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The Journal of Obstetrics and... Aug 2021Postpartum hemorrhage (PPH) has remained the leading cause of maternal mortality. While anemia is a leading contributor to maternal morbidity, molecular, cellular and... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Postpartum hemorrhage (PPH) has remained the leading cause of maternal mortality. While anemia is a leading contributor to maternal morbidity, molecular, cellular and anemia-induced hypoxia, clinical studies of the relationship between prenatal-anemia and PPH have reported conflicting results. Therefore, our objective was to investigate the outcomes of studies on the relationships between prenatal anemia and PPH-related mortality.
MATERIALS AND METHODS
Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, and the Cochrane Central Register of Controlled Trials) were searched for studies published before August 2019. Keywords included "anemia," "hemoglobin," "postpartum hemorrhage," and "postpartum bleeding." Only studies involving the association between anemia and PPH were included in the meta-analysis. Our primary analysis used random effects models to synthesize odds-ratios (ORs) extracted from the studies. Heterogeneity was formally assessed with the Higgins' I statistics, and explored using meta-regression and subgroup analysis.
RESULTS
We found 13 eligible studies investigating the relationship between prenatal anemia and PPH. Our findings suggest that severe prenatal anemia increases PPH risk (OR = 3.54; 95% CI: 1.20, 10.4, p-value = 0.020). There was no statistical association with mild (OR = 0.60; 95% CI: 0.31, 1.17, p-value = 0.130), or moderate anemia (OR = 2.09; 95% CI: 0.40, 11.1, p-value = 0.390) and the risk of PPH.
CONCLUSION
Severe prenatal anemia is an important predictive factor of adverse outcomes, warranting intensive management during pregnancy. PROSPERO Registration Number: CRD42020149184; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=149184.
Topics: Anemia; Female; Humans; Maternal Mortality; Oxytocics; Postpartum Hemorrhage; Postpartum Period; Pregnancy
PubMed: 34002432
DOI: 10.1111/jog.14834 -
Psychoneuroendocrinology Oct 2020Postpartum depression (PPD) is a significant mental health concern, especially for women in vulnerable populations. Oxytocin (OT), a hormone essential for a variety of...
Postpartum depression (PPD) is a significant mental health concern, especially for women in vulnerable populations. Oxytocin (OT), a hormone essential for a variety of maternal tasks, including labor, lactation, and infant bonding, has also been hypothesized to have a role in postpartum depression. Women are routinely given synthetic oxytocin to induce or augment labor and to prevent postpartum hemorrhage. The aim of this study was to review the quality and reliability of literature that examines potential relationships between OT and PPD to determine if there is sufficient data to reliably assess the strength of these relationships. We conducted a literature search in December of 2018 using five databases (PubMed, Web of Science, Embase, PsycInfo, and CINAHL). Eligible studies were identified, selected, and appraised using the Newcastle-Ottawa quality assessment scale and Cochrane Collaboration's tool for assessing risk of bias, as appropriate. Sixteen studies were included in the analysis and broken into two categories: correlations of endogenous OT with PPD and administration of synthetic OT with PPD. Depressive symptoms were largely measured using the Edinburgh Postnatal Depression Scale. OT levels were predominately measured in plasma, though there were differences in laboratory methodology and control of confounders (primarily breast feeding). Of the twelve studies focused on endogenous oxytocin, eight studies suggested an inverse relationship between plasma OT levels and depressive symptoms. We are not able to draw any conclusions regarding the relationship between intravenous synthetic oxytocin and postpartum depression based on current evidence due to the heterogeneity and small number of studies (n = 4). Considering limitations of the current literature and the current clinical prevalence of synthetic OT administration, we strongly recommend that rigorous studies examining the effects of synthetic OT exposure on PPD should be performed as well as continued work in defining the relationship between endogenous OT and PPD.
Topics: Adult; Anxiety; Breast Feeding; Depression; Depression, Postpartum; Female; Humans; Infant; Lactation; Mothers; Oxytocin; Postpartum Period; Pregnancy; Reproducibility of Results
PubMed: 32683141
DOI: 10.1016/j.psyneuen.2020.104793 -
Molecular Autism Mar 2022There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD.
METHODS
We searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (from inception up to July 8, 2018), CENTRAL and PubMed (up to November 3, 2021). The co-primary outcomes were core symptoms (social-communication difficulties-SCD, repetitive behaviors-RB, overall core symptoms-OCS) measured by validated scales and standardized-mean-differences (SMDs). Associated symptoms, e.g., irritability/aggression and attention-deficit/hyperactivity disorder (ADHD) symptoms, dropouts and important side-effects, were investigated as secondary outcomes. Studies in children/adolescents and adults were analyzed separately in random-effects pairwise and network meta-analyses.
RESULTS
We analyzed data for 41 drugs and 17 dietary-supplements, from 125 RCTs (n = 7450 participants) in children/adolescents and 18 RCTs (n = 1104) in adults. The following medications could improve at least one core symptom domain in comparison with placebo: aripiprazole (k = 6 studies in analysis, SCD: SMD = 0.27 95% CI [0.09, 0.44], RB: 0.48 [0.26, 0.70]), atomoxetine (k = 3, RB:0.49 [0.18, 0.80]), bumetanide (k = 4, RB: 0.35 [0.09, 0.62], OCS: 0.61 [0.31, 0.91]), and risperidone (k = 4, SCM: 0.31 [0.06, 0.55], RB: 0.60 [0.29, 0.90]; k = 3, OCS: 1.18 [0.75, 1.61]) in children/adolescents; fluoxetine (k = 1, RB: 1.20 [0.45, 1.96]), fluvoxamine (k = 1, RB: 1.04 [0.27, 1.81]), oxytocin (k = 6, RB:0.41 [0.16, 0.66]) and risperidone (k = 1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin. Medications differed substantially in improving associated symptoms, and in their side-effect profiles.
LIMITATIONS
Most of the studies were inadequately powered (sample sizes of 20-80 participants), with short duration (8-13 weeks), and about a third focused on associated symptoms. Networks were mainly star-shaped, and there were indications of reporting bias. There was no optimal rating scale measuring change in core symptoms.
CONCLUSIONS
Some medications could improve core symptoms, although this could be likely secondary to the improvement of associated symptoms. Evidence on their efficacy and safety is preliminary; therefore, routine prescription of medications for the core symptoms cannot be recommended. Trial registration PROSPERO-ID CRD42019125317.
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Humans; Network Meta-Analysis; Oxytocin; Risperidone
PubMed: 35246237
DOI: 10.1186/s13229-022-00488-4 -
The Cochrane Database of Systematic... Sep 2020Engorgement 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...
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.
Topics: Acupuncture Therapy; Brassica; Breast Diseases; Cryotherapy; Female; Humans; Lactation Disorders; Massage; Mastodynia; Oxytocin; Peptide Hydrolases; Phytotherapy; Plant Leaves; Pregnancy; Randomized Controlled Trials as Topic; Ultrasonic Therapy
PubMed: 32944940
DOI: 10.1002/14651858.CD006946.pub4 -
The Cochrane Database of Systematic... Mar 2023Mechanical methods were the first methods developed to ripen the cervix and induce labour. During recent decades they have been substituted by pharmacological methods.... (Review)
Review
BACKGROUND
Mechanical methods were the first methods developed to ripen the cervix and induce labour. During recent decades they have been substituted by pharmacological methods. Potential advantages of mechanical methods, compared with pharmacological methods may include reduction in side effects that could improve neonatal outcomes. This is an update of a review first published in 2001, last updated in 2012.
OBJECTIVES
To determine the effectiveness and safety of mechanical methods for third trimester (> 24 weeks' gestation) induction of labour in comparison with prostaglandin E2 (PGE2) (vaginal and intracervical), low-dose misoprostol (oral and vaginal), amniotomy or oxytocin.
SEARCH METHODS
For this update, 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 (9 January 2018). We updated the search in March 2019 and added the search results to the awaiting classification section of the review.
SELECTION CRITERIA
Clinical trials comparing mechanical methods used for third trimester cervical ripening or labour induction with pharmacological methods. Mechanical methods include: (1) the introduction of a catheter through the cervix into the extra-amniotic space with balloon insufflation; (2) introduction of laminaria tents, or their synthetic equivalent (Dilapan), into the cervical canal; (3) use of a catheter to inject fluid into the extra-amniotic space (EASI). This review includes the following comparisons: (1) specific mechanical methods (balloon catheter, laminaria tents or EASI) compared with prostaglandins (different types, different routes) or with oxytocin; (2) single balloon compared to a double balloon; (3) addition of prostaglandins or oxytocin to mechanical methods compared with prostaglandins or oxytocin alone.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and assessed risk of bias. Two review authors independently extracted data and assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
This review includes a total of 112 trials, with 104 studies contributing data (22,055 women; 21 comparisons). Risk of bias of trials varied. Overall, the evidence was graded from very-low to moderate quality. All evidence was downgraded for lack of blinding and, for many comparisons, the effect estimates were too imprecise to make a valid judgement. Balloon versus vaginal PGE2: there may be little or no difference in vaginal deliveries not achieved within 24 hours (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.82 to 1.26; 7 studies; 1685 women; low-quality evidence) and there probably is little or no difference in caesarean sections (RR 1.00, 95% CI 0.92 to 1.09; 28 studies; 6619 women; moderate-quality evidence) between induction of labour with a balloon catheter and vaginal PGE2. A balloon catheter probably reduces the risk of uterine hyperstimulation with fetal heart rate (FHR) changes (RR 0.35, 95% CI 0.18 to 0.67; 6 studies; 1966 women; moderate-quality evidence), serious neonatal morbidity or perinatal death (RR 0.48, 95% CI 0.25 to 0.93; 8 studies; 2757 women; moderate-quality evidence) and may slightly reduce the risk of aneonatal intensive care unit (NICU) admission (RR 0.82, 95% CI 0.65 to 1.04; 3647 women; 12 studies; low-quality evidence). It is uncertain whether there is a difference in serious maternal morbidity or death (RR 0.20, 95% CI 0.01 to 4.12; 4 studies; 1481 women) or five-minute Apgar score < 7 (RR 0.74, 95% CI 0.49 to 1.14; 4271 women; 14 studies) because the quality of the evidence was found to be very low and low, respectively. Balloon versus low-dose vaginal misoprostol: it is uncertain whether there is a difference in vaginal deliveries not achieved within 24 hours between induction of labour with a balloon catheter and vaginal misoprostol (RR 1.09, 95% CI 0.85 to 1.39; 340 women; 2 studies; low-quality evidence). A balloon catheter probably reduces the risk of uterine hyperstimulation with FHR changes (RR 0.39, 95% CI 0.18 to 0.85; 1322 women; 8 studies; moderate-quality evidence) but may increase the risk of a caesarean section (RR 1.28, 95% CI 1.02 to 1.60; 1756 women; 12 studies; low-quality evidence). It is uncertain whether there is a difference in serious neonatal morbidity or perinatal death (RR 0.58, 95% CI 0.12 to 2.66; 381 women; 3 studies), serious maternal morbidity or death (no events; 4 studies, 464 women), both very low-quality evidence, and five-minute Apgar score < 7 (RR 1.00, 95% CI 0.50 to 1.97; 941 women; 7 studies) and NICU admissions (RR 1.00, 95% CI 0.61 to 1.63; 1302 women; 9 studies) both low-quality evidence. Balloon versus low-dose oral misoprostol: a balloon catheter probably increases the risk of a vaginal delivery not achieved within 24 hours (RR 1.28, 95% CI 1.13 to 1.46; 782 women, 2 studies, and probably slightly increases the risk of a caesarean section (RR 1.17, 95% CI 1.04 to 1.32; 3178 women; 7 studies; both moderate-quality evidence) when compared to oral misoprostol. It is uncertain whether there is a difference in uterine hyperstimulation with FHR changes (RR 0.81, 95% CI 0.48 to 1.38; 2033 women; 2 studies), serious neonatal morbidity or perinatal death (RR 1.11, 95% CI 0.60 to 2.06; 2627 women; 3 studies), both low-quality evidence, serious maternal morbidity or death (RR 0.50, 95% CI 0.05 to 5.52; 2627 women; 3 studies), very low-quality evidence, five-minute Apgar scores < 7 (RR 0.71, 95% CI 0.38 to 1.32; 2693 women; 4 studies) and NICU admissions (RR 0.82, 95% CI 0.58 to 1.17; 2873 women; 5 studies) both low-quality evidence.
AUTHORS' CONCLUSIONS
Low- to moderate-quality evidence shows mechanical induction with a balloon is probably as effective as induction of labour with vaginal PGE2. However, a balloon seems to have a more favourable safety profile. More research on this comparison does not seem warranted. Moderate-quality evidence shows a balloon catheter may be slightly less effective as oral misoprostol, but it remains unclear if there is a difference in safety outcomes for the neonate. When compared to low-dose vaginal misoprostol, low-quality evidence shows a balloon may be less effective, but probably has a better safety profile. Future research could be focused more on safety aspects for the neonate and maternal satisfaction.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Cesarean Section; Dinoprostone; Labor, Induced; Misoprostol; Oxytocin; Perinatal Death
PubMed: 36996264
DOI: 10.1002/14651858.CD001233.pub4 -
The Cochrane Database of Systematic... Jun 2021Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime. An estimated 15% of pregnancies end in miscarriage. Miscarriage can lead to serious morbidity, including haemorrhage, infection, and even death, particularly in settings without adequate healthcare provision. Early miscarriages occur during the first 14 weeks of pregnancy, and can be managed expectantly, medically or surgically. However, there is uncertainty about the relative effectiveness and risks of each option.
OBJECTIVES
To estimate the relative effectiveness and safety profiles for the different management methods for early miscarriage, and to provide rankings of the available methods according to their effectiveness, safety, and side-effect profile using a network meta-analysis.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth's Trials Register (9 February 2021), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (12 February 2021), and reference lists of retrieved studies.
SELECTION CRITERIA
We included all randomised controlled trials assessing the effectiveness or safety of methods for miscarriage management. Early miscarriage was defined as less than or equal to 14 weeks of gestation, and included missed and incomplete miscarriage. Management of late miscarriages after 14 weeks of gestation (often referred to as intrauterine fetal deaths) was not eligible for inclusion in the review. Cluster- and quasi-randomised trials were eligible for inclusion. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. We excluded non-randomised trials.
DATA COLLECTION AND ANALYSIS
At least three review authors independently assessed the trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for the primary outcomes of complete miscarriage and composite outcome of death or serious complications. The certainty of evidence was assessed using GRADE. Relative effects for the primary outcomes are reported subgrouped by the type of miscarriage (incomplete and missed miscarriage). We also performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available methods.
MAIN RESULTS
Our network meta-analysis included 78 randomised trials involving 17,795 women from 37 countries. Most trials (71/78) were conducted in hospital settings and included women with missed or incomplete miscarriage. Across 158 trial arms, the following methods were used: 51 trial arms (33%) used misoprostol; 50 (32%) used suction aspiration; 26 (16%) used expectant management or placebo; 17 (11%) used dilatation and curettage; 11 (6%) used mifepristone plus misoprostol; and three (2%) used suction aspiration plus cervical preparation. Of these 78 studies, 71 (90%) contributed data in a usable form for meta-analysis. Complete miscarriage Based on the relative effects from the network meta-analysis of 59 trials (12,591 women), we found that five methods may be more effective than expectant management or placebo for achieving a complete miscarriage: · suction aspiration after cervical preparation (risk ratio (RR) 2.12, 95% confidence interval (CI) 1.41 to 3.20, low-certainty evidence), · dilatation and curettage (RR 1.49, 95% CI 1.26 to 1.75, low-certainty evidence), · suction aspiration (RR 1.44, 95% CI 1.29 to 1.62, low-certainty evidence), · mifepristone plus misoprostol (RR 1.42, 95% CI 1.22 to 1.66, moderate-certainty evidence), · misoprostol (RR 1.30, 95% CI 1.16 to 1.46, low-certainty evidence). The highest ranked surgical method was suction aspiration after cervical preparation. The highest ranked non-surgical treatment was mifepristone plus misoprostol. All surgical methods were ranked higher than medical methods, which in turn ranked above expectant management or placebo. Composite outcome of death and serious complications Based on the relative effects from the network meta-analysis of 35 trials (8161 women), we found that four methods with available data were compatible with a wide range of treatment effects compared with expectant management or placebo: · dilatation and curettage (RR 0.43, 95% CI 0.17 to 1.06, low-certainty evidence), · suction aspiration (RR 0.55, 95% CI 0.23 to 1.32, low-certainty evidence), · misoprostol (RR 0.50, 95% CI 0.22 to 1.15, low-certainty evidence), · mifepristone plus misoprostol (RR 0.76, 95% CI 0.31 to 1.84, low-certainty evidence). Importantly, no deaths were reported in these studies, thus this composite outcome was entirely composed of serious complications, including blood transfusions, uterine perforations, hysterectomies, and intensive care unit admissions. Expectant management and placebo ranked the lowest when compared with alternative treatment interventions. Subgroup analyses by type of miscarriage (missed or incomplete) agreed with the overall analysis in that surgical methods were the most effective treatment, followed by medical methods and then expectant management or placebo, but there are possible subgroup differences in the effectiveness of the available methods. AUTHORS' CONCLUSIONS: Based on relative effects from the network meta-analysis, all surgical and medical methods for managing a miscarriage may be more effective than expectant management or placebo. Surgical methods were ranked highest for managing a miscarriage, followed by medical methods, which in turn ranked above expectant management or placebo. Expectant management or placebo had the highest chance of serious complications, including the need for unplanned or emergency surgery. A subgroup analysis showed that surgical and medical methods may be more beneficial in women with missed miscarriage compared to women with incomplete miscarriage. Since type of miscarriage (missed and incomplete) appears to be a source of inconsistency and heterogeneity within these data, we acknowledge that the main network meta-analysis may be unreliable. However, we plan to explore this further in future updates and consider the primary analysis as separate networks for missed and incomplete miscarriage.
Topics: Abortion, Incomplete; Abortion, Missed; Abortion, Spontaneous; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Network Meta-Analysis; Oxytocics; Placebos; Pregnancy; Pregnancy Trimester, First; Randomized Controlled Trials as Topic; Suction; Vacuum Curettage; Watchful Waiting
PubMed: 34061352
DOI: 10.1002/14651858.CD012602.pub2 -
The Cochrane Database of Systematic... Jun 2021Misoprostol given orally is a commonly used labour induction method. Our Cochrane Review is restricted to studies with low-dose misoprostol (initially ≤ 50 µg), as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Misoprostol given orally is a commonly used labour induction method. Our Cochrane Review is restricted to studies with low-dose misoprostol (initially ≤ 50 µg), as higher doses pose unacceptably high risks of uterine hyperstimulation.
OBJECTIVES
To assess the efficacy and safety of low-dose oral misoprostol for labour induction in women with a viable fetus in the third trimester of pregnancy.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (14 February 2021) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised trials comparing low-dose oral misoprostol (initial dose ≤ 50 µg) versus placebo, vaginal dinoprostone, vaginal misoprostol, oxytocin, or mechanical methods; or comparing oral misoprostol protocols (one- to two-hourly versus four- to six-hourly; 20 µg to 25 µg versus 50 µg; or 20 µg hourly titrated versus 25 µg two-hourly static).
DATA COLLECTION AND ANALYSIS
Using Covidence, two review authors independently screened reports, extracted trial data, and performed quality assessments. Our primary outcomes were vaginal birth within 24 hours, caesarean section, and hyperstimulation with foetal heart changes.
MAIN RESULTS
We included 61 trials involving 20,026 women. GRADE assessments ranged from moderate- to very low-certainty evidence, with downgrading decisions based on imprecision, inconsistency, and study limitations. Oral misoprostol versus placebo/no treatment (four trials; 594 women) Oral misoprostol may make little to no difference in the rate of caesarean section (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.59 to 1.11; 4 trials; 594 women; moderate-certainty evidence), while its effect on uterine hyperstimulation with foetal heart rate changes is uncertain (RR 5.15, 95% CI 0.25 to 105.31; 3 trials; 495 women; very low-certainty evidence). Vaginal births within 24 hours was not reported. In all trials, oxytocin could be commenced after 12 to 24 hours and all women had pre-labour ruptured membranes. Oral misoprostol versus vaginal dinoprostone (13 trials; 9676 women) Oral misoprostol probably results in fewer caesarean sections (RR 0.84, 95% CI 0.78 to 0.90; 13 trials, 9676 women; moderate-certainty evidence). Subgroup analysis indicated that 10 µg to 25 µg (RR 0.80, 95% CI 0.74 to 0.87; 9 trials; 8652 women) may differ from 50 µg (RR 1.10, 95% CI 0.91 to 1.34; 4 trials; 1024 women) for caesarean section. Oral misoprostol may decrease vaginal births within 24 hours (RR 0.93, 95% CI 0.87 to 1.00; 10 trials; 8983 women; low-certainty evidence) and hyperstimulation with foetal heart rate changes (RR 0.49, 95% CI 0.40 to 0.59; 11 trials; 9084 women; low-certainty evidence). Oral misoprostol versus vaginal misoprostol (33 trials; 6110 women) Oral use may result in fewer vaginal births within 24 hours (average RR 0.81, 95% CI 0.68 to 0.95; 16 trials, 3451 women; low-certainty evidence), and less hyperstimulation with foetal heart rate changes (RR 0.69, 95% CI 0.53 to 0.92, 25 trials, 4857 women, low-certainty evidence), with subgroup analysis suggesting that 10 µg to 25 µg orally (RR 0.28, 95% CI 0.14 to 0.57; 6 trials, 957 women) may be superior to 50 µg orally (RR 0.82, 95% CI 0.61 to 1.11; 19 trials; 3900 women). Oral misoprostol probably does not increase caesarean sections overall (average RR 1.00, 95% CI 0.86 to 1.16; 32 trials; 5914 women; low-certainty evidence) but likely results in fewer caesareans for foetal distress (RR 0.74, 95% CI 0.55 to 0.99; 24 trials, 4775 women). Oral misoprostol versus intravenous oxytocin (6 trials; 737 women, 200 with ruptured membranes) Misoprostol may make little or no difference to vaginal births within 24 hours (RR 1.12, 95% CI 0.95 to 1.33; 3 trials; 466 women; low-certainty evidence), but probably results in fewer caesarean sections (RR 0.67, 95% CI 0.50 to 0.90; 6 trials; 737 women; moderate-certainty evidence). The effect on hyperstimulation with foetal heart rate changes is uncertain (RR 0.66, 95% CI 0.19 to 2.26; 3 trials, 331 women; very low-certainty evidence). Oral misoprostol versus mechanical methods (6 trials; 2993 women) Six trials compared oral misoprostol to transcervical Foley catheter. Misoprostol may increase vaginal birth within 24 hours (RR 1.32, 95% CI 0.98 to 1.79; 4 trials; 1044 women; low-certainty evidence), and probably reduces the risk of caesarean section (RR 0.84, 95% CI 0.75 to 0.95; 6 trials; 2993 women; moderate-certainty evidence). There may be little or no difference in hyperstimulation with foetal heart rate changes (RR 1.31, 95% CI 0.78 to 2.21; 4 trials; 2828 women; low-certainty evidence). Oral misoprostol one- to two-hourly versus four- to six-hourly (1 trial; 64 women) The evidence on hourly titration was very uncertain due to the low numbers reported. Oral misoprostol 20 µg hourly titrated versus 25 µg two-hourly static (2 trials; 296 women) The difference in regimen may have little or no effect on the rate of vaginal births in 24 hours (RR 0.97, 95% CI 0.80 to 1.16; low-certainty evidence). The evidence is of very low certainty for all other reported outcomes.
AUTHORS' CONCLUSIONS
Low-dose oral misoprostol is probably associated with fewer caesarean sections (and therefore more vaginal births) than vaginal dinoprostone, and lower rates of hyperstimulation with foetal heart rate changes. However, time to birth may be increased, as seen by a reduced number of vaginal births within 24 hours. Compared to transcervical Foley catheter, low-dose oral misoprostol is associated with fewer caesarean sections, but equivalent rates of hyperstimulation. Low-dose misoprostol given orally rather than vaginally is probably associated with similar rates of vaginal birth, although rates may be lower within the first 24 hours. However, there is likely less hyperstimulation with foetal heart changes, and fewer caesarean sections performed due to foetal distress. The best available evidence suggests that low-dose oral misoprostol probably has many benefits over other methods for labour induction. This review supports the use of low-dose oral misoprostol for induction of labour, and demonstrates the lower risks of hyperstimulation than when misoprostol is given vaginally. More trials are needed to establish the optimum oral misoprostol regimen, but these findings suggest that a starting dose of 25 µg may offer a good balance of efficacy and safety.
Topics: Administration, Intravaginal; Administration, Oral; Apgar Score; Cesarean Section; Dinoprostone; Drug Administration Schedule; Female; Heart Rate, Fetal; Humans; Intensive Care, Neonatal; Labor, Induced; Misoprostol; Oxytocics; Oxytocin; Parturition; Placebos; Pregnancy; Randomized Controlled Trials as Topic; Time Factors; Uterus
PubMed: 34155622
DOI: 10.1002/14651858.CD014484 -
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... May 2023Breech presentation at term can cause complications during birth and increase the chance of caesarean section. Moxibustion (a type of Chinese medicine which involves... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Breech presentation at term can cause complications during birth and increase the chance of caesarean section. Moxibustion (a type of Chinese medicine which involves burning a herb close to the skin) at the acupuncture point Bladder 67 (BL67) (Chinese name Zhiyin), located at the tip of the fifth toe, has been proposed as a way of changing breech presentation to cephalic presentation. This is an update of a review first published in 2005 and last published in 2012.
OBJECTIVES
To examine the effectiveness and safety of moxibustion on changing the presentation of an unborn baby in the breech position, the need for external cephalic version (ECV), mode of birth, and perinatal morbidity and mortality.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register (which includes trials from CENTRAL, MEDLINE, Embase, CINAHL, and conference proceedings), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) (4 November 2021). We also searched MEDLINE, CINAHL, AMED, Embase and MIDIRS (inception to 3 November 2021), and the reference lists of retrieved studies.
SELECTION CRITERIA
The inclusion criteria were published and unpublished randomised or quasi-randomised controlled trials comparing moxibustion either alone or in combination with other techniques (e.g. acupuncture or postural techniques) with a control group (no moxibustion) or other methods (e.g. acupuncture, postural techniques) in women with a singleton breech presentation.
DATA COLLECTION AND ANALYSIS
Two review authors independently determined trial eligibility, assessed trial quality, and extracted data. Outcome measures were baby's presentation at birth, need for ECV, mode of birth, perinatal morbidity and mortality, maternal complications and maternal satisfaction, and adverse events. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: This updated review includes 13 studies (2181 women), of which six trials are new. Most studies used adequate methods for random sequence generation and allocation concealment. Blinding of participants and personnel is challenging with a manual therapy intervention; however, the use of objective outcomes meant that the lack of blinding was unlikely to affect the results. Most studies reported little or no loss to follow-up, and few trial protocols were available. One study that was terminated early was judged as high risk for other sources of bias. Meta-analysis showed that compared to usual care alone, the combination of moxibustion plus usual care probably reduces the chance of non-cephalic presentation at birth (7 trials, 1152 women; risk ratio (RR) 0.87, 95% confidence interval (CI) 0.78 to 0.99, I = 38%; moderate-certainty evidence), but the evidence is very uncertain about the effect of moxibustion plus usual care on the need for ECV (4 trials, 692 women; RR 0.62, 95% CI 0.32 to 1.21, I = 78%; low-certainty evidence) because the CIs included both appreciable benefit and moderate harm. Adding moxibustion to usual care probably has little to no effect on the chance of caesarean section (6 trials, 1030 women; RR 0.94, 95% CI 0.83 to 1.05, I = 0%; moderate-certainty evidence). The evidence is very uncertain about the effect of moxibustion plus usual care on the the chance of premature rupture of membranes (3 trials, 402 women; RR 1.31, 95% CI 0.17 to 10.21, I = 59%; low-certainty evidence) because there were very few data. Moxibustion plus usual care probably reduces the use of oxytocin (1 trial, 260 women; RR 0.28, 95% CI 0.13 to 0.60; moderate-certainty evidence). The evidence is very uncertain about the chance of cord blood pH less than 7.1 (1 trial, 212 women; RR 3.00, 95% CI 0.32 to 28.38; low-certainty evidence) because there were very few data. We are very uncertain whether the combination of moxibustion plus usual care increases the chance of adverse events (including nausea, unpleasant odour, abdominal pain and uterine contractions; intervention: 27/65, control: 0/57), as only one study presented data in a way that could be reanalysed (122 women; RR 48.33, 95% CI 3.01 to 774.86; very low-certainty evidence). When moxibustion plus usual care was compared with sham moxibustion plus usual care, we found that moxibustion probably reduces the chance of non-cephalic presentation at birth (1 trial, 272 women; RR 0.74, 95% CI 0.58 to 0.95; moderate-certainty evidence) and probably results in little to no effect on the rate of caesarean section (1 trial, 272 women; RR 0.84, 95% CI 0.68 to 1.04; moderate-certainty evidence). No study that compared moxibustion plus usual care with sham moxibustion plus usual care reported on the clinically important outcomes of need for ECV, premature rupture of membranes, use of oxytocin, and cord blood pH less than 7.1, and one trial that reported adverse events reported data for the whole sample. When moxibustion was combined with acupuncture and usual care, there was very little evidence about the effect of the combination on non-cephalic presentation at birth (1 trial, 226 women; RR 0.73, 95% CI 0.57 to 0.94) and at the end of treatment (2 trials, 254 women; RR 0.73, 95% CI 0.57 to 0.93), and on the need for ECV (1 trial, 14 women; RR 0.45, 95% CI 0.07 to 3.01). There was very little evidence about whether moxibustion plus acupuncture plus usual care reduced the chance of caesarean section (2 trials, 240 women; RR 0.80, 95% CI 0.65 to 0.99) or pre-eclampsia (1 trial, 14 women; RR 5.00, 95% CI 0.24 to 104.15). The certainty of the evidence for this comparison was not assessed.
AUTHORS' CONCLUSIONS
We found moderate-certainty evidence that moxibustion plus usual care probably reduces the chance of non-cephalic presentation at birth, but uncertain evidence about the need for ECV. Moderate-certainty evidence from one study shows that moxibustion plus usual care probably reduces the use of oxytocin before or during labour. However, moxibustion plus usual care probably results in little to no difference in the rate of caesarean section, and we are uncertain about its effects on the chance of premature rupture of membranes and cord blood pH less than 7.1. Adverse events were inadequately reported in most trials.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Breech Presentation; Cesarean Section; Moxibustion; Oxytocin; Parturition; Premature Birth
PubMed: 37158339
DOI: 10.1002/14651858.CD003928.pub4 -
Neuroscience and Biobehavioral Reviews Nov 2022The last couple of decades have witnessed a rapid accumulation of studies implicating oxytocin (OT) in several neurobiological underpinnings of human behaviour and their... (Review)
Review
The last couple of decades have witnessed a rapid accumulation of studies implicating oxytocin (OT) in several neurobiological underpinnings of human behaviour and their impairment in psychiatric illness. Specifically, a neuroimaging genetics approach is helping elucidate the impact of variations in OT pathway genes on the human brain. In this review, we provide the first systematic account and discussion of all previous findings arising from human neuroimaging (epi)genetic studies of OT-related genes. To improve our mechanistic interpretation of such findings, we used data from the Genotype-Tissue Expression project to explore the functional impact the genetic variations may have on the human transcriptome. As a result, we provide an up-to-date summary of brain circuits found to be impacted by OT-relevant (epi)genetic variability, map brain pathways linking OT genes to disease, and highlight several (epi)genetic factors that modulate brain responses to intranasal OT. Finally, we provide some suggestions we believe might improve future research in the field.
Topics: Humans; Administration, Intranasal; Brain; Neuroimaging; Oxytocin; Transcriptome
PubMed: 36228928
DOI: 10.1016/j.neubiorev.2022.104912