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F1000Research 2019The rate of labor induction is steadily increasing and, in industrialized countries, approximately one out of four pregnant women has their labor induced. Induction of... (Review)
Review
The rate of labor induction is steadily increasing and, in industrialized countries, approximately one out of four pregnant women has their labor induced. Induction of labor should be considered when the benefits of prompt vaginal delivery outweigh the maternal and/or fetal risks of waiting for the spontaneous onset of labor. However, this procedure is not free of risks, which include an increase in operative vaginal or caesarean delivery and excessive uterine activity with risk of fetal heart rate abnormalities. A search for "Induction of Labor" retrieves more than 18,000 citations from 1844 to the present day. The aim of this review is to summarize the controversies concerning the indications, the methods, and the tools for evaluating the success of the procedure, with an emphasis on the scientific evidence behind each.
Topics: Cesarean Section; Female; Humans; Labor, Induced; Oxytocics; Pregnancy
PubMed: 31723412
DOI: 10.12688/f1000research.17587.1 -
Journal of Midwifery & Women's Health Jul 2021Induction of labor is increasingly a common component of the intrapartum care. Knowledge of the current evidence on methods of labor induction is an essential component... (Review)
Review
Induction of labor is increasingly a common component of the intrapartum care. Knowledge of the current evidence on methods of labor induction is an essential component of shared decision-making to determine which induction method meets an individual's health needs and personal preferences. This article provides a review of the current research evidence on labor induction methods, including cervical ripening techniques, and contraction stimulation techniques. Current evidence about expected duration of labor following induction, use of the Bishop score to guide induction, and guidance on the use of combination methods for labor induction are reviewed.
Topics: Cervical Ripening; Female; Humans; Labor, Induced; Oxytocics; Oxytocin; Pregnancy
PubMed: 33984171
DOI: 10.1111/jmwh.13238 -
The Cochrane Database of Systematic... Feb 2019Active management of the third stage of labour involves giving a prophylactic uterotonic, early cord clamping and controlled cord traction to deliver the placenta. With... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Active management of the third stage of labour involves giving a prophylactic uterotonic, early cord clamping and controlled cord traction to deliver the placenta. With expectant management, signs of placental separation are awaited and the placenta is delivered spontaneously. Active management was introduced to try to reduce haemorrhage, a major contributor to maternal mortality in low-income countries. This is an update of a review last published in 2015.
OBJECTIVES
To compare the effects of active versus expectant management of the third stage of labour on severe primary postpartum haemorrhage (PPH) and other maternal and infant outcomes.To compare the effects of variations in the packages of active and expectant management of the third stage of labour on severe primary PPH and other maternal and infant outcomes.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the World health Organization International Clinical Trials Registry Platform (ICTRP), on 22 January 2018, and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing active versus expectant management of the third stage of labour. Cluster-randomised trials were eligible for inclusion, but none were identified.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the studies for inclusion, assessed risk of bias, carried out data extraction and assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
We included eight studies, involving analysis of data from 8892 women. The studies were all undertaken in hospitals, seven in higher-income countries and one in a lower-income country. Four studies compared active versus expectant management, and four compared active versus a mixture of managements. We used a random-effects model in the analyses because of clinical heterogeneity. Of the eight studies included, we considered three studies as having low risk of bias in the main aspects of sequence generation, allocation concealment and completeness of data collection. There was an absence of high-quality evidence according to GRADE assessments for our primary outcomes, which is reflected in the cautious language below.The evidence suggested that, for women at mixed levels of risk of bleeding, it is uncertain whether active management reduces the average risk of maternal severe primary PPH (more than 1000 mL) at time of birth (average risk ratio (RR) 0.34, 95% confidence interval (CI) 0.14 to 0.87, 3 studies, 4636 women, I = 60%; GRADE: very low quality). For incidence of maternal haemoglobin (Hb) less than 9 g/dL following birth, active management of the third stage may reduce the number of women with anaemia after birth (average RR 0.50, 95% CI 0.30 to 0.83, 2 studies, 1572 women; GRADE: low quality). We also found that active management of the third stage may make little or no difference to the number of babies admitted to neonatal units (average RR 0.81, 95% CI 0.60 to 1.11, 2 studies, 3207 infants; GRADE: low quality). It is uncertain whether active management of the third stage reduces the number of babies with jaundice requiring treatment (RR 0.96, 95% CI 0.55 to 1.68, 2 studies, 3142 infants, I = 66%; GRADE: very low quality). There were no data on our other primary outcomes of very severe PPH at the time of birth (more than 2500 mL), maternal mortality, or neonatal polycythaemia needing treatment.Active management reduces mean maternal blood loss at birth and probably reduces the rate of primary blood loss greater than 500 mL, and the use of therapeutic uterotonics. Active management also probably reduces the mean birthweight of the baby, reflecting the lower blood volume from interference with placental transfusion. In addition, it may reduce the need for maternal blood transfusion. However, active management may increase maternal diastolic blood pressure, vomiting after birth, afterpains, use of analgesia from birth up to discharge from the labour ward, and more women returning to hospital with bleeding (outcome not pre-specified).In the comparison of women at low risk of excessive bleeding, there were similar findings, except it was uncertain whether there was a difference identified between groups for severe primary PPH (average RR 0.31, 95% CI 0.05 to 2.17; 2 studies, 2941 women, I = 71%), maternal Hb less than 9 g/dL at 24 to 72 hours (average RR 0.17, 95% CI 0.02 to 1.47; 1 study, 193 women) or the need for neonatal admission (average RR 1.02, 95% CI 0.55 to 1.88; 1 study, 1512 women). In this group, active management may make little difference to the rate of neonatal jaundice requiring phototherapy (average RR 1.31, 95% CI 0.78 to 2.18; 1 study, 1447 women).Hypertension and interference with placental transfusion might be avoided by using modifications to the active management package, for example, omitting ergot and deferring cord clamping, but we have no direct evidence of this here.
AUTHORS' CONCLUSIONS
Although the data appeared to show that active management reduced the risk of severe primary PPH greater than 1000 mL at the time of birth, we are uncertain of this finding because of the very low-quality evidence. Active management may reduce the incidence of maternal anaemia (Hb less than 9 g/dL) following birth, but harms such as postnatal hypertension, pain and return to hospital due to bleeding were identified.In women at low risk of excessive bleeding, it is uncertain whether there was a difference between active and expectant management for severe PPH or maternal Hb less than 9 g/dL (at 24 to 72 hours). Women could be given information on the benefits and harms of both methods to support informed choice. Given the concerns about early cord clamping and the potential adverse effects of some uterotonics, it is critical now to look at the individual components of third-stage management. Data are also required from low-income countries.It must be emphasised that this review includes only a small number of studies with relatively small numbers of participants, and the quality of evidence for primary outcomes is low or very low.
Topics: Birth Weight; Constriction; Delivery, Obstetric; Female; Humans; Infant, Newborn; Jaundice, Neonatal; Labor Stage, Third; Oxytocics; Placenta; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic; Watchful Waiting
PubMed: 30754073
DOI: 10.1002/14651858.CD007412.pub5 -
Anaesthesia Oct 2019It is routine to give a uterotonic drug following delivery of the neonate during caesarean section. However, there is much heterogeneity in the relevant research, which...
It is routine to give a uterotonic drug following delivery of the neonate during caesarean section. However, there is much heterogeneity in the relevant research, which has largely been performed in low-risk elective cases or women with uncomplicated labour. This is reflected in considerable variation in clinical practice. There are significant differences between dose requirements during elective and intrapartum caesarean section. Standard recommended doses are higher than required, with the potential for acute cardiovascular adverse effects. We recommend a small initial bolus dose of oxytocin, followed by a titrated infusion. The recommended doses of oxytocin may have to be increased in women with risk factors for uterine atony. Carbetocin at equipotent doses to oxytocin has similar actions, while avoiding the requirement for a continuous infusion after the initial dose and reducing the need for additional uterotonics. As with oxytocin, carbetocin dose requirements are higher for intrapartum caesarean sections. A second-line agent should be considered early if oxytocin/carbetocin fails to produce good uterine tone. Women with cardiac disease may be very sensitive to the adverse effects of oxytocin and other uterotonics, and their management needs to be individualised.
Topics: Adult; Cesarean Section; Consensus; Female; Guidelines as Topic; Humans; Infant, Newborn; Oxytocics; Oxytocin; Pregnancy
PubMed: 31347151
DOI: 10.1111/anae.14757 -
Lancet (London, England) Sep 2020The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone.
METHODS
MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/mvs ≥35 kg/m), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024.
FINDINGS
Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups.
INTERPRETATION
Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery.
FUNDING
UK National Institute for Health Research Health Technology Assessment Programme.
Topics: Abortion, Missed; Adult; Double-Blind Method; Drug Therapy, Combination; Humans; Mifepristone; Misoprostol; Oxytocics; Treatment Outcome
PubMed: 32853559
DOI: 10.1016/S0140-6736(20)31788-8 -
Medicine Nov 2019To evaluate the efficacy and safety of carbetocin for prevention of postpartum hemorrhage in women undergoing vaginal delivery compared with oxytocin. (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of carbetocin for prevention of postpartum hemorrhage in women undergoing vaginal delivery compared with oxytocin.
METHODS
We conducted a systemic literature search in PubMed, the Cochrane Library, and Embase without language restrictions from inception of each of database to November 18th, 2018. Randomized controlled trials with outcome measure of blood loss ≥500 ml were eligible if they compared carbetocin with oxytocin to prevent postpartum hemorrhage during the third stage of labor in women undergoing vaginal delivery.
RESULTS
This meta-analysis of 5 randomized controlled trials (30,314 women) indicated that there was no significant difference between carbetocin and oxytocin in blood loss ≥500 ml in women undergoing vaginal delivery (relative risks (RRs), 0.52; 95% confidence intervals (CIs), 0.24 to 1.15; P = .11; I = 69%). Sensitivity analyses showed the same results. No significant differences were found in blood loss ≥1000 ml, use of additional uterotonic agents, blood transfusion, uterine massage, flushing, vomiting, abdominal pain, nausea, dizziness, headache, palpitation, itching, and shivering.
CONCLUSIONS
This meta-analysis showed that carbetocin was as effective and safe as oxytocin for prevention of postpartum hemorrhage in women undergoing vaginal delivery, and the choice of carbetocin for routine prophylaxis will depend on cost-effectiveness.
Topics: Delivery, Obstetric; Female; Humans; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31764790
DOI: 10.1097/MD.0000000000017911 -
BMC Pregnancy and Childbirth Jan 2019Oxytocin for postpartum hemorrhage (PPH) prophylaxis is commonly administered by either intramuscular (IM) injection or intravenous (IV) infusion with both routes... (Randomized Controlled Trial)
Randomized Controlled Trial
Intramuscular injection, intravenous infusion, and intravenous bolus of oxytocin in the third stage of labor for prevention of postpartum hemorrhage: a three-arm randomized control trial.
BACKGROUND
Oxytocin for postpartum hemorrhage (PPH) prophylaxis is commonly administered by either intramuscular (IM) injection or intravenous (IV) infusion with both routes recommended equally and little discussion of potential differences between the two. This trial assesses the effectiveness and safety of 10 IU oxytocin administered as IM injection versus IV infusion and IV bolus during the third stage of labor for PPH prophylaxis.
METHODS
In two tertiary level Egyptian maternity hospitals, women delivering vaginally without exposure to pre-delivery uterotonics were randomized to one of three prophylactic oxytocin administration groups after delivery of the baby. Blood loss was measured 1 h after delivery, and side effects were recorded. Primary outcomes were mean postpartum blood loss and proportion of women with postpartum blood loss ≥500 ml in this open-label, three-arm, parallel, randomized controlled trial.
RESULTS
Four thousand nine hundred thirteen eligible, consenting women were randomized. Compared to IM injection, mean blood loss was 5.9% less in the IV infusion arm (95% CI: -8.5, - 3.3) and 11.1% less in the IV bolus arm (95% CI: -14.7, - 7.8). Risk of postpartum blood loss ≥500 ml in the IV infusion arm was significantly less compared to IM injection (0.8% vs. 1.5%, RR = 0.50, 95% CI: 0.27, 0.91). No side effects were reported in any arm.
CONCLUSIONS
Intravenous oxytocin is more effective than intramuscular injection for the prevention of PPH in the third stage of labor. Oxytocin delivered by IV bolus presents no safety concerns after vaginal delivery and should be considered a safe option for PPH prophylaxis.
TRIAL REGISTRATION
clinicaltrials.gov # NCT01914419 , posted August 2, 2013.
Topics: Administration, Intravenous; Adult; Delivery, Obstetric; Egypt; Female; Humans; Infusions, Intravenous; Injections, Intramuscular; Labor Stage, Third; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Treatment Outcome
PubMed: 30658605
DOI: 10.1186/s12884-019-2181-2 -
Anaesthesia Aug 2022Carbetocin or oxytocin are given routinely as first-line uterotonic drugs following delivery of the neonate during caesarean delivery to prevent postpartum haemorrhage....
Carbetocin or oxytocin are given routinely as first-line uterotonic drugs following delivery of the neonate during caesarean delivery to prevent postpartum haemorrhage. Low doses may be as effective as high doses with a potential reduction in adverse effects. In this double-blind, randomised, controlled, non-inferiority trial, we assigned low-risk patients undergoing elective caesarean delivery under spinal anaesthesia to one of four groups: carbetocin 20 μg; carbetocin 100 μg; oxytocin 0.5 IU bolus + infusion; and oxytocin 5 IU bolus + infusion. The study drug was given intravenously after delivery of the neonate. Uterine tone was assessed by the obstetrician 2, 5 and 10 minutes after study drug administration according to an 11-point verbal numerical rating scale (0 = atonic, 10 = excellent tone). The primary outcome measure was uterine tone 2 min after study drug administration. The pre-specified non-inferiority margin was 1.2 points on the 11-point scale. Secondary outcomes included uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects. Data were available for 277 patients. Carbetocin 20 μg resulting in uterine tone of (median (IQR [range])) 8 (7-8 [1-10]) was non-inferior to carbetocin 100 μg with tone 8 (7-9 [3-10]), median (95%CI) difference 0 (-0.44-0.44). Similarly, oxytocin 0.5 IU with tone 7 (6-8 [3-10]) was non-inferior to oxytocin 5 IU with tone 8 (6-8 [2-10]), median (95%CI) difference 1 (0.11-1.89). Carbetocin 20 μg was also non-inferior to oxytocin 5 IU, and oxytocin 0.5 IU was non-inferior to carbetocin 100 μg. Uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects were similar in all groups.
Topics: Cesarean Section; Double-Blind Method; Female; Humans; Infant, Newborn; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy
PubMed: 35343585
DOI: 10.1111/anae.15714 -
Taiwanese Journal of Obstetrics &... Aug 2018
Topics: Female; Humans; Oxytocics; Oxytocin; Postpartum Hemorrhage
PubMed: 30122562
DOI: 10.1016/j.tjog.2018.06.001 -
International Journal of Molecular... Feb 2021Recently, oxytocin (OXT) has been investigated for its potential therapeutic role in addiction. OXT has been found to diminish various drug-seeking and drug-induced... (Review)
Review
Recently, oxytocin (OXT) has been investigated for its potential therapeutic role in addiction. OXT has been found to diminish various drug-seeking and drug-induced behaviors. Although its behavioral effects are well-established, there is not much consensus on how this neuropeptide exerts its effects. Previous research has given thought to how dopamine (DA) may be involved in oxytocinergic mechanisms, but there has not been as strong of a focus on the role that glutamate (Glu) has. The glutamatergic system is critical for the processing of rewards and the disruption of glutamatergic projections produces the behaviors seen in drug addicts. We introduce the idea that OXT has direct effects on Glu transmission within the reward processing pathway. Thus, OXT may reduce addictive behaviors by restoring abnormal drug-induced changes in the glutamatergic system and in its interactions with other neurotransmitters. This review offers insight into the mechanisms through which a potentially viable therapeutic target, OXT, could be used to reduce addiction-related behaviors.
Topics: Animals; Behavior, Addictive; Drug-Seeking Behavior; Glutamic Acid; Humans; Oxytocics; Oxytocin; Substance-Related Disorders
PubMed: 33673694
DOI: 10.3390/ijms22052405