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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 -
American Journal of Obstetrics and... Mar 2024Oxytocin is a reproductive hormone implicated in the process of parturition and widely used during labor. Oxytocin is produced within the supraoptic nucleus and... (Review)
Review
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.
Topics: Pregnancy; Female; Humans; Oxytocin; Receptors, Oxytocin; Peripartum Period; Labor, Obstetric; Oxytocics; Labor, Induced
PubMed: 38462255
DOI: 10.1016/j.ajog.2023.04.011 -
Hormone Molecular Biology and Clinical... Nov 2016Osteoporosis and overweight/obesity constitute major worldwide public health burdens. Aging is associated with a decrease in hormonal secretion, lean mass and bone mass,... (Review)
Review
Osteoporosis and overweight/obesity constitute major worldwide public health burdens. Aging is associated with a decrease in hormonal secretion, lean mass and bone mass, and an increase in fat accumulation. It is established that both obesity and osteoporosis are affected by genetic and environmental factors, bone remodeling and adiposity are both regulated through the hypothalamus and sympathetic nervous system. Oxytocin (OT), belongs to the pituitary hormone family and regulates the function of peripheral target organs, its circulating levels decreased with age. Nowadays, it is well established that OT plays an important role in the control of bone and fat mass and their metabolism. Of note, OT and oxytocin receptor knock out mice develop bone defects and late-onset obesity. Thus OT emerges as a promising molecule in the treatment of osteoporosis and obesity as well as associated metabolic disorders such as type 2 diabetes and cardiovascular diseases. In this review, we will discuss findings regarding the OT effects on bone and fat mass.
Topics: Adipose Tissue; Animals; Bone and Bones; Humans; Mice; Osteoporosis; Oxytocics; Oxytocin
PubMed: 27865092
DOI: 10.1515/hmbci-2016-0045 -
Danish Medical Journal Mar 2018This thesis is comprised of three studies focusing on severe postpartum haemorrhage (PPH). PPH is a major cause of maternal morbidity and mortality worldwide. Risk... (Review)
Review
This thesis is comprised of three studies focusing on severe postpartum haemorrhage (PPH). PPH is a major cause of maternal morbidity and mortality worldwide. Risk factors include retained placenta, prolonged duration of the third stage of labour, previous caesarean section, and operative vaginal delivery. Occurrence and development of PPH are, however, unpredictable and can sometimes give rise to massive haemorrhage or even hysterectomy and maternal death. Severe haemorrhage can lead to coagulopathy causing further haemorrhage and requiring substitution with blood transfusions. The aim of this thesis was to investigate causes of severe PPH and investigate methods of early prevention. The first study was a randomised controlled double-blinded trial investigating the effect of treatment with pre-emptive fibrinogen on women with severe PPH. The primary outcome was the need for red blood cell transfusion at 6 weeks postpartum. A total of 249 women were randomised to either 2 grams of fibrinogen or placebo. The mean concentration of fibrinogen increased significantly in the intervention group compared to the placebo group (0.40 g/l, confidence interval: 0.15-0.65), but there was no difference in the need for postpartum blood transfusions (relative risk 0.95, confidence interval: 0.15-1.54). No thromboembolic complications were detected. The second study was a population-based observational study including 245 women receiving ≥10 red blood cell transfusion due to PPH. The cohort was identified by combining data from The Danish Transfusion Database with The Danish Medical Birth Registry, with further data extraction and validation through review of patient charts. The main causes of massive postpartum transfusion were atony (38%) and abnormal invasive placenta (25%). Two of the women in the cohort died, an additional six had a cardiac arrest, and a total of 128 women (52%) required a hysterectomy. Hysterectomy was associated with increased blood loss, increased number of blood transfusions, a higher fresh frozen plasma to red blood cell ratio (p=0.010), and an increased number of red blood cells before first platelet transfusion (p=0.023). Hysterectomy led to haemostasis in only 70% of cases. The third study was a register-based cohort study, includ-ing 43,357 vaginal deliveries from two large Danish maternity units. Different cut-offs were used to define PPH. There was a difference in distribution of causes depending on the cut-off used, with atony playing a decreasing role and a retained placenta an increasing role the higher the cut-off used. In a multivariate linear regression model retained placenta was identified as a strong predictor of quantity of blood loss. The duration of the third stage of labour was a very weak predictor after adjusting for the influence of a retained placenta. In conclusion, an improved diagnosis of the causes of PPH especially retained placenta, together with an early recognition and treatment of coagulopathy, seem to be important in reducing severe PPH in an aim to minimize associated maternal morbidity.
Topics: Erythrocyte Transfusion; Female; Fibrinogen; Hemostatics; Humans; Hysterectomy; Oxytocics; Oxytocin; Placenta, Retained; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 29510809
DOI: No ID Found -
Lancet (London, England) Dec 2023Oxytocin is effective in reducing labour duration but can be associated with fetal and maternal complications that could potentially be reduced by discontinuing the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Oxytocin is effective in reducing labour duration but can be associated with fetal and maternal complications that could potentially be reduced by discontinuing the treatment during labour. We aimed to assess the impact of discontinuing oxytocin during active labour on neonatal morbidity.
METHODS
STOPOXY was a multicentre, randomised, open-label, controlled, superiority trial conducted in 21 maternity units in France. Participants who received oxytocin before 4 cm dilation were randomly assigned 1:1 to either discontinuous oxytocin (oxytocin infusion stopped beyond a cervical dilation equal to or greater than 6 cm) or continuous oxytocin (administration of oxytocin continued until delivery). Randomisation was stratified by centre and parity. The primary outcome, neonatal morbidity, was assessed at birth using a composite variable defined by an umbilical arterial pH at birth less than 7·10, a base excess greater than 10 mmol/L, umbilical arterial lactates greater than 7 mmol/L, a 5-min Apgar score less than 7, or admission to the neonatal intensive care unit. Efficacy and safety was assessed in participants who were randomly assigned (excluding those who withdrew consent or were deemed ineligible after randomisation) and had reached a cervical dilation of at least 6 cm. This trial is registered with ClinicalTrials.gov, NCT03991091.
FINDINGS
Of 2459 participants randomly assigned between Jan 13, 2020, and Jan 24, 2022, 2170 were eligible to receive the intervention and were included in the final modified intention-to-treat analysis. The primary outcome occurred for 102 (9·6%) of 1067 participants (95% CI 7·9 to 11·5) in the discontinuous oxytocin group and for 101 (9·2%) of 1103 participants (7·6 to 11·0) in the continuous oxytocin group; absolute difference 0·4% (95% CI -2·1 to 2·9); relative risk 1·0 (95% CI 0·8 to 1·4). There were no clinically significant differences in adverse events between the two groups of the safety population.
INTERPRETATION
Among participants receiving oxytocin in early labour, discontinuing oxytocin when the active phase is reached does not clinically or statistically significantly reduce neonatal morbidity compared with continuous oxytocin.
FUNDING
French Ministry of Health and the Département de la Recherche Clinique et du Développement de l'Assistance Publique-Hôpitaux de Paris.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Oxytocin; Oxytocics; Labor, Induced; Labor, Obstetric; Morbidity
PubMed: 37952548
DOI: 10.1016/S0140-6736(23)01803-2 -
The Cochrane Database of Systematic... Feb 2015Cervical priming before first-trimester surgical abortion is recommended in certain groups of women. Nitric oxide (NO) donors induce cervical ripening without uterine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cervical priming before first-trimester surgical abortion is recommended in certain groups of women. Nitric oxide (NO) donors induce cervical ripening without uterine contractions, but the efficacy and side effects are of concern.
OBJECTIVES
To evaluate NO donors for cervical ripening before first-trimester surgical abortion, in terms of efficacy, side effects, and reduction of complications.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and POPLINE. We also searched reference lists of retrieved papers. We contacted experts in the field for information on both published and unpublished trials.
SELECTION CRITERIA
Randomised controlled trials comparing NO donors alone or in combination with other methods for cervical ripening in first-trimester surgical abortion.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected and extracted the data onto a data extraction form. We processed the data using Review Manager (RevMan 5) software.
MAIN RESULTS
We included 9 studies involving 766 participants. There were no serious complications (infection requiring antibiotic treatment, blood transfusion, complications requiring unintended operation, cervical injury, uterine perforation, death or serious morbidity) in the included trials.NO donors were more effective in cervical ripening when compared with placebo or no treatment. Baseline cervical dilatation before the procedure was higher in NO donors group (mean difference (MD) 0.30, 95% confidence interval (CI) 0.01 to 0.58) The cumulative force required to dilate the cervix to 8 mm (MD -4.29, 95% CI -9.92 to 1.35), headache (risk ratio (RR) 1.73, 95% CI 0.86 to 3.46), abdominal pain (RR 0.87, 95% CI 0.50 to 1.50), or patient satisfaction (RR 0.95, 95% CI 0.84 to 1.07) were not different. More nausea and vomiting occurred in the women who received a NO donor (RR 2.62, 95% CI 1.07 to 6.45).NO donors were inferior to prostaglandins for cervical ripening. The cumulative force required to dilate the cervix to 8 mm to 9 mm was higher (MD 13.12, 95% CI 9.72 to 16.52), and baseline cervical dilatation was less (MD -0.73, 95% CI -1.01 to -0.45) in the NO donor group. However, the probability of dilation greater than 8 mm at three hours was higher in the NO donor group (RR 6.67, 95% CI 2.21 to 20.09). Side effects including headache (RR 5.13, 95% CI 3.29 to 8.00), palpitation (RR 3.43, 95% CI 1.64 to 7.15), dizziness (RR 3.29, 95% CI 1.46 to 7.41), and intraoperative blood loss (MD 33.59 ml, 95% CI 24.50 to 42.67) were also higher. However, abdominal pain (RR 0.33, 95% CI 0.25 to 0.44) and vaginal bleeding (RR 0.14, 95% CI 0.07 to 0.27) were less in the NO donor group. No difference for nausea/vomiting in both groups(RR 1.17, 95% CI 0.94 to 1.46). Patient satisfaction was not different.One trial compared a NO donor with a NO donor plus prostaglandin. The cumulative force required to dilate the cervix to 8 mm was higher (MD 14.50, 95% CI 0.50 to 28.50) in the NO donor group. There was no difference in headache (RR 0.88, 95% CI 0.38 to 2.00), abdominal pain (RR 0.14, 95% CI 0.02 to 1.07), or intraoperative blood loss (MD -50, 95% CI -164.19 to 64.19).
AUTHORS' CONCLUSIONS
NO donors are superior to placebo or no treatment, but inferior to prostaglandins for first-trimester cervical ripening, and associated with more side effects.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Cervical Ripening; Female; Humans; Nitric Oxide Donors; Oxytocics; Pregnancy; Pregnancy Trimester, First; Prostaglandins; Randomized Controlled Trials as Topic
PubMed: 25927092
DOI: 10.1002/14651858.CD007444.pub4 -
Revista Brasileira de Ginecologia E... Jun 2023
Topics: Humans; Pregnancy; Female; Misoprostol; Obstetrics; Oxytocics; Gynecology
PubMed: 37494579
DOI: 10.1055/s-0043-1770931 -
The Cochrane Database of Systematic... Nov 2015Retained placenta affects 0.5% to 3% of women following delivery, with considerable morbidity if left untreated. Use of nitroglycerin (NTG), either alone or in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Retained placenta affects 0.5% to 3% of women following delivery, with considerable morbidity if left untreated. Use of nitroglycerin (NTG), either alone or in combination with uterotonics, may be of value to minimise the need for manual removal of the placenta in theatre under anaesthesia.
OBJECTIVES
To evaluate the benefits and harms of NTG as a tocolytic, either alone or in addition to uterotonics, in the management of retained placenta.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 January 2015), reference lists of retrieved studies and contacted experts in the field.
SELECTION CRITERIA
Any adequately randomised controlled trial (RCT) comparing the use of NTG, either alone or in combination with uterotonics, with no intervention or with other interventions in the management of retained placenta. All women having a vaginal delivery with a retained placenta, regardless of the management of the third stage of labour (expectant or active). We included all trials with haemodynamically stable women in whom the placenta was not delivered at least within 15 minutes after delivery of the baby.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.
MAIN RESULTS
We included three randomised controlled trials (RCTs) with 175 women. The three published RCTs compared NTG alone versus placebo. The detachment status of retained placenta was unknown in all three RCTs. Collectively, among the three included trials, two were judged to be at low risk of bias and the third trial was judged to be at high risk of bias for two domains: incomplete outcome data and selective reporting. The three trials reported seven out of 23 of the review's pre-specified outcomes.The primary outcome "manual removal of the placenta" was reported in all three studies. No differences were seen between NTG and placebo for manual removal of the placenta (average risk ratio (RR) 0.83, 95% confidence interval (CI) 0.47 to 1.46; women = 175; I² = 81%). A random-effects model was used because of evidence of substantial heterogeneity in the analysis. There were also no differences between groups for risk of severe postpartum haemorrhage (RR 0.93, 95% CI 0.62 to 1.39; women = 150; studies = two; I² = 0%). Blood transfusion was only reported in one study (40 women) and again there was no difference between groups (RR 1.00, 95% CI 0.07 to 14.90; women = 40; I² = 0%). Mean blood loss (mL) was reported in the three studies and no differences were observed (mean difference (MD) -115.31, 95% CI -306.25 to 75.63; women = 169; I² = 83%). Nitroglycerin administration was not associated with an increase in headaches (RR 1.09, 95% CI 0.80 to 1.47; women = 174; studies = three; I² = 0%). However, nitroglycerin administration was associated with a significant, though mild, decrease in systolic and diastolic blood pressure and a significant increase in pulse rate (MD -3.75, 95% CI -7.47 to -0.03) for systolic blood pressure, and (MD 6.00, 95% CI 3.07 to 8.93) for pulse rate (beats per minute) respectively (reported by only one study including 24 participants). Maternal mortality and addition of therapeutic uterotonics were not reported in any study.
AUTHORS' CONCLUSIONS
In cases of retained placenta, currently available data showed that the use of NTG alone did not reduce the need for manual removal of placenta. This intervention did not increase the incidence of severe postpartum haemorrhage nor the need for blood transfusion. Haemodynamically, NTG had a significant though mild effect on both pulse rate and blood pressure.
Topics: Administration, Sublingual; Female; Headache; Humans; Nitroglycerin; Oxytocics; Oxytocin; Placenta, Retained; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 26558329
DOI: 10.1002/14651858.CD007708.pub3 -
The Cochrane Database of Systematic... Sep 2018There is general agreement that oxytocin given either through the intramuscular or intravenous route is effective in reducing postpartum blood loss. However, it is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is general agreement that oxytocin given either through the intramuscular or intravenous route is effective in reducing postpartum blood loss. However, it is unclear whether the subtle differences between the mode of action of these routes have any effect on maternal and infant outcomes. This is an update of a review first published in 2012.
OBJECTIVES
To determine the comparative effectiveness and safety of oxytocin administered intramuscularly or intravenously for prophylactic management of the third stage of labour after vaginal birth.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (7 September 2017) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised trials comparing intramuscular with intravenous oxytocin for prophylactic management of the third stage of labour after vaginal birth. We excluded quasi-randomised trials.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
Three studies with 1306 women are included in the review and compared intramuscular versus intravenous oxytocin administered just after the birth of the anterior shoulder or soon after the birth of the baby. Studies were carried out in hospital settings in Turkey and Thailand and recruited women with singleton, term pregnancies. Overall, the included studies were at moderate risk of bias: none of the studies provided clear information on allocation concealment or attempted to blind staff or women. For GRADE outcomes the quality of the evidence was very low, with downgrading due to study design limitations and imprecision of effect estimates.Only one study reported severe postpartum haemorrhage (blood loss 1000 mL or more) and showed no clear difference between the intramuscular and intravenous oxytocin groups (risk ratio (RR) 0.11, 95% confidence interval (CI) 0.01 to 2.04; 256 women; very low-quality evidence). No woman required hysterectomy in either group in one study (no estimable data, very low-quality evidence), and in another study one woman in each group received a blood transfusion (RR 1.00, 95% CI 0.06 to 15.82; 256 women; very low-quality evidence). Other important outcomes (maternal death, hypotension, maternal dissatisfaction with the intervention and neonatal jaundice) were not reported by any of the included studies. There were no clear differences between groups for other prespecified secondary outcomes reported (postpartum haemorrhage 500 mL or more, use of additional uterotonics, retained placenta or manual removal of the placenta).
AUTHORS' CONCLUSIONS
Very low-quality evidence indicates no clear difference between the comparative benefits and risks of intramuscular and intravenous oxytocin when given to prevent excessive blood loss after vaginal birth. Appropriately designed randomised trials with adequate sample sizes are needed to assess whether the route of prophylactic oxytocin after vaginal birth affects maternal or infant outcomes. Such studies could be large enough to detect clinically important differences in major side effects that have been reported in observational studies and should also consider the acceptability of the intervention to mothers and providers as important outcomes.
Topics: Blood Transfusion; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Labor Stage, Third; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 30246877
DOI: 10.1002/14651858.CD009332.pub3