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Psychiatry Research Oct 2023Positive allosteric modulators of γ-aminobutyric acid-A (GABA) receptors, or GABAkines, play important roles in the treatment of depression, epilepsy, insomnia, and... (Meta-Analysis)
Meta-Analysis
Positive allosteric modulators of γ-aminobutyric acid-A (GABA) receptors, or GABAkines, play important roles in the treatment of depression, epilepsy, insomnia, and other disorders. Recently, some new GABAkines (zuranolone and brexanolone) have been administrated to patients with major depressive disorder (MDD) or postpartum depression (PPD) in randomized controlled trials (RCTs). This study aims to systematically review and examine the efficacy and safety of zuranolone or brexanolone for treatment of depression. A systematic literature retrieval was conducted through August 20, 2023. RCTs evaluating the efficacy and safety of zuranolone or brexanolone for treatment of depression were included. Eight studies (nine reports) were identified in the study. The percentages of patients with PPD achieving Hamilton Depression Rating Scale (HAM-D) response and remission were significantly higher after brexanolone or zuranolone administration compared with placebo at different points. The percentages of patients with MDD achieving HAM-D response and remission were significantly increased during the zuranolone treatment period compared with placebo. In addition, zuranolone caused more adverse events in patients with MDD compared with placebo. Our findings support the effects of brexanolone on improving the core symptoms of depression in patients with PPD, and the potential of zuranolone in treating patients with MDD or PPD.
Topics: Female; Humans; Antidepressive Agents; Depression, Postpartum; Depression; Randomized Controlled Trials as Topic; Depressive Disorder, Major
PubMed: 37683318
DOI: 10.1016/j.psychres.2023.115450 -
International Journal of Environmental... Apr 2020: The aim of this systematic review was to summarize the key findings of empirical studies assessing the influence of maternal depression on child attachment security...
: The aim of this systematic review was to summarize the key findings of empirical studies assessing the influence of maternal depression on child attachment security measured before 24 months after birth. : The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. A literature search was conducted on the EBSCO (Academic Search Complete; Health Source: Nursing/Academic Edition; MEDLINE; PsycARTICLES) and PubMed databases, with AND as search terms with Boolean operators. Study design or sample size did not affect inclusion. After screening, 29 of the 1510 unique publications originally identified were included in the review. : The studies reveal an equivocal association between maternal depression and child attachment security. Our findings indicate that depression had a significant influence on the attachment style almost only when diagnosed by structured interview: Depression measured by self-descriptive questionnaires was unrelated to attachment style. Furthermore, postpartum depression was found to be significant only when measured up to six months after childbirth. : The relationship between maternal depression and infant attachment is both complex and dynamic, and the possible negative effects of depression might be compensated by maternal involvement in childcare. Therefore, further studies in this area should employ a reliable methodology for diagnosing depression and a suitable time point for measuring it; they should also adopt a multifactorial and prospective approach. It is important to note that breastfeeding/formula feeding was omitted as a factor in the majority of studies.
Topics: Child; Depression; Depression, Postpartum; Female; Humans; Infant; Infant, Newborn; Mother-Child Relations; Mothers; Object Attachment; Research Design; Surveys and Questionnaires
PubMed: 32295106
DOI: 10.3390/ijerph17082675 -
Archives of Women's Mental Health Feb 2019Postpartum depression can have detrimental effects on both a mother's physical and mental health and on her child's growth and emotional development. The aim of this... (Meta-Analysis)
Meta-Analysis
Postpartum depression can have detrimental effects on both a mother's physical and mental health and on her child's growth and emotional development. The aim of this study is to assess the effectiveness of exercise/physical activity-based interventions in preventing and treating postpartum depressive symptoms in primiparous and multiparous women to the end of the postnatal period at 52 weeks postpartum. Electronic databases were searched for published and unpublished randomised controlled trials of exercise/physical activity-based interventions in preventing and treating depressive symptoms and increasing health-related quality of life in women from 4 to 52 weeks postpartum. The results of the studies were meta-analysed and effect sizes with confidence intervals were calculated. The Grading of Recommendations Assessment and Development and Evaluation (GRADE) system was used to determine the confidence in the effect estimates. Eighteen trials conducted across a range of countries met the inclusion criteria. Most of the exercise interventions were aerobic and coaching compared to usual care, non-intervention and active controls. Small effect sizes of exercise-based interventions in reducing depressive symptoms were observed collectively and the quality of evidence was low across the individual studies. Although exercise-based interventions could create an alternative therapeutic approach for preventing major depression in postpartum women who experience subthreshold elevated depressive symptoms, the clinical effectiveness and the cost-effectiveness of exercise-based and physical activity interventions need to be better established. There is a need for further more rigorous testing of such interventions in high-quality randomised controlled trials against active control conditions before large-scale roll-out of these interventions in clinical practice is proposed.
Topics: Depression; Depression, Postpartum; Exercise; Exercise Therapy; Female; Humans; Postpartum Period; Quality of Life; Treatment Outcome
PubMed: 29882074
DOI: 10.1007/s00737-018-0869-3 -
Journal of Women's Health (2002) Jun 2022Breastfeeding has many positive effects on the health of infants and mothers, however, the effect of breastfeeding on maternal mental health is largely unknown. The...
Breastfeeding has many positive effects on the health of infants and mothers, however, the effect of breastfeeding on maternal mental health is largely unknown. The goal of this systematic review was to (1) synthesize the existing literature on the effects of breastfeeding on maternal mental health, and (2) inform breastfeeding recommendations. A literature search was conducted in electronic databases using search terms related to breastfeeding ( breastfeeding, infant feeding practices) and mental health conditions ( mental illness, anxiety, depression), resulting in 1,110 records. After reviewing article titles and abstracts, 339 articles were advanced to full-text review. Fifty-five articles were included in the final analysis. Thirty-six studies reported significant relationships between breastfeeding and maternal mental health outcomes, namely symptoms of postpartum depression and anxiety: 29 found that breastfeeding is associated with fewer mental health symptoms, one found it was associated with more, and six reported a mixed association between breastfeeding and mental health. Five studies found that breastfeeding challenges were associated with a higher risk of negative mental health symptoms. Overall, breastfeeding was associated with improved maternal mental health outcomes. However, with challenges or a discordance between breastfeeding expectations and actual experience, breastfeeding was associated with negative mental health outcomes. Breastfeeding recommendations should be individualized to take this into account. Further research, specifically examining the breastfeeding experiences of women who experienced mental health conditions, is warranted to help clinicians better personalize breastfeeding and mental health counseling.
Topics: Anxiety; Breast Feeding; Depression, Postpartum; Female; Humans; Infant; Mental Health; Mothers
PubMed: 35442804
DOI: 10.1089/jwh.2021.0504 -
American Journal of Obstetrics &... Aug 2023Tranexamic acid is a cost-effective intervention for the prevention of postpartum hemorrhage among women who undergo cesarean delivery, but the evidence to support its... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Tranexamic acid is a cost-effective intervention for the prevention of postpartum hemorrhage among women who undergo cesarean delivery, but the evidence to support its use is conflicting. We conducted this meta-analysis to evaluate the efficacy and safety of tranexamic acid in low- and high-risk cesarean deliveries.
DATA SOURCES
We searched MEDLINE (via PubMed), Embase, the Cochrane Library, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform portal from inception to April 2022 (updated October 2022 and February 2023) with no language restrictions. In addition, grey literature sources were also explored.
STUDY ELIGIBILITY CRITERIA
All randomized controlled trials that investigated the prophylactic use of intravenous tranexamic acid in addition to standard uterotonic agents among women who underwent cesarean deliveries in comparison with a placebo, standard treatment, or prostaglandins were included in this meta-analysis.
METHODS
We used the revised Cochrane Risk of Bias tool (RoB 2.0) to assess the quality of the included randomized controlled trials. RevMan 5.4 was used to conduct all statistical analyses using a random-effects model.
RESULTS
We included 50 randomized controlled trials (6 in only high-risk patients and 2 with prostaglandins as the comparator) that evaluated tranexamic acid in our meta-analysis. Tranexamic acid reduced the risk for blood loss >1000 mL, the mean total blood loss, and the need for blood transfusion in both low- and high-risk patients. Tranexamic acid was associated with a beneficial effect in the secondary outcomes, including a decline in hemoglobin levels and the need for additional uterotonic agents. Tranexamic acid increased the risk for nonthromboembolic adverse events but, based on limited data, did not increase the incidence of thromboembolic events. The administration of tranexamic acid before skin incision, but not after cord clamping, was associated with a large benefit. The quality of evidence was rated as low to very low for outcomes in the low-risk population and moderate for most outcomes in the high-risk subgroup.
CONCLUSION
Tranexamic acid may reduce the risk for blood loss in cesarean deliveries with a higher benefit observed in high-risk patients, but the lack of high-quality evidence precludes any strong conclusions. The administration of tranexamic acid before skin incision, but not after cord clamping, was associated with a large benefit. Additional studies, especially in the high-risk population and focused on evaluating the timing of tranexamic acid administration, are needed to confirm or refute these findings.
Topics: Humans; Female; Pregnancy; Tranexamic Acid; Blood Loss, Surgical; Cesarean Section; Randomized Controlled Trials as Topic; Postpartum Hemorrhage; Antifibrinolytic Agents; Prostaglandins
PubMed: 37311484
DOI: 10.1016/j.ajogmf.2023.101049 -
American Journal of Obstetrics and... Apr 2020To assess the efficacy, effectiveness, and safety of uterine balloon tamponade for treating postpartum hemorrhage. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the efficacy, effectiveness, and safety of uterine balloon tamponade for treating postpartum hemorrhage.
STUDY DESIGN
We searched electronic databases (from their inception to August 2019) and bibliographies. We included randomized controlled trials, nonrandomized studies, and case series that reported on the efficacy, effectiveness, and/or safety of uterine balloon tamponade in women with postpartum hemorrhage. The primary outcome was the success rate of uterine balloon tamponade for treating postpartum hemorrhage (number of uterine balloon tamponade success cases/total number of women treated with uterine balloon tamponade). For meta-analyses, we calculated pooled success rate for all studies, and relative risk with 95% confidence intervals for studies that included a comparative arm.
RESULTS
Ninety-one studies, including 4729 women, met inclusion criteria (6 randomized trials, 1 cluster randomized trial, 15 nonrandomized studies, and 69 case series). The overall pooled uterine balloon tamponade success rate was 85.9% (95% confidence interval, 83.9-87.9%). The highest success rates corresponded to uterine atony (87.1%) and placenta previa (86.8%), and the lowest to placenta accreta spectrum (66.7%) and retained products of conception (76.8%). The uterine balloon tamponade success rate was lower in cesarean deliveries (81.7%) than in vaginal deliveries (87.0%). A meta-analysis of 2 randomized trials that compared uterine balloon tamponade vs no uterine balloon tamponade in postpartum hemorrhage due to uterine atony after vaginal delivery showed no significant differences between the study groups in the risk of surgical interventions or maternal death (relative risk, 0.59; 95% confidence interval, 0.02-16.69). A meta-analysis of 2 nonrandomized before-and-after studies showed that introduction of uterine balloon tamponade in protocols for managing severe postpartum hemorrhage significantly decreased the use of arterial embolization (relative risk, 0.29; 95% confidence interval, 0.14-0.63). A nonrandomized cluster study reported that use of invasive procedures was significantly lower in the perinatal network that routinely used uterine balloon tamponade than that which did not use uterine balloon tamponade (3.0/1000 vs 5.1/1000; P < .01). A cluster randomized trial reported that the frequency of postpartum hemorrhage-related invasive procedures and/or maternal death was significantly higher after uterine balloon tamponade introduction than before uterine balloon tamponade introduction (11.6/10,000 vs 6.7/10,000; P = .04). Overall, the frequency of complications attributed to uterine balloon tamponade use was low (≤6.5%).
CONCLUSION
Uterine balloon tamponade has a high success rate for treating severe postpartum hemorrhage and appears to be safe. The evidence on uterine balloon tamponade efficacy and effectiveness from randomized and nonrandomized studies is conflicting, with experimental studies suggesting no beneficial effect, in contrast with observational studies. Further research is needed to determine the most effective programmatic and healthcare delivery strategies on uterine balloon tamponade introduction and use.
Topics: Cesarean Section; Female; Humans; Maternal Mortality; Parturition; Placenta Accreta; Placenta Previa; Placenta, Retained; Postpartum Hemorrhage; Pregnancy; Uterine Artery Embolization; Uterine Balloon Tamponade; Uterine Inertia
PubMed: 31917139
DOI: 10.1016/j.ajog.2019.11.1287 -
JBI Database of Systematic Reviews and... Aug 2019The aim of this systematic review was to identify the effectiveness of breast massage as a treatment for women with breastfeeding problems. More specifically, the...
OBJECTIVES
The aim of this systematic review was to identify the effectiveness of breast massage as a treatment for women with breastfeeding problems. More specifically, the objective was to identify if breast massage as an intervention led to less pain or increased milk supply, or assisted in a reduction or resolution of blocked ducts, breast engorgement and mastitis.
INTRODUCTION
Breastfeeding protects babies against many illnesses, and the health benefits for women have been well documented. However, breastfeeding rates steadily drop to approximately 15% by six months, which is the World Health Organization's recommended length of time for exclusive breastfeeding. Breastfeeding problems such as blocked ducts, breast engorgement and mastitis are major complications attributing to the decline in breastfeeding rates. Breast massage may relieve pain and resolve symptoms associated with conditions that contribute to discontinued breastfeeding.
INCLUSION CRITERIA
This review considered both experimental and epidemiological study designs and included breastfeeding women of any age, parity or geographical location. The types of interventions considered for inclusion were any type of breast massage that was offered to women for breastfeeding problems. Comparators included the usual care provided to women with breastfeeding problems. Primary outcomes of interest were an increase in breast milk supply, reduction of breast pain, and symptom resolution of blocked ducts, engorgement and mastitis. Secondary outcomes included duration of breastfeeding.
METHODS
Studies published from 1980 to 2017 in English and Japanese were considered for inclusion in this review. The databases searched with the majority of results included CINAHL, Cochrane Library, Embase, PubMed, Science Direct, Scopus and Web of Science. Search for unpublished studies included Google Scholar, ClinicalTrials.gov and ProQuest Dissertations and Theses.
RESULTS
There were six studies included in this review: three randomized controlled trials and three quasi-experimental studies. There was considerable heterogeneity of study outcome measures, and the use of unvalidated tools in many of the studies led to the inability to pool the results. Furthermore, the heterogeneity of the interventions themselves coupled with small sample sizes for each study greatly decreased generalizability of the outcomes and reduced the overall effectiveness of the interventions. However, all included studies reported a reduction in pain regardless of the breast massage technique used. Overall, varying types of breast massage were helpful in reducing immediate pain and resolving symptoms.
CONCLUSIONS
Overall, different types of breast massage were reported as effective in reducing immediate pain for the participants. However, the lack of detailed explanation of the breast massage technique and the extensive training needed to undertake the breast massage decrease the ability to replicate the results. These outcomes may be useful for healthcare professionals caring for women with breastfeeding problems. Future research needs include validating a universal measurement tool for breastfeeding problems and the need for more robust randomized controlled trials, particularly in vulnerable groups such as mothers of preterm infants. Longer follow-up periods are also suggested to establish if breast massage impacts breastfeeding duration.
Topics: Breast Feeding; Female; Humans; Infant, Newborn; Lactation Disorders; Massage; Mastitis; Milk, Human; Mothers; Pain; Pregnancy
PubMed: 31135656
DOI: 10.11124/JBISRIR-2017-003932 -
Archives of Women's Mental Health Apr 2019Postpartum depression (PPD) is a major public health problem affecting 10-57% of adolescent mothers which can affect not only adolescent mothers but also their infants....
Postpartum depression (PPD) is a major public health problem affecting 10-57% of adolescent mothers which can affect not only adolescent mothers but also their infants. Thus, there is a need for interventions to prevent PPD in adolescent mothers. However, recent systematic reviews have been focused on effective interventions to prevent PPD in adult mothers. These interventions may not necessarily be applicable for adolescent mothers. Therefore, the purpose of this review was to examine the effectiveness of the existing interventions to prevent PPD in adolescent mothers. A systematic search was performed in MEDLINE, CINAHL, and SCOPUS databases between January 2000 and March 2017 with English language and studies involving human subjects. Studies reporting on the outcomes of intervention to prevent PPD particularly in adolescent mothers were selected. Non-comparative studies were excluded. From 2002 identified records, 13 studies were included, reporting on 2236 adolescent pregnant women. The evidence from this systematic review suggests that 6 of 13 studies from both psychological and psychosocial interventions including (1) home-visiting intervention, (2) prenatal antenatal and postnatal educational program, (3) CBT psycho-educational, (4) the REACH program based on interpersonal therapy, and (5) infant massage training is successful in reducing rates of PPD symptoms in adolescent mothers in the intervention group than those mothers in the control group. These interventions might be considered for incorporation in antenatal care interventions for adolescent pregnant women. However, this review did not find evidence identifying the most effective intervention for preventing postpartum depression symptoms in adolescent mothers.
Topics: Adolescent; Depression, Postpartum; Female; House Calls; Humans; Postnatal Care; Pregnancy; Pregnancy Complications; Pregnancy in Adolescence; Prenatal Care; Social Support
PubMed: 30116896
DOI: 10.1007/s00737-018-0901-7 -
The Cochrane Database of Systematic... Nov 2020Postpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization (WHO) recommends that all women giving birth should receive a prophylactic uterotonic agent. Despite the routine administration of a uterotonic agent for prevention, PPH remains a common complication causing one-quarter of all maternal deaths globally. When prevention fails and PPH occurs, further administration of uterotonic agents as 'first-line' treatment is recommended. However, there is uncertainty about which uterotonic agent is best for the 'first-line' treatment of PPH.
OBJECTIVES
To identify the most effective uterotonic agent(s) with the least side-effects for PPH treatment, and generate a meaningful ranking among all available agents according to their relative effectiveness and side-effect profile.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 May 2020), and the reference lists of all retrieved studies.
SELECTION CRITERIA
All randomised controlled trials or cluster-randomised trials comparing the effectiveness and safety of uterotonic agents with other uterotonic agents for the treatment of PPH were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed all trials for inclusion, extracted data and assessed each trial for risk of bias. Our primary outcomes were additional blood loss of 500 mL or more after recruitment to the trial until cessation of active bleeding and the composite outcome of maternal death or severe morbidity. Secondary outcomes included blood loss-related outcomes, morbidity outcomes, and patient-reported outcomes. We performed pairwise meta-analyses and indirect comparisons, where possible, but due to the limited number of included studies, we were unable to conduct the planned network meta-analysis. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
Seven trials, involving 3738 women in 10 countries, were included in this review. All trials were conducted in hospital settings. Randomised women gave birth vaginally, except in one small trial, where women gave birth either vaginally or by caesarean section. Across the seven trials (14 trial arms) the following agents were used: six trial arms used oxytocin alone; four trial arms used misoprostol plus oxytocin; three trial arms used misoprostol; one trial arm used Syntometrine® (oxytocin and ergometrine fixed-dose combination) plus oxytocin infusion. Pairwise meta-analysis of two trials (1787 participants), suggests that misoprostol, as first-line treatment uterotonic agent, probably increases the risk of blood transfusion (risk ratio (RR) 1.47, 95% confidence interval (CI) 1.02 to 2.14, moderate-certainty) compared with oxytocin. Low-certainty evidence suggests that misoprostol administration may increase the incidence of additional blood loss of 1000 mL or more (RR 2.57, 95% CI 1.00 to 6.64). The data comparing misoprostol with oxytocin is imprecise, with a wide range of treatment effects for the additional blood loss of 500 mL or more (RR 1.66, 95% CI 0.69 to 4.02, low-certainty), maternal death or severe morbidity (RR 1.98, 95% CI 0.36 to 10.72, low-certainty, based on one study n = 809 participants, as the second study had zero events), and the use of additional uterotonics (RR 1.30, 95% CI 0.57 to 2.94, low-certainty). The risk of side-effects may be increased with the use of misoprostol compared with oxytocin: vomiting (2 trials, 1787 participants, RR 2.47, 95% CI 1.37 to 4.47, high-certainty) and fever (2 trials, 1787 participants, RR 3.43, 95% CI 0.65 to 18.18, low-certainty). According to pairwise meta-analysis of four trials (1881 participants) generating high-certainty evidence, misoprostol plus oxytocin makes little or no difference to the use of additional uterotonics (RR 0.99, 95% CI 0.94 to 1.05) and to blood transfusion (RR 0.95, 95% CI 0.77 to 1.17) compared with oxytocin. We cannot rule out an important benefit of using the misoprostol plus oxytocin combination over oxytocin alone, for additional blood loss of 500 mL or more (RR 0.84, 95% CI 0.66 to 1.06, moderate-certainty). We also cannot rule out important benefits or harms for additional blood loss of 1000 mL or more (RR 0.76, 95% CI 0.43 to 1.34, moderate-certainty, 3 trials, 1814 participants, one study reported zero events), and maternal mortality or severe morbidity (RR 1.09, 95% CI 0.35 to 3.39, moderate-certainty). Misoprostol plus oxytocin increases the incidence of fever (4 trials, 1866 participants, RR 3.07, 95% CI 2.62 to 3.61, high-certainty), and vomiting (2 trials, 1482 participants, RR 1.85, 95% CI 1.16 to 2.95, high-certainty) compared with oxytocin alone. For all outcomes of interest, the available evidence on the misoprostol versus Syntometrine® plus oxytocin combination was of very low-certainty and these effects remain unclear. Although network meta-analysis was not performed, we were able to compare the misoprostol plus oxytocin combination with misoprostol alone through the common comparator of oxytocin. This indirect comparison suggests that the misoprostol plus oxytocin combination probably reduces the risk of blood transfusion (RR 0.65, 95% CI 0.42 to 0.99, moderate-certainty) and may reduce the risk of additional blood loss of 1000 mL or more (RR 0.30, 95% CI 0.10 to 0.89, low-certainty) compared with misoprostol alone. The combination makes little or no difference to vomiting (RR 0.75, 95% CI 0.35 to 1.59, high-certainty) compared with misoprostol alone. Misoprostol plus oxytocin compared to misoprostol alone are compatible with a wide range of treatment effects for additional blood loss of 500 mL or more (RR 0.51, 95% CI 0.20 to 1.26, low-certainty), maternal mortality or severe morbidity (RR 0.55, 95% CI 0.07 to 4.24, low-certainty), use of additional uterotonics (RR 0.76, 95% CI 0.33 to 1.73, low-certainty), and fever (RR 0.90, 95% CI 0.17 to 4.77, low-certainty).
AUTHORS' CONCLUSIONS
The available evidence suggests that oxytocin used as first-line treatment of PPH probably is more effective than misoprostol with less side-effects. Adding misoprostol to the conventional treatment of oxytocin probably makes little or no difference to effectiveness outcomes, and is also associated with more side-effects. The evidence for most uterotonic agents used as first-line treatment of PPH is limited, with no evidence found for commonly used agents, such as injectable prostaglandins, ergometrine, and Syntometrine®.
Topics: Bias; Blood Transfusion; Confidence Intervals; Drug Therapy, Combination; Ergonovine; Female; Humans; Misoprostol; Network Meta-Analysis; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 33232518
DOI: 10.1002/14651858.CD012754.pub2 -
The Cochrane Database of Systematic... Apr 2019Active management of the third stage of labour reduces the risk of postpartum blood loss (postpartum haemorrhage (PPH)), and is defined as administration of a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Active management of the third stage of labour reduces the risk of postpartum blood loss (postpartum haemorrhage (PPH)), and is defined as administration of a prophylactic uterotonic, early umbilical cord clamping and controlled cord traction to facilitate placental delivery. The choice of uterotonic varies across the globe and may have an impact on maternal outcomes. This is an update of a review first published in 2001 and last updated in 2013.
OBJECTIVES
To determine the effectiveness of prophylactic oxytocin to prevent PPH and other adverse maternal outcomes in the third stage of labour.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (6 March 2019) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised, quasi- or cluster-randomised trials including women undergoing vaginal delivery who received prophylactic oxytocin during management of the third stage of labour. Primary outcomes were blood loss 500 mL or more after delivery, need for additional uterotonics, and maternal all-cause mortality.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion, extracted data, and assessed trial quality. Data were checked for accuracy. We assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
This review includes 24 trials, with 23 trials involving 10,018 women contributing data. Due to many trials assessed at high risk of bias, evidence grade ranged from very low to moderate quality.Prophylactic oxytocin versus no uterotonics or placebo (nine trials)Prophylactic oxytocin compared with no uterotonics or placebo may reduce the risk of blood loss of 500 mL after delivery (average risk ratio (RR) 0.51, 95% confidence interval (C) 0.37 to 0.72; 4162 women; 6 studies; Tau² = 0.10, I² = 75%; low-quality evidence), and blood loss 1000 mL after delivery (RR 0.59, 95% CI 0.42 to 0.83; 4123 women; 5 studies; low-quality evidence). Prophylactic oxytocin probably reduces the need for additional uterotonics (average RR 0.54, 95% CI 0.36 to 0.80; 3135 women; 4 studies; Tau² = 0.07, I² = 44%; moderate-quality evidence). There may be no difference in the risk of needing a blood transfusion in women receiving oxytocin compared to no uterotonics or placebo (RR 0.88, 95% CI 0.44 to 1.78; 3081 women; 3 studies; low-quality evidence). Oxytocin may be associated with an increased risk of a third stage greater than 30 minutes (RR 2.55, 95% CI 0.88 to 7.44; 1947 women; 1 study; moderate-quality evidence), however the confidence interval is wide and includes 1.0, indicating that there may be little or no difference.Prophylactic oxytocin versus ergot alkaloids (15 trials)It is uncertain whether oxytocin reduces the likelihood of blood loss 500 mL (average RR 0.84, 95% CI 0.56 to 1.25; 3082 women; 10 studies; Tau² = 0.14, I² = 49%; very low-quality evidence) or the need for additional uterotonics compared to ergot alkaloids (average RR 0.89, 95% CI 0.43 to 1.81; 2178 women; 8 studies; Tau² = 0.76, I² = 79%; very low-quality evidence), because the quality of this evidence is very low. The quality of evidence was very low for blood loss of 1000 mL (RR 1.13, 95% CI 0.63 to 2.01; 1577 women; 3 studies; very low-quality evidence), and need for blood transfusion (average RR 1.37, 95% CI 0.34 to 5.51; 1578 women; 7 studies; Tau² = 1.34, I² = 45%; very low-quality evidence), making benefit of oxytocin over ergot alkaloids uncertain. Oxytocin probably increases the risk of a prolonged third stage greater than 30 minutes (RR 4.69, 95% CI 1.63 to 13.45; 450 women; 2 studies; moderate-quality evidence), although it is uncertain if this translates into increased risk of manual placental removal (average RR 1.10, 95% CI 0.39 to 3.10; 3127 women; 8 studies; Tau² = 1.07, I² = 76%; very low-quality evidence). Oxytocin may make little or no difference to risk of diastolic blood pressure > 100 mm Hg (average RR 0.28, 95% CI 0.04 to 2.05; 960 women; 3 studies; Tau² = 1.23, I² = 50%; low-quality evidence), and is probably associated with a lower risk of vomiting (RR 0.09, 95% CI 0.05 to 0.14; 1991 women; 7 studies; moderate-quality evidence), although the impact of oxytocin on headaches is uncertain (average RR 0.19, 95% CI 0.03 to 1.02; 1543 women; 5 studies; Tau² = 2.54, I² = 72%; very low-quality evidence).Prophylactic oxytocin-ergometrine versus ergot alkaloids (four trials)Oxytocin-ergometrine may slightly reduce the risk of blood loss greater than 500 mL after delivery compared to ergot alkaloids (RR 0.44, 95% CI 0.20 to 0.94; 1168 women; 3 studies; low-quality evidence), based on outcomes from quasi-randomised trials with a high risk of bias. There were no maternal deaths reported in either treatment group in the one trial that reported this outcome (RR not estimable; 1 trial, 807 women; moderate-quality evidence). Need for additional uterotonics was not reported.No subgroup differences were observed between active or expectant management, or different routes or doses of oxytocin for any of our comparisons.
AUTHORS' CONCLUSIONS
Prophylactic oxytocin compared with no uterotonics may reduce blood loss and the need for additional uterotonics. The effect of oxytocin compared to ergot alkaloids is uncertain with regards to blood loss, need for additional uterotonics, and blood transfusion. Oxytocin may increase the risk of a prolonged third stage compared to ergot alkaloids, although whether this translates into increased risk of manual placental removal is uncertain. This potential risk must be weighed against the possible increased risk of side effects associated with ergot alkaloids. Oxytocin-ergometrine may reduce blood loss compared to ergot alkaloids, however the certainty of this conclusion is low. More high-quality trials are needed to assess optimal dosing and route of oxytocin administration, with inclusion of important outcomes such as maternal mortality, shock, and transfer to a higher level of care. A network meta-analysis of uterotonics for PPH prevention plans to address issues around optimal dosing and routes of oxytocin and other uterotonics.
Topics: Blood Transfusion; Delivery, Obstetric; Female; Humans; Labor Stage, Third; Odds Ratio; Oxytocin; Postpartum Hemorrhage; Pregnancy
PubMed: 31032882
DOI: 10.1002/14651858.CD001808.pub3