Boie, S., Glavind, J., Uldbjerg, N., Steer, P. J., Bor, P., & CONDISOX trial group (2021). Continued versus discontinued oxytocin stimulation in the active phase of labour (CONDISOX): double blind randomised controlled trial. BMJ (Clinical research ed.), 373, n716. https://doi.org/10.1136/bmj.n716
Boie S, Glavind J, Uldbjerg N, Steer PJ, Bor P, CONDISOX trial group. Continued versus discontinued oxytocin stimulation in the active phase of labour (CONDISOX): double blind randomised controlled trial. BMJ (Clinical research ed.). 2021;373:n716. doi:10.1136/bmj.n716
Boie, S., et al. "Continued versus discontinued oxytocin stimulation in the active phase of labour (CONDISOX): double blind randomised controlled trial." BMJ (Clinical research ed.), vol. 373, 2021, pp. n716.
For EndNote, Zotero or Mendeley:
Open access
No open license is recorded for this paper. Reuse terms are set by the publisher.
Open Access
Free full text on PubMed Central (PMC8044921)
Abstract
Objective
To determine whether discontinuing oxytocin stimulation in the active phase of induced labour is associated with lower caesarean section rates.
Design
International multicentre, double blind, randomised controlled trial.
Setting
Nine hospitals in Denmark and one in the Netherlands between 8 April 2016 and 30 June 2020.
Participants
1200 women stimulated with intravenous oxytocin infusion during the latent phase of induced labour.
Intervention
Women were randomly assigned to have their oxytocin stimulation discontinued or continued in the active phase of labour.
Main Outcome Measures
Delivery by caesarean section.
Results
A total of 607 women were assigned to discontinuation and 593 to continuation of the oxytocin infusion. The rates of caesarean section were 16.6% (n=101) in the discontinued group and 14.2% (n=84) in the continued group (relative risk 1.17, 95% confidence interval 0.90 to 1.53). In 94 parous women with no previous caesarean section, the caesarean section rate was 7.5% (11/147) in the discontinued group and 0.6% (1/155)in the continued group (relative risk 11.6, 1.15 to 88.7). Discontinuation was associated with longer duration of labour (median from randomisation to delivery 282 v 201 min; P<0.001), a reduced risk of hyperstimulation (20/546 (3.7%) v 70/541 (12.9%); P<0.001), and a reduced risk of fetal heart rate abnormalities (153/548 (27.9%) v 219/537 (40.8%); P<0.001) but rates of other adverse maternal and neonatal outcomes were similar between groups.
Conclusions
In a setting where monitoring of the fetal condition and the uterine contractions can be guaranteed, routine discontinuation of oxytocin stimulation may lead to a small increase in caesarean section rate but a significantly reduced risk of uterine hyperstimulation and abnormal fetal heart rate patterns.
Bay B et al., 2019·BJOG : an international journal of obstetrics and gynaecology
To assess the risk of stillbirth in low-risk in vitro fertilisation (IVF) pregnancies. Register-based national cohort study. Denmark 2003-2013. Cohort of 425 732 singleton pregnancies including 10 235 conceived following IVF/intracytoplasmic sperm injection (ICSI), 4521 conceived following intrauterine insemination (IUI), and 410 976 spontaneously conceived. Information on pregnancy, obstetrical risk factors, stillbirth, and fertility treatment was obtained from the Danish national health registers for all pregnancies after gestational week 21+6 . We estimated the overall and gestational age-specific risk of stillbirth in low-risk term pregnancies following IVF, ICSI, and IUI. Further, we estimated the association between stillbirth and IVF and ICSI respectively as well as fresh or frozen-thawed embryo transfer. Risk of stillbirth. The number of stillbirths in spontaneously conceived and IVF/ICSI low-risk term pregnancies was 525 (0.1%) and 35 (0.3%), respectively. In multivariate analysis, the risk of stillbirth in pregnancies following IVF/ICSI was increased (odds ratio 2.1, 95% CI 1.4-3.1). The risk of stillbirth was correspondingly increased in time-to-event analyses taking risk time for each fetus into account from gestational week 37 and onwards (hazard ratio 2.4, 95% CI 1.6-3.6). In sub-analyses, the risk of stillbirth was increased for pregnancies following ICSI (odds ratio 2.2, 95% CI 1.2-3.1), but not IVF (odds ratio 1.7, 95% CI 0.9-3.1). We found a systematically increased risk of stillbirth in low-risk term pregnancies following IVF/ICSI. Whether the risk was related to the treatment or to underlying subfertility is uncertain. The results may indicate a need for obstetrical surveillance for these pregnancies when reaching term. Increased risk of stillbirth in low-risk term pregnancies following fresh cycle IVF/ICSI.
Whitley J et al., 2025·American journal of obstetrics and gynecology·Free to read
Our objective was to determine if oxytocin discontinuation in the active phase of labor impacts the rate of cesarean delivery compared to continuation of oxytocin. This study was a systematic review and meta-analysis of randomized controlled trials. A research librarian performed a database search using a combination of standardized terms and keywords related to oxytocin discontinuation and stages of labor from database inception until February 2024. This protocol was registered in The International Prospective Register of Systematic Reviews (PROSPERO). Randomized controlled trials of pregnant patients who received oxytocin for induction or augmentation of labor, whose outcomes compared discontinuation and continuation of oxytocin in active labor, were included. We defined "active phase of labor" as defined by each trial. Nonrandomized trials, quasi-randomized trials, and animal models were excluded. The primary outcome was the rate of cesarean delivery. Secondary maternal outcomes included postpartum hemorrhage, total blood loss, and infectious outcomes. Secondary neonatal outcomes included Apgar score at 5 minutes <7, umbilical arterial pH <7.10, neonatal therapeutic hypothermia, neonatal intensive care unit admission, neonatal resuscitation at birth, and neonatal death. STUDY APPRAISAL The risk of bias in each study was assessed using the guidelines outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Heterogeneity was measured using Higgins I2. Meta-analysis was performed in Review Manager 5.4.1 and StataSE 16 to determine summary treatment effects in terms of relative risk or mean difference with 95% confidence intervals. The adherence of each included trial to the trustworthiness criteria outlined by the OBGYN Editors' Integrity Group was assessed, and a leave-1-out analysis was performed to evaluate the effect of studies with concerns regarding trustworthiness. Fifteen randomized controlled trials, including 5734 patients, were ultimately included in the meta-analysis. The rate of cesarean delivery, reported in 13 studies, was lower with discontinuation of oxytocin in the active phase of labor (relative risk=0.80; 95% confidence interval, 0.66-0.97; 95% prediction interval, 0.38-1.22). Discontinuation of oxytocin was also associated with a lower risk of uterine tachysystole (relative risk=0.45; 95% confidence interval, 0.34-0.60; I2, 26%), and nonreassuring fetal heart rate tracing (relative risk=0.64; 95% confidence interval, 0.49-0.82; I2, 41%). Discontinuation of oxytocin increased the duration of active labor by an average of 30 minutes and second stage of labor by an average of 6 minutes. Although associated with an extension of labor by half an hour, discontinuation of oxytocin in the active phase of labor was associated with a 20% decreased risk of cesarean delivery and a lower risk of uterine tachysystole and nonreassuring fetal heart rate tracing. While the pooled analysis suggests a beneficial effect, this finding is dependent on the inclusion of studies with concerns regarding trustworthiness.
Jonas W et al., 2009·Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine
Oxytocin and prolactin stimulate milk ejection and milk production during breastfeeding. The aim of the present study was to make a detailed analysis of maternal release of oxytocin and prolactin in response to breastfeeding during the second day postpartum in mothers who had received oxytocin either intravenously for stimulation of labor or intramuscularly for prevention of postpartum hemorrhage and/or epidural analgesia or those who had received no such treatment in connection with birth. In a descriptive comparative study plasma oxytocin and prolactin concentrations were measured in response to suckling during the second day postpartum in women who had received intravenous intrapartum oxytocin (n = 8), intramuscular postpartum oxytocin (n = 13), or epidural analgesia, either with (n = 14) or without (n = 6) intrapartum oxytocin infusion, and women who received none of these interventions (n = 20). Hormone levels were analyzed by enzyme immunoassay. All mothers showed a pulsatile oxytocin pattern during the first 10 minutes of breastfeeding. Women who had received epidural analgesia with oxytocin infusion had the lowest endogenous median oxytocin levels. The more oxytocin infusion the mothers had received during labor, the lower their endogenous oxytocin levels were during a breastfeeding during the second day postpartum. A significant rise of prolactin was observed after 20 minutes in all women, but after 10 minutes in mothers having received oxytocin infusion during labor. In all women, oxytocin variability and the rise of prolactin levels between 0 and 20 minutes correlated significantly with median oxytocin and prolactin levels. Oxytocin, released in a pulsatile way, and prolactin were released by breastfeeding during the second day postpartum. Oxytocin infusion decreased endogenous oxytocin levels dose-dependently. Furthermore, oxytocin infusion facilitated the release of prolactin. Epidural analgesia in combination with oxytocin infusion influenced endogenous oxytocin levels negatively.
Anti-Infective and Anti-Inflammatory Agents · Nonsteroidal Anti-Inflammatory Drugs
To examine the effectiveness of any tocolytic compared with a placebo or no tocolytic for preterm labor. We checked MEDLINE (1966-1998) and the Cochrane Controlled Trials Register for articles, using the search terms "randomized controlled trial" (RCT), "preterm labor," "tocolysis," "betamimetics," "ritodrine," "terbutaline," "hexaprenaline," "isoxuprine," "prostaglandin synthetase inhibitors," "indomethacin," "sulindac," "calcium channel blockers," "nifedipine," "oxytocin receptor blockers," "atosiban," "nitroglceride," and "magnesium sulfate." We included all RCTs that compared effect of a tocolytic with a placebo or no tocolytic in women in preterm labor, and reported perinatal, neonatal, or maternal outcomes. Studies were excluded if loss to follow-up exceeded 20% of those originally enrolled, or if data were not reported on a per-patient-treated basis. Eighteen of 76 articles retrieved met the inclusion criteria. TABULATION, INTEGRATION, Two authors independently reviewed the articles and abstracted the data. Discrepancies were resolved by consensus. Meta-analyses (odds ratio [OR] and 95% confidence interval [CI]) were done for each outcome for all trials and for specific types of tocolytic therapy when possible. Tocolytics decreased the risk of delivery within 7 days (OR 0.60, 95% CI 0.38, 0.95). Betamimetics, indomethacin, atosiban, and ethanol, but not magnesium sulfate, were associated with significant prolongations in pregnancy. Tocolytics were not associated with improved perinatal outcomes. Maternal side effects significantly associated with tocolytic use were palpitations, nausea, tremor, chorioamnionitis, hyperglycemia, hypokalemia, and need to discontinue treatment. Although tocolytics prolong pregnancy, they have not been shown to improve perinatal or neonatal outcomes and have adverse effects on women in preterm labor.
Prescribing Safety · Medication Safety in Pregnancy
Our aim was to determine the efficacy and safety of tocolytic agents currently used to treat premature labor. We carried out a comprehensive review of tocolytic agents in the treatment of premature labor. Three hundred twenty-eight studies published between 1933 and 1992 were analyzed. An analysis of randomized, placebo-controlled, clinical trials showed that magnesium sulfate is not better than placebo in the treatment of premature labor. beta-Adrenergic receptor agonists effectively stop premature labor for only 24 to 48 hours. Calcium channel blockers and oxytocin antagonists inhibit uterine contractions, but their role in stopping labor is undefined. Prostaglandin inhibitors appear to be effective in treating premature labor and have few adverse side effects. The only tocolytic drugs that might be effective are the prostaglandin inhibitors. Tocolytic agents should be used only between 24 and 32 completed weeks of gestation. Magnesium sulfate should not be used to treat premature labor. Oxytocin antagonists should be used only in experimental clinical trials. Calcium channel blockers and beta-adrenergic receptor agonists inhibit uterine contractions but do not prolong gestation for longer than 48 hours.
Birth and Delivery › Labor and Birth › Induction of Labor · Therapeutics › Hormonal Agents › Gonadotropins
PMID 33853878 33853878 DOI 10.1136/bmj.n716 10.1136/bmj.n716 Boie et al. 2021, Boie 2021
Cite this article
Boie, S., Glavind, J., Uldbjerg, N., Steer, P. J., Bor, P., & CONDISOX trial group (2021). Continued versus discontinued oxytocin stimulation in the active phase of labour (CONDISOX): double blind randomised controlled trial. BMJ (Clinical research ed.), 373, n716. https://doi.org/10.1136/bmj.n716
Boie S, Glavind J, Uldbjerg N, Steer PJ, Bor P, CONDISOX trial group. Continued versus discontinued oxytocin stimulation in the active phase of labour (CONDISOX): double blind randomised controlled trial. BMJ (Clinical research ed.). 2021;373:n716. doi:10.1136/bmj.n716
Boie, S., et al. "Continued versus discontinued oxytocin stimulation in the active phase of labour (CONDISOX): double blind randomised controlled trial." BMJ (Clinical research ed.), vol. 373, 2021, pp. n716.