Desmopressin to prevent and treat bleeding in pregnant women with an inherited bleeding disorder: A systematic literature review
Journal of thrombosis and haemostasis : JTH. 2023
BACKGROUND Although desmopressin (DDAVP) is an accessible and inexpensive hemostatic drug, its use in pregnancy is still debated due to safety uncertainties. OBJECTIVE We aim to review safety and effectiveness of DDAVP in women with an inherited bleeding disorder during pregnancy and delivery. METHODS Databases were searched for articles up to July 25(th) 2022, reporting maternal and/or neonatal outcomes. PRISMA methodology was followed (PROSPERO CRD42022316490). RESULTS Fifty-three studies were included, comprising 273 pregnancies. Regarding maternal outcomes, DDAVP was administered in 73 pregnancies during pregnancy and in 232 pregnancies during delivery. Safety outcome was reported in 245 pregnancies, with severe adverse event reported in two (1%; hyponatremia with neurological symptoms).Overall, DDAVP was used as monotherapy in 234 pregnancies with effectiveness reported in 153 pregnancies (82% effective; 18% ineffective). Regarding neonatal outcomes, out of 60 pregnancies with reported neonatal outcomes after DDAVP use during pregnancy, two children (3%) had a severe adverse event (preterm delivery n=1; fetal growth restriction n=1). Of the 232 deliveries, 169 neonates were exposed to DDAVP during delivery and in 114 neonates, safety outcome was reported. Two children (2%) experienced a moderate adverse event (low Apgar score n=1; transient hyperbilirubinemia not associated with DDAVP n=1). CONCLUSION DDAVP use during pregnancy and delivery seems safe for the mother with special attention to the occurrence of hyponatremia and for the child, especially during delivery. However, due to poor study designs and limited documentation of outcomes, a well-designed prospective study is warranted.
Comparison of Clinical Efficacy and Safety between Misoprostol and Oxytocin in the Prevention of Postpartum Hemorrhage: A Meta-Analysis
Journal of healthcare engineering. 2022;2022:3254586
In order to systematically evaluate the clinical efficacy and safety of misoprostol versus oxytocin in the prevention of postpartum hemorrhage, this paper provides evidence-based reference for clinical medication, computerized retrieval of Chinese biomedical literature database (CBM), PubMed, Embase, Cochrane Library, and clinical trials. The retrieval period is from the establishment of each database to October 1, 2021. Published randomized controlled trials (RCTS) are included in this study. The literature is screened and evaluated according to inclusion and exclusion criteria, and meta-analysis is performed using RevMan 5.3 software. A total of 13 RCTS are included, with a total of 24754 parturients. The meta-analysis shows the average blood loss (SMD = 0.10, 95% CI (-0.11, 0.32), P=0.35), the time of the third stage of labor (SMD = 0, 95% CI (-0.07, 0.08), P=0.95), and blood transfusion rate (RR = 0.80, 95% CI (0.63, 1.02), P=0.07). However, the incidences of shivering (RR = 2.61, 95% CI (1.79, 0.81), P < 0.00001) and vomiting (RR = 2.78, 95% CI (1.85, 4.18), P < 0.00001) are significantly higher than those in oxytocin group. The effect of misoprostol on preventing postpartum hemorrhage is similar to that of oxytocin, but the incidence of adverse reactions is high, and the occurrence of adverse reactions should be closely watched in the use process. Due to the limitations of the included studies, multicenter, large-sample, and high-quality RCTS are still needed in the future to further verify this conclusion.
Effectiveness and safety of carboxytocin versus oxytocin in preventing postpartum hemorrhage: A systematic review and meta-analysis
The journal of obstetrics and gynaecology research. 2022
OBJECTIVE This study compared the effectiveness and safety of carbetocin and oxytocin in preventing postpartum hemorrhage (PPH). METHODS A systematic literature search was performed on PubMed, Embase, and the Cochrane Library for relevant studies published up to February 2019. Next, two independent reviewers screened the studies according to the selection criteria as well as the strategies recommended by the Cochrane Collaboration. Data were then extracted and evaluated. All statistical analyses were performed using RevMan 5.1. RESULTS A total of 24 studies involving 37 383 patients were included for analysis. For cesarean section patients, carbetocin was superior to oxytocin in reduction of the need for additional uterine contraction (odds ratio [OR] = 0.48, 95% confidence interval [CI] [0.35, 0.65], p < 0.00001), PPH (OR = 0.70, 95% CI [0.51, 0.95], p = 0.02), blood loss (mean [MD] = -64.36, 95% CI [-107.78, -20.93], p = 0.004), and transfusion (OR = 0.59, 95% CI [0.42, 0.82], p = 0.002), and there was no significant difference in severe PPH (OR = 0.84, 95% CI [0.66, 1.090], p = 0.19). For vaginal delivery patients, carbetocin was superior to oxytocin in reduction of the need for additional uterine contractions (OR = 0.48, 95% CI [0.25, 0.93], p = 0.03), PPH (OR = 0.28, 95% CI [0.09, 0.91], p = 0.03), and blood loss (MD = -63.52, 95% CI [-113.43, -13.60], p = 0.01), and there were no significant differences in severe PPH (OR = 0.82, 95% CI [0.40, 1.69], p = 0.59) and transfusion (OR = 0.60, 95% CI [0.22, 1.61], p = 0.31). With regard to safety, for cesarean section patients, carbetocin was superior to oxytocin in reduction of the incidence of headache (OR = 0.72, [0.55, 0.95], p = 0.02), and there were no significant differences in nausea, vomiting, abdominal pain, flushing, tremors, itching, dizziness, and fever. For vaginal delivery patients, there were no significant differences in nausea, vomiting, headache, abdominal pain, flushing, tremors, itching, dizziness, and fever between the two drugs. CONCLUSION For patients undergoing cesarean section and vaginal delivery, carbetocin was superior to oxytocin in effectiveness and similar in safety. Therefore, carbetocin is expected to be an alternative uterine contraction agent for preventing PPH.
Effect of Carbetocin on Postpartum Hemorrhage after Vaginal Delivery: A Meta-Analysis
Computational and Mathematical Methods in Medicine. 2022;2022:6420738
BACKGROUND The efficacy of oxytocin and carbetocin in preventing postpartum hemorrhage (PPH) in women with vaginal delivery has been controversial. This study is aimed at conducting a meta-analysis that compares the efficacy of carbetocin and oxytocin in the prevention of PPH among women with vaginal delivery. METHODS Literature was retrieved from PubMed, Medline, Embase, CENTRAL, and CNKI databases. The randomized controlled trials (RCTs) that compare the efficacy of carbetocin and oxytocin to prevent PPH were searched. Data from the included literatures were extracted by two researchers, including author, title, publication date, study type, study number, the incidence of PPH, number of patients requiring additional uterotonics, and number of patients requiring blood transfusion. Jadad scale was used to evaluate the quality of the included RCTs. The Chi-square test was adopted for the heterogeneity test. A fixed-effect model was used for analysis if heterogeneity did not exist between literatures. If heterogeneity exists between literatures, a random-effect model was used for analysis. The source of heterogeneity was explored by subgroup analysis and sensitivity analysis. RESULTS The incidence of PPH in the carbetocin group was lower than that in the oxytocin group (OR = 0.62, 95% CI (0.46, 0.84), Z = 3.14, P = 0.002). There was no heterogeneity among studies (χ (2) = 7.29, P = 0.12, I (2) = 45%) and no significant publication bias (P > 0.05). The proportion of women requiring additional uterotonics in the carbetocin group was lower than that in the oxytocin group (OR = 0.41, 95% CI (0.29, 0.56), Z = 5.34, P < 0.00001). There was no heterogeneity among studies (χ (2) = 0.82, P = 0.84, I (2) = 0%) and no significant publication bias (P > 0.05). There was no significant difference in the proportion of women needing blood transfusion between the carbetocin group and the oxytocin group (OR = 0.92, 95% CI (0.66, 1.29), Z = 0.46, P = 0.64). There was no heterogeneity among studies (χ (2) = 3.06, P = 0.55, I (2) = 0%) and no significant publication bias (P > 0.05). CONCLUSION Carbetocin is superior to oxytocin in preventing PPH among women with vaginal delivery and can be widely used in clinical practice.
Elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid: a systematic review and meta-analysis
BMC women's health. 2022;22(1):14
BACKGROUND Elagolix is effective and safe for treating menorrhagia in women with uterine fibroid. However, it is reported to be associated with hypoestrogenism that can be alleviated by adding estradiol/norethindrone acetate. This systematic review and meta-analysis aimed to determine the effectiveness of elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid by comparing: elagolix versus placebo and elagolix versus estradiol/norethindrone acetate. METHODOLOGY The Cochrane Central Register of Controlled Trials (CENTRAL 2021, Issue 3 of 12), MEDLINE databases (1980 to December week 1, 2020), and trial registries for relevant randomized clinical trials were used. All randomized clinical trials were reviewed and evaluated. Random effects models were used to estimate the dichotomous outcomes and mean differences with 95% confidence intervals. Data for risk of bias, heterogeneity, sensitivity, reporting bias and quality of evidence were assessed. RESULTS Four randomized controlled trials with 1949 premenopausal women from 323 locations were included. Elagolix improved menstrual blood loss of less than 80 ml (RR 4.81, 95% CI 2.45 to 9.45; four trials, 869 participants; moderate quality evidence) or more than 50% reduction from baseline (RR 4.87, 95% CI 2.55 to 9.31; four trials, 869 participants; moderate quality evidence) compared to placebo. There was no difference in menstrual blood loss of less than 80 ml (RR 1.08, 95% CI 1.00 to 1.16; five trials, 1365 participants; moderate quality evidence) or more than 50% reduction from baseline between the elagolix (RR 1.08, 95% CI 1.01 to 1.15; five trials, 1365 participants; high quality evidence) and elagolix with estradiol/norethindrone acetate. In both comparisons, elagolix has reduced the mean percentage change in uterine and fibroid volume, improved symptoms, and health-related quality of life. More patients had hot flush, and bone mineral density loss in the elagolix treatment compared to both placebo and elagolix with estradiol/norethindrone acetate. CONCLUSIONS Elagolix appeared to be effective in reducing heavy menstrual bleeding caused by uterine fibroid and combination with estradiol/norethindrone acetate was able to alleviate the hypoestrogenism side effects in premenopausal women. Review registration PROSPERO CDR 42021233898.
Side-effects of oxytocin in postpartum hemorrhage: a systematic review and meta-analysis
American Journal of Translational Research. 2022;14(3):1934-1951
OBJECTIVE To evaluate the side-effects of oxytocin for the prevention of postpartum hemorrhage (PPH) in randomized controlled trials (RCTs). METHODS Electronic databases (Web of Science, Embase, PubMed, Elsevier ScienceDirect, the Cochrane Library, and ClinicalTrials.gov) were searched from the beginning of indexing to Sep 2021. RCTs comparing oxytocin with non-oxytocin uterotonic agent(s) or non-pharmacologic interventions for the prevention of PPH were eligible. RESULTS Overall, sixty-one RCTs meeting the inclusion criteria were included, involving 68834 participants. Twenty-seven types of side-effects were reported in this study. There were 24, 35, or 2 trials assessed as high medium and low quality, respectively. Compared with non-oxytocin, oxytocin had significantly lower risk for shivering (RR=0.31, 95% CI=0.23-0.41, n=36680), fever (RR=0.27, 95% CI=0.20-0.37, n=34031), and diarrhea (RR=0.48, 95% CI=0.35-0.66, n=30883). Other side-effects were not found associated with oxytocin. CONCLUSION Oxytocin use was association with a significantly lower incidence of shivering, fever, and diarrhea events and did not increase risk of other side-effects during the third stage of labor. These observations may aid obstetricians and gynecologists in weighing up the benefits and risks associated with oxytocin in prevention and treatment of PPH during the third stage of labor.
Comparing and combining evidence of treatment effects in randomized and nonrandomized studies on the use of misoprostol to prevent postpartum hemorrhage
Journal of evidence-based medicine. 2021
OBJECTIVE Postpartum hemorrhage (PPH) is a preventable condition and the main cause of maternal death worldwide. Evidence on the effectiveness of misoprostol in the prevention of PPH has been generated from both randomized controlled trials (RCTs) and nonrandomized studies (NRS). This study aimed to compare the results of RCTs and NRS, and to compare Classical and Bayesian approaches of combining the results of RCTs and NRS on the use of misoprostol versus placebo in the prevention of PPH. METHODS We searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials for appropriate studies. We pooled estimates of effects from RCTs and NRS seperately, using random-effects models, then merged them using classical and Bayesian random effects meta-analysis. RESULTS A total of 34 studies (20 RCTs and 14 NRS) involving 74 204 participants were identified. The summary odds ratio (OR) from RCTs for the use of misoprostol in the prevention of PPH was 0.69 (95% confidence interval [CI]: 0.59 to 0.80). The summary OR from NRS was 0.46 (95% CI: 0.36 to 0.63). Classical and Bayesian approaches of combining the two study designs both showed benefit of misoprostol in preventing PPH, with similar effects. CONCLUSIONS Both RCTs and NRS show comparable significant benefit for the use of misoprostol in the prevention of PPH.
Side-effects of carbetocin to prevent postpartum hemorrhage: A systematic review and meta-analysis of randomized controlled trials
Pharmacology research & perspectives. 2021;9(2):e00745
Postpartum hemorrhage (PPH) increases the risk of maternal death worldwide. Heat-stable carbetocin, a long-acting oxytocin analog, is a newer uterotonic agent. Clinicians do not fully understand its side-effects, particularly the unanticipated side-effects. The aim of this study is to investigate the side-effects of carbetocin to PPH. The Cochrane Library, Web of Science, PubMed, Elsevier ScienceDirect, Embase, and ClinicalTrials.gov were searched from the inception to September 2020. Randomized controlled trials (RCTs) that considered pregnant women who received carbetocin before delivery and provided at least one adverse event were included. Statistical analysis included random or fixed-effect meta-analyses using relative risk. Stratified analyses and sensitivity analyses were also performed. Begger's and Egger's test and funnel plots were used to assess the publication bias. Seventeen RCTs involving 32,702 women were included, and all these studies ranked as medium- to high-quality. Twenty-four side-effects were reported. The use of carbetocin had a lower risk of vomiting in intravenously (0.53, 0.30 to 0.93) and cesarean birth (0.51, 0.32 to 0.81) women, and had a slightly higher risk of diarrhea (8.00, 1.02 to 62.79) compared with oxytocin intervention. No significant difference was found among other side-effects. Evidence from our systematic review and meta-analysis of 17 RCTs suggested that the risk of vomiting decreased with carbetocin use in the prevention of PPH after delivery.
The Effect of Chamomile on Pain and Menstrual Bleeding in Primary Dysmenorrhea: A Systematic Review
International journal of community based nursing and midwifery. 2021;9(3):174-186
BACKGROUND Primary dysmenorrhea is characterized by pain during menstruation without any pelvic pathology. It is a common problem among females in their reproductive age which is caused by increased production of prostaglandin in the endometrium as one of leading causes. Chamomile extract ceases the production of prostaglandins and leukotrienes. The aim of this study was to systematically review the clinical trials to determine the effect of Chamomile on pain and menstural bleeding in primary dysmenorrhea. METHODS Search process to find relevant articles was conducted on electronic Iranian (MagIran, SID) and international databases (Google Scholar, Science Direct, PubMed, ProQuest, Cochrane library, Scopus, Web of Science and EBSCO), using English keywords and Persian equivalents such a "Dysmenorrhea", "Pain", "Menstrual bleeding" and "Chamomil" without a time limit until March 2020. Irrelevant, duplicate, descriptive, or qualitative studies were excluded. To evaluate the quality of articles, we used the Cochran's Risk of Bias tool. RESULTS Among124 articles found in the initial search, finally 7 clinical trials (with a sample size of 1033) were systematically examined. Two out of 7 studies examined the effect of Chamomile on the pain of primary dysmenorrhea, 2 studies on the effect of Chamomile on menstrual bleeding volume, and 3 on the effect of Chamomileon pain and menstural bleeding in primary dysmenorrhea. CONCLUSION Based on results of the most reviewed studies, Chamomile can be considered as an effective treatment for primary dysmenorrhea and reducing menstrual bleeding.
Oriahnn: New Drug Approved for Treating Heavy Menstrual Bleeding in Women With Uterine Fibroids
The Annals of pharmacotherapy. 2021;:10600280211015987
OBJECTIVE To review data of elagolix plus estradiol and norethindrone acetate as add-back therapy for the treatment of heavy menstrual bleeding (HMB) in premenopausal women with uterine fibroids. DATA SOURCES Literature search of PubMed/MEDLINE and SCOPUS was performed using the search terms Oriahnn; elagolix, estradiol, norethindrone AND heavy menstrual bleeding; elagolix AND heavy menstrual bleeding; and gonadotropin-releasing hormone receptor antagonist AND heavy menstrual bleeding between January 1, 1996, to March 2, 2021. Additional data were obtained from prescribing information, references of identified articles, and abstracts from scientific meetings. STUDY SELECTION/DATA EXTRACTION Clinical trials and articles discussing elagolix plus add-back therapy for the management of HMB in women with leiomyomas were included. DATA SYNTHESIS Phase 3 trials met the primary end point of menstrual blood loss (MBL) less than 80 mL at month 6 and at least a 50% reduction in MBL from baseline to the final month in 68.5% of women taking elagolix plus add-back therapy enrolled in UF-1 (8.7% placebo) and 76.5% of women in UF-2 (10% placebo). The most common adverse effects include hot flushes, nausea, headache, and night sweats. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE Women with symptomatic uterine fibroids can experience significant HMB resulting in distress, depression, and anxiety. Surgical intervention remains the most commonly recommended and chosen treatment. Elagolix plus add-back therapy is a nonsurgical, oral option. CONCLUSIONS Elagolix plus add-back therapy is effective in reducing menstrual bleeding associated with uterine fibroids. However, there are several warnings and precautions that must be considered.