The effectiveness of oxytocin for treating substance use disorders:A systematic review of randomized placebo-controlled trials.

Oxytocin is gaining traction in the treatment of various substance use disorders (SUD). We performed a systematic review assessing the efficacy of oxytocin for treating different SUD. The electronic databases MEDLINE, EMBASE, CENTRAL, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials examining the effects of oxytocin vs. placebo in SUD samples. Quality assessment was conducted using a Cochrane validated checklist. A total of 17 trials with unique samples were identified. These were conducted on participants with SUD involving alcohol (n = 5), opioids (n = 3), opioids and/or cocaine/other stimulants (n = 3), cannabis (n = 2), or nicotine (n = 4). Across the SUD-groups, oxytocin reduced withdrawal symptoms (3/5 trials), negative emotional states (4/11 trials), cravings (4/11 trials), cue-induced cravings (4/7 trials), and consumption (4/8 trials). Sixteen trials had an overall considerable risk of bias. In conclusion, although oxytocin showed some promising therapeutic effects, the findings are too inconsistent and the trials too heterogeneous to derive any firm conclusions. Sounder methodological and well-powered trials are warranted.

The mechanism of ginger and its processed products in the treatment of estradiol valerate coupled with oxytocin-induced dysmenorrhea in mice via regulating the TRP ion channel-mediated ERK1/2/NF-κB signaling pathway.

Ginger (Rhizoma zingiberis, RZ) has been used as a food, spice, supplement, flavoring agent, and as an edible herbal medicine. It is characterized by its pungency and aroma, and is rich in nutrients with remarkable pharmacological effects. It is used in traditional medicine clinics to treat diseases and symptoms, such as colds, headache, and primary dysmenorrhea (PD). In China, a variety of processed products of RZ are used as herbal medicines, such as baked ginger (BG) or ginger charcoal (GC) to treat different diseases and symptoms. However, the molecular mechanism of the therapeutic effect of RZ and its processed products (RZPPs, including BG or GC) against PD has not been well characterized. Moreover, whether the transient receptor potential (TRP) ion channels are involved in this process is not clear. In the present study, UHPLC-Q-TOF MS was adopted to analyse the differential quality markers (DQMs) between RZ and RZPPs. In addition, differential metabolomics (DMs) was acquired between RZ- and RZPPs-treated estradiol valerate coupled with an oxytocin-induced PD mouse uterus using untargeted metabolomics (UM). A correlation analysis between DQMs and DMs was also conducted. Benzenoids, lipids, and lipid-like molecules were the main DQMs between RZ and RZPPs. RZ and RZPPs were found to improve the pathological status of the uterus of a PD mouse, with significantly decreased serum levels of E2, PGF2α, TXB2 and remarkably increased levels of PROG and 6-keto-PGF1α. Moreover, RZ and RZPPs alleviated PD in mice via regulating the TRP ion channel-mediated ERK1/2/NF-κB signaling pathway. Our results indicate that the therapeutic effect of RZ and RZPPs against PD may be mediated by regulating the TRP ion channel-mediated ERK1/2/NF-κB signaling pathway, and provide a reference for the development of new dietary supplements or medicines.

Promptness of oxytocin administration for first-line treatment of postpartum hemorrhage: a national vignette-based study among midwives.

BACKGROUND: Postpartum hemorrhage (PPH) remains a leading cause of maternal morbidity and mortality worldwide. Midwives play a key role in the initial management of PPH. Uterotonic agents are widely used in its prevention and treatment, with oxytocin the first-line agent. Nonetheless, a standardized guideline for optimal dose and rate of administration has not been clearly defined. The aim of this study was to investigate French midwives' practices regarding first-line oxytocin treatment and the factors influencing its delayed administration. METHODS: This multicenter study was based on clinical vignettes of PPH management collected using an anonymous online questionnaire. A random sample of midwives from 145 maternity units in France from 15 randomly selected perinatal networks were invited to participate by email. The Previously validated case vignettes described two different scenarios of severe PPH. Vignette 1 described a typical immediate, severe PPH, and vignette 2 a less typical case of severe but gradual PPH They were constructed in three successive steps and included multiple-choice questions proposing several types of clinical practice options at each stage. For each vignette separately, we analyzed the lack of prompt oxytocin administration and the factors contributing to them, that is, characteristics of the midwives and organizational features of maternity units. Bivariate analysis and multivariable logistic regression analysis were applied. RESULTS: In all, 450 midwives from 87 maternity units provided complete responses. Lack of promptness was observed in 21.6% of responses (N = 97) in Vignette 1 and in 13.8% (N = 62) in Vignette 2 (p < .05). After multivariate analysis, the risk of delay was lower among with midwives working in university maternity hospitals (ORa 0.47, 95% 0.21, 0.97) and in units with 1500 to 2500 births per year (ORa 0.49, 95% CI 0.26, 0.90) for Vignette 1. We also noticed that delay increased with the midwives' years of experience (per 10-year period) (ORa 1.30, 95% CI 1.01, 1.69). CONCLUSIONS: This study using clinical vignettes showed delays in oxytocin administration for first-line treatment of PPH. Because delay in treatment is a major cause of preventable maternal morbidity in PPH, these findings suggest that continuing training of midwives should be considered, especially in small maternity units.

The Effects of Oxytocin on Appetite Regulation, Food Intake and Metabolism in Humans.

The hypothalamic peptide oxytocin and its receptor are involved in a range of physiological processes, including parturition, lactation, cell growth, wound healing, and social behavior. More recently, increasing evidence has established the effects of oxytocin on food intake, energy expenditure, and peripheral metabolism. In this review, we provide a comprehensive description of the central oxytocinergic system in which oxytocin acts to shape eating behavior and metabolism. Next, we discuss the peripheral beneficial effects oxytocin exerts on key metabolic organs, including suppression of visceral adipose tissue inflammation, skeletal muscle regeneration, and bone tissue mineralization. A brief summary of oxytocin actions learned from animal models is presented, showing that weight loss induced by chronic oxytocin treatment is related not only to its anorexigenic effects, but also to the resulting increase in energy expenditure and lipolysis. Following an in-depth discussion on the technical challenges related to endogenous oxytocin measurements in humans, we synthesize data related to the association between endogenous oxytocin levels, weight status, metabolic syndrome, and bone health. We then review clinical trials showing that in humans, acute oxytocin administration reduces food intake, attenuates fMRI activation of food motivation brain areas, and increases activation of self-control brain regions. Further strengthening the role of oxytocin in appetite regulation, we review conditions of hypothalamic insult and certain genetic pathologies associated with oxytocin depletion that present with hyperphagia, extreme weight gain, and poor metabolic profile. Intranasal oxytocin is currently being evaluated in human clinical trials to learn whether oxytocin-based therapeutics can be used to treat obesity and its associated sequela. At the end of this review, we address the fundamental challenges that remain in translating this line of research to clinical care.

Treatments for breast engorgement during lactation.

BACKGROUND: Engorgement is the overfilling of breasts with milk, often occurring in the early days postpartum. It results in swollen, hard, painful breasts and may lead to premature cessation of breastfeeding, decreased milk production, cracked nipples and mastitis. Various treatments have been studied but little consistent evidence has been found on effective interventions. OBJECTIVES: To determine the effectiveness and safety of different treatments for engorgement in breastfeeding women. SEARCH METHODS: On 2 October 2019, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies. SELECTION CRITERIA: All types of randomised controlled trials and all forms of treatment for breast engorgement were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility, extracted data, conducted 'Risk of bias' assessment and assessed the certainty of evidence using GRADE. MAIN RESULTS: For this udpate, we included 21 studies (2170 women randomised) conducted in a variety of settings. Six studies used individual breasts as the unit of analysis. Trials examined a range of interventions: cabbage leaves, various herbal compresses (ginger, cactus and aloe, hollyhock), massage (manual, electromechanical, Oketani), acupuncture, ultrasound, acupressure, scraping therapy, cold packs, and medical treatments (serrapeptase, protease, oxytocin). Due to heterogeneity, meta-analysis was not possible and data were reported from single trials. Certainty of evidence was downgraded for limitations in study design, imprecision and for inconsistency of effects. We report here findings from key comparisons. Cabbage leaf treatments compared to control For breast pain, cold cabbage leaves may be more effective than routine care (mean difference (MD) -1.03 points on 0-10 visual analogue scale (VAS), 95% confidence intervals (CI) -1.53 to -0.53; 152 women; very low-certainty evidence) or cold gel packs (-0.63 VAS points, 95% CI -1.09 to -0.17; 152 women; very low-certainty evidence), although the evidence is very uncertain. We are uncertain about cold cabbage leaves compared to room temperature cabbage leaves, room temperature cabbage leaves compared to hot water bag, and cabbage leaf extract cream compared to placebo cream because the CIs were wide and included no effect. For breast hardness, cold cabbage leaves may be more effective than routine care (MD -0.58 VAS points, 95% CI -0.82 to -0.34; 152 women; low-certainty evidence). We are uncertain about cold cabbage leaves compared to cold gel packs because the CIs were wide and included no effect. For breast engorgement, room temperature cabbage leaves may be more effective than a hot water bag (MD -1.16 points on 1-6 scale, 95% CI -1.36 to -0.96; 63 women; very low-certainty evidence). We are uncertain about cabbage leaf extract cream compared to placebo cream because the CIs were wide and included no effect. More women were satisfied with cold cabbage leaves than with routine care (risk ratio (RR) 1.42, 95% CI 1.22 to 1.64; 152 women; low certainty), or with cold gel packs (RR 1.23, 95% CI 1.10 to 1.38; 152 women; low-certainty evidence). We are uncertain if women breastfeed longer following treatment with cold cabbage leaves than routine care because CIs were wide and included no effect. Breast swelling and adverse events were not reported. Compress treatments compared to control For breast pain, herbal compress may be more effective than hot compress (MD -1.80 VAS points, 95% CI -2.07 to -1.53; 500 women; low-certainty evidence). Massage therapy plus cactus and aloe compress may be more effective than massage therapy alone (MD -1.27 VAS points, 95% CI -1.75 to -0.79; 100 women; low-certainty evidence). In a comparison of cactus and aloe compress to massage therapy, the CIs were wide and included no effect. For breast hardness, cactus and aloe cold compress may be more effective than massage (RR 0.66, 95% CI 0.51 to 0.87; 102 women; low-certainty evidence). Massage plus cactus and aloe cold compress may reduce the risk of breast hardness compared to massage alone (RR 0.38, 95% CI 0.25 to 0.58; 100 women; low-certainty evidence). We are uncertain about the effects of compress treatments on breast engorgement and cessation of breastfeeding because the certainty of evidence was very low. Among women receiving herbal compress treatment, 2/250 experienced skin irritation compared to 0/250 in the hot compress group (moderate-certainty evidence). Breast swelling and women's opinion of treatment were not reported. Medical treatments compared to placebo Protease may reduce breast pain (RR 0.17, 95% CI 0.04, 0.74; low-certainty evidence; 59 women) and breast swelling (RR 0.34, 95% CI 0.15 to 0.79; 59 women; low-certainty evidence), whereas serrapeptase may reduce the risk of engorgement compared to placebo (RR 0.36, 95% CI 0.14 to 0.88; 59 women; low-certainty evidence). We are uncertain if serrapeptase reduces breast pain or swelling, or if oxytocin reduces breast engorgement compared to placebo, because the CIs were wide and included no effect. No women experienced adverse events in any of the groups receiving serrapeptase, protease or placebo (low-certainty evidence). Breast induration/hardness, women's opinion of treatment and breastfeeding cessation were not reported. Cold gel packs compared to control For breast pain, we are uncertain about the effectiveness of cold gel packs compared to control treatments because the certainty of evidence was very low. For breast hardness, cold gel packs may be more effective than routine care (MD -0.34 points on 1-6 scale, 95% CI -0.60 to -0.08; 151 women; low-certainty evidence). It is uncertain if women breastfeed longer following cold gel pack treatment compared to routine care because the CIs were wide and included no effect. There may be little difference in women's satisfaction with cold gel packs compared to routine care (RR 1.17, 95% CI 0.97 to 1.40; 151 women; low-certainty evidence). Breast swelling, engorgement and adverse events were not reported. AUTHORS' CONCLUSIONS: Although some interventions may be promising for the treatment of breast engorgement, such as cabbage leaves, cold gel packs, herbal compresses, and massage, the certainty of evidence is low and we cannot draw robust conclusions about their true effects. Future trials should aim to include larger sample sizes, using women - not individual breasts - as units of analysis.

Factors affecting third-stage management and postpartum hemorrhage in planned midwife-led home and birth center births in the United States.

BACKGROUND: Postpartum hemorrhage (PPH) is a potential childbirth complication. Little is known about how third-stage labor is managed by midwives in the United States, including use of uterotonic medication during community birth. Access to uterotonic medication may vary based on credentials of the midwife or state regulations governing midwifery. METHODS: Using data from the Midwives of North America 2.0 database (2004-2009), we describe the PPH incidence for women giving birth in the community, their demographic and clinical characteristics, and methods used by midwives to address PPH. We also examined PPH rates by midwifery credentials and by the presence of regulations for legal midwifery practice. RESULTS: Of the 17 836 vaginal births, 15.9% had blood loss of over 500 mL and 3.3% had 1000 mL or greater blood loss. Midwives used pharmaceuticals to prevent or treat postpartum bleeding in 6.3% and 13.9% of births, respectively, and the rate of hospital transfer after birth was 1.4% (n = 247). In adjusted analyses, PPH was less likely when births occurred at home vs a birth center, if the midwife had a CNM/CM credential vs a CPM/LM/LDM credential, or if the woman was multiparous without a history of PPH or prior cesarean birth. PPH was more likely in states with barriers to midwifery practice compared with regulated states (OR: 1.26; 95% CI, 1.16-1.38). CONCLUSIONS: Women giving birth in the community experienced low overall incidence of PPH-related hospital transfer. However, the occurrence of PPH itself would likely be reduced with improved legal access to uterotonic medication.

On maternal Post-Partum/Natal depression. A global underrecognized problem and the need for better Treatment strategies.

BACKGROUND: Maternal Postpartum (PPD) or Postnatal Depression (PND) is believed to be the commonest medical complication postpartum. Evidence suggests a significantly higher prevalence of the disease compared to the often reported 10-15%. METHOD: Studies were identified by accessing several databases including PubMed/Medline, PubMed Central, EBSCO, and PsycINFO. RESULTS: Vitamin D (VD) deficiency, hormonal levels alteration (estrogen, progesterone, testosterone, oxytocin, and prolactin), thyroid dysfunction, and increased oxidative stress, play a critical role in PPD etiopathogenesis and pathophysiology. CONCLUSIONS: Treatment strategies should include an integrated approach of antidepressants and psychotherapy, melatonin, diet, sleep improvement, exercise, VD and antioxidants supplementation, and economic and social support.

Oxytocin ameliorates bone cancer pain by suppressing toll-like receptor 4 and proinflammatory cytokines in rat spinal cord.

Bone cancer pain is considered to be mechanistically unique compared with inflammatory or neuropathic pain states. Toll-like receptor 4 (TLR4) is a transmembrane receptor protein which has been reported to be involved in neuropathic pain. However, the role of TLR4 in bone cancer pain is still unclear. Therefore, the aim of this study is to investigate the hypothesis that oxytocin may ameliorate bone cancer pain by suppressing TLR4 in spinal cord. Behavioral analysis and molecular biological experiments were carried out. Our data demonstrated that intrathecally delivery of oxytocin significantly ameliorated the mechanical allodynia and thermal hyperalgesia in bone cancer pain rats. Moreover, oxytocin suppressed the up-regulation of TLR4 and proinflammatory cytokines TNFα and IL-1ß in spinal cord of bone cancer pain rats. Therefore, we concluded that intrathecal administration of oxytocin relieves bone cancer pain by suppressing the up-regulation of TLR4, TNFα and IL-1ß in spinal cord. Oxytocin possesses analgesic efficacy against bone cancer pain and deserves further to confirm its effectiveness in clinically relevant of cancer pain.

Acute effects of oxytocin in music performance anxiety: a crossover, randomized, placebo-controlled trial.

RATIONALE: Individuals with music performance anxiety (MPA) present physical, behavioral, and cognitive manifestations of anxiety, in addition to information processing deficits, especially in facial emotion recognition (FER). OBJECTIVES: To assess the effects of a single dose of intranasal oxytocin (24 IU) on FER in a sample of musicians with high and low MPA (primary outcome), as well as indicators of mood/anxiety and self-assessed performance (secondary outcomes). METHODS: Crossover, randomized, double-blind, placebo-controlled trial involving 43 male musicians with different levels of MPA. Participants completed a static facial emotion recognition task and self-rated mood and performance scales. Data were analyzed using ANOVA 2 × 0 for crossover trials and the Omnibus test (measure of separability between intervention and carryover effects). RESULTS: Only musicians with high MPA treated with oxytocin had a higher accuracy in the recognition of happiness (p < 0.03; d > 0.72). No effects of oxytocin were found on mood indicators or on self-perceived performance, regardless of MPA level. CONCLUSIONS: The results indicate possible benefits of the acute treatment with oxytocin in MPA, which may improve the management of this common and disabling condition that affects professional musicians. The appropriate perception of positive feedback may increase confidence and feelings of social acceptance, reducing symptoms associated with the condition. The lack of effects on mood/anxiety and cognition may be explained by the context-dependent characteristic of the effects of oxytocin, since the experiment did not represent an actual situation of social threat. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos): No. RBR-9cph2q.

Clinical outcomes of prophylactic compression sutures for treatment of uterine atony during the cesarean delivery of twins.

BACKGROUND: Twin pregnancy has a high risk for developing uterine atony (UA). This study aimed to evaluate efficacy and clinical outcomes of prophylactic compression sutures to treat UA during twin cesarean section (CS). METHODS: All patient records of twin deliveries by CS after gestational age of 24 weeks in a large maternity hospital in South Korea between January 2013 and June 2018 were reviewed. Patients with monochorionic monoamniotic twins were excluded from data analysis. In total, 953 women were eligible for data analysis. RESULTS: Of the 953 patients, compression sutures were applied to 147 cases with postpartum bleeding that were refractory to uterine massage and uterotonics. Out of the 147, two patients (1.4%) proceeded to additional uterine artery ligation to achieve hemostasis, yielding a success rate of 98.6%. The rate of transfusion after the first 24 h of delivery in the suture group was not significantly different from that in the non-suture group, suggesting that both groups achieved hemostasis at an equal rate after the first 24 h of delivery. The difference in the operation time between the two groups was only 8.5 min. The rate of subsequent pregnancy among the patients who received compression sutures was 44.4%. CONCLUSIONS: Overall, our findings suggest that with early and fast implementation of compression sutures, UA can be treated in the setting of twin cesarean delivery without significantly increasing maternal morbidity.

Improvement in viability and mineralization of osteoporotic bone marrow mesenchymal stem cell through combined application of photobiomodulation therapy and oxytocin.

The probable positive effects of photobiomodulation therapy (PBMT) and oxytocin (OT) treatments together or alone were evaluated on cell viability along with the changes in the gene expression of Osteocalcin (OC), Osteoprotegerin (OPG), and Runt-related transcription factor 2 (Runx2) levels of sham (healthy)-Bone marrow mesenchymal stem cell(BMMSC) and ovariectomy-induced osteoporosis (OVX)-BMMSC. BMMSC was harvested from healthy and OVX rats and was cultured in osteogenic induction medium (OIM). There were five groups of BMMSCs: (1) sham -BMMSCs; (2) control -OVX-BMMSCs; (3) OT-treated-OVX-BMMSCs; (4) PBMT-treated-OVX-BMMSCs, and (5) OT + PBMT-OVX-BMMSCs. In all 5 groups, BMMSC viability and proliferation as well as gene expression of OC, OPG, and RUNX2 were evaluated. PBMT and PBMT + OT treatments showed a promising effect on the increased viability of OVX-BMMSC (ANOVA test; LSD test, p = 0.01, p = 0.002). The results of gene expression analysis revealed that the sham- BMMSCs responded optimally to OT treatment. It was also found that OVX-BMMSCs responded optimally to PBMT + OT and PBMT treatments at early and middle stages of osteogenic induction process. Nevertheless, they responded optimally to PBMT + OT and OT especially at the late stage of osteogenic induction process. PBMT and PBMT + OT treatments significantly increased viability of OVX-BMMSC in OIM in vitro. Both PBMT and PBMT + OT treatments could promote mineralization of OVX-BMMSC in the culture medium at early and middle stages of osteogenic induction process. Both OT and PBMT + OT treatments could promote mineralization of OVX-BMMSC in vitro at late stages of osteogenic induction process.

Effects of Boiled Dill Seed on Anxiety During Labor: A Randomized Clinical Trial.

OBJECTIVE: To evaluate the effect of boiled dill seed (Anethum graveolens) on anxiety during childbirth compared with oxytocin. METHODS: This study was a randomized clinical trial with 100 pregnant women who were assigned to the oxytocin (50 cases) and the boiled dill seed (50 cases) group by a table of random number. In the boiled dill seed group, 10 g of dill seed was boiled in 100 mL for 10 min and was given to women after filtration once orally at the beginning of active phase. In the oxytocin group, 10 IU of oxytocin in 1000 mL of Ringer solution was prescribed according to the clinical routine. The State-Trait Anxiety Inventory (STAI) in both groups before (at the beginning of the active phase) and after (6 h after the delivery) was completed. Meanwhile, pain intensity and duration of labor, dilatation and effacement scores, Apgar score of newborns, and FHR were measured and evaluated. RESULTS: No statistically significant differences were shown in obvious anxiety scores between the two groups at baseline (P0.05). After the delivery, in the boiled dill seed group, the number of women with severe [0 vs. 8.0% (4/50)] and almost severe [0 vs. 14.0% (7/50)] trait and almost severe [0 vs. 14.0% (7/50)] state anxiety was lower than those in the control group (P=0.050, P=0.041, respectively). Moreover, labor was shorter in the 1st (P 0.01), 2nd (P=0.78) and 3rd (P=0.10) stages in the boiled dill seed group compared to the control group CONCLUSIONS: Dill seed could be used as an effective treatment to reduce anxiety during labor. Dill seed can be effective in reducing the length of labor. Due to lack of maternal and fetal complications, the boiled dill seed could also be used to reduce cesarean section rates in women who are fearful and anxious of delivery. (RCT Code: IRCT201607177065N2).

Carbetocin vs oxytocin for prevention of postpartum hemorrhage after vaginal delivery: A 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.

Empowering midwives to manage postpartum haemorrhage in rural areas of Islamic Republic of Iran: lessons learnt from cases of maternal death.

BACKGROUND: Postpartum haemorrhage is the main cause of maternal mortality in rural areas of low-income countries. AIMS: This study investigated the causes of maternal death from postpartum haemorrhage in rural areas of Sistan and Baluchestan, Islamic Republic of Iran, and determined the effect of three interventions on midwives' management of haemorrhage. METHODS: Maternal deaths in women with postpartum haemorrhage between 9 April 2012 and 9 April 2013 were reviewed to determine what contributed to the death. Following the review, prostaglandin was permitted for use in rural maternity units. A flowchart on managing haemorrhagic shock and a training workshop on management of postpartum haemorrhage were also developed for midwives working in rural areas. After the interventions, all cases of postpartum haemorrhage (n = 81) that occurred during 23 September 2014-23 February 2015 in rural maternity facilities were reviewed based on 19 indicators. A control group (n = 81) was selected from women with postpartum haemorrhage who had been admitted to the same maternity units before the interventions. RESULTS: After the training interventions, more midwives used more than one method to estimate blood loss and higher doses of oxytocin to control haemorrhage. They showed improvements in the use of intravenous fluid therapy, pulse and blood pressure checks, external uterine massage, and uterotonic drugs. Following training, more women were admitted to hospital in a stable condition and recovered and were discharged (P = 0.002), and fewer had surgical interventions (P = 0.007). CONCLUSION: Midwives' management of postpartum haemorrhage improved after the interventions. Training programmes should be based on study of the local situation to identify shortcomings. Regular monitoring of outcomes is needed to detect and resolve failures.

Protocols using detomidine and oxytocin induce ex copula ejaculation in stallions.

Tricyclic antidepressives, such as imipramine, indirectly induce ejaculation by increasing the noradrenaline concentration, which triggers an α-adrenergic response, whereas α-adrenergic agonists, such as xylazine and detomidine, directly trigger ejaculation by activating the α-1 adrenergic receptors. Furthermore, serum oxytocin concentrations in stallions increase drastically before ejaculation, but decline immediately thereafter, implicating the role of this hormone in emission. The objectives of the present study were to: 1) compare the efficiency of various protocols for inducing ex copula ejaculation in stallions, 2) evaluate the benefits of including oxytocin in the protocols, and 3) compare the semen characteristics of ex copula versus in copula ejaculates. Nine protocols were used to induce ex copula ejaculation using various combinations of xylazine (X; 0.66 mg/kg, iv); oxytocin (O; 20 IU, iv), imipramine (I; 3 mg/kg, orally), and detomidine (D; 0.02 mg/kg, iv). Imipramine was given 2 h prior to the administration of α-adrenergic agonist (detomidine or xylazine) and oxytocin. If ejaculation did not occur within 10 min after treatment with an α-adrenergic agonist, a half-dose of the same product was injected. Twelve sexually mature stallions (6-26 y) were used; 9 of 12 stallions responded to the treatment. Two stallions responded to X or XO, four stallions responded to IX and IXO, one stallion responded to DO, and five responded to IDO. Stallions that responded to detomidine did not respond to xylazine. No stallion ejaculated in response to D, ID, or IO. Erections and masturbation occurred only in imipramine-treated stallions. Sperm quality was similar among all the protocols and was not significantly different from those in in copula ejaculates collected with an artificial vagina. In a separate trial, none of these protocols induced ex copula ejaculation in 2-3 y old stallions. The side effects included sialorrhea after imipramine administration in all the stallions and sedation after administration of xylazine or detomidine. In conclusion, the new protocol, IDO, and the traditional protocol, IX, had similar results, with IDO being a useful alternative protocol in stallions for which IX was not effective. Therefore, attempts using both the protocols are encouraged, as stallions that ejaculated upon administration of detomidine did not ejaculate when xylazine was administered, whereas those that responded to xylazine did not respond to detomidine.

Cumulative Risk of the Oxytocin Receptor Gene Interacts with Prenatal Exposure to Oxytocin Receptor Antagonist to Predict Children's Social Communication Development.

Compelling evidence for the far-reaching role of oxytocin (OT) in social cognition and affiliative behaviors set the basis for examining the association between genetic variation in the OT receptor (OXTR) gene and risk for autism spectrum disorder (ASD). In the current study, gene-environment interaction between OXTR and prenatal exposure to either OT or OXTR antagonist (OXTRA) in predicting early social communication development was examined. One hundred and fifty-three children (age: M = 4.32, SD = 1.07) were assigned to four groups based on prenatal history: children whose mothers prenatally received OXTRA and Nifedipine to delay preterm labor (n = 27); children whose mothers received Nifedipine only to delay preterm labor (n = 35); children whose mothers received OT for labor augmentation (n = 56), and a no intervention group (n = 35). Participants completed a developmental assessment of intelligence quotient (IQ), adaptive behavior, and social communication abilities. DNA was extracted via buccal swab. A genetic risk score was calculated based on four OXTR single nucleotide polymorphisms (rs53576, rs237887, rs1042778, and rs2254298) previously reported to be associated with ASD symptomatology. OXTRrisk-allele dosage was associated with more severe autism diagnostics observation schedule (ADOS) scores only in the OXTRA group. In contrast, in the Nifedipine, OT, and no intervention groups, OXTRrisk-allele dosage was not associated with children's ADOS scores. These findings highlight the importance of both genetic and environmental pathways of OT in signaling early social development and raise the need for further research in this field. Autism Res 2019, 12: 1087-1100. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In the current study, we examined if the association between prenatal exposure to an oxytocin receptor antagonist (OXTRA) and autism spectrum disorder (ASD) related impairments are dependent on an individual's genetic background for the oxytocin receptor gene (OXTR). Children who carried a greater number of risk alleles for the OXTR gene and whose mothers received OXTRA to delay preterm labor showed more ASD-related impairments. The results highlight the importance of both genetic and environmental pathways of oxytocin in shaping early social development.

Effects of Prophylactic Oxytocin on Bleeding Outcomes in Women Undergoing Dilation and Evacuation: A Randomized Controlled Trial.

OBJECTIVE: To estimate whether routine use of intravenous oxytocin decreases the frequency of interventions to control excess blood loss during dilation and evacuation (D&E). METHODS: In this multisite, randomized, double-blind, placebo-controlled trial, women undergoing D&E at 18-24 weeks of gestation received 30 units of oxytocin in 500 mL of intravenous fluid or 500 mL of intravenous fluid alone initiated on speculum placement. The primary outcome was the frequency of interventions to control excess bleeding. A sample size of 75 patients per group was needed to detect a 15% decrease in intervention from 20% to 5% with 80% power and two-sided alpha 0.05. Secondary outcomes included measured blood loss, complications, procedure duration, postoperative pain, and patient satisfaction. RESULTS: From November 2014 to February 2018, we screened 337 women and randomized 160 to receive prophylactic oxytocin (n=82) or placebo (n=78). Demographic characteristics were similar between groups. The frequency of interventions for bleeding, our primary outcome, was 7.3% in the oxytocin group vs 16.7% in the placebo group, difference of 9.4% (95% CI -21.0% to 1.9%). Interventions primarily included uterine massage and uterotonic administration. Among our secondary outcomes, median measured blood loss was lower in the oxytocin group at 152 (interquartile range 98-235) mL vs 317 (interquartile range 168-464) mL (95% CI 71.6-181.5). Frequency of hemorrhage, defined as blood loss of 500 mL or more and 1,000 mL or more, was lower in the oxytocin group at 3.7% vs 21.8%, difference of 18% (95% CI -29 to -6.9%) and 1.2% vs 10.3%, difference of 9.0% (95% CI -17 to -0.7%), respectively. Procedures were shorter in the oxytocin group at a median of 11.0 (interquartile range 8.0-14.0) vs 13.5 (interquartile range 10.0-19.0) minutes in the placebo group (95% CI 1.0-4.0). We found no differences in the frequency of nonhemorrhage complications, pain scores, or satisfaction scores between groups. CONCLUSION: Prophylactic use of oxytocin during D&E at 18-24 weeks of gestation did not decrease the frequency of interventions to control bleeding. However, oxytocin did decrease blood loss and frequency of hemorrhage. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT02083809.

Administration of carbetocin after the first piglet was born reduced farrowing duration but compromised colostrum intake in newborn piglets.

Carbetocin is an oxytocin-like compound with long acting properties that has recently been introduced to both human and domestic animal obstetrics. The aims of the present study were to evaluate the effects of carbetocin administration after the first piglet was born on farrowing duration, birth interval, colostrum consumption and vitality index in newborn piglets. In total, 186 sows and their offspring (n = 2611 piglets) were distributed into three groups: 1) CONTROL: sows were allowed to farrow naturally (n = 66); 2) OXY: sows were administered oxytocin 20 IU intramuscularly after the first piglet was born (n = 62); and 3) CARBE: sows were administered carbetocin 0.6 µg/kg intramuscularly after the first piglet was born (n = 58). The reproductive data of sows including farrowing duration, total number of piglets born per litter (TB), number of piglets born alive per litter (BA), proportion of stillborn piglets per litter (SB) and proportion of mummified fetuses per litter (MF) were recorded. Piglet vitality index including skin colour, integrity of the umbilical cord, heart rate, blood oxygen saturation, screaming score, udder stimulation score, movement capacity and number of completed circles around enclosure were determined. Birth weights of the piglets were measured immediately at birth and again at 24 h thereafter to determine the individual colostrum intake of the piglets. On average, the farrowing duration, birth interval and BA were 188.0 ±â€¯95.7 min, 12.5 ±â€¯18.3 min, and 12.3 ±â€¯2.9 piglets per litter, respectively. The farrowing duration of the sows was reduced in CARBE group (151.2 ±â€¯11.9 min) compared to OXY (180.2 ±â€¯11.5 min, P = 0.003) and CONTROL (227.7 ±â€¯11.2 min, P < 0.001) groups. Birth interval of piglets in all categories of birth weight in the CARBE group was shorter than those in the CONTROL group (P < 0.05). However, the colostrum yield of sows in CARBE group (2398 ±â€¯133 g) was lower than CONTROL and OXY groups (3371 ±â€¯125 g and 3549 ±â€¯128 g, respectively; P < 0.001). Similarly, colostrum intake of piglets in the CONTROL and OXY groups was higher than in the CARBE group (276.4 ±â€¯11.0 g, 286.4 ±â€¯13.6 g and 225.3 ±â€¯14.0 g, respectively; P < 0.05). The percentage of stillborn piglets in CARBE was higher than OXY (8.7 ±â€¯1.1% vs 5.3 ±â€¯1.1%, P < 0.05) but did not differ significantly compared to CONTROL (7.5 ±â€¯1.1%, P > 0.05). The piglet movement capacity in CONTROL was lower than CARBE group (1.36 vs 1.48, P < 0.05) but was not different compared to OXY group (1.40, P > 0.05). In conclusion, administration of carbetocin after the birth of the first piglet reduced the farrowing duration of sows, but increased the number of stillborn piglets and reduced the colostrum yield of sows.

'Nausicaa' compression suture: a simple and effective alternative to hysterectomy in placenta accreta spectrum and other causes of severe postpartum haemorrhage.

Postpartum haemorrhage (PPH), especially resulting from placenta accreta spectrum (PAS), has become a worldwide concern in maternity care. We describe a novel method of uterine compression sutures (the 'Nausicaa' technique) as an alternative to hysterectomy for patients who have suffered from major PPH. We applied this technique in 68 patients with major PPH during caesarean section (including 43 patients with PAS, 20 patients with placenta praevia totalis, and five patients with uterine atony), and none of these patients required further hysterectomy. We conclude that our Nausicaa suture is a simple and feasible alternative to hysterectomy in patients suffering from major PPH.