Desirability of outcome ranking for obstetrical trials: illustration and application to the ARRIVE trial.

BACKGROUND: In randomized trials, 1 primary outcome is typically chosen to evaluate the consequences of an intervention, whereas other important outcomes are relegated to secondary outcomes. This issue is amplified for many obstetrical trials in which an intervention may have consequences for both the pregnant person and the child. In contrast, desirability of outcome ranking, a paradigm shift for the design and analysis of clinical trials based on patient-centric evaluation, allows multiple outcomes-including from >1 individual-to be considered concurrently. OBJECTIVE: This study aimed to describe desirability of outcome ranking methodology tailored to obstetrical trials and to apply the methodology to maternal-perinatal paired (dyadic) outcomes in which both individuals may be affected by an intervention but may experience discordant outcomes (eg, an obstetrical intervention may improve perinatal but worsen maternal outcomes). STUDY DESIGN: This secondary analysis applies the desirability of outcome ranking methodology to data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network ARRIVE trial. The original analysis found no substantial difference in the primary (perinatal composite) outcome, but a decreased risk of the secondary outcome of cesarean delivery with elective induction at 39 weeks. In the present desirability-of-outcome-ranking analysis, dyadic outcomes ranging from spontaneous vaginal delivery without severe neonatal complication (most desirable) to cesarean delivery with perinatal death (least desirable) were classified into 8 categories ranked by overall desirability by experienced investigators. Distributions of the desirability of outcome ranking were compared by estimating the probability of having a more desirable dyadic outcome with elective induction at 39 weeks of gestation than with expectant management. To account for various perspectives on these outcomes, a complementary analysis, called the partial credit strategy, was used to grade outcomes on a 100-point scale and estimate the difference in overall treatment scores between groups using a t test. RESULTS: All 6096 participants from the trial were included. The probability of a better dyadic outcome for a randomly selected patient who was randomized to elective induction was 53% (95% confidence interval, 51-54), implying that elective induction led to a better overall outcome for the dyad when taking multiple outcomes into account concurrently. Furthermore, the desirability-of-outcome-ranking probability of averting cesarean delivery with elective induction was 52% (95% confidence interval, 51-53), which was not at the expense of an operative vaginal delivery or a poorer outcome for the perinate (ie, survival with a severe neonatal complication or perinatal death). Randomization to elective induction was also advantageous in most of the partial credit score scenarios. CONCLUSION: Desirability-of-outcome-ranking methodology is a useful tool for obstetrical trials because it provides a concurrent view of the effect of an intervention on multiple dyadic outcomes, potentially allowing for better translation of data for decision-making and person-centered care.

The role of labor induction in modern obstetrics.

A primary goal of obstetrical practice is the optimization of maternal and perinatal health. This goal translates into a seemingly simple assessment with regard to considerations of the timing of delivery: delivery should occur when the benefits are greater than those of continued pregnancy. In the absence of an indication for cesarean delivery, planned delivery is initiated with induction of labor. When medical or obstetrical complications exist, they may guide recommendations regarding the timing of delivery. In the absence of these complications, gestational age also has been used to guide delivery timing, given its association with both maternal and perinatal adverse outcomes. If there is no medical indication, delivery before 39 weeks has been discouraged, given its association with greater chances of adverse perinatal outcomes. Conversely, it has been recommended that delivery occur by 42 weeks of gestation, given the perinatal risks that accrue in the post-term period. Historically, a 39-week induction of labor, particularly for individuals with no previous birth, has not been routinely offered in the absence of medical or obstetrical indications. That approach was based on numerous observational studies that demonstrated an increased risk of cesarean delivery and other adverse outcomes among individuals who underwent labor induction compared to those in spontaneous labor. However, from a management and person-centered-choice perspective, the relevant comparison is between those undergoing planned labor induction at a given time vs those planning to continue pregnancy beyond that time. When individuals have been compared using that rubric-either in observational studies or randomized trials that have been performed in a wide variety of locations and populations- there has not been evidence that induction increases adverse perinatal or maternal outcomes. Conversely, even when the only indication for delivery is the achievement of a full-term gestational age, evidence suggests that multiple different outcomes, including cesarean delivery, hypertensive disorders of pregnancy, neonatal respiratory impairment, and perinatal mortality, are less likely when induction is performed. This information underscores the importance of making the preferences of pregnant individuals for different birth processes and outcomes central to the approach to delivery timing.

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.

The ethics of induction of labor at 39 weeks in low-risk nulliparas in research and clinical practice.

The "A Randomized Trial of Induction Versus Expectant Management" trial (ARRIVE trial) published in 2018 suggested that induction of labor can be considered a "reasonable option" for low-risk nulliparous women at ≥39 weeks of gestation. The study results led some professional societies to endorse the option for elective induction of labor at 39 weeks of gestation in low-risk nulliparas, and this has begun to change obstetrical practice. The ARRIVE trial provided valuable information supporting the benefits of induction of labor; however, the trial is insufficient to serve as the primary justification for widespread elective induction of labor at 39 weeks of gestation in low-risk nulliparas because of concerns about external validity. Thus, the French ARRIVE trial was designed to test the hypothesis in a different setting that elective induction of labor at 39 weeks of gestation in low-risk nulliparas leads to a lower cesarean delivery rate than expectant management. This ongoing trial has been criticized as "pseudoscientific" and telling "women where, when, and how to give birth." We reject these allegations and extensively examine the ethical framework that should govern clinical and research interventions, including elective induction of labor at 39 weeks of gestation in low-risk nulliparas. This study aimed to discuss the ethical issues that emerge from randomized trials of elective induction of labor at 39 weeks of gestation in low-risk nulliparas and the ethics of the clinical practice itself. The analysis of existing evidence shows the importance of further research on induction of labor at 39 weeks of gestation in low-risk women. Certain aspects of research ethics in this area, particularly the consent of pregnant women in a context where autonomy remains fragile, call for vigilance. In addition, we emphasize that childbirth is not only a medical object but also a social phenomenon that cannot be regarded only from the perspective of a health risk to be managed by clinical research. Further research on this issue is needed to allow pregnant women to make informed decisions, and the results should be integrated with social issues. The perspective of women is required in constructing, evaluating, and implementing medical interventions in childbirth, such as induction of labor at 39 weeks of gestation.

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.

Induction of labor vs expectant management among low-risk patients with 1 prior cesarean delivery.

BACKGROUND: Studies that have compared induction of labor in individuals with 1 prior cesarean delivery to expectant management have shown conflicting results. OBJECTIVE: To determine the association between clinical outcomes and induction of labor at 39 weeks in a national sample of otherwise low-risk patients with 1 prior cesarean delivery. STUDY DESIGN: This cross-sectional study analyzed 2016 to 2021 US Vital Statistics birth certificate data. Individuals with vertex, singleton pregnancies, and 1 prior cesarean delivery were included. Patients with prior vaginal deliveries, delivery before 39 weeks 0 days or after 42 weeks 6 days of gestation, and medical comorbidities were excluded. The primary exposure of interest was induction of labor at 39 weeks 0 days to 39 weeks 6 days compared to expectant management with delivery from 40 weeks 0 days to 42 weeks 6 days. The primary outcome was vaginal delivery. The main secondary outcomes were separate maternal and neonatal morbidity composites. The maternal morbidity composite included uterine rupture, operative vaginal delivery, peripartum hysterectomy, intensive care unit admission, and transfusion. The neonatal morbidity composite included neonatal intensive care unit admission, Apgar score less than 5 at 5 minutes, immediate ventilation, prolonged ventilation, and seizure or serious neurological dysfunction. Unadjusted and adjusted log binomial regression models accounting for demographic variables and the exposure of interest (induction vs expectant management) were performed. Results are presented as unadjusted and adjusted risk ratios with 95% confidence intervals. RESULTS: From 2016 to 2021, a total of 198,797 individuals with vertex, singleton pregnancies, and 1 prior cesarean were included in the primary analysis. Of these individuals, 25,915 (13.0%) underwent induction of labor from 39 weeks 0 days to 39 weeks 6 days and 172,882 (87.0%) were expectantly managed with deliveries between 40 weeks 0 days and 42 weeks 6 days. In adjusted analyses, patients induced at 39 weeks were more likely to have a vaginal delivery when compared to those expectantly managed (38.0% vs 31.8%; adjusted risk ratio 1.32, 95% confidence interval 1.28, 1.36). Among those who had vaginal deliveries, induction of labor was associated with increased likelihood of operative vaginal delivery (11.1% vs 10.0; adjusted risk ratio 1.15, 95% confidence interval 1.07, 1.24). The maternal morbidity composite occurred in 0.9% of individuals in both the induction and expectant management groups (adjusted risk ratio 0.92, 95% confidence interval 0.79, 1.06). The rates of uterine rupture (0.3%), peripartum hysterectomy (0.04% vs 0.05%), and intensive care unit admission (0.1% vs 0.2%) were all relatively low and did not differ significantly between groups. There was also no significant difference in the neonatal morbidity composite between the induction and expectant management groups (7.3% vs 6.7%; adjusted risk ratio 1.04, 95% confidence interval 0.98, 1.09). CONCLUSION: When compared to expectant management, elective induction of labor at 39 weeks in low-risk patients with 1 prior cesarean delivery was associated with a significantly higher likelihood of vaginal delivery with no difference in composite maternal and neonatal morbidity outcomes. Prospective studies are needed to better elucidate the risks and benefits of induction of labor in this patient population.

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

BACKGROUND: The prevalence and risk factors of postpartum depression after cesarean delivery remain unclear. OBJECTIVE: To assess the prevalence of postpartum depression and its risk factors 2 months after cesarean delivery. METHODS: Prospective ancillary cohort study of the Tranexamic Acid for Preventing Postpartum Hemorrhage after Cesarean Delivery (TRAAP2) trial, conducted in 27 French hospitals in 2018-2020 and enrolling women undergoing cesarean delivery before or during labor at 34 or more weeks of gestation. After randomization, characteristics of the cesarean delivery, postpartum blood loss, and immediate postpartum period, including memories of delivery and postoperative pain, were prospectively collected. Women's characteristics, particularly any psychiatric history, were collected from medical records. Two months after childbirth, a postpartum depression provisional diagnosis was defined as a score of 13 or higher 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. Multivariate logistic regression analyzed associations between potential risk factors and postpartum depression. A sensitivity analysis used an EPDS cutoff value of 11 or higher. RESULTS: The questionnaire was returned by 2793/4431 women (63.0% response rate). The corrected prevalence of postpartum depression provisional diagnosis was 16.4% (95% confidence interval (CI), 14.9-18.0%) with an EPDS score of 13 or higher and 23.1% (95%CI, 21.4-24.9%) with a cutoff value of 11 or higher. Characteristics associated with a higher risk of postpartum depression were pre-pregnancy characteristics such as young age (aOR 0.83, 95%CI 0.74-0.93 for each 5-year increase in maternal age) and non-European country of birth (aOR 2.58, 95%CI 1.85-3.59 for North Africa; aOR 1.57, 95%CI 1.09-2.26 for Sub-Saharan Africa and aOR 1.99, 95%CI 1.28-3.10 for other country of birth; reference: Europe) and some aspects of the cesarean delivery, notably its timing and context, emergency before labor (aOR 1.70, 95%CI 1.15-2.50; reference: before labor without emergency) and during labor after induction of labor (aOR 1.36, 95%CI 1.03-1.84; reference: before labor without emergency). Also at higher risk were women reporting high intensity pain during the postpartum stay (aOR 1.73, 95%CI 1.32-2.26) and bad memories of delivery on day 2 postpartum (aOR 1.67, 95%CI 1.14-2.45). Conversely, women who had social support in the operating room had a lower risk of postpartum depression (aOR 0.73, 95%CI 0.53-0.97). CONCLUSION: Around one woman in six had postpartum depression symptoms 2 months after cesarean delivery. Some cesarean-related obstetric factors may increase this risk: cesareans before labor for emergency situations or during labor after medically indicated induction of labor, severe postoperative pain and bad memories of delivery before discharge. Specific subgroups of at-risk women could benefit from early screening or intervention to reduce the onset of postpartum depression. Perinatal professionals should pay particular attention to postoperative pain management.

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.

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.

Obstetric violence is a misnomer.

The term "obstetric violence" has been used in the legislative language of several countries to protect mothers from abuse during pregnancy. Subsequently, it has been expanded to include a spectrum of obstetric procedures, such as induction of labor, episiotomy, and cesarean delivery, and has surfaced in the peer-reviewed literature. The term "obstetric violence" can be seen as quite strong and emotionally charged, which may lead to misunderstandings or misconceptions. It might be interpreted as implying a deliberate act of violence by healthcare providers when mistreatment can sometimes result from systemic issues, lack of training, or misunderstandings rather than intentional violence. "Obstetric mistreatment" is a more comprehensive term that can encompass a broader range of behaviors and actions. "Violence" generally refers to the intentional use of physical force to cause harm, injury, or damage to another person (eg, physical assault, domestic violence, street fights, or acts of terrorism), whereas "mistreatment" is a more general term and refers to the abuse, harm, or control exerted over another person (such as nonconsensual medical procedures, verbal abuse, disrespect, discrimination and stigmatization, or neglect, to name a few examples). There may be cases where unprofessional personnel may commit mistreatment and violence against pregnant patients, but as obstetrics is dedicated to the health and well-being of pregnant and fetal patients, mistreatment of obstetric patients should never be an intended component of professional obstetric care. It is necessary to move beyond the term "obstetric violence" in discourse and acknowledge and address the structural dimensions of abusive reproductive practices. Similarly, we do not use the term "psychiatric violence" for appropriately used professional procedures in psychiatry, such as electroshock therapy, or use the term "neurosurgical violence" when drilling a burr hole. There is an ongoing need to raise awareness about the potential mistreatment of obstetric patients within the context of abuse against women in general. Using the term "mistreatment in healthcare" instead of the more limited term "obstetric violence" is more appropriate and applies to all specialties when there is unprofessional abuse and mistreatment, such as biased care, neglect, emotional abuse (verbal), or physical abuse, including performing procedures that are unnecessary, unindicated, or without informed patient consent. Healthcare providers must promote unbiased, respectful, and patient-centered professional care; provide an ethical framework for all healthcare personnel; and work toward systemic change to prevent any mistreatment or abuse in our specialty.

Parturition at term: induction, second and third stages of labor, and optimal management of life-threatening complications-hemorrhage, infection, and uterine rupture.

Childbirth is a defining moment in anyone's life, and it occurs 140 million times per year. Largely a physiologic process, parturition does come with risks; one mother dies every two minutes. These deaths occur mostly among healthy women, and many are considered preventable. For each death, 20 to 30 mothers experience complications that compromise their short- and long-term health. The risk of birth extends to the newborn, and, in 2020, 2.4 million neonates died, 25% in the first day of life. Hence, intrapartum care is an important priority for society. The American Journal of Obstetrics & Gynecology has devoted two special Supplements in 2023 and 2024 to the clinical aspects of labor at term. This article describes the content of the Supplements and highlights new developments in the induction of labor (a comparison of methods, definition of failed induction, new pharmacologic agents), management of the second stage, the value of intrapartum sonography, new concepts on soft tissue dystocia, optimal care during the third stage, and common complications that account for maternal death, such as infection, hemorrhage, and uterine rupture. All articles are available to subscribers and non-subscribers and have supporting video content to enhance dissemination and improve intrapartum care. Our hope is that no mother suffers because of lack of information.

Timing of induction of labor in suspected macrosomia: retrospective cohort study, systematic review and meta-analysis.

OBJECTIVES: Large-for-gestational age (LGA) is associated with several adverse maternal and neonatal outcomes. Although many studies have found that early induction of labor (IOL) in case of a LGA fetus reduces the incidence of shoulder dystocia, no current guidelines recommend this particular clinical strategy, owing to concerns about increased rates of Cesarean delivery (CD) and neonatal complications. The purpose of this study was to assess whether the timing of IOL in LGA fetuses affected maternal and neonatal outcomes in a single center, and to combine these results with evidence reported in the literature. METHODS: This study comprised two parts. The first part was a retrospective cohort study that included consecutive patients with a singleton pregnancy and an estimated fetal weight ≥ 90th percentile on ultrasound between 35 + 0 and 39 + 0 weeks' gestation, who were eligible for normal vaginal delivery. The second part of the study was a systematic review of the literature and meta-analysis, including the results of our cohort study as well as those of previous studies that compared IOL with expectant management in patients with a LGA fetus. The perinatal outcomes of the study were CD, operative vaginal delivery, shoulder dystocia, brachial plexus palsy, anal sphincter injury, postpartum hemorrhage, Apgar score, umbilical artery pH, admission to the neonatal intensive care unit, use of continuous positive airway pressure, intracranial hemorrhage, need for phototherapy and bone fracture. RESULTS: Of the 547 patients included in this retrospective cohort study, 329 (60.1%) underwent IOL and 218 (39.9%) experienced spontaneous labor. Following covariate balancing, the odds of CD were significantly higher in the IOL group compared with the spontaneous-labor group. This difference only became apparent beyond 40 weeks' gestation (hazard ratio, 1.90; P = 0.030). The difference between the IOL and spontaneous-labor groups for the rate of shoulder dystocia was not statistically significant (hazard ratio, 1.57; P = 0.200). Seventeen studies, in addition to our own results, were included in the systematic review and meta-analysis, giving a total population of 111 300 participants. Although there was no significant difference in the rate of CD between IOL and expectant management after pooling the results of included studies, the risk for shoulder dystocia was significantly lower in the IOL group (odds ratio (OR), 0.64 (95% CI, 0.42-0.98); I2 = 19% from 12 studies) when considering only IOL performed before 40 + 0 weeks. When the studies in which IOL was carried out exclusively before 40 + 0 weeks were removed from the analysis, the risk for CD in the remaining studies was significantly higher in the IOL group (OR, 1.46 (95% CI, 1.02-2.09); I2 = 56%). There were no statistically significant differences between the IOL and expectant-management groups for the remaining perinatal outcomes. Nulliparity, history of CD and low Bishop score, but not method of induction, were independent risk factors for intrapartum CD in patients that underwent IOL for LGA. CONCLUSIONS: The timing of IOL in patients with suspected macrosomia significantly impacts on perinatal adverse outcomes. IOL has no impact on rates of shoulder dystocia but increases the odds of CD when considered irrespective of gestational age; in contrast, IOL may decrease the risk of shoulder dystocia without increasing the risk of other adverse maternal outcomes, in particular CD, when performed before 40 + 0 weeks (GRADE: low/very low). © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Projecting future prolapse outcomes with induction of labor at 39 weeks: a decision analysis.

INTRODUCTION AND HYPOTHESIS: In 2018, the ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management) concluded that routine induction of labor (IOL) at 39 weeks gestation decreases cesarean delivery risk, with slightly lighter birthweight infants. We debated whether routine IOL would improve, worsen, or not change POP risk compared with expectant management (EM). METHODS: We constructed a decision analysis model with a lifetime horizon where nulliparous women reaching 39 weeks underwent IOL or EM. Subsequent vaginal versus cesarean delivery varied based on prior deliveries for up to four births. Subsequent delivery prior to 39 weeks and distribution of gestational age, birthweight, and delivery mode between 24 and 39 weeks was modeled from national data. We modeled increased POP risk with increasing vaginal parity, forceps delivery, and weight of largest infant delivered vaginally, accounting for differential infant weights in each strategy. RESULTS: IOL and EM have similar population-wide POP risk (15.9% and 15.7% respectively). Among women with only spontaneous vaginal deliveries that reached 39 weeks or beyond, the prevalence of POP was 20% after one delivery and 29% after four deliveries, with no difference between groups. The cesarean rate was lower with IOL (27.8% versus 29.8%). Sensitivity analysis revealed no meaningful thresholds among the variables, supporting model robustness. CONCLUSION: While routine induction of labor at 39 weeks results in a meaningfully higher vaginal delivery rate, there was no increase in POP, possibly due to the protective effect of lower birthweight.

A double-blind, randomized, placebo-controlled trial of melatonin as an adjuvant agent for induction of labor: The MILO trial.

INTRODUCTION: Melatonin has been suggested to have a biological role in the onset and progress of labor. We tested the hypothesis that the addition of melatonin during an induction of labor will reduce the need for a cesarean birth. MATERIAL AND METHODS: This trial underwent protocol amendments that are detailed in the main text of the article. This trial is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12616000311459). At a multi-center health service including secondary and tertiary obstetric hospitals, we performed a randomized, double-blind, placebo-controlled trial in women with a singleton cephalic pregnancy, free of significant maternal or perinatal complications who were undergoing induction of labor (with or without cervical ripening). Women were randomized to 10 mg melatonin vs placebo, with cervical ripening as required, and then 6-h during their induction of labor to a maximum of four doses or until birth. The primary outcome was cesarean birth. Secondary outcomes included labor, maternal, and neonatal outcomes. Data were analyzed using intention to treat. Sub-group analyses based on mode of ripening and parity were also performed. RESULTS: Between 2019 and 2021 we randomized 189 women (103 to melatonin and 86 to placebo). The study was prematurely terminated due to logistical complications resulting from the COVID-19 pandemic. Cesarean rates were 28/103 (27.2%) in the melatonin group versus 20/84 (23.3%) in the placebo group (RR 1.17 95% CI 0.71-1.92). There were no significant differences in rate of cesarean birth between the melatonin and placebo groups for failure to progress (13.4% and 9.3%, respectively, RR 1.46; 95% CI 0.64-3.32) or suspected fetal distress (10.7% and 10.5%, respectively, RR 1.02; 95% CI 0.44-2.34). The melatonin group had significantly lower rates of spontaneous vaginal birth within 24 h (35.0% vs. 50.0%; RR 0.70 95% CI 0.50-0.98). The rates of secondary outcomes such as total length of labor, rate of postpartum hemorrhage, and instrumental birth were comparable. Babies born in the melatonin group were more likely to need admission to the special care nursery, namely for hypoglycemic monitoring (18.5% vs. 8.1% RR 2.26; 95% CI 1.00-5.10). CONCLUSIONS: In women undergoing induction of labor, melatonin does not reduce the cesarean section rate. Melatonin use intrapartum may also be associated with neonatal hypoglycemia.

Motivations for and experience with labor induction at 39 weeks in women with obesity-A qualitative study.

INTRODUCTION: Timing of induction of labor (IOL) at term has been investigated in multiple settings. In Denmark, the 'When to INDuce for OverWeight' (WINDOW) study compares IOL at 39 weeks of gestation versus expectant management in low-risk women with obesity. However, knowledge on women's expectations of and experience with IOL is sparse. The aim of this study was to explore women's motivation to join the WINDOW study and their experience when randomized to IOL at 39 gestational weeks. MATERIAL AND METHODS: A qualitative interview study of 25 pregnant women with obesity randomized in the WINDOW study to IOL at 39 weeks of gestation was conducted. Participants were recruited from four hospitals in Central Denmark Region and were interviewed four to six weeks after giving birth. A thematic analysis was performed using a phenomenological approach. RESULTS: The analysis resulted in three main themes, (1) Motivation for IOL, (2) The IOL process, and (3) IOL in recollection and in the future. Participants perceived inclusion into the WINDOW study as a "great opportunity," as they hoped to be randomized to IOL at 39 weeks of gestation. Their main motivation for participating was physical discomfort in late pregnancy and a wish for "knowing" the timing of the birth. BMI-related risk factors were mentioned by few as a motivating factor. Some participants described the IOL process as a team effort between the couple and the midwives and were positive towards future IOL. Others associated the IOL process with prolonged labor or described the body as "reluctant" to respond to the induction regime. A desire to experience spontaneous onset of labor in a future pregnancy was mentioned. CONCLUSIONS: Physical discomfort and wanting to "control" the onset of labor were main motivations for women's decision to participate in the WINDOW study, hoping they would be allocated for IOL. Comprehensive information and being supported by midwives through the IOL process was crucial for a positive IOL experience. Some participants were positive towards a future IOL. Others speculated if their body was not ready for birth in 39 weeks of gestation and/or associated the IOL process with a challenging labor.

Incidence and risk factors for umbilical cord prolapse in labor when amniotomy is used and with spontaneous rupture of membranes: A Swedish nationwide register study.

INTRODUCTION: Umbilical cord prolapse (UCP) is a rare but severe obstetric complication in the presence of a rupture of the membranes. Although it is not possible to prevent a spontaneous rupture of the membranes (SROM), it is possible to prevent an amniotomy, which is a commonly used intervention in labor. This study aimed to explore the incidence and risk factors that are associated with UCP in labor when amniotomy is used vs SROM. MATERIAL AND METHODS: A retrospective nationwide register study was conducted of all births in Sweden from January 2014 to June 2020 that were included in the Swedish Pregnancy Register (n = 717 336). The main outcome, UCP, was identified in the data by the International Classification of Diseases (ICD-10) diagnosis code O69.0. Multiple binary logistic regression analysis was used to identify the risk factors. RESULTS: Amniotomy was performed in 230 699 (43.6%) of all pregnancies. A UCP occurred in 293 (0.13%) of these cases. SROM occurred in 298 192 (56.4%) of all cases, of which 352 (0.12%) were complicated by UCP. Risk factors that increased the odds of UCP for both amniotomy and SROM were: higher parity, non-cephalic presentation and an induction of labor. Greater gestational age reduced the odds of UCP. Risk factors associated with only amniotomy were previous cesarean section and the presence of polyhydramnios. Identified risk factors for UCP in labor with SROM were a higher maternal age and maternal origin outside of the EU. CONCLUSIONS: UCP is a rare complication in Sweden. Beyond confirming the previously recognized risk factors, this study found induction of labor and previous cesarean section to be risk factors in labor when amniotomy is used.

Neonatal and maternal outcomes at early vs. full term following induction of labor; A secondary analysis of the OBLIGE randomized trial.

INTRODUCTION: Birth at early term (37+0-38+6 completed gestational weeks [GW] and additional days) is associated with adverse neonatal outcomes compared with waiting to ≥39 GW. Most studies report outcomes after elective cesarean section or a mix of all modes of births; it is unclear whether these adverse outcomes apply to early-term babies born after induction of labor (IOL). We aimed to determine, in women with a non-urgent induction indication (elective/planned >48 h in advance), if IOL at early and late term was associated with adverse neonatal and maternal outcomes compared with IOL at full term. MATERIAL AND METHODS: An observational cohort study as a secondary analysis of a multicenter randomized controlled trial of 1087 New Zealand women with a planned IOL ≥37+0 GW. Multivariable logistic regression was used to analyze neonatal and maternal outcomes in relation to gestational age; 37+0-38+6 (early term), 39+0-40+6 (full term) and ≥41+0 (late term) GW. Neonatal outcome analyses were adjusted for sex, birthweight, mode of birth and induction indication, and maternal outcome analyses for parity, age, body mass index and induction method. The primary neonatal outcome was admission to neonatal intensive care unit (NICU) for >4 hours; the primary maternal outcome was cesarean section. RESULTS: Among the 1087 participants, 266 had IOL at early term, 480 at full term, and 341 at late term. Babies born following IOL at early term had increased odds for NICU admission for >4 hours (adjusted odds ratio [aOR] 2.16, 95% confidence intervals (CI) 1.16-4.05), compared with full term. Women having IOL at early term had no difference in emergency cesarean rates but had an increased need for a second induction method (aOR 1.70, 95% CI 1.15-2.51) and spent 4 h longer from start of IOL to birth (Hodges-Lehmann estimator 4.10, 95% CI 1.33-6.95) compared with those with IOL at full term. CONCLUSIONS: IOL for a non-urgent indication at early term was associated with adverse neonatal and maternal outcomes and no benefits compared with IOL at full term. These findings support international guidelines to avoid IOL before 39 GW unless there is an evidence-based indication for earlier planned birth and will help inform women and clinicians in their decision-making about timing of IOL.

Likelihood of primary cesarean section following induction of labor in singleton cephalic pregnancies at term, compared with expectant management: An Australian population-based, historical cohort study.

INTRODUCTION: There has been increased use of both induction of labor (IOL) and cesarean section for women with term pregnancies in many high-income countries, and a trend toward birth at earlier gestational ages. Existing evidence regarding the association between IOL and cesarean section for term pregnancies is mixed and conflicting, and little evidence is available on the differential effect at each week of gestation, stratified by parity. MATERIAL AND METHODS: To explore the association between IOL and primary cesarean section for singleton cephalic pregnancies at term, compared with two definitions of expectant management (first: at or beyond the week of gestation at birth following IOL; and secondary: only beyond the week of gestation at birth following IOL), we performed analyses of population-based historical cohort data on women who gave birth in one Australian state (Queensland), between July 1, 2012 and June 30, 2018. Women who gave birth before 37+0 or after 41+6 weeks of gestation, had stillbirths, no-labor, multiple births (twins or triplets), non-cephalic presentation at birth, a previous cesarean section, or missing data on included variables were excluded. Four sub-datasets were created for each week at birth (37-40). Unadjusted relative risk, adjusted relative risk using modified Poisson regression, and their 95% confidence intervals were calculated in each sub-dataset. Analyses were stratified by parity (nulliparas vs. parous women with a previous vaginal birth). Sensitivity analyses were conducted by limiting to women with low-risk pregnancies. RESULTS: A total of 239 094 women were included in the analysis, 36.7% of whom gave birth following IOL. The likelihood of primary cesarean section following IOL in a Queensland population-based cohort was significantly higher at 38 and 39 weeks, compared with expectant management up to 41+6 weeks, for both nulliparas and paras with singleton cephalic pregnancies, regardless of risk status of pregnancy and definition of expectant management. No significant difference was found for nulliparas at 37 and 40 weeks; and for paras at 40 weeks. CONCLUSIONS: Future studies are suggested to investigate further the association between IOL and other maternal and neonatal outcomes at each week of gestation in different maternal populations, before making any recommendation.

Effect of cervical Bishop score on induction of labor at term in primiparas using Foley catheter balloon: a retrospective study.

BACKGROUND: Previous studies had found that the mechanical methods were as effective as pharmacological methods in achieving vaginal delivery. However, whether balloon catheter induction is suitable for women with severe cervical immaturity and whether it will increase the related risks still need to be further explored. RESEARCH AIM: To evaluate the efficacy and safety of Foley catheter balloon for labor induction at term in primiparas with different cervical scores. METHODS: A total of 688 primiparas who received cervical ripening with a Foley catheter balloon were recruited in this study. They were divided into 2 groups: Group 1 (Bishop score ≤ 3) and Group 2 (3 < Bishop score < 7). Detailed medical data before and after using of balloon were faithfully recorded. RESULTS: The cervical Bishop scores of the two groups after catheter placement were all significantly higher than those before (Group 1: 5.49 ± 1.31 VS 2.83 ± 0.39, P<0.05; Group 2: 6.09 ± 1.00 VS 4.45 ± 0.59, P<0.05). The success rate of labor induction in group 2 was higher than that in group 1 (P<0.05). The incidence of intrauterine infection in Group 1 was higher than that in Group 2 (18.3% VS 11.3%, P<0.05). CONCLUSION: The success rates of induction of labor by Foley catheter balloon were different in primiparas with different cervical conditions, the failure rate of induction of labor and the incidence of intrauterine infection were higher in primiparas with severe cervical immaturity.

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.