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Background: Oxytocin is a key hormone in childbirth, and synthetic oxytocin is widely administered to induce or speed labour. Due to lack of synthetized knowledge, we conducted a systematic review of maternal plasma levels of oxytocin during physiological childbirth, and in response to infusions of synthetic oxytocin, if reported in the included studies., Methods: An a priori protocol was designed and a systematic search was conducted in PubMed, CINAHL, and PsycINFO in October 2015. Search hits were screened on title and abstract after duplicates were removed (n = 4039), 69 articles were examined in full-text and 20 papers met inclusion criteria. As the articles differed in design and methodology used for analysis of oxytocin levels, a narrative synthesis was created and the material was categorised according to effects., Results: Basal levels of oxytocin increased 3-4-fold during pregnancy. Pulses of oxytocin occurred with increasing frequency, duration, and amplitude, from late pregnancy through labour, reaching a maximum of 3 pulses/10 min towards the end of labour. There was a maximal 3- to 4-fold rise in oxytocin at birth. Oxytocin pulses also occurred in the third stage of labour associated with placental expulsion. Oxytocin peaks during labour did not correlate in time with individual uterine contractions, suggesting additional mechanisms in the control of contractions. Oxytocin levels were also raised in the cerebrospinal fluid during labour, indicating that oxytocin is released into the brain, as well as into the circulation. Oxytocin released into the brain induces beneficial adaptive effects during birth and postpartum. Oxytocin levels following infusion of synthetic oxytocin up to 10 mU/min were similar to oxytocin levels in physiological labour. Oxytocin levels doubled in response to doubling of the rate of infusion of synthetic oxytocin., Conclusions: Plasma oxytocin levels increase gradually during pregnancy, and during the first and second stages of labour, with increasing size and frequency of pulses of oxytocin. A large pulse of oxytocin occurs with birth. Oxytocin in the circulation stimulates uterine contractions and oxytocin released within the brain influences maternal physiology and behaviour during birth. Oxytocin given as an infusion does not cross into the mother's brain because of the blood brain barrier and does not influence brain function in the same way as oxytocin during normal labour does.

Many black South African women use traditional herbal remedies as antenatal medications or to induce or augment labour. Very little is known about the pharmacology and potential toxicity of the plants used in these herbal remedies. The ethnic background and traditional usage of these remedies was researched and a literature survey revealed that 57 different plants were used in herbal remedies during pregnancy and childbirth. Several of these plants are poisonous and details of their toxicity are given.

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

Oxytocin (OXT) plays a significant role during pregnancy, especially toward the end of pregnancy. Some studies have reported that OXT is involved in the stimulation of steroidogenesis in several organs. However, the effects of OXT on placental steroidogenesis have not yet been established. In this study, we investigated the regulation of steroid hormones and steroidogenic enzymes by OXT-associated signaling in vitro and in vivo. OXT increased the gene expression of steroidogenic enzymes, which convert pregnenolone to progesterone and dehydroepiandrosterone (DHEA) in vitro. In OXT-administered pregnant rats, pregnenolone and DHEA levels were significantly enhanced in the plasma and the expression of the enzymes synthesizing DHEA, testosterone, and estradiol (E2) was increased in placental tissues. Furthermore, OXT was found to affect placental cell differentiation, which is closely related to steroid hormone synthesis. After treatment of the pregnant rats with atosiban, an antagonist of the OXT receptor, the concentration of E2 in the plasma and the expression of E2-synthesizing enzyme were reduced. This regulation may be due to OXT-mediated differentiation, because OXT increases the expression of corticotropin-releasing hormone, which is a biomarker of placental cell differentiation. Our findings suggest that OXT contributes to maintaining pregnancy by regulating the differentiation of placental cells and steroidogenesis during pregnancy. [ABSTRACT FROM AUTHOR]

Oxytocin is used in approximately half of all births in the United States during labor induction and/or augmentation. However, the effects of maternal oxytocin administration on offspring development have not been fully characterized. Here, we used the socially monogamous prairie vole to examine the hypothesis that oxytocin exposure at birth can have long-term developmental consequences. Maternally administered oxytocin increased methylation of the oxytocin receptor (Oxtr) in the fetal brain. As adults, oxytocin-exposed voles were more gregarious, with increased alloparental caregiving toward pups and increased close social contact with other adults. Cross-fostering indicated that these effects were the result of direct action on the offspring, rather than indirect effects via postnatal changes in maternal behavior. Male oxytocin-exposed offspring had increased oxytocin receptor density and expression in the brain as adults. These results show that long-term effects of perinatal oxytocin may be mediated by an epigenetic mechanism.

BACKGROUND: Mozambique has a high maternal mortality ratio, and postpartum hemorrhage (PPH) is a leading cause of maternal deaths. In 2015, the Mozambican Ministry of Health (MOH) commenced a program to distribute misoprostol at the community level in selected districts as a strategy to reduce PPH. This case study uses the ExpandNet/World Health Organization (WHO) scale-up framework to examine the planning, management, and outcomes of the early expansion phase of the scale-up of misoprostol for the prevention of PPH in 2 provinces in Mozambique. METHODS: Qualitative semistructured interviews were conducted between February and October 2017 in 5 participating districts in 2 provinces. Participants included program stakeholders, health staff, community health workers (CHWs), and traditional birth attendants (TBAs). Interviews were analyzed using the ExpandNet/WHO framework alongside national policy and planning documents and notes from a 2017 national Ministry of Health maternal, newborn, and child health workshop. Outcomes were estimated using misoprostol coverage and access in 2017 for both provinces. RESULTS: The study revealed a number of barriers and facilitators to scale-up. Facilitators included a supportive political and legal environment; a clear, credible, and relevant innovation; early expansion into some Ministry of Health systems and a strong network of CHWs and TBAs. Barriers included a reduction in reach due to a shift from universal distribution to application of eligibility criteria; fear of misdirecting misoprostol for abortion or labor induction; limited communication and understanding of the national PPH prevention strategy; inadequate monitoring and evaluation; challenges with logistics systems; and the inability to engage remote TBAs. Lower coverage was found in Inhambane province than Nampula province, possibly due to NGO support and political champions. CONCLUSION: This study identified the need for a formal review of the misoprostol program to identify adaptations and to develop a systematic scale-up strategy to guide national scale-up.

Background: Secondary postpartum haemorrhage (PPH) complicates ~1% of pregnancies and can cause serious maternal morbidity. However, evidence guiding optimal management is scarce and often based on case series and expert opinion. Aims: To measure the success of primary medical therapy in managing secondary PPH and to identify factors associated with need for surgical management. Materials and methods: Postpartum patients presenting to a tertiary women's hospital emergency department between July 2020 and October 2021 with secondary PPH were recruited. Data from the acute presentation were prospectively collected. Antenatal and intrapartum data were collected from medical record review. The primary outcome was the success of medical management for secondary PPH, defined by the implementation of medical or expectant measures without subsequent need for surgical intervention. Results: One‐hundred and twenty patients underwent primary medical management for secondary PPH. Ninety‐eight (82%) were managed successfully with medical management and 22 (18%) required surgery. Medical management involved misoprostol (n = 33; 27.5%), antibiotics (n = 108; 90%), and less commonly other uterotonics (n = 6; 5%). Factors associated with lower rates of successful medical management included: antecedent manual removal of placenta (MROP) (odds ratio (OR) 0.2, P = 0.047), primary PPH ≥500 mL (OR 0.39, P = 0.048) or ≥1 L (OR 0.24, P = 0.009), >200 mL blood loss at presentation (OR 0.17, P = 0.015), increasing time post‐delivery (OR 0.84, P = 0.044), retained products of conception (RPOC) on ultrasound (OR 0.024, P = 0.001) and vaginal birth (OR 0.27, P = 0.027). Conclusion: Medical management was highly successful. Vaginal birth, MROP, primary PPH, RPOC on ultrasound and increasing time post‐delivery were associated with increased need for surgical management. [ABSTRACT FROM AUTHOR]

Purpose: Vitamin D deficiency is common during pregnancy and may cause complications such as preterm labor (PTL). This study was aimed to investigate the effect of the vitamin D-binding protein (VDBP) rs7041 genotype, which has a significant effect on vitamin D metabolism and PTL. Methods: This cross-sectional study was conducted with 32 pregnant women who had spontaneous PTL and 54 pregnant women who had no specific findings as a control group. Serum total vitamin D 25-hydroxy vitamin D (25(OH)D) levels were measured using the Elecsys Vitamin D Total Kit. VDBP was measured using a VDBP Quantikine ELISA Kit. The levels of bioavailable 25(OH)D were calculated based on the total 25(OH)D and VDBP concentrations. DNA was extracted using the DNeasy Blood and Tissue Kit. Single nucleotide polymorphisms (rs7041) in GC were analyzed using a TaqMan SNP Genotyping Assay Kit. The unpaired t-test, Chi-squared, and ANCOVA tests were performed. Firth’s penalized logistic regression was applied. The area under the curve (AUC) was calculated and the cutoff value was determined. All statistical analyses were performed using R version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria). Results: Total 25(OH)D levels were not significantly different between the two groups. Bioavailable 25(OH)D was significantly decreased in PTL women (p= .011), and VDBP was significantly increased in PTL women (p= .004) compared to the controls. Bioavailable 25(OH)D was lower in women with GT/TG and TT rs7041 genotypes than in those with GG, with statistical significance in women with the TT allele (p= .048). VDBP was higher in women with GT/TG and TT than those with GG, but there was no statistical significance. In PTL prevalence, bioavailable 25(OH)D and VDBP, the odds ratio increased by 1.463 times in GT/TG (p= .728) and increased by 1.675 times in TT compared to the GG allele (p= .640). In receiver operating characteristic (ROC) analysis for bioavailable 25(OH)D and VDBP, the AUC was 0.665 and 0685, respectively. The optimum cutoff of bioavailable 25(OH)D and VDBP levels for the diagnosis of PTL was calculated as 0.6 ng/mL and 523 µg/mL, respectively. Conclusions: Pregnant women with the VDBP rs7041(c.1296 T > G) T allele genotype had reduced serum levels of bioavailable 25(OH)D and were more likely to develop PTL. Therefore, if the T allele is found in the VDBP rs7041 SNP genotyping test before or during pregnancy, more careful prenatal care may be required because of the increased risk of PTL. [ABSTRACT FROM AUTHOR]

Preterm prelabor rupture of membranes (pPROM) accounts for nearly half of premature births. Although several risk factors have been identified, no markers allowing for effective prevention have been discovered. In this study, we investigated how the maternal serum levels of galectin-1 and galectin-9 change in patients with pPROM in comparison to uncomplicated pregnancies. A total of 75 patients were enrolled to both study and control group (37 vs. 38, respectively). The serum concentration of galectin-1 and galectin-9 were assayed in duplicate using an enzyme-linked immunoassay. All analyses were performed using PQ Stat v. 1.8.4 software. Galectin-1 levels were significantly higher in the controls (13.32 vs. 14.71 ng/mL, p = 0.02). Galectin-9 levels were similar in both groups (13.31 vs. 14.76 ng/mL, p = 0.30). Lower galectin levels were detected for early pPROM (before 32nd GW) in comparison to late pPROM and the controls (8.85 vs. 14.45 vs. 14.71 ng/mL, p = 0.0004). Similar trend was observed in galectin-9 levels, although no statistical significance was found (11.57 vs. 14.25 vs. 14.76 ng/mL, p = 0.26). Low galectin-1 maternal serum level is associated with the incidence of preterm prelabor rupture of membranes. Galectin-9 maternal serum levels were not significantly correlated with pPROM. However, in order to investigate gal-1 and gal-9 levels as potential, promising markers of pPROM, further clinical studies on larger groups are required. [ABSTRACT FROM AUTHOR]

Objective: To conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that evaluated the efficacy and safety of isosorbide mononitrate (IMN) in promoting cervical ripening during labour induction.Methods: Six major databases were searched from inception until 22 April 2021. The risk of bias of included studies was assessed. Various endpoints (n = 21) were meta-analysed, and the endpoints were pooled as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI).Results: In total, 23 RCTs were included in this review, comprising 26 intervention arms and a total of 4305 patients (2210 and 2095 patients were allocated to the IMN and control groups, respectively). Pertaining to obstetric-related maternal outcomes, the pooled analysis showed that admission to delivery time and rate of caesarean delivery were significantly reduced in the IMN group. Moreover, the mean Bishop score and the mean change in Bishop score were significantly increased in the IMN group. Pertaining to drug-related maternal side effect outcomes, the pooled analysis showed that the rates of headache, palpitations, nausea and flushing were significantly lower in the IMN group. Pertaining to neonatal outcomes, the pooled analysis showed no significant difference between the two groups in terms of the rates of neonatal intensive care unit admission, neonatal death, fetal distress, meconium-stained water, Apgar score < 7 at 1 and 5 min, and mean Apgar score at 1 and 5 min.Conclusion: IMN correlated with several obstetric-related maternal outcomes. IMN was not associated with adverse neonatal outcomes, but was associated with substantial drug-related maternal side effects. [ABSTRACT FROM AUTHOR]

ObjectiveTo assess adverse event (AE) resolution, delivery mode and neonatal outcomes after misoprostol or dinoprostone vaginal insert (MVI or DVI) retrieval due to AE during induction of labour (IOL).DesignRandomised, double-blind trial, EXPEDITE.SettingThirty five obstetric departments, USA.PopulationConsisted of 1358 pregnant women with modified Bishop score ≤4 eligible for pharmacological IOL.MethodsPost hoc analysis.Main outcome measuresAEs prompting insert retrieval, times to AE resolution, delivery, delivery mode and neonatal intensive care unit (NICU) admissions.Results77/678 (11.4%) and 27/680 (4.0%) women had MVI and DVI retrieved due to AE, respectively (P

Oxytocin is secreted into the periphery by magnocellular neurons of the hypothalamic supraoptic and paraventricular nuclei (SON and PVN) to trigger uterine contraction during birth and milk ejection during suckling. Peripheral oxytocin secretion is triggered by action potential firing, which is regulated by afferent input activity and by feedback from oxytocin secreted into the extracellular space from magnocellular neuron somata and dendrites. A prominent input to oxytocin neurons arises from proopiomelanocortin neurons of the hypothalamic arcuate nucleus that secrete an alpha‐melanocyte‐stimulating hormone (α‐MSH), which inhibits oxytocin neuron firing in non‐pregnant rats by increasing somato‐dendritic oxytocin secretion. However, α‐MSH inhibition of oxytocin neuron firing is attenuated in mid‐pregnancy and somato‐dendritic oxytocin becomes auto‐excitatory in late‐pregnancy and lactation. Therefore, we hypothesized that attenuated α‐MSH inhibition of oxytocin neuron firing marks the beginning of a transition from inhibition to excitation to facilitate peripheral oxytocin secretion for parturition and lactation. Intra‐SON microdialysis administration of α‐MSH inhibited oxytocin neuron firing rate by 33 ± 9% in non‐pregnant rats but increased oxytocin neuron firing rate by 37 ± 12% in late‐pregnant rats and by 28 ± 10% in lactating rats. α‐MSH‐induced somato‐dendritic oxytocin secretion measured ex vivo with oxytocin receptor‐expressing "sniffer" cells, was of similar amplitude in PVN slices from non‐pregnant and lactating rats but longer‐lasting in slices from lactating rats. Hence, α‐MSH inhibition of oxytocin neuron activity switches to excitation over pregnancy while somato‐dendritic oxytocin secretion is maintained, which might enhance oxytocin neuron excitability to facilitate the increased peripheral secretion that is required for normal parturition and milk ejection. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare intracervical (IC) and intravaginal (IV) application of prostaglandin E2 (PGE2) for labor induction in term pregnancies with unfavorable cervix.Study Design: This prospective randomized trial included 212 pregnant women with term pregnancy and unfavorable cervix randomly assigned for labor induction with either IC (0.5 mg) or IV (2 mg) PGE2 formulation. Main outcome measured was time interval from labor induction to delivery. Difference in mode of delivery and adverse perinatal outcomes between two studied groups was also investigated. Significance was set at p < 0.05.Results: Studied groups did not significantly differ regarding main characteristics such as age, parity, body mass index or Bishop score. Women in IV group compared to those in IC group had shorter induction to delivery time interval (p < 0.001) and induction to active phase time interval (p = 0.001), higher prevalence of vaginal delivery within 24 h of labor induction (63,3% vs 40,6%, p = 0.002) and higher prevalence of successful induction of labor (95,9% vs. 86,5%, p = 0.020). The analysis did not reveal significant difference in mode of delivery between groups (p = 0.453) or other adverse perinatal outcomes.Conclusion: IV application of PGE2 compared to IC application is more efficacious and comparably safe for labor induction in term pregnancies with unfavorable cervix and should be the method of choice for labor induction. [ABSTRACT FROM AUTHOR]

While Yoda1 treatment alone reduced the contractions of the myometrium to 17% of interested control, competitive inhibition by Dooku1 rescued oxytocin-induced contractions to 90%, indicating a direct effect of PIEZO1 activation in relaxation of human myometrium. Keywords: cardiovascular; PIEZO1; preterm birth; preterm labour EN cardiovascular PIEZO1 preterm birth preterm labour 719 721 3 02/17/23 20230215 NES 230215 During pregnancy, the uterus undergoes significant distention to accommodate the growing fetus. [Extracted from the article]

ObjectiveTo determine induction start time(s) that would maximise daytime deliveries when using prostaglandin vaginal inserts.MethodsWomen enrolled into the Phase III trial, EXPEDITE (clinical trial registration: NCT01127581), had labour induced with either a misoprostol or dinoprostone vaginal insert (MVI or DVI). A secondary analysis was conducted to determine the optimal start times for induction by identifying the 12-h period with the highest proportion of deliveries by parity and treatment.ResultsOptimal start times for achieving daytime deliveries when using MVI appear to be 19:00 in nulliparae and 23:00 in multiparae. Applying these start times, the median time of onset of active labour would be approximately 08:30 for both parities and the median time of delivery would be the following day at approximately 16:30 for nulliparae and 12:00 (midday) for multiparae. Optimal start times when using DVI appear to be 07:00 for nulliparae and 23:00 for multiparae. Using these start times, the median time of onset of active labour would be the following day at approximately 04:00 and 11:50, and the median time of delivery would be approximately 13:40 and 16:10, respectively.ConclusionsWhen optimising daytime deliveries, different times to initiate induction of labour may be appropriate depending on parity and the type of retrievable prostaglandin vaginal insert used.

Postpartum hemorrhage is a leading cause of maternal death worldwide. Rapid provision of uterotonics after childbirth is recommended to reduce the incidence and severity of postpartum hemorrhage. Data obtained through direct observation of childbirth practices, collected in a study of the World Health Organization's Safe Childbirth Checklist in Karnataka, India, were used to measure if oxytocin prepared for administration and available at the bedside before birth was associated with decreased time to administration after birth. This was an observational study of provider behavior: data were obtained during a baseline assessment of health worker practices prior to introduction of the Safe Childbirth Checklist, representing behavior in the absence of any intervention. Analysis was based on 330 vaginal deliveries receiving oxytocin at any point postpartum. Oxytocin was prepared and available at bedside for approximately 39% of deliveries. We found that advance preparation and bedside availability of oxytocin was associated with increased likelihood of oxytocin administration within 1 minute after delivery (adjusted risk ratio = 4.89, 95% CI = 2.61, 9.16), as well as with decreased overall time to oxytocin administration after delivery (2.9 minutes sooner in adjusted models, 95% CI = -5.0, -0.9). Efforts to reduce postpartum hemorrhage should include recommendations and interventions to ensure advance preparation and bedside availability of oxytocin to facilitate prompt administration of the medicine after birth.

Induction of labor is one of the most commonly performed obstetric procedures and will likely become more common as the reproductive population in developed nations changes. As the proportion of women undergoing induction grows, there is a constant search for more efficacious ways to induce labor while maintaining fetal and maternal safety as well as patient satisfaction. With almost half of induced labors requiring cervical ripening, methods for achieving active labor and vaginal delivery are constantly being investigated. Prostaglandins have been shown to be effective induction agents, and specifically vaginal misoprostol, used off-label, have been widely utilized to initiate cervical ripening and active labor. The challenge is to administer this medication accurately while maintaining the ability to discontinue the medication when needed. The misoprostol vaginal insert initiates cervical ripening utilizing a delivery system that controls medication release and can be rapidly removed. This paper reviews the design, development, and clinical utility of the misoprostol vaginal insert for induction of labor as well as patient considerations related to the delivery system.

BackgroundBangladesh is one of the few countries that may actually achieve the fifth Millennium Development Goal (MDG) in time, despite skilled birth attendance remaining low. The purpose of this paper is to examine the potential role misoprostol can play in the decline of maternal deaths attributed to postpartum hemorrhage (PPH) in Bangladesh.MethodsUsing data from a misoprostol and blood loss measurement tool feasibility study in Bangladesh, observed cause specific maternal mortality ratios (MMRs) were estimated and contrasted with expected ratios using estimates from the Bangladesh Maternal Mortality Survey (BMMS) data. Using Crystal Ball 7 we employ Monte Carlo simulation techniques to estimate maternal deaths in four scenarios, each with different levels of misoprostol coverage. These scenarios include project level misoprostol coverage (69%), no (0%), low (40%), and high (80%) misoprostol coverage. Data on receipt of clean delivery kit, use of misoprostol, experience of PPH, and cause of death were used in model assumptions.ResultsUsing project level misoprostol coverage (69%), the mean number of PPH deaths expected was 40 (standard deviation = 8.01) per 100,000 live births. Assuming no misoprostol coverage (0%), the mean number of PPH deaths expected was 51 (standard deviation = 9.30) per 100,000 live births. For low misoprostol coverage (40%), the mean number of PPH deaths expected was 45 (standard deviation = 8.26) per 100,000 live births, and for high misoprostol coverage (80%), the mean number of PPH deaths expected was 38 (standard deviation = 7.04) per 100,000 live births.ConclusionThis theoretical exercise hypothesizes that prophylactic use of misoprostol at home births may contribute to a reduction in the risk of death due to PPH, in addition to reducing the incidence of PPH. If findings from this modeling exercise are accurate and uterotonics can prevent maternal death, misoprostol could be the tool countries need to further reduce maternal mortality at home births.

Purpose: To evaluate the effectiveness of adding carbetocin to regular uterotonic agents for prevention of postpartum hemorrhage (PPH) after cesarean section for twin pregnancies.Methods: This is a retrospective uncontrolled before-after study done in a tertiary center in Taiwan, 2010-2017. Women with twin pregnancies that underwent cesarean section were enrolled. The control group (n = 114) received oxytocin infusion and direct uterine injection. In addition to these, the study group (n = 127) received 100ug of intravenous carbetocin. Primary endpoint was the change in hemoglobin. Secondary endpoints included risk of PPH and undiagnosed PPH (Hb dropped more than 2 g/dL), blood loss, the need for additional uterotonic maneuvers, and blood transfusion. Hemodynamic changes were also investigated.Results: After adjusting for confounding factors, the change in Hb (0.35 g/dL, 95% CI: -0.03∼0.74) and incidence of PPH (OR 0.30, 95% CI: 0.03∼3.28) were comparable in both groups. However, women with undiagnosed PPH decreased (OR 0.43, 95% CI:0.22∼0.85). Total blood loss in 24 h after delivery also decreased (-40.33 mL, 95%CI: -80.32∼ -0.34). The use of extra uterotonic medications and the need for blood transfusion did not differ. The systolic blood pressure 4 h after childbirth was higher in the carbetocin group (6.71, 95% CI: 2.27∼11.15).Conclusion: The use of carbetocin in addition to regular uterotonic agents decreased total blood loss and undiagnosed PPH. Also, systolic blood pressure 4 h after childbirth is higher in the carbetocin group. There was no significant difference in hemoglobin change and risk of PPH. [ABSTRACT FROM AUTHOR]

A consensus emerged in the late 1990s among leaders in global maternal health that traditional birth attendants (TBAs) should no longer be trained in delivery skills and should instead be trained as promoters of facility-based care. Many TBAs continue to be trained in places where home deliveries are the norm and the potential impacts of this training are important to understand. The primary objective of this study was to gain a more nuanced understanding of the full impact of training TBAs to use misoprostol and a blood measurement tool (mat) for the prevention of postpartum haemorrhage (PPH) at home deliveries through the perspective of those involved in the project. This qualitative study, conducted between July 2009 and July 2010 in Bangladesh, was nested within larger operations research, testing the feasibility and acceptability of scaling up community-based provision of misoprostol and a blood measurement tool for prevention of PPH. A total of 87 in-depth interviews (IDIs) were conducted with TBAs, community health workers (CHWs), managers, and government-employed family welfare visitors (FWVs) at three time points during the study. Computer-assisted thematic data analysis was conducted using ATLAS.ti (version 5.2). Four primary themes emerged during the data analysis, which all highlight changes that occurred following the training. The first theme describes the perceived direct changes linked to the two new interventions. The following three themes describe the indirect changes that interviewees perceived: strengthened linkages between TBAs and the formal healthcare system; strengthened linkages between TBAs and the communities they serve; and improved quality of services/service utilization. The data indicate that training TBAs and CHW supervisors resulted in perceived broader and more nuanced changes than simply improvements in TBAs' knowledge, attitudes, and practices. Acknowledgeing TBAs' important role in the community and in home deliveries and integrating them into the formal healthcare system has the potential to result in changes similar to those seen in this study.

Labor induction and cervical ripening are widely utilized and new methods are constantly being investigated. Prostaglandins have been shown to be effective labor induction agents and, in particular, were compared with other prostaglandin preparations; vaginal misoprostol used off-label was associated with reduced failure to achieve vaginal delivery. The challenge is to provide this medication with the correct dosing for this indication and with the ability to discontinue the medication if needed, all while ensuring essential maternal and neonatal safety. The misoprostol vaginal insert initiates cervical ripening using a delivery system that controls misoprostol release and can be rapidly removed. This article reviews the development, safety and efficacy of the misoprostol vaginal insert for induction of labor and cervical ripening, and will focus on vaginally administered prostaglandins.

Purpose: To identify predictors of complete miscarriage after expectant management or misoprostol treatment of non-viable early pregnancy in women with vaginal bleeding.Methods: This was a planned secondary analysis of data from a published randomized controlled trial comparing expectant management with vaginal single dose of 800 µg misoprostol treatment of women with embryonic or anembryonic miscarriage. Predefined variables-serum-progesterone, serum-β-human chorionic gonadotropin, parity, previous vaginal deliveries, gestational age, clinical symptoms (bleeding and pain), mean diameter and shape of the gestational sac, crown-rump-length, type of miscarriage, and presence of blood flow in the intervillous space-were tested as predictors of treatment success (no gestational sac in the uterine cavity and maximum anterior-posterior intracavitary diameter was ≤ 15 mm as measured with transvaginal ultrasound on a sagittal view) in univariable and multivariable logistic regression.Results: Variables from 174 women (83 expectant management versus 91 misoprostol) were analyzed for prediction of complete miscarriage at ≤ 17 days. In patients managed expectantly, the rate of complete miscarriage was 62.7% (32/51) in embryonic miscarriages versus 37.5% (12/32) in anembryonic miscarriages (P = 0.02). In multivariable logistic regression, the likelihood of success increased with increasing gestational age, increasing crown-rump-length and decreasing gestational sac diameter. Misoprostol treatment was successful in 80.0% (73/91). No variable predicted success of misoprostol treatment.Conclusions: Complete miscarriage after expectant management is significantly more likely in embryonic miscarriage than in anembryonic miscarriage. Gestational age, crown-rump-length, and gestational sac diameter are independent predictors of success of expectant management. Predictors of treatment success may help counselling women with early miscarriage. [ABSTRACT FROM AUTHOR]

Introduction: Induction of labor (IOL) is used to improve the outcome of pregnancy for mother and child. Since 2013, oral misoprostol has been used for IOL at Aarhus University Hospital, Denmark. The purpose of the present paper is to describe our experience of the use of a new, 25-µg misoprostol tablet commercially manufactured for the purpose of IOL regarding efficacy and outcome for mother and neonate in both an inpatient and an outpatient regimen.Material and Methods: We performed an audit from 1 April 2016, including data on all IOL in women with singleton pregnancies until 1000 consecutive women were registered. Data from 976 consecutive women with gestational age ≥37+0  weeks induced in accordance with the "Aarhus protocol" were included in the present analyses. All inductions were by oral misoprostol. Outpatient induction is standard procedure in low-risk pregnancies, that is, pregnancies with a healthy mother and no signs of placental insufficiency. In the outpatient IOL, the first dose of misoprostol is administered after a normal cardiotocography registration at the hospital. Subsequent doses are taken at home according to a predefined regimen. Following delivery, data on baseline variables and outcome variables for the mother and neonate were retrieved from the medical records.Results: In 71.9% of cases, the women were induced in an outpatient regimen. Delivery within 24 hours was achieved in 38.8% of women (nulliparous 32.3%, multiparous 50.9%) and within 48 hours in 70.1% (nulliparous 66.2%, multiparous 77.2%). Hyperstimulation during induction occurred in 0.6%. The mode of delivery was spontaneous vaginal in 75.5% of cases. The cesarean section rate was 14.9% (nulliparous 20.7%, multiparous 4.1%). Apgar <7 at 5 minutes and pH <7.0 in the umbilical artery was seen in 0.9% and 0.7%, respectively.Conclusions: Induction of labor by a commercially produced low-dose (25 µg) misoprostol tablet for oral induction according to the "Aarhus protocol" is feasible in an outpatient as well as an inpatient regimen. Delivery was achieved within 48 hours for 70.1% of women. Few adverse events were seen; however, the audit was underpowered for safety. [ABSTRACT FROM AUTHOR]

Purpose: To compare the effectiveness of the Cook vaginal cervical ripening balloon (CCRB) with prostaglandin E2 (PGE2) insert for induction of labor in late pregnancy in primipara.Methods: We evaluated the effectiveness and safety of induction of labor using the improved Bishop score after CCRB or PGE2 administration, total stage of labor, hours until delivery (hours from placement of CCRB or PGE2 insert to parturition and delivery), delivery rate within 24 h, spontaneous delivery rate, successful induction rate, overstimulation syndrome, urgent delivery rate, pain scores, cesarean section rate, and outcomes related to delivery and perinatal morbidity, such as puerperal infection rate, total cost, satisfaction survey, and so on.Results: The improved Bishop Score and delivery rate within 24 h in the CCRB group were significantly higher than in the PGE2 group. The total stage of labor and hours until delivery in the CCRB group were significantly shorter than that in the PGE2 group. Rate of overstimulation syndrome and pain scores in the CCRB group were significantly lower than in the PGE2 group. Compared with the PGE2 group, the mean duration of hospitalization in the CCRB group was shorter and the total cost was less. No difference in satisfaction between the PGE2 and CCRB groups was observed.Conclusions: Compared with PGE2, CCRB reduced the total stage of labor, hours until delivery, pain scores, mean length of hospitalization, and total cost. CCRB increased the rate of delivery within 24 h with similar safety and maternal satisfaction compared with PGE2. [ABSTRACT FROM AUTHOR]

Prolonged pregnancies are associated with foetal and neonatal complications. This study was performed to evaluate the efficacy of intravaginal isosorbide mononitrate (IMN) for cervical ripening in prolonged pregnancies. 122 pregnant women were recruited. Women were assigned to 25 µg sublingual misoprostol plus 40 mg isosorbide mononitrate or placebo. Statistical analysis was done using SPSS software (version 23) and T-test, Mann-Whitney and Chi-square test. p ≤ .05 was considered significant. The mean time between beginning of cervical ripening to Bishop score >6 was significantly shorter in IMN plus misoprostol group when compared to misoprostol plus placebo group (p = .02). The mean time from beginning of cervical ripening to the beginning of active phase of Labour was comparable between two groups (p = .274). The misoprostol plus IMN group had significantly shorter interval from the beginning of cervical ripening to the time of delivery. Isosorbide mononitrate in combination with misoprostol has a promising effect on cervical ripening and progress in labour.IMPACT STATEMENTWhat is already known on this subject? Prolonged pregnancy is associated with foetal, neonatal, and maternal complications. Because of these complications, many obstetricians tend toward the induction of prolonged pregnancies to reduce perinatal morbidity and mortality. Isosorbide mononitrate is a nitric oxide donor agent which is used vaginally for cervical ripening in term pregnancies resulting in various outcomes.What do the results of this study add? Isosorbide mononitrate in combination with misoprostol had a greater effect on cervical ripening and progress in labour than misoprostol alone in prolonged pregnancies.What are the implications of these findings for clinical practice and/or further research? According to results of the current study; using isosorbide mononitrate in combination with misoprostol could enhance successful vaginal delivery in prolonged pregnancy. Evaluation of maternal satisfaction by using this protocol is recommended in future studies. [ABSTRACT FROM AUTHOR]

Objective: To determine if oral methylergometrine administration during the first 10 d following spontaneous vaginal delivery has any beneficial effect on the increase of hemoglobin levels.Methods: This was a parallel group double-blind placebo-controlled clinical trial conducted at single center university hospital in Italy. Participants were puerperal women, who delivered singleton gestation with spontaneous vaginal delivery at term. Participants were randomized into a 1:1 ratio to receive either 0.125 mg methylergometrine per os twice a day or placebo for 10 d. Hemoglobin levels were recorded on the day of delivery and after 10 d. The primary outcome was the variation in hemoglobin levels between the first and the 10th day of treatment.Results: From December 2012 to October 2015, 220 agreed to take part in the study, underwent randomization, and were enrolled and followed-up. Of the randomized women, 110 (50%) were randomized to the methylergometrine group and 110 (50%) to the placebo group. No women were excluded after randomization or lost to follow-up (100%). We found no significant difference in the median variation of hemoglobin levels between the intervention and the placebo groupConclusions: The use of 10 d oral methylergometrine in puerperal women was not associated with any benefit in the variation of hemoglobin levels from delivery to 10 d after delivery.Key MessageMethylergometrine in puerperal women was not associated with any benefit. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was to evaluate the efficacy and safety of oral mifepristone use for cervical ripening and the initiation of labor in women with normal pregnancies at or beyond term.Study Design: We conducted a monocentric, prospective, comparative study on the induction of labor in women with an unfavorable cervix after 37 or more weeks of gestation in the Franck Joly Hospital, French Guiana. The immediate induction of labor by mifepristone was compared to expectant management and the induction of labor with routine cervical ripening agents during two consecutive periods. During the first period, patients received mifepristone (600 mg orally at the moment of enrollment) and were evaluated after 48 h. In the second period, patients did not receive any drugs and were evaluated after 48 h of expectant management.Primary Outcomes: Spontaneous labor or a Bishop Score ≥6 within 48 h of mifepristone administration.Secondary Outcomes: enrollment-induction to delivery interval, rate of failed induction, doses of prostaglandin used, mode of delivery, requirement of oxytocin augmentation, and neonatal outcomes.Results: This study enrolled 231 women, 108 in the first and 123 in the second period undergoing induced labor at term caused by various obstetric conditions. There were no significant differences between groups for age, body mass index, gravida, parity, the initial Bishop Score, scarred uterus, or post-term pregnancy. There were statistically significant differences between the two groups concerning spontaneous labor and/ or a Bishop Score ≥6 within 48 h (p < 10-3) and received doses of misoprostol (p = 0.01). Patients receiving mifepristone were 10 times more likely to be in labor after 48 h of inclusion (RR = 9.98, CI 95 % = [4.47-22.29]). The enrollment-induction to delivery interval was significantly shorter for the mifepristone group (p < 0.001). There were no other differences in mode of delivery, placenta abnormalities or neonatal outcomes.Conclusion: Mifepristone efficiently induced cervical ripening and labor initiation in women with normal pregnancies at or beyond term. It may offer an alternative method to the classic induction especially for patients seeking spontaneous labor. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the effect of premature rupture of membranes (PROM) in full-term pregnancies with dinoprostone-induced labour.Patients and Methods: This historical cohort study analysed 2166 full-term pregnancies with dinoprostone-induced labour between 1 August 2016 and 30 April 2018. A group that underwent induction of labour for PROM (PROM group) was compared to a group that underwent labour induction for other indications (no-PROM group). Time to delivery and perinatal outcome were compared between the two groups.Results: A total of 2166 pregnancies (662 PROM and 1504 no-PROM) were included. The two groups demonstrated no significant differences except in biparietal diameter and gestational age (P < 0.001). The caesarean section delivery rate in the PROM group was significantly lower than in the non-PROM group (26.89 vs. 33.58%, P < 0.0001). In the PROM group, the induction-to-delivery time was shorter (P < 0.0001) and the rates of vaginal birth within 24 h (P < 0.0001) and 48 h (P < 0.0001) were higher than those in the control group. The incidence rate of amniotic fluid contamination in the PROM group was significantly lower than that in the non-PROM group (19.18 vs. 25.20%, P = 0.002).Conclusion: PROM significantly affects perinatal outcome in Chinese women who undergo dinoprostone-induced labour, especially the caesarean delivery rate and the induction-to-delivery time. [ABSTRACT FROM AUTHOR]

A double-blind randomised trial was conducted on women with gestational age of 40-42 weeks of pregnancy and Bishop score of more than 5. The first group received oxytocin infusion and the second group received a titrated oral solution of misoprostol. Then, the two groups were compared by the primary outcome (the number of deliveries in the first 24 hours of intervention). The two groups did not have any significant difference in maternal and gestational age at the time of intervention, primary Bishop score, parity and neonatal weight. The number of deliveries in the first 24 hours was greater in the misoprostol group. Duration of onset of intervention to proper contractions was longer in the misoprostol group. However, the number of deliveries between 6-12 hours, 12-18 hours and 18-24 hours after induction was greater in the misoprostol group. The incidence of tachysystole and meconium was greater in the misoprostol group.Impact statementWhat is already known on this subject? Labour induction is widely used where the continuation of pregnancy might be dangerous for the mother or the baby. Of the various methods used for induction, misoprostol which is a prostaglandin E1 analogue has been reviewed more in recent years. Misoprostol has various routes of administration but in most studies only vaginal administration has been evaluated, leaving us with limited data about oral administration.What do the results of this study add? Oral misoprostol is a suitable method for labour induction and can be used as an alternative to oxytocin.What are the implications of these findings for clinical practice and/or further research? Misoprostol is not expensive, has a long shelf life, accessible in underdeveloped countries and rural areas and has several routes of administrations such as oral, sublingual and vaginal. Despite the fact that the oral route of misoprostol has a fast absorption and easier administration, there are relatively few studies assessing the the use of the oral route of misoprostol. Misoprostol is a suitable method for Labour induction and it has the potentials of being used as an alternative for oxytocin, however, the optimum dosages, the preferred route of administration, the maximum dose, the maximum time for administration, and maternal and neonatal safety should be studied more. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to compare the uterine activity response between women administered dinoprostone (prostaglandin E2) and misoprostol (prostaglandin E1) for induction of labour (IOL) by analysing not only the traditional obstetric data but also the parameters extracted from uterine electrohysterogram (EHG).Methods: Two cohorts were defined: misoprostol (25-µg vaginal tablets; 251 women) and dinoprostone cohort (10 mg vaginal inserts; 249 women). All the mothers were induced by a medical indication of a Bishop Score < = 6.Results: The misoprostol cohort was associated with a shorter time to achieve active labour (p = .017) and vaginal delivery (p = .009) and with a higher percentage of vaginal delivery in less than 24 h in mothers with a very unfavourable cervix score (risk ratio (RR): 1.41, IC95% 1.17-1.69, p = .002). Successful inductions with misoprostol showed EHG parameter values significantly higher than basal state for amplitude and pseudo Montevideo units (PMU) 60' after drug administration, while spectral parameters significantly increased after 150'. This response was not observed in failed inductions. In the successful dinoprostone group, the duration and number of contractions increased significantly after 120', PMU did so after 180', and no significant differences were found for spectral parameters, possibly due to the slower pharmacokinetics of this drug.Conclusion: Successful inductions of labour by misoprostol are associated with earlier effective contractions than in labours induced by dinoprostone. [ABSTRACT FROM AUTHOR]

Background: The optimal oxytocin infusion regimen to induce labour with the lowest caesarean section rate, instrumental delivery rate and length of active labour is unclear. We compared the effect of a low-dose to high-dose oxytocin regimen to induce labour.Materials and Methods: We conducted a retrospective study of nulliparous women induced at term in a single tertiary centre from 2009 to 2015. The oxytocin induction protocol changed from a high to low-dose regimen in November 2012, affording us the opportunity to compare outcomes 3 years prior to, and following the change in protocol. Main outcome measures were caesarean section rate, instrumental delivery rate and length of active labour.Results: Four thousand eight hundred and eighty-five participants were included, 2211 were induced via the low-dose regimen, and 2674 using the high-dose regimen. There was no difference in caesarean section rate (adjusted OR 0.99; 95% CI 0.87-1.13) or instrumental delivery rates once adjusted for regional anaesthesia (adjusted OR 1.16; 95% CI 0.99-1.36) between the different regimens. Surprisingly, the length of labour was longer in the high-dose oxytocin group (adjusted mean difference 0.60 h; 95%CI 0.81-0.12). There were significantly more postpartum haemorrhage ≥1000 ml (10.5% versus 7.8%, p < .001) and regional anaesthesia use (55.8% versus 52.1%, p = .03) in the low-dose cohort. There were no differences in neonatal outcomes.Conclusion: Outcomes between high- and low-dose oxytocin induction regimens are relatively comparable with similar caesarean section and instrumental delivery rates. Therefore, either regimen is acceptable for use for induction of labour. [ABSTRACT FROM AUTHOR]