of 360 women were randomized (180 women in each group). The mean neonatal hemoglobin did not show a significant difference between the intravenous infusion group (194.3 ± 21.7 g/L) and the intramyometrial groups (195.2 ± 24.3 g/L) (p = 0.715). Secondary neonatal outcomes, involving phototherapy for jaundice, feeding at 1 month and neonatal intensive care unit admission were similar between the two groups. The maternal outcomes did not differ significantly between the two groups, except for a 200 mL higher intraoperative infusion volume observed in the intravenous group compared to the intramyometrial group. CONCLUSION: Among women undergoing elective cesarean delivery of term singleton pregnancies, there was no significant difference in neonatal hemoglobin at 48 to 96 h after birth between infants with delayed cord clamping, whether the oxytocin was administrated by intravenous infusion or intramyometrial injection. TRIAL REGISTRATION: Chinese Clinical trial registry: ChiCTR2300067953 (1 February 2023).