The efficacy and safety of oral and vaginal misoprostol versus dinoprostone on women experiencing labor: A systematic review and updated meta-analysis of 53 randomized controlled trials.

BACKGROUND: Induction of labor is the process of artificially stimulating the uterus to start labor before the spontaneous onset of labor. It has several medical indications. Commonly used agents are vaginal misoprostol, vaginal prostaglandin E2 (dinoprostone), and oral misoprostol. METHODS: Through October 2023, a literature review was carried out in Cochrane, PubMed, Web of Science, and Scopus to identify randomized clinical studies assessing if oral and vaginal misoprostol has better efficacy of induction of labor over vaginal prostaglandin E2 or dinoprostone as a primary outcome. The data were pooled as mean difference, risk ratio, and 95% confidence interval. RESULTS: Fifty-three RCTs involving 10,455 patients showed a statistically significant difference in the overall success rate of induction between the misoprostol and prostaglandins E2 (PGE2) groups. They required less additional oxytocin compared to the PGE2 groups. The frequency of tachysystole, uterine hyperstimulation, abnormal cardiotocography, meconium-stained amniotic fluid, and Apgar score <7 at 1 minute were all higher in misoprostol groups than in PGE2 groups. No difference was found in cesarean section, fever, Neonatal Intensive Care Unit admission, or Apgar scores at 1 minute or 5 minutes. CONCLUSION: Vaginal misoprostol is more effective at inducing labor but may be less safe than vaginal dinoprostone. Oral misoprostol is generally as safe as vaginal dinoprostone. Vaginal dinoprostone requires lower doses but may need more oxytocin administration.

Comparison of two labor induction regimens with intravaginal misoprostol 25 µg and adverse perinatal outcomes.

OBJECTIVE: The aim of the study was to compare two labor induction regimens (4 and 6 h), to determine predictors of successful labor induction with intravaginal misoprostol 25 µg tablets, and to evaluate the association with adverse perinatal outcomes. METHODS: This was a retrospective cohort study that included singleton pregnancies undergoing induction of labor with an intravaginal misoprostol 25 µg tablet between 37 and 42 weeks of gestation. The pregnant women were divided into two groups: Group 1-intravaginal misoprostol 25 µg every 4 h and Group 2-intravaginal misoprostol 25 µg every 6 h. RESULTS: Pregnant women were divided into Group 1 (n=289) and Group 2 (n=278). Group 1 had a higher median number of intravaginal misoprostol 25 µg tablets (3.0 vs. 2.0 tablets, p<0.001), a lower prevalence of postpartum hemorrhage (7.6 vs. 32.7%, p<0.001), and a higher need for oxytocin (odds ratio [OR]: 2.1, 95%CI: 1.47-2.98, p<0.001) than Group 2. Models including intravaginal misoprostol 25 µg tablets every 4 and 6 h [x2(1)=23.7, OR: 4.35, p<0.0001], parity [x2(3)=39.4, OR: 0.59, p=0.031], and Bishop's score [x2(4)=10.8, OR: 0.77, p=0.019] were the best predictors of failure of labor induction. A statistically significant difference between groups was observed between the use of the first intravaginal misoprostol 25 µg tablet at the beginning (Breslow p<0.001) and the end of the active labor phase (Long Hank p=0.002). CONCLUSION: Pregnant women who used intravaginal misoprostol 25 µg every 4 h had a longer time from the labor induction to the beginning of the active phase of labor and higher rates of adverse perinatal outcomes than women who used intravaginal misoprostol 25 µg every 6 h.

Vaginal dinoprostone vs Foley catheter for induction of labor at term with an unfavorable cervix: an open-label randomized controlled trial.

BACKGROUND: Induction of labor (IOL) with mechanical methods or pharmacological agents is used in about 20% to 30% of all pregnant women. We specialized in comparing the effectiveness and safety of dinoprostone vs transcervical Foley catheter for IOL in term pregnant women with an unfavorable cervix with adequate samples. OBJECTIVE: To compare the effectiveness and safety of dinoprostone vs transcervical Foley catheter for IOL in term pregnant women with an unfavorable cervix. STUDY DESIGN: This is a parallel, open-label randomized controlled trial in two maternal centers in Shanghai, China between October 2019 and July 2022. Women with a singleton pregnancy in cephalic presentation at term and an unfavorable cervix (Bishop score <6) scheduled for IOL were eligible. A total of 1860 women were randomly allocated to cervical ripening with either a dinoprostone vaginal insert (10 mg) or a 60 cc Foley catheter for up to 24 hours. The primary outcomes were vaginal delivery rate and time to vaginal delivery. Secondary outcomes included time to delivery and maternal and neonatal morbidity. Analysis was done from an intention-to-treat perspective. The trial was registered with the China trial registry (CTR2000038435). RESULTS: The vaginal birth rates were 72.8% (677/930) vs 69.9% (650/930) in vaginal dinoprostone and Foley catheter, respectively (aRR 1.04, 95% confidence interval [CI] 0.98-1.10, risk difference: 0.03). Time to vaginal delivery was not significantly different between the two groups (sub-distribution hazard ratio 1.11, 95% CI 0.99-1.24). Vaginal dinoprostone was more likely complicated with hyperstimulation with fetal heart rate changes (5.8% vs 2.8%, aRR 2.09, 95% CI 1.32-3.31) and placenta abruption (0.9% vs 0.1%, aRR: 8.04, 95% CI 1.01-64.15), while Foley catheter was more likely complicated with suspected intrapartum infection (5.1% vs 8.2%, aRR: 0.62, 95% CI 0.44-0.88) and postpartum infection (1.4% vs 3.7%, aRR: 0.38, 95% CI 0.20-0.72). The composite of poor neonatal outcomes was not significantly different between the two groups (4.5% vs 3.8%, aRR 1.21, 95% CI 0.78-1.88), while more neonatal asphyxia occurred in the dinoprostone group (1.2% vs 0.2%, aRR 5.39, 95% CI 1.22-23.92). In a subgroup analysis, vaginal dinoprostone decreased vaginal birth rate slightly in multiparous women (90.6% vs 97.0%, aRR 0.93, 95% CI 0.88-0.99). CONCLUSIONS: In term pregnant women with an unfavorable cervix, IOL with vaginal dinoprostone or Foley catheter has similar effectiveness. Foley catheter leads to better safety for neonates, while it may result in a higher risk of maternal infection. Furthermore, Foley catheter should be preferred in multiparous women.

Shenghua decoction for postpartum hemorrhage attributed to uterine atony: An observational study.

This retrospective study aimed to investigate the preventive effects of Shenghua decoction (SHD) for postpartum hemorrhage (PPH) attributed to uterine atony (UA). Records of 84 patients were retrospectively analyzed, with 42 assigned to the treatment group and 42 to the control group. Both groups received carbetocin, and patients in the treatment group additionally underwent SHD. Primary endpoints included blood loss and changes in hemoglobin levels. Secondary endpoints encompassed the number of patients requiring uterine massage, additional oxytocic drugs, pulse rate, respiratory rate, systolic blood pressure, and treatment-related adverse events. Patients in the treatment group exhibited superior outcomes in terms of blood loss (P < .01), hemoglobin levels (P = .03), and pulse rate (P < .01) compared to those in the control group. However, no significant differences were observed in the number of patients requiring uterine massage (P = .13), the number of patients needing additional oxytocic drugs (P = .19), respiratory rate (P = .05), and systolic blood pressure (P = .80) between the 2 groups. There were no significant disparities in treatment-related adverse events between the 2 groups. The findings of this study suggest that the preventive effects of SHD combined with carbetocin were superior to those of carbetocin alone for preventing postpartum hemorrhage. However, high-quality prospective studies are needed to validate and confirm these results.

Comparison of Misoprostol for Labor Induction: Vaginal Insert Versus Oral Application Concerning Efficiency and Safety.

BACKGROUND/AIM: The aim of the present retrospective study was to examine the efficiency and safety of the induction of labor with Misoprostol, administered either vaginally or orally. PATIENTS AND METHODS: This retrospective cohort study included pregnant women with a gestational age of ≥36 +0 weeks and a singleton pregnancy who underwent induction of labor with Misoprostol as vaginal insert or as tablet (oral) between January 2014 and January 2019 at the Department of Obstetrics and Gynecology of the University Hospital of Cologne. The objective of this study was to analyze the time until delivery and the maternal and neonatal outcomes. RESULTS: A total of 1,511 patients were included in this retrospective analysis, of whom 1,035 patients (68.5%) underwent induction of labor with a misoprostol vaginal insert (MVI) and 476 (31.5%) with tablets (oral misoprostol: OM). MVI significantly shortened the time from application to delivery (p<0.001) in comparison to OM, reduced the need for epidural anesthesia (EA) (p=0.018) without an increase in caesarean sections (CS) (p=1), ventouse deliveries (VD) (p=0.715), maternal birth injuries or a reduced neonatal outcome (APGAR-Score, umbilical cord pH). CONCLUSION: MVI is superior to OM in terms of efficiency (primary outcome: time from application to delivery) and is equally safe (primary outcome: CS rate). Our study, along with existing literature, highlights the need for further research, particularly regarding neonatal outcomes. Additionally, it underscores the importance of careful consideration when inducing labor and ensuring informed consent.

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.

Association of oxytocin augmentation with postpartum hemorrhage: a systematic review and meta-analysis.

OBJECTIVE: The current study aims to evaluate the correlation between oxytocin augmentation and postpartum hemorrhage. METHOD: PubMed, Web of Science, and Scopus has been searched for studies assessing the correlation between oxytocin augmentation and postpartum hemorrhage up to January 24, 2024. The search strategy included relevant keywords related to PPH and oxytocin augmentation. The risk of bias assessment was conducted by two reviewers using the Newcastle-Ottawa Scale (NOS). To pool the effects sized of included studies odds ratios (OR) of interest outcome with their 95% confidence interval (CI) were used. RESULTS: Eight studies were included in this meta-analysis. The pooled analysis of the included studies showed a statistically significant association between oxytocin augmentation and increased odds of PPH (pooled odds ratio [OR] = 1.27, 95% confidence interval [CI]: 1.05-1.53; I2 = 84.94%; p = 0.01). Publication bias was assessed using funnel plots, which appeared relatively asymmetrical, indicating significant publication bias. Galbraith plot and trim and fill plot were used for publication bias. Sensitivity analyses were performed by leave one out method. CONCLUSION: This meta-analysis suggests that using oxytocin for labor augmentation is linked to a significant increase in the risk of PPH. It highlights the need for careful monitoring and consideration when using oxytocin, especially in low and middle-income countries where guidelines and supervision are crucial.

Oral misoprostol alone, compared with oral misoprostol followed by oxytocin, in women induced for hypertension of pregnancy: A multicentre randomised trial.

OBJECTIVE: To assess whether, in those requiring continuing uterine stimulation after cervical ripening with oral misoprostol and membrane rupture, augmentation with low-dose oral misoprostol is superior to intravenous oxytocin. DESIGN: Open-label, superiority randomised trial. SETTING: Government hospitals in India. POPULATION: Women who were induced for hypertensive disease in pregnancy and had undergone cervical ripening with oral misoprostol, but required continuing stimulation after artificial membrane rupture. METHODS: Participants received misoprostol (25 micrograms, orally, 2-hourly) or titrated oxytocin through an infusion pump. All women had one-to-one care; fetal monitoring was conducted using a mixture of intermittent and continuous electronic fetal monitoring. MAIN OUTCOME MEASURES: Caesarean birth. RESULTS: A total of 520 women were randomised and the baseline characteristics were comparable between the groups. The caesarean section rate was not reduced with the use of misoprostol (misoprostol, 84/260, 32.3%, vs oxytocin, 71/260, 27.3%; aOR 1.23; 95% CI 0.81-1.85; P = 0.33). The interval from randomisation to birth was somewhat longer with misoprostol (225 min, 207-244 min, vs 194 min, 179-210 min; aOR 1.137; 95% CI 1.023-1.264; P = 0.017). There were no cases of hyperstimulation in either arm. The rates of fetal heart rate abnormalities and maternal side effects were similar. Fewer babies in the misoprostol arm were admitted to the special care unit (10 vs 21 in the oxytocin group; aOR 0.463; 95% CI 0.203-1.058; P = 0.068) and there were no neonatal deaths in the misoprostol group, compared with three neonatal deaths in the oxytocin arm. Women's acceptability ratings were high in both study groups. CONCLUSIONS: Following cervical preparation with oral misoprostol and membrane rupture, the use of continuing oral misoprostol for augmentation did not significantly reduce caesarean rates, compared with the use of oxytocin. There were no hyperstimulation or significant adverse events in either arm of the trial.

Comparing labour induction outcomes using misoprostol and dinoprostone in term pregnancies: A retrospective study at Kiambu Level 5 Hospital between 2018 and 2020.

BACKGROUND: The Maternal and Perinatal Death Surveillance and Response (MPDSR) was introduced in Kenya in 2016 and implemented at Kiambu Level 5 Hospital (KL5H) three years later in 2019. During a routine MPDSR meeting at KL5H, committee members identified a possible link between the off-label use of 200mcg misoprostol tablets divided eight times to achieve the necessary dose for labour induction (25mcg) and maternal deaths. Following this, an administrative decision was made to switch from misoprostol to dinoprostone for the induction of labour in June of 2019. This study aimed to assess the overall impact of MPDSR as well as the effect of replacing misoprostol with dinoprostone on uterine rupture, maternal and neonatal deaths at KL5H. METHODS: We conducted a retrospective cohort study of women who gave birth at KL5H between January 2018 and December 2020. We defined the pre-intervention period as January 2018-June 2019, and the intervention period as July 2019-December 2020. We randomly selected the records of 411 mothers, 167 from the pre-intervention period and 208 from the intervention period, all of whom were induced. We used Bayes-Poisson Generalised Linear Models to fit the risk of uterine rupture, maternal and perinatal death. 12 semi-structured key person questionnaires was used to describe staff perspectives regarding the switch from misoprostol to dinoprostone. Inductive and deductive data analysis was done to capture the salient emerging themes. RESULTS: We reviewed 411 patient records and carried out 12 key informant interviews. Mothers induced with misoprostol (IRR = 3.89; CI = 0.21-71.6) had an increased risk of death while mothers were less likely to die if they were induced with dinoprostone (IRR = 0.23; CI = 0.01-7.12) or had uterine rupture (IRR = 0.56; CI = 0.02-18.2). The risk of dying during childbearing increased during Jul 2019-Dec 2020 (IRR = 5.43, CI = 0.68-43.2) when the MPDSR activities were strengthened. Induction of labour (IRR = 1.01; CI = 0.06-17.1) had no effect on the risk of dying from childbirth in our setting. The qualitative results exposed that maternity unit staff preferred dinoprostone to misoprostol as it was thought to be more effective (fewer failed inductions) and safer, regardless of being more expensive compared to misoprostol. CONCLUSION: While the period immediately following the implementation of MPDSR at KL5H was associated with an increased risk of death, the switch to dinoprostone for labour induction was associated with a lower risk of maternal and perinatal death. The use of dinoprostone, however, was linked to an increased risk of uterine rupture, possibly attributed to reduced labour monitoring given that staff held the belief that it is inherently safer than misoprostol. Consequently, even though the changeover was warranted, further investigation is needed to determine the reasons behind the rise in maternal mortalities, even though the MPDSR framework appeared to have been put in place to quell such an increase.

Protocolized oxytocin infusion for elective cesarean delivery: a retrospective before-and-after study.

PURPOSE: To elucidate the clinical impact of the novel oxytocin protocol using a syringe pump with a stratified dose compared with the conventional practice of putting oxytocin into the bag. METHODS: This is a retrospective cohort study. We collected the data of the patients who underwent elective cesarean delivery under neuraxial anesthesia between June 2019 and May 2020. The patients were allocated to two groups according to oxytocin administration methods; the control group (the attending anesthesiologist put oxytocin 5-10 units in the infusion bag and adjusted manually after childbirth) and the protocol group (the oxytocin protocol gave oxytocin bolus 1 or 3 units depending on the PPH risk, followed by 5 or 10 unit h-1 via a syringe pump). We compared the total amount of oxytocin within 24 h postpartum, estimated blood loss, and adverse clinical events within 24 h postpartum between the two groups. RESULTS: During the study period, 262 parturients were included. Oxytocin doses of intraoperative and postoperative were significantly lower in the protocol group (9.7 vs. 11.7 units, intraoperative, 15.9 vs. 18 units, postoperative). The subgroup analyses showed that the impact was more remarkable in the low PPH risk than in the high PPH risk. The multivariate linear regression analyses also confirmed the difference. The groups had no significant difference in blood loss, requirement of additional uterotonics, and other adverse events. CONCLUSIONS: Our oxytocin infusion protocol significantly reduced oxytocin requirements in elective cesarean delivery under neuraxial anesthesia without increasing blood loss. However, we could not find other clinical benefits of the novel protocol.

Efficacy and safety of oral and vaginal administration of misoprostol for induction of labor in high-risk obese pregnant women with hypertension or diabetes mellitus.

OBJECTIVE: This study aims to compare the safety and efficacy of misoprostol administered orally and vaginally in obese pregnant women at term with either gestational hypertension or diabetes. METHODS: A total of 264 pregnant women were enrolled and categorized into two groups based on their primary condition: hypertension (134 cases) or diabetes mellitus (130 cases) and were further divided into subgroups for misoprostol administration: orally (Oral group) or vaginally (Vaginal group). The primary outcomes measured were changes in the Bishop score following treatment, induction of labor (IOL) success rates, requirement for oxytocin augmentation, duration of labor, mode of delivery, and cesarean section rates. RESULTS: Significant enhancements in Bishop scores, decreased cesarean section rates and increased success rates of IOL were noted in both administration groups. The incidence of vaginal delivery within 24 h was significantly higher in the Vaginal group compared to the Oral group. Adverse effects, including nausea, uterine overcontraction, hyperfrequency of uterine contraction and uterine hyperstimulation without fetal heart rate deceleration, were significantly more prevalent in the Vaginal group than in the Oral group. CONCLUSION: Misoprostol administration, both orally and vaginally, proves effective for labor induction in obese pregnant women with hypertension or diabetes. However, the oral route presents a lower risk of adverse maternal and neonatal outcomes, suggesting its preference for safer labor induction in this demographic.

Cumulative oxytocin dose in spontaneous labour - Adverse postpartum outcomes, childbirth experience, and breastfeeding.

OBJECTIVES: This study aimed to determine the association between the total cumulative oxytocin dose during labour and adverse postpartum outcomes, childbirth experience and breastfeeding in term primiparous women with spontaneous onset of labour. STUDY DESIGN: A prospective observational multicentre study, including 1395 women with spontaneous labour, in seven hospitals in Southeast Sweden. Multivariable logistic regression (Crude Odds Ratios (OR) and adjusted OR (aOR) for relevant confounders) was used to analyze the association between oxytocin dose and postpartum outcomes. The exposure was the cumulative oxytocin dose during labour, classified in percentiles (<25th, 25-75th, >75th). The outcomes were occurrence of obstetric anal sphincter injury, postpartum haemorrhage (blood loss > 1000 ml), Apgar score < 7 at five minutes, umbilical cord arterial pH, postpartum bladder overdistension, exclusive breastfeeding at one week and three months, and the woman's perceived birth experience. RESULTS: Women receiving high amounts (>75th percentile, >4370 mU) of oxytocin infusion during labour had an increased risk of postpartum haemorrhage (OR 2.73 (1.78-4.19)), an overdistended bladder (OR 2.19 (1.11-4.31)), an infant with an Apgar score < 7 at five minutes (OR 2.89 (1.27-6.57)), a negative birth experience (OR 1.83 (1.25-2.69)), and a decreased chance of exclusive breastfeeding at one week (OR 0.63 (0.41-0.96)). After adjusting for confounders, all outcomes remained statistically significant except risk of low Apgar score and chance of exclusive breastfeeding. CONCLUSION: In women with high cumulative oxytocin dose during labour prompt, and prophylactic administration of uterotonics after delivery of the placenta should be considered to reduce the risk of postpartum haemorrhage. The risk for bladder overdistension can be reduced by implementing routines for observation for signs of bladder filling in the early postpartum period, as well as routine use of bladder scans post micturition to assess for successful bladder emptying. As women's birth experience have a major impact on their future mental health, should be routinely assessed postpartum, and support should be offered to women with negative experiences.

A Comparison of the Efficacy and Safety of Mifepristone and Misoprostol Versus Misoprostol alone for Induction of Labour in Nigerian Women with Intrauterine Fetal Death: A Triple Blind Randomized Controlled Trial.

BACKGROUND: Intrauterine foetal death (IUFD) is an unpleasant pregnancy outcome and prompt delivery of the dead foetus is usually desired by mothers. Unfortunately, spontaneous labour and delivery may not occur early and prolonged retention of the dead foetus in utero is life-threatening. Many of the agents currently used for the induction of labour may result in a prolonged delivery process. OBJECTIVES: To compare the efficacy and safety of mifepristone and misoprostol versus misoprostol alone for induction of labour in women with intrauterine foetal death. MATERIALS AND METHODS: This was a triple-blind randomized controlled trial. Eighty women were randomized into two groups. The intervention group received a single oral dose of 200 mg mifepristone, followed by 6-hourly 50 µg misoprostol vaginal insertion, after 24-hour intervals. The control group received a placebo, followed by 6-hourly 50 µg misoprostol vaginal insertion, after 24-hour intervals. The primary outcome measure was the induction to delivery interval. RESULTS: Maternal age, gestational age, parity and pre-induction bishop's score were comparable between the two groups. The mean induction to the delivery interval in the intervention group was significantly less in the intervention group than the control group (18.78 ± 6.51 hours versus 37.10 ± 10.10; P < 0.001). The total dose of misoprostol required for induction of labour; the need for oxytocin augmentation of labour; and the observed side effects of misoprostol were all significantly less in intervention group than control group (P < 0.001; P < 0.01; and P = 0.03, respectively). CONCLUSION: The combination of mifepristone and misoprostol has greater efficacy and better safety profile than the use of misoprostol alone for induction of labour. This combination should be considered when induction of labour is indicated for IUFD.

Timing of cesarean delivery for fetal heart rate abnormalities in hypertensive pregnancies induced with oral misoprostol or Foley catheter: Secondary analysis of a randomized clinical trial.

OBJECTIVE: The study aims to assess how oral misoprostol for cervical ripening affects the time of cesarean delivery (CD) for fetal heart rate (FHR) abnormalities in pre-eclampsia patients. Secondary goals include determining the role of uterine hyperstimulation, comparing misoprostol with Foley catheter, and identifying risk factors for FHR abnormalities associated with CD. METHODS: A previously published randomized clinical trial was subjected to a secondary analysis (NCT01801410). We conducted a time-dependent analysis, stratifying the population based on the final mode of induction used (low-dose oral misoprostol vs Foley catheter). RESULTS: There was no CD for FHR abnormalities within 2 h of starting misoprostol. At 5 h, the cumulative incidence of CD for FHR abnormalities in the misoprostol group was 2.10%, while it was 1.00% in the Foley group (P = 0.565). After 25 h, the CD risk for FHR abnormalities remained constant in both groups at 21.00% (95% confidence interval [CI] 15.00%-28.00%). Within 5 h of misoprostol induction, the risk of uterine hyperstimulation was similar in both groups (0.33% in misoprostol vs 0.34% in Foley group, P = 0.161). The risk of CD for FHR abnormalities was unaffected by newborn weight centiles. CONCLUSION: There was no significant difference in CD risk for FHR abnormalities between misoprostol and Foley catheter induction. Nonetheless, the cumulative incidence of CD for FHR abnormalities increased faster in the misoprostol group, indicating that FHR monitoring timing should be tailored to the induction method.

Induction of labor and risk of postpartum hemorrhage in women with vaginal delivery: A propensity score analysis.

OBJECTIVE: To explore the association between induction of labor (IOL) and postpartum hemorrhage (PPH) after vaginal delivery. METHODS: We included women from the merged database of three randomized prospective trials (TRACOR, CYTOCINON, and TRAAP) that measured postpartum blood loss precisely, with standardized methods. IOL was considered overall and according to its method. The association between IOL and PPH was tested by multivariate logistic regression modeling, adjusted for confounders, and by propensity score matching. The role of potential intermediate factors, i.e. estimated quantity of oxytocin administered during labor and operative vaginal delivery, was assessed with structural equation modeling. RESULTS: Labor was induced for 1809 of the 9209 (19.6%) women. IOL was associated with a significantly higher risk of PPH of 500 mL or more (adjusted odds ratio 1.56, 95% confidence interval 1.42-1.70) and PPH of 1000 mL or more (adjusted odds ratio 1.51, 95% confidence interval 1.16-1.96). The risk of PPH increased similarly regardless of the method of induction. The results were similar after propensity score matching (odds ratio for PPH ≥500 mL 1.57, 95% confidence interval 1.33-1.87, odds ratio for PPH ≥1000 mL 1.57, 95% confidence interval 1.06-2.07). Structural equation modeling showed that 34% of this association was mediated by the quantity of oxytocin administered during labor and 1.3% by women who underwent operative vaginal delivery. CONCLUSION: Among women with vaginal delivery, the risk of PPH is higher in those with IOL, regardless of its method, and after accounting for indication bias. The quantity of oxytocin administered during labor may explain one third of this association.

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

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

The efficacy and safety of 25 µg or 50 µg oral misoprostol versus 25 µg vaginal misoprostol given at 4- or 6-hourly intervals for induction of labour in women at or beyond term with live singleton pregnancies: A systematic review and meta-analysis.

BACKGROUND: Misoprostol is widely used for cervical ripening and labour induction as it is heat-stable and inexpensive. Oral misoprostol 25 µg given 2-hourly is recommended over vaginal misoprostol 25 µg given 6-hourly, but the need for 2-hourly fetal monitoring makes oral misoprostol impractical for routine use in high-volume obstetric units in resource-constrained settings. OBJECTIVES: To compare the efficacy and safety of oral misoprostol initiated at 25 or 50 µg versus 25 µg vaginal misoprostol given at 4- to 6-hourly intervals for labor induction in women at or beyond term (≥ 37 weeks) with a single viable fetus and an unscarred uterus. SEARCH STRATEGY: We identified eligible randomized, parallel-group, labor-induction trials from recent systematic reviews. We additionally searched PubMed, Cochrane CENTRAL, Epistemonikos, and clinical trials registries from February 1, 2020 to December 31, 2022 without language restrictions. Database-specific keywords for cervical priming, labor induction, and misoprostol were used. SELECTION CRITERIA: We excluded labor-induction trials exclusively in women with ruptured membranes, in the third trimester, and those that initiated misoprostol at doses not specified in the review's objectives. The primary outcomes were vaginal birth within 24 h, cesarean section, perinatal mortality, neonatal morbidity, and maternal morbidity. The secondary outcomes were uterine hyperstimulation with fetal heart rate changes, and oxytocin augmentation. DATA COLLECTION AND ANALYSIS: Two or more authors selected studies independently, assessed risk of bias, and extracted data. We derived pooled weighted risk ratios with 95% confidence intervals (CIs) for each outcome, subgrouping trials by the dose and frequency of misoprostol regimens. We used the I2 statistic to quantify heterogeneity and the random-effects model for meta-analysis when appropriate. We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach to assess certainty (confidence) in the effect estimates. MAIN RESULTS: Thirteen trials, from Canada, India, Iran, and the US, randomizing 2941 women at ≥37 weeks of gestation with an unfavorable cervix (Bishop score <6), met the eligibility criteria. Five misoprostol regimens were compared: 25 µg oral versus 25 µg vaginal, 4-hourly (three trials); 50 µg oral versus 25 µg vaginal, 4-hourly (five trials); 50 µg followed by 100 µg oral versus 25 µg vaginal, 4-hourly (two trials); 50 µg oral, 4-hourly versus 25 µg vaginal, 6-hourly (one trial); and 50 µg oral versus 25 µg vaginal, 6-hourly (two trials). The overall certainty in the evidence ranged from moderate to very low, due to high risk of bias in 11/13 trials (affecting all outcomes), unexplained heterogeneity (1/7 outcomes), indirectness (1/7 outcomes), and imprecision (4/7 outcomes). Vaginal misoprostol probably increased vaginal deliveries within 24 h compared with oral misoprostol (risk ratio [RR] 0.82, 95% CI 0.70-0.96; 11 trials, 2721 mothers; moderate-certainty evidence); this was more likely with 4-hourly than with 6-hourly vaginal regimens. The risk of cesarean sections did not appreciably differ (RR 1.00, 95% CI 0.80-1.26; 13 trials, 2941 mothers; very low-certainty evidence), although oral misoprostol 25 µg 4-hourly probably increased this risk compared with 25 µg vaginal misoprostol 4-hourly (RR 1.69, 95% CI 1.21-2.36; three trials, 515 mothers). The risk of perinatal mortality (RR 0.67, 95% CI 0.11-3.90; one trial, 196 participants; very low-certainty evidence), neonatal morbidity (RR 0.84, 95% CI 0.67-1.06; 13 trials, 2941 mothers; low-certainty evidence), and maternal morbidity (RR 0.83, 95% CI 0.48-1.44; 6 trials; 1945 mothers; moderate-certainty evidence) did not differ appreciably. The risk of uterine hyperstimulation with fetal heart rate changes may be lower with oral misoprostol (RR 0.70, 95% CI 0.52-0.95; 10 trials, 2565 mothers; low-certainty evidence). Oxytocin augmentation was probably more frequent with oral compared with vaginal misoprostol (RR 1.29, 95% CI 1.10-1.51; 13 trials, 2941 mothers; moderate-certainty evidence). CONCLUSIONS: Low-dose, 4- to 6-hourly vaginal misoprostol regimens probably result in more vaginal births within 24 h and less frequent oxytocin use compared with low-dose, 4- to 6-hourly, oral misoprostol regimens. Vaginal misoprostol may increase the risk of uterine hyperstimulation with fetal heart changes compared with oral misoprostol, without increasing the risk of perinatal mortality, neonatal morbidity, or maternal morbidity. Indirect evidence indicates that 25 µg vaginal misoprostol 4-hourly may be more effective and as safe as the recommended 6-hourly vaginal regimen. This evidence could inform clinical decisions in high-volume obstetric units in resource-constrained settings.

Efficacy and safety of double balloon catheter and dinoprostone for labor induction in multipara at term.

PURPOSE: The aim of this study was to comparatively assess the efficacy and safety of double balloon catheter (DBC) and dinoprostone as labor-inducing agents just for multipara at term. METHODS: A retrospective cohort study was conducted among multipara at term with a Bishop score < 6 who needed planned labor induction from January 1, 2020, to December 30, 2020 in Maternal and Child Health Hospital of Hubei province, Tongji Medical College, Huazhong University of Science and Technology. They were divided into DBC group and dinoprostone group, respectively. Baseline maternal data, maternal and neonatal outcomes were recorded for statistical analysis. Total vaginal delivery rate, rate of vaginal delivery within 24 h, rate of uterine hyperstimulation combined with abnormal fetal heart rate(FHR) were regarded as the primary outcome variables. The difference between groups was considered statistically significant when p value < 0.05. RESULTS: A total of 202 multiparas was included for analysis (95 women in DBC group vs 107 women in dinoprostone group). There were no significant differences in total vaginal delivery rate and rate of vaginal delivery within 24 h between groups. Uterine hyperstimulation combined with abnormal FHR occurred exclusively in dinoprostone group. CONCLUSION: DBC and dinoprostone seem to be equally effective, while, DBC seems to be safer than dinoprostone.

Weight-based versus fixed dose oxytocin infusion for preventing uterine atony during cesarean section in laboring patients: A randomized trial.

OBJECTIVE: We compared efficacy of weight-based (0.4 IU/kg/h) versus fixed-dose (34 IU/h) oxytocin infusion during cesarean section. METHODS: The oxytocin infusion in either group (n = 32 each) was initiated upon cord clamping. Primary outcome measure was adequacy of uterine tone at 4 min after initiating oxytocin infusion. Oxytocin associated side effects were also observed. RESULTS: Significantly less oxytocin was used with the weight-based versus fixed-dose regimen (16.3 [11.2-22.4] IU vs 20.4 [15.8-26.9] IU; P = 0.036). Incidence of adequate uterine tone was clinically greater but not significantly different with the weight-based versus fixed-dose regimen (81.3% vs 71.9%; P = 0.376). The weight-based regimen was associated with clinically lesser, although not statistically significant need for rescue oxytocin (25% vs 46.9%; P = 0.068) and additional uterotonic (9.4% vs 15.6%; P = 0.708); as well as oxytocin associated side effects (hypotension [34.4% vs 46.9%; P = 0.309], nausea/vomiting [18.8% vs 40.6%; P = 0.055], and ST-T changes [0% vs 3.1%; P = 1.000]). CONCLUSION: Weight-based oxytocin was not significantly different from the fixed-dose regimen in terms of uterotonic efficacy or associated side-effects, despite significantly lower doses being used. Use of weight-based oxytocin infusion (0.4 IU/kg/h) can be considered in clinical practice. TRIAL REGISTRATION: Clinical Trial Registry of India (ctri.nic.in, number. CTRI/2021/01/030642).