-
Progress in Neuro-psychopharmacology &... Jul 2022Increased interest in understanding how changes in the oxytocinergic system are associated with the etiology and progression of psychiatric disorders has currently... (Review)
Review
Increased interest in understanding how changes in the oxytocinergic system are associated with the etiology and progression of psychiatric disorders has currently boosted the publication of studies. We present a systematic literature review followed by meta-analyses assessing whether peripheral oxytocin (OXT) levels among psychiatric patients differ from healthy controls, considering the moderating role of methodological aspects and samples' characteristics. The following electronic databases were searched: PubMed, Web of Science, PsycINFO, SciELO, LILACS, and Scopus. Fifty-five papers were included in the analysis, and nine independent meta-analyses were performed according to the different diagnoses. Lower OXT concentrations were found in groups of specific disorders (i.e., schizophrenia, restricting and binge-eating/purging subtypes of anorexia nervosa, and borderline personality disorder) with medium to large effect sizes. Great heterogeneity was found among the studies, so that caution is needed to interpret the results. High OXT levels with an effect size of the same magnitude were found for bipolar disorder - type I and obsessive disorder. In contrast, no differences were found for bulimia, autism spectrum, depression, or social anxiety. No meta-analyses were performed for body dysmorphic disorder, post-traumatic stress disorder, or trichotillomania because only one study was identified for each of these disorders. Altered endogenous OXT concentrations are found in several disorders addressed and must be analyzed according to each disorder's specificities.
Topics: Anorexia Nervosa; Borderline Personality Disorder; Feeding and Eating Disorders; Humans; Oxytocin; Schizophrenia
PubMed: 35461971
DOI: 10.1016/j.pnpbp.2022.110561 -
Journal of Healthcare Engineering 2022Hypertensive disorders of pregnancy (HDP) can cause serious prenatal and postnatal complications and is a threat to maternal and fetal health. To offer guidance for... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hypertensive disorders of pregnancy (HDP) can cause serious prenatal and postnatal complications and is a threat to maternal and fetal health. To offer guidance for clinical decisions, we systematically reviewed the effects of misoprostol on induction of labour in HDP patients.
METHODS
PubMed, Web of Science, Embase, CNKI, and Wanfang databases were searched for relevant literature from 2010 to 2020. Subsequently, a meta-analysis was performed to compare the effective rate of induction of labour and reducing postpartum hemorrhage (PPH) between the intervention group ( = 544, misoprostol) and the control group ( = 543, oxytocin).
RESULTS
A total of 10 studies with 1087 patients were included. The 10 studies compared the effective rate of induction of labour between the two groups and confirmed that the effective rate in the intervention group was significantly higher than that in the control group (OR = 4.37; 95% CI: 2.73, 7.00). Seven studies compared PPH between the groups and showed that it was significantly reduced in the intervention group compared to the control group (SMD = -1.32; 95% CI: -2.05, -0.59; < 0.0001).
CONCLUSION
Misoprostol has a high effective rate of induction of labour in HDP patients and is an effective uterotonic agent in reducing PPH. This meta-analysis provides clinicians with meaningful information to help them make evidence-based decisions.
Topics: Female; Humans; Hypertension, Pregnancy-Induced; Labor, Induced; Misoprostol; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy
PubMed: 35432818
DOI: 10.1155/2022/8448690 -
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 -
BMJ Sexual & Reproductive Health Apr 2022Globally, access to safe abortion is limited. We aimed to assess the safety, effectiveness and acceptability of harm reduction counselling for abortion, which we define... (Review)
Review
Reducing the harms of unsafe abortion: a systematic review of the safety, effectiveness and acceptability of harm reduction counselling for pregnant persons seeking induced abortion.
BACKGROUND
Globally, access to safe abortion is limited. We aimed to assess the safety, effectiveness and acceptability of harm reduction counselling for abortion, which we define as the provision of information about safe abortion methods to pregnant persons seeking abortion.
METHODS
We searched PubMed, EMBASE, ClinicalTrials.gov, Cochrane, Global Index Medicus and the grey literature up to October 2021. We included studies in which healthcare providers gave pregnant persons information on safe use of abortifacient medications without providing the actual medications. We conducted a descriptive summary of results and a risk of bias assessment using the ROBINS-I tool. Our primary outcome was the proportion of pregnant persons who used misoprostol to induce abortion rather than other methods among those who received harm reduction counselling.
RESULTS
We included four observational studies with a total of 4002 participants. Most pregnant persons who received harm reduction counselling induced abortion using misoprostol (79%-100%). Serious complication rates were low (0%-1%). Uterine aspiration rates were not always reported but were in the range of 6%-22%. Patient satisfaction with the harm reduction intervention was high (85%-98%) where reported. We rated the risk of bias for all studies as high due to a lack of comparison groups and high lost to follow-up rates.
DISCUSSION
Based on a synthesis of four studies with serious methodological limitations, most recipients of harm reduction counselling use misoprostol for abortion, have low complication rates, and are satisfied with the intervention. More research is needed to determine abortion success outcomes from the harm reduction approach.
FUNDING
This work did not receive any funding.
PROSPERO REGISTRATION NUMBER
We registered the review in the PROSPERO database of systematic reviews (ID number: CRD42020200849).
Topics: Abortion, Induced; Counseling; Female; Harm Reduction; Humans; Misoprostol; Pregnancy
PubMed: 35017226
DOI: 10.1136/bmjsrh-2021-201389 -
The Yale Journal of Biology and Medicine Dec 2021Williams Syndrome (WS) is a rare genetic multisystem disorder that occurs because of a deletion of approximately 25 genes in the 7q11.23 chromosome region. This causes... (Review)
Review
Williams Syndrome (WS) is a rare genetic multisystem disorder that occurs because of a deletion of approximately 25 genes in the 7q11.23 chromosome region. This causes dysmorphic facial appearances, multiple congenital cardiovascular defects, delayed motor skills, and abnormalities in connective tissues and the endocrine system. The patients are mostly diagnosed with mild to moderate mental retardation, however, they have a hyper sociable, socially dis-inhibited, and outgoing personality, empathetic behavior, and are highly talkative. Oxytocin (OT), a neuropeptide synthesized at the hypothalamus, plays an important role in cognition and behavior, and is thought to be affecting WS patients' attitudes at its different amounts. Oxytocin receptor gene (), on chromosome 3p25.3, is considered regulating oxytocin receptors, via which OT exerts its effect. WS is a crucial disorder to understand gene, hormone, brain, and behavior associations in terms of sociality and neuropsychiatric conditions. Alterations to the WS gene region offer an opportunity to deepen our understandings of autism spectrum disorder, schizophrenia, anxiety, or depression. We aim to systematically present the data available of OT/ regulation and expression, and the evidence for whether these mechanisms are dysregulated in WS. These results are important, as they predict strong epigenetic control over social behavior by methylation, single nucleotide polymorphisms, and other alterations. The comparison and collaboration of these studies may help to establish a better treatment or management approach for patients with WS if backed up with future research.
Topics: Autism Spectrum Disorder; Humans; Oxytocin; Receptors, Oxytocin; Social Behavior; Williams Syndrome
PubMed: 34970101
DOI: No ID Found -
PloS One 2021Prostaglandins are thought to be important mediators in the initiation of human labour, however the evidence supporting this is not entirely clear. Determining how, and...
Prostaglandins are thought to be important mediators in the initiation of human labour, however the evidence supporting this is not entirely clear. Determining how, and which, prostaglandins change during pregnancy and labour may provide insight into mechanisms governing labour initiation and the potential to predict timing of labour onset. The current study systematically searched the existing scientific literature to determine how biofluid levels of prostaglandins change throughout pregnancy before and during labour, and whether prostaglandins and/or their metabolites may be useful for prediction of labour. The databases EMBASE and MEDLINE were searched for English-language articles on prostaglandins measured in plasma, serum, amniotic fluid, or urine during pregnancy and/or spontaneous labour. Studies were assessed for quality and risk of bias and a qualitative summary of included studies was generated. Our review identified 83 studies published between 1968-2021 that met the inclusion criteria. As measured in amniotic fluid, levels of PGE2, along with PGF2α and its metabolite 13,14-dihydro-15-keto-PGF2α were reported higher in labour compared to non-labour. In blood, only 13,14-dihydro-15-keto-PGF2α was reported higher in labour. Additionally, PGF2α, PGF1α, and PGE2 were reported to increase in amniotic fluid as pregnancy progressed, though this pattern was not consistent in plasma. Overall, the evidence supporting changes in prostaglandin levels in these biofluids remains unclear. An important limitation is the lack of data on the complexity of the prostaglandin pathway outside of the PGE and PGF families. Future studies using new methodologies capable of co-assessing multiple prostaglandins and metabolites, in large, well-defined populations, will help provide more insight as to the identification of exactly which prostaglandins and/or metabolites consistently change with labour. Revisiting and revising our understanding of the prostaglandins may provide better targets for clinical monitoring of pregnancies. This study was supported by the Canadian Institutes of Health Research.
Topics: Amniotic Fluid; Body Fluids; Databases, Factual; Dinoprost; Female; Humans; Labor Onset; Labor, Obstetric; Oxytocics; Plasma; Pregnancy; Prostaglandins; Prostaglandins E; Prostaglandins F; Serum; Urine
PubMed: 34793529
DOI: 10.1371/journal.pone.0260115 -
BMC Pregnancy and Childbirth Oct 2021Oxytocin is widely used for induction and augmentation of labour, particularly in low- and middle-income countries (LMICs). In this systematic review and meta-analysis,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oxytocin is widely used for induction and augmentation of labour, particularly in low- and middle-income countries (LMICs). In this systematic review and meta-analysis, we examined the effect of intra-partum Oxytocin use on neonatal encephalopathy.
METHODS
The protocol for this study was registered with PROSPERO (ID: CRD42020165049). We searched Medline, Embase and Web of Science Core Collection databases for papers published between January 1970 and May 2021. We considered all studies involving term and near-term (≥36 weeks' gestation) primigravidae and multiparous women. We included all randomised, quasi-randomised clinical trials, retrospective studies and non-randomised prospective studies reporting intra-partum Oxytocin administration for induction and/or augmentation of labour. Our primary outcome was neonatal encephalopathy. Risk of bias was assessed in non-randomised studies using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. The RoB 2.0 tool was used for randomised studies. A Mantel-Haenszel statistical method and random effects analysis model were used for meta-analysis. Odds ratios were used to determine effect measure and reported with 95% confidence intervals.
RESULTS
We included data from seven studies (6 Case-control studies, 1 cluster-randomised trial) of which 3 took place in high-income countries (HICs) and 4 in LMICs. The pooled data included a total of 24,208 women giving birth at or after 36 weeks; 7642 had intra-partum Oxytocin for induction and/or augmentation of labour, and 16,566 did not receive intra-partum Oxytocin. Oxytocin use was associated with an increased prevalence of neonatal encephalopathy (Odds Ratio 2.19, 95% CI 1.58 to 3.04; p < 0.00001).
CONCLUSIONS
Intra-partum Oxytocin may increase the risk of neonatal encephalopathy. Future clinical trials of uterotonics should include neonatal encephalopathy as a key outcome.
Topics: Bias; Brain Diseases; Case-Control Studies; Developed Countries; Developing Countries; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Labor, Obstetric; Odds Ratio; Oxytocics; Oxytocin; Pregnancy
PubMed: 34717571
DOI: 10.1186/s12884-021-04216-3 -
BMJ Open Sep 2021Assess the effects of different routes of prophylactic oxytocin administration for preventing blood loss at caesarean section (CS). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Assess the effects of different routes of prophylactic oxytocin administration for preventing blood loss at caesarean section (CS).
DESIGN
Systematic review and meta-analysis.
METHODS
Medline, EMBASE, CINAHL, Cochrane Library, BVS, SciELO and Global Index Medicus were searched through 24 May 2020 for randomised controlled trials (RCTs) comparing different routes of prophylactic oxytocin administration during CS. Study selection, data extraction and quality assessment were conducted by two investigators independently. We pooled results in fixed effects meta-analyses and calculated average risk ratio (RR), mean difference (MD) and 95% CI. We used GRADE to assess the overall quality of evidence for each outcome.
RESULTS
Three trials (180 women) were included in the review. All studies compared intramyometrial (IMY) versus intravenous oxytocin in women having prelabour CS. IMY compared with intravenous oxytocin administration may result in little or no difference in the incidence of postpartum haemorrhage (RR 0.14, 95% CI 0.01 to 2.70; N=100 participants; 1 RCT), hypotension (RR 1.00, 95% CI 0.29 to 3.45; N=40; 1 RCT), headache (RR 3.00, 95% CI 0.13 to 69.52; N=40; 1 RCT) or facial flushing (RR 0.50, 95% CI 0.05 to 5.08; N=40; 1 RCT); IMY oxytocin may reduce nausea/vomiting (RR 0.13, 95% CI 0.02 to 0.69; N=140; 2 RCTs). We are very uncertain about the effect IMY versus intravenous oxytocin on the need for additional uterotonics (RR 0.82; 95% CI 0.25 to 2.69; N=140; 2 RCTs). IMY oxytocin may reduce blood loss slightly (MD -57.40 mL, 95% CI -101.71 to -13.09; N=40; 1 RCT).
CONCLUSIONS
There is limited, low to very low certainty evidence on the effects of IMY versus intravenous oxytocin at CS for preventing blood loss. The evidence is insufficient to support choosing one route over another. More trials, including studies that assess intramuscular oxytocin administration, are needed on this relevant question.
PROSPERO REGISTRATION NUMBER
CRD42020186797.
Topics: Cesarean Section; Ergonovine; Female; Humans; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy
PubMed: 34531222
DOI: 10.1136/bmjopen-2021-051793 -
The Cochrane Database of Systematic... Sep 2021Embryo transfer (ET) is a crucial step of in vitro fertilisation (IVF) treatment, and involves placing the embryo(s) in the woman's uterus. There is a negative... (Review)
Review
BACKGROUND
Embryo transfer (ET) is a crucial step of in vitro fertilisation (IVF) treatment, and involves placing the embryo(s) in the woman's uterus. There is a negative association between endometrial wave-like activity (contractile activities) at the time of ET and clinical pregnancy, but no specific treatment is currently used in clinical practice to counteract their effects. Oxytocin is a hormone produced by the hypothalamus and released by the posterior pituitary. Its main role involves generating uterine contractions during and after childbirth. Atosiban is the best known oxytocin antagonist (and is also a vasopressin antagonist), and it is commonly used to delay premature labour by halting uterine contractions. Other oxytocin antagonists include barusiban, nolasiban, epelsiban, and retosiban. Administration of oxytocin antagonists around the time of ET has been proposed as a means to reduce uterine contractions that may interfere with embryo implantation. The intervention involves administering the medication before, during, or after the ET (or a combination).
OBJECTIVES
To evaluate the effectiveness and safety of oxytocin antagonists around the time of ET in women undergoing assisted reproduction.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers in March 2021; and checked references and contacted study authors and experts in the field to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of the use of oxytocin antagonists for women undergoing ET, compared with the non-use of this intervention, the use of placebo, or the use of another similar drug.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. Primary review outcomes were live birth and miscarriage; secondary outcomes were clinical pregnancy and other adverse events.
MAIN RESULTS
We included nine studies (including one comprising three separate trials, 3733 women analysed in total) investigating the role of three different oxytocin antagonists administered intravenously (atosiban), subcutaneously (barusiban), or orally (nolasiban). We found very low- to high-certainty evidence: the main limitations were serious risk of bias due to poor reporting of study methods, and serious or very serious imprecision. Intravenous atosiban versus normal saline or no intervention We are uncertain of the effect of intravenous atosiban on live birth rate (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.88 to 1.24; 1 RCT, N = 800; low-certainty evidence). In a clinic with a live birth rate of 38% per cycle, the use of intravenous atosiban would be associated with a live birth rate ranging from 33.4% to 47.1%. We are uncertain whether intravenous atosiban influences miscarriage rate (RR 1.08, 95% CI 0.75 to 1.56; 5 RCTs, N = 1424; I² = 0%; very low-certainty evidence). In a clinic with a miscarriage rate of 7.2% per cycle, the use of intravenous atosiban would be associated with a miscarriage rate ranging from 5.4% to 11.2%. Intravenous atosiban may increase clinical pregnancy rate (RR 1.50, 95% CI 1.18 to 1.89; 7 RCTs, N = 1646; I² = 69%; low-certainty evidence), and we are uncertain whether multiple or ectopic pregnancy and other complication rates were influenced by the use of intravenous atosiban (very low-certainty evidence). Subcutaneous barusiban versus placebo One study investigated barusiban, but did not report on live birth or miscarriage. We are uncertain whether subcutaneous barusiban influences clinical pregnancy rate (RR 0.96, 95% CI 0.69 to 1.35; 1 RCT, N = 255; very low-certainty evidence). Trialists reported more mild to moderate injection site reactions with barusiban than with placebo, but there was no difference in severe reactions. They reported no serious drug reactions; and comparable neonatal outcome between groups. Oral nolasiban versus placebo Nolasiban does not increase live birth rate (RR 1.13, 95% CI 0.99 to 1.28; 3 RCTs, N = 1832; I² = 0%; high-certainty evidence). In a clinic with a live birth rate of 33% per cycle, the use of oral nolasiban would be associated with a live birth rate ranging from 32.7% to 42.2%. We are uncertain of the effect of oral nolasiban on miscarriage rate (RR 1.45, 95% CI 0.73 to 2.88; 3 RCTs, N = 1832; I² = 0%; low-certainty evidence). In a clinic with a miscarriage rate of 1.5% per cycle, the use of oral nolasiban would be associated with a miscarriage rate ranging from 1.1% to 4.3%. Oral nolasiban improves clinical pregnancy rate (RR 1.15, 95% CI 1.02 to 1.30; 3 RCTs, N = 1832; I² = 0%; high-certainty evidence), and probably does not increase multiple or ectopic pregnancy, or other complication rates (moderate-certainty evidence).
AUTHORS' CONCLUSIONS
We are uncertain whether intravenous atosiban improves pregnancy outcomes for women undergoing assisted reproductive technology. This conclusion is based on currently available data from seven RCTs, which provided very low- to low-certainty evidence across studies. We could draw no clear conclusions about subcutaneous barusiban, based on limited data from one RCT. Further large well-designed RCTs reporting on live births and adverse clinical outcomes are still required to clarify the exact role of atosiban and barusiban before ET. Oral nolasiban appears to improve clinical pregnancy rate but not live birth rate, with an uncertain effect on miscarriage and adverse events. This conclusion is based on a phased study comprising three trials that provided low- to high-certainty evidence. Further large, well-designed RCTs, reporting on live births and adverse clinical outcomes, should focus on identifying the subgroups of women who are likely to benefit from this intervention.
Topics: Abortion, Spontaneous; Embryo Transfer; Female; Humans; Infant, Newborn; Live Birth; Oxytocin; Pregnancy; Pregnancy Rate
PubMed: 34467530
DOI: 10.1002/14651858.CD012375.pub2 -
Anaesthesia Nov 2021Oxytocin is one of the most commonly used medications during labour and delivery. Recent insights from basic neuroscience research suggest that the uterotonic effects of...
Oxytocin is one of the most commonly used medications during labour and delivery. Recent insights from basic neuroscience research suggest that the uterotonic effects of oxytocin may arguably be trivial when compared with its profound effects on higher-order human behaviour. The purpose of this review is to highlight the potential consequences of manipulating oxytocinergic signalling during the peripartum period and its long-term impact on the maternal-infant dyad. We identified four domains where modulation of oxytocinergic signalling might be consequential: postpartum depression; breastfeeding; neurodevelopment; and chronic pain, and performed a literature search to address the impact of peripartum oxytocin administration. We have shown modest, but inconsistent, evidence linking peripartum oxytocin administration with postpartum depression. Breastfeeding success appeared to be negatively correlated with peripartum oxytocin exposure, perhaps secondary to impaired primitive neonatal reflexes and maternal-infant bonding. The association between perinatal oxytocin exposure and subsequent development of neurodevelopmental disorders such as autism in the offspring was weak, but these studies were limited by the lack of information on the cumulative dose. Finally, we identified substantial evidence for analgesic and anti-hypersensitivity effects of oxytocin which might partly explain the low incidence of chronic pain after caesarean birth. Although most data presented here are observational, our review points to a compelling need for robust clinical studies to better dissect the impact of peripartum oxytocin administration, and as stewards of its use, increase the precision with which we administer oxytocin to prevent overuse of the drug.
Topics: Attention Deficit and Disruptive Behavior Disorders; Breast Feeding; Depression, Postpartum; Female; Humans; Oxytocics; Oxytocin; Peripartum Period; Postpartum Hemorrhage; Pregnancy
PubMed: 34389972
DOI: 10.1111/anae.15553