Third stage of labor: evidence-based practice for prevention of adverse maternal and neonatal outcomes.

The third stage of labor is defined as the time period between delivery of the fetus through delivery of the placenta. During a normal third stage, uterine contractions lead to separation and expulsion of the placenta from the uterus. Postpartum hemorrhage is a relatively common complication of the third stage of labor. Strategies have been studied to mitigate the risk of postpartum hemorrhage, leading to the widespread implementation of active management of the third stage of labor. Initially, active management of the third stage of labor consisted of a bundle of interventions including administration of a uterotonic agent, early cord clamping, controlled cord traction, and external uterine massage. However, the effectiveness of these interventions as a bundle has been questioned, leading to abandonment of some components in recent years. Despite this, upon review of selected international guidelines, we found that the term "active management of the third stage of labor" was still used, but recommendations for and against individual interventions were variable and not necessarily supported by current evidence. In this review, we: (1) examine the physiology of the third stage of labor, (2) present evidence related to interventions that prevent postpartum hemorrhage and promote maternal and neonatal health, (3) review current global guidelines and recommendations for practice, and (4) propose future areas of investigation. The interventions in this review include pharmacologic agents to prevent postpartum hemorrhage, cord clamping, cord milking, cord traction, cord drainage, early skin-to-skin contact, and nipple stimulation. Treatment of complications of the third stage of labor is outside of the scope of this review. We conclude that current evidence supports the use of effective pharmacologic postpartum hemorrhage prophylaxis, delayed cord clamping, early skin-to-skin contact, and controlled cord traction at delivery when feasible. The most effective uterotonic regimens for preventing postpartum hemorrhage after vaginal delivery include oxytocin plus ergometrine; oxytocin plus misoprostol; or carbetocin. After cesarean delivery, carbetocin or oxytocin as a bolus are the most effective regimens. There is inconsistent evidence regarding the use of tranexamic acid in addition to a uterotonic compared with a uterotonic alone for postpartum hemorrhage prevention after all deliveries. Because of differences in patient comorbidities, costs, and availability of resources and staff, decisions to use specific prevention strategies are dependent on patient- and system-level factors. We recommend that the term "active management of the third stage of labor" as a combined intervention no longer be used. Instead, we recommend that "third stage care" be adopted, which promotes the implementation of evidence-based interventions that incorporate practices that are safe and beneficial for both the woman and neonate.

Cumulative oxytocin dose in spontaneous labour - Adverse postpartum outcomes, childbirth experience, and breastfeeding.

OBJECTIVES: This study aimed to determine the association between the total cumulative oxytocin dose during labour and adverse postpartum outcomes, childbirth experience and breastfeeding in term primiparous women with spontaneous onset of labour. STUDY DESIGN: A prospective observational multicentre study, including 1395 women with spontaneous labour, in seven hospitals in Southeast Sweden. Multivariable logistic regression (Crude Odds Ratios (OR) and adjusted OR (aOR) for relevant confounders) was used to analyze the association between oxytocin dose and postpartum outcomes. The exposure was the cumulative oxytocin dose during labour, classified in percentiles (<25th, 25-75th, >75th). The outcomes were occurrence of obstetric anal sphincter injury, postpartum haemorrhage (blood loss > 1000 ml), Apgar score < 7 at five minutes, umbilical cord arterial pH, postpartum bladder overdistension, exclusive breastfeeding at one week and three months, and the woman's perceived birth experience. RESULTS: Women receiving high amounts (>75th percentile, >4370 mU) of oxytocin infusion during labour had an increased risk of postpartum haemorrhage (OR 2.73 (1.78-4.19)), an overdistended bladder (OR 2.19 (1.11-4.31)), an infant with an Apgar score < 7 at five minutes (OR 2.89 (1.27-6.57)), a negative birth experience (OR 1.83 (1.25-2.69)), and a decreased chance of exclusive breastfeeding at one week (OR 0.63 (0.41-0.96)). After adjusting for confounders, all outcomes remained statistically significant except risk of low Apgar score and chance of exclusive breastfeeding. CONCLUSION: In women with high cumulative oxytocin dose during labour prompt, and prophylactic administration of uterotonics after delivery of the placenta should be considered to reduce the risk of postpartum haemorrhage. The risk for bladder overdistension can be reduced by implementing routines for observation for signs of bladder filling in the early postpartum period, as well as routine use of bladder scans post micturition to assess for successful bladder emptying. As women's birth experience have a major impact on their future mental health, should be routinely assessed postpartum, and support should be offered to women with negative experiences.

Association between duration of intrapartum oxytocin exposure and obstetric hemorrhage.

PURPOSE: Prolonged duration of intrapartum oxytocin exposure is included as a risk factor within widely adopted obstetric hemorrhage risk stratification tools. However, the duration of exposure that confers increased risk is poorly understood. This study aimed to assess the association between duration of intrapartum oxytocin exposure and obstetric blood loss, as measured by quantitative blood loss, and hemorrhage-related maternal morbidity. METHODS: This was a retrospective cohort study of all deliveries from 2018 to 2019 at a single medical center. We included patients who had received any intrapartum oxytocin, and we categorized them into 1 of 5 groups: > 0-2, ≥ 2-4, ≥ 4-6, ≥ 6-12, and ≥ 12 h of intrapartum oxytocin exposure. The primary outcomes were mean quantitative blood loss, proportion with obstetric hemorrhage (defined as quantitative blood loss ≥ 1000 mL), and proportion with obstetric hemorrhage-related morbidity, a composite of hemorrhage-related morbidity outcomes. Secondary outcomes were hemorrhage-related pharmacologic and procedural interventions. A stratified analysis was also conducted to examine primary and secondary outcomes by delivery mode. RESULTS: Of 5332 deliveries between January 1, 2018 and December 31, 2019 at our institution, 2232 (41.9%) utilized oxytocin for induction or augmentation. 326 (14.6%) had exposure of > 0-2 h, 295 (13.2%) ≥ 2-4 h, 298 (13.4%) ≥ 4-6 h, 562 (25.2%) ≥ 6-12 h, and 751 (33.6%) ≥ 12 h. Across all deliveries, there was higher mean quantitative blood loss (p < 0.01) as well as increased odds of obstetric hemorrhage (adjusted odds ratio [aOR] 1.52, 95% confidence interval [CI] 1.21-1.91) for those with ≥ 12 h of oxytocin compared to all groups between > 0-12 h of exposure. In our stratified analysis, ≥ 12 h of oxytocin exposure was associated with higher mean quantitative blood loss (p = 0.04) and odds of obstetric hemorrhage in vaginal deliveries (aOR 1.47, 95% CI: 1.03-2.11), though not in cesarean deliveries (aOR 1.16, 95% CI 0.82-1.62). There were no differences in proportion with obstetric hemorrhage-related morbidity across all deliveries (p = 0.40) or in the stratified analysis. CONCLUSION: Intrapartum oxytocin exposure of ≥ 12 h was associated with increased quantitative blood loss and odds of obstetric hemorrhage in vaginal, but not cesarean, deliveries.

Propensity score analysis of low-dose aspirin and bleeding complications in pregnancy.

OBJECTIVE: Low-dose aspirin (LDA) has been shown to reduce the risk of preterm pre-eclampsia and it has been suggested that it should be recommended for all pregnancies. However, some studies have reported an association between LDA and an increased risk of bleeding complications in pregnancy. Our aim was to evaluate the risk of placental abruption and postpartum hemorrhage (PPH) in patients for whom their healthcare provider had recommended prophylactic aspirin. METHODS: This multicenter cohort study included 72 598 singleton births at 19 hospitals in the USA, between January 2019 and December 2021. Pregnancies complicated by placenta previa/accreta, birth occurring at less than 24 weeks' gestation, multiple pregnancy or those with data missing for aspirin recommendation were excluded. Propensity scores were calculated using 20 features spanning sociodemographic factors, medical history, year and hospital providing care. The association between LDA recommendation and placental abruption or PPH was estimated by inverse-probability treatment weighting using the propensity scores. RESULTS: We included 71 627 pregnancies in the final analysis. Aspirin was recommended to 6677 (9.3%) and was more likely to be recommended for pregnant individuals who were 35 years or older (P < 0.001), had a body mass index of 30 kg/m2 or higher (P < 0.001), had prepregnancy hypertension (P < 0.001) and who had a Cesarean delivery (P < 0.001). Overall, 1.7% of the study cohort (1205 pregnancies) developed preterm pre-eclampsia: 1.3% in the no-aspirin and 5.8% in the aspirin group. After inverse-probability weighting with propensity scores, aspirin was associated with increased risk of placental abruption (adjusted odds ratio (aOR), 1.44 (95% CI, 1.04-2.00)) and PPH (aOR, 1.21 (95% CI, 1.05-1.39)). The aOR translated to a number needed to harm with LDA of 79 (95% CI, 43-330) for PPH and 287 (95% CI, 127-3151) for placental abruption. CONCLUSIONS: LDA recommendation in pregnancy was associated with increased risk for placental abruption and for PPH. Our results support the need for more research into aspirin use and bleeding complications in pregnancy before recommending it beyond the highest-risk pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

When to use tranexamic acid for the treatment of major bleeding?

Tranexamic acid (TXA) is an antifibrinolytic agent originally developed for the management of bleeding in the setting of postpartum hemorrhage (PPH). Over the last 15 years, there has been accumulating evidence on the use of TXA for the treatment of active bleeding in a variety of clinical contexts. Clinical trials have shown that the efficacy and safety of TXA for the treatment of bleeding differ according to the clinical context in which it is being administered, timing of administration, and dose. Early administration is important for efficacy, particularly in trauma and PPH. Further studies are needed to understand the mechanisms by which TXA provides benefit, optimal modes of administration and dosing, and its effect in some clinical settings, such as spontaneous intracerebral hemorrhage. There is no evidence that TXA increases the risk of thrombotic events in patients with major bleeding overall. However, there is evidence of increased risk of venous thrombosis in patients with gastrointestinal bleeding. There is also evidence of increased risk of seizures with the use of higher doses. This review summarizes the current evidence for the use of TXA for patients with active bleeding and highlights the importance of generating evidence of efficacy and safety of hemostatic interventions specific to the bleeding contexts-as findings from 1 clinical setting may not be generalizable to other contexts-and that of individual patient assessment for bleeding, thrombotic, and other risks, as well as important logistical and other practical considerations, to optimize care and outcomes in these settings.

Effects of oxytocin induction on early postpartum hemorrhage, perineal integrity, and breastfeeding: a case-control study.

OBJECTIVE: The aim of this study was to evaluate the postpartum hemorrhage, perineal integrity, and breastfeeding results of mothers who underwent oxytocin induction in the first stage of labor in the early postpartum period. METHODS: This single-center observational case-control study was conducted in the obstetric unit of a public hospital in Istanbul. The study sampling included 44 pregnant women who received oxytocin induction (case group) and 44 pregnant women who did not receive oxytocin (control group). The Personal Information Form, LATCH Breastfeeding Assessment Tool, Breastfeeding Self-Efficacy Scale, Redness, Edema, Ecchymosis, Discharge, and Approximation Scale, and Postpartum Hemorrhage Collection Bag were used in data collection, and pad follow-up was carried out. RESULTS: The amount of hemorrhage in the first 24 h of the postpartum period and the mean Redness, Edema, Ecchymosis, Discharge, and Approximation Scale score were significantly higher in the case group. While 47.7% of the oxytocin-induced women had 1st or 2nd, and 11.4% had 3rd or 4th degrees of lacerations, 20.5% of the control group had 1st or 2nd, and 2.3% had 3rd or 4th degrees of lacerations. There was no significant difference between the mean scores of the Breastfeeding Self-Efficacy Scale and LATCH Breastfeeding Assessment Tool in both groups. CONCLUSION: According to the study findings, it was determined that oxytocin induction administered in the first stage of labor increased hemorrhage and perineal trauma in the early postpartum period but did not affect the results of breastfeeding. CLINICAL TRIAL REGISTRATION NUMBER: NCT04441125.

Effects of a LPG stove and fuel intervention on adverse maternal outcomes: A multi-country randomized controlled trial conducted by the Household Air Pollution Intervention Network (HAPIN).

Household air pollution from solid cooking fuel use during gestation has been associated with adverse pregnancy and birth outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial of free liquefied petroleum gas (LPG) stoves and fuel in Guatemala, Peru, India, and Rwanda. A primary outcome of the main trial was to report the effects of the intervention on infant birth weight. Here we evaluate the effects of a LPG stove and fuel intervention during pregnancy on spontaneous abortion, postpartum hemorrhage, hypertensive disorders of pregnancy, and maternal mortality compared to women who continued to use solid cooking fuels. Pregnant women (18-34 years of age; gestation confirmed by ultrasound at 9-19 weeks) were randomly assigned to an intervention (n = 1593) or control (n = 1607) arm. Intention-to-treat analyses compared outcomes between the two arms using log-binomial models. Among the 3195 pregnant women in the study, there were 10 spontaneous abortions (7 intervention, 3 control), 93 hypertensive disorders of pregnancy (47 intervention, 46 control), 11 post postpartum hemorrhage (5 intervention, 6 control) and 4 maternal deaths (3 intervention, 1 control). Compared to the control arm, the relative risk of spontaneous abortion among women randomized to the intervention was 2.32 (95% confidence interval (CI): 0.60, 8.96), hypertensive disorders of pregnancy 1.02 (95% CI: 0.68, 1.52), postpartum hemorrhage 0.83 (95% CI: 0.25, 2.71) and 2.98 (95% CI: 0.31, 28.66) for maternal mortality. In this study, we found that adverse maternal outcomes did not differ based on randomized stove type across four country research sites.

Pharmacokinetics and safety of inhaled oxytocin compared with intramuscular oxytocin in women in the third stage of labour: A randomized open-label study.

AIMS: To compare pharmacokinetics (PK) and safety of heat-stable inhaled (IH) oxytocin with intramuscular (IM) oxytocin in women in third stage of labour (TSL), the primary endpoint being PK profiles of oxytocin IH and secondary endpoint of safety. METHODS: A phase 1, randomized, cross-over study was undertaken in 2 UK and 1 Australian centres. Subjects were recruited into 2 groups: Group 1, women in TSL; Group 2, nonpregnant women of childbearing potential (Cohort A, combined oral contraception; Cohort B, nonhormonal contraception). Participants were randomized 1:1 to: Group 1, oxytocin 10 IU (17 µg) IM or oxytocin 240 IU (400 µg) IH immediately after delivery; Group 2, oxytocin 5 IU (8.5 µg) intravenously and oxytocin 240 IU (400 µg) IH at 2 separate dosing sessions. RESULTS: Participants were recruited between 23 November 2016 to 4 March 2019. In Group 1, 17 participants were randomized; received either IH (n = 9) or IM (n = 8) oxytocin. After IH and IM administration, most plasma oxytocin concentrations were below quantification limits (2 pg/mL). In Group 2 (n = 14), oxytocin IH concentrations remained quantifiable ≤3 h postdose. Adverse events were reported in both groups, with no deaths reported: Group 1, IH n = 3 (33%) and IM n = 2 (25%); Group 2, n = 14 (100%). CONCLUSION: Safety profiles of oxytocin IH and IM were similar. However, PK profiles could not be established for oxytocin IH or IM in women in TSL, despite using a highly sensitive and specific assay.

Low-Dose Aspirin during Pregnancy and Postpartum Bleeding.

OBJECTIVE: This study aimed to investigate whether aspirin 81 mg daily for preeclampsia prevention is associated with increased risk of postpartum blood loss at the time of delivery. STUDY DESIGN: This is a retrospective cohort study performed at a tertiary hospital from January 2018 to April 2021. Data were extracted from the electronic medical record. Patients prescribed low-dose aspirin (LDA) were compared with patients who were not. The primary outcome was a composite of postpartum blood loss, defined as: estimated blood loss (EBL) >1,000 mL, documentation of International Classification of Diseases-9/-10 codes for postpartum hemorrhage (PPH), or red blood cell (RBC) transfusion. Bivariate analysis, and unadjusted and adjusted logistic regression modeling were performed. RESULTS: Among 16,980 deliveries, 1,922 (11.3%) were prescribed LDA. Patients prescribed LDA were more likely to be >35 years old, nulliparous, obese, taking other anticoagulants, or have diagnoses of diabetes, systemic lupus erythematosus, fibroids, or hypertensive disease of pregnancy. After adjusting for potential confounders, the significant association between LDA use and the composite did not persist (adjusted odds ratio [aOR]: 1.1, 95% confidence interval [CI]: 1.0-1.3) nor did the association between EBL > 1,000 mL (aOR: 1.0, 95% CI: 0.9-1.3) and RBC transfusion (aOR: 1.3, 95% CI: 0.9-1.7). The association between LDA and PPH remained significant (aOR: 1.3, 95% CI: 1.1-1.6). Patients who discontinued LDA <7 days prior to delivery had an increased risk of the postpartum blood loss composite compared discontinuation ≥7 days (15.0 vs. 9.3%; p = 0.03). CONCLUSION: There may be an association between LDA use and increased risk of postpartum bleeding. This suggests that use of LDA outside the recommended guidelines should be cautioned and further investigation is needed to determine its ideal dosing and timing of discontinuation. KEY POINTS: · There may be an association with LDA and an increased risk of postpartum bleeding.. · Patients who discontinued LDA less than 7 days prior to delivery had an increased rate of postpartum bleeding.. · Additional research is need to determine optimal LDA dose and timing of discontinuation..

Low-dose asprin use during pregnancy may be a potential risk for postpartum hemorrhage and increased blood loss: a systematic review and meta-analysis.

OBJECTIVE: The association between aspirin use during pregnancy and the risk of postpartum hemorrhage remains unclear. This study aimed to explore the incidence of postpartum hemorrhage and the amount of postpartum blood loss among women who used aspirin during pregnancy. DATA SOURCES: From inception to October 2022, this study searched the following databases: MEDLINE, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials. STUDY ELIGIBILITY CRITERIA: Studies comparing pregnancy outcomes that covered the incidence of postpartum hemorrhage or the amount of postpartum blood loss in pregnancies with aspirin vs placebo (or no aspirin) were included. METHODS: Reviewers separately ascertained studies, obtained data, and gauged study quality. The meta-analysis was conducted using a random effects model owing to the probable heterogeneity of the included studies. The rates of postpartum hemorrhage or the mean amounts of postpartum blood loss were compared, and the odds ratios or mean differences with 95% confidence intervals were estimated. Of note, 2 parts performed both a pooled analysis of randomized controlled trials and cohort studies and a separate analysis of randomized controlled trials. RESULTS: Overall, 21 studies with 373,926 women were included in the postpartum hemorrhage part, and 7 studies with 10,163 women were included in the postpartum blood loss part. The results suggested that aspirin (dose 60-150mg a day) use during pregnancy was associated with an increased incidence of postpartum hemorrhage (odds ratio, 1.20; 95% confidence interval, 1.07-1.34). When only randomized controlled trials were retained, the results remained significant (odds ratio, 1.12; 95% confidence interval, 1.00-1.25). In the second part, higher total blood loss after delivery was obtained (mean difference, 12.85 mL; 95% confidence interval, 3.28-22.42), and the result was unaltered when cohort studies were eliminated (mean difference, 13.72 mL; 95% confidence interval, 4.63-22.81). The conclusions are more likely to be obtained in developed countries. CONCLUSION: Low-dose aspirin use during pregnancy is a potential risk of postpartum hemorrhage and does slightly increase the amount of postpartum blood loss. Without denying the combined value of aspirin, our conclusions raised an alarm for clinicians about postpartum hemorrhage in women using aspirin during pregnancy.

Postpartum hemorrhage drills or simulations and adverse outcomes: a systematic review and Bayesian meta-analysis.

OBJECTIVE: To compare the rates of adverse outcomes with postpartum hemorrhage (PPH) before and after implementation of drills or simulation exercises. STUDY ELIGIBILITY CRITERIA: We included all English studies that reported on rates of PPH and associated complications during the pre- and post-implementation of interventional exercises. STUDY APPRASIAL AND SYNTHESIS METHODS: Two investigators independently reviewed the abstracts, and full articles for eligibility of all studies. Inconsistencies related to study evaluation or data extraction were resolved by a third author. The co-primary outcomes were the rate of PPH and of any transfusion; the secondary outcomes included admission to the intensive care unit (ICU), transfusion ≥ 4 units of packed red blood cells, hysterectomy, or maternal death. Study effects were combined by Bayesian meta-analysis and reported as risk ratios (RR) and 95% credible intervals (Cr). RESULTS: We reviewed 142 full length articles. Of these, 18 publications, with 355,060 deliveries-150,562 (42%) deliveries during the pre-intervention and 204,498 (57.6%) deliveries in the post-interventional period-were included in the meta-analysis. Using the Newcastle-Ottawa Scale, only three studies were considered good quality, and none of them were done in the US. The rate of PPH prior to intervention was 5.06% and 5.46% afterwards (RR 1.09, 95% CI 0.87-1.36; probability of reduction in the diagnosis being 21%). The likelihood of transfusion decreased from 1.68% in the pre-intervention to 1.27% in the post-intervention period (RR 0.80, 95% Cr 0.57-1.09). The overall probability of reduction in transfusion was 93%, albeit it varied among studies done in non-US countries (96%) versus in the US (23%). Transfusion of 4 units or more of blood occurred in 0.44% of deliveries before intervention and 0.37% afterwards (RR of 0.85, 95% CI 0.50-1.52), with the overall probability of reduction being 72% (76% probability of reduction in studies from non-US countries and 49% reduction with reports from the US). Surgical interventions to manage PPH, which was not reported in any US studies, occurred in 0.14% before intervention and 0.28% afterwards (RR 1.29; 95% CI 0.56-3.06; probability of reduction 27%). Admission to the ICU occurred in 0.10% before intervention and 0.08% subsequently (RR 0.92, 95% CI 0.58-1.43), with the overall probability of reduction being 65% (81% in studies from non-US countries and 27% from the study done in the US). Maternal death occurred in 0.17% in the pre-intervention period and 0.09% during the post-intervention (RR 0.62, 95% CI 0.33-1.05; probability of reduction 93% in studies from non-US countries and 82% in one study from the US). CONCLUSIONS: Interventions to reduce the sequelae of PPH are associated with decrease in adverse outcomes. The conclusion, however, ought not to be accepted reflexively for the US population. All of the studies on the topic done in the US are of poor quality and the associated probability of reduction in sequelae are consistently lower than those done in other countries. SYNOPSIS: Since the putative benefits of PPH drills or simulation exercises are based on poor quality pre- and post-intervention trials, policies recommending them ought to be revisited.

Exploring cardiac effects after oxytocin 2.5 IU or carbetocin 100 µg: A randomised controlled trial in women undergoing planned caesarean delivery.

BACKGROUND: Oxytocin can stimulate release of myocardial biomarkers troponin I and T, prolong QTc and induce ST-depression. OBJECTIVE: To explore cardiac changes after either intravenous carbetocin or oxytocin. STUDY DESIGN: Exploratory phase 4 randomised controlled trial. SETTING: Obstetrics units of Oslo University Hospital, Norway between September 2015 and May 2018. PARTICIPANTS: Forty healthy, singleton pregnant women aged 18 to 50 years at gestational age at least 36 weeks with a planned caesarean delivery. INTERVENTIONS: Participants were randomised to receive either oxytocin 2.5 IU or carbetocin 100 µg immediately after delivery. MAIN OUTCOME MEASURES: The primary endpoint was the assessment of troponin I within 48 h of study drug administration. Troponin I and T, and creatine kinase myocardial band assessments were measured before spinal anaesthesia (baseline), and again at 4, 10 and 24 h after delivery. QTc, ST-depression and relative increase in heart rate were recorded from start of study drug administration to 10 min after delivery. All adverse events were monitored. RESULTS: Compared with the carbetocin group, higher troponin I levels were observed in the oxytocin group at 4 h and 10 h after delivery. For both treatment groups, an increase from baseline in troponin I and T was most pronounced at 10 h after delivery, and it had begun to decline by 24 h. QTc increased with time after administration of both study drugs, with a mean maximum increase of 10.4 ms observed at 9 min (P   <  0.001). No statistical differences were observed in QTc ( P  = 0.13) or ST-depression ( P  = 0.11) between the treatment groups. CONCLUSIONS: Oxytocin 2.5 IU and carbetocin 100 µg caused a similar increase in QTc. The trial was underpowered with regards to ST-depression and the release of myocardial biomarkers and these warrant further investigation. Data from this trial will inform a larger phase 4 trial to determine potential drug differences in troponin release. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02528136.

Association of maternal perfluoroalkyl substance exposure with postpartum haemorrhage in Guangxi, China.

Postpartum haemorrhage (PPH) is the leading cause of maternal death worldwide, and it may be caused by environmental endocrine disruptors. Prenatal exposure to perfluoroalkyl substances (PFASs) in women has been linked to pregnancy disorders and adverse birth outcomes, but no data are available on the relationship between PFAS exposure during pregnancy and postpartum haemorrhage. This study aimed to explore the associations of maternal PFAS exposure with the postpartum haemorrhage risk and total blood loss. A total of 1496 mother-infant pairs in the Guangxi Zhuang birth cohort were included between June 2015 and May 2018. The concentration of PFASs in serum was detected using ultrahigh liquid chromatography-tandem mass spectrometry. Multiple binomial regression and linear regression models were used to analyse individual PFAS exposures. The mixture of PFASs was analysed using Bayesian Kernel Machine Regression (BKMR). In single substance exposure models, exposure to perfluorohexanesulfonic acid (PFHxS) increased the risk of postpartum haemorrhage (OR: 3.42, 95 % CI: 1.45, 8.07), while exposure to perfluorododecanoic acid (PFDoA) was inversely associated with the risk of postpartum haemorrhage (OR: 0.42, 95 % CI: 0.22, 0.80). The concentrations of perfluoroundecanoic acid (PFUnA) (ß: 0.06, 95 % CI: 12.32, 108.82) and perfluorononanoic acid (PFNA) (ß: 0.05, 95 % CI: 0.40, 88.95) exposure were positively correlated with the amount of postpartum haemorrhage; this result occurred only in the absence of covariate adjustment. In BKMR models, the risk of postpartum haemorrhage increased with increasing exposure to a PFAS mixture. In conclusion, our study suggested that maternal serum PFAS exposure during pregnancy was associated with the risk of postpartum haemorrhage.

Is there a role for carbetocin in the prophylaxis of postpartum obstetric haemorrhage?

Postpartum haemorrhage is a common complication of pregnancy, most commonly due to uterine atony. Uterotonics have a vital role in preventing postpartum haemorrhage but the choice of the most effective agent with the fewest adverse effects is a subject of debate. Carbetocin, a synthetic analogue of oxytocin has been available in the UK since 2007 but is not currently widely used. It has a longer duration of action than oxytocin, which avoids the need for an infusion and as it is heat-stable it can be stored at room temperature. Current UK clinical guidelines, based on the results of older meta-analyses, do not recommend carbetocin as a first-line agent. A Cochrane review, published in 2018, ranked carbetocin in the top three drug regimens for preventing postpartum haemorrhage and an international consensus statement on uterotonic use for caesarean birth concluded that carbetocin may become the preferred drug for caesarean birth, by reducing the need for additional uterotonics. The higher cost of carbetocin when compared with oxytocin is a limiting factor, but the significant healthcare costs of a postpartum haemorrhage and the physiological impact of this event suggests it a reasonable alternative to consider, especially if ergometrine is contraindicated or in those who are undergoing a caesarean birth or are at high risk of bleeding.

Effects of Misoprostol on Induction of Labour in Patients with Hypertensive Disorders of Pregnancy: A 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 (n = 544, misoprostol) and the control group (n = 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; P < 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.

Image Analysis Application of Motherwort Total Alkaloid Injection in the Treatment of Postabortion Hemorrhage.

In order to reduce the possibility of postabortion hemorrhage leading to maternal death, the author studied the image analysis of postpartum hemorrhage based on Leonurus total alkaloid injection, combining research results, in order to explore the curative effect of Leonurus injection in treating postpartum hemorrhage. After treatment, the time and volume of vaginal bleeding were significantly lower than those in the control group (P < 0.05); it is suggested that the combination of oxytocin and motherwort can effectively reduce the time and volume of vaginal bleeding after medical abortion, conducive to postoperative recovery. The results show that motherwort injection can effectively reduce the amount of bleeding and reduce the risk of postpartum hemorrhage; in addition, adverse reactions have been reduced, and an image analysis consensus has been formed, which is worthy of promotion.

Selective Serotonin Reuptake Inhibitor Use in Pregnancy and Risk of Postpartum Hemorrhage.

Selective serotonin reuptake inhibitors (SSRIs) may predispose to postpartum hemorrhage (PPH) by interfering with platelet-mediated hemostasis and serotonin-mediated myometrial contractility. A meta-analysis of 8 observational studies found that, regardless of drug class, gestational exposure to antidepressants was associated with a small (odds ratio, 1.25) but statistically significantly increased risk of PPH; however, this finding was true only when antidepressant exposure was proximal to the date of delivery. A recent, moderately large, nationally representative, Swedish observational study also found that gestational exposure to SSRIs was associated with a significantly increased risk of PPH; the crude number needed to harm was 48. For reasons related to the methodology employed, it is possible that the risk was underestimated in this study. The findings of the meta-analysis and of the observational study are examined with a view to help readers understand how to critically read and interpret the research literature in the field. A reasonable viewpoint is that the increase in risk of PPH associated with gestational exposure to SSRIs is smaller than the increase in risk associated with obstetric risk factors for PPH; nevertheless, following precautionary measures would be wise. Such measures would include the routine administration of a uterotonic agent immediately after delivery to all women who have received serotonin reuptake inhibitor treatment during the month preceding delivery; the choice of uterotonic agent would depend on local hospital protocols. Women at risk should also be closely monitored for continued blood loss during the first 24 hours after delivery.

Interrupted versus continuous magnesium sulfate and blood loss at cesarean delivery.

OBJECTIVE: Magnesium sulfate is standard of care for prevention of eclampsia in women with preeclampsia with severe features. The American College of Obstetrics and Gynecology endorses its use throughout labor, delivery and the immediate postpartum period. Some providers pause magnesium sulfate infusion preoperatively due to concern for increased risk of uterine atony and postpartum hemorrhage. Using a non-inferiority analysis, we investigated the effect of interrupted versus continuous infusion of magnesium sulfate on postpartum hemorrhage in women with preeclampsia with severe features undergoing cesarean delivery. STUDY DESIGN: Retrospective non-inferiority cohort study of women with preeclampsia with severe features treated with magnesium sulfate undergoing cesarean delivery with singleton pregnancies at tertiary care hospital from 2013 to 2018. The primary outcome was postpartum hemorrhage. Secondary outcomes included estimated blood loss, change in hematocrit and a composite of postpartum hemorrhage severity, including transfusion of blood products, use of more than one uterotonic and additional surgical interventions. RESULTS: Of 249 women, magnesium sulfate infusion was interrupted in 171 (69%) and continued in 78 (31%). Women with interrupted magnesium sulfate infusion were more likely to be Caucasian (73% vs 67%, p = .024), have chronic hypertension (23% vs 1%, p < .001), labor prior to cesarean delivery (84% vs 55%, p < .001), undergo primary cesarean delivery (86% vs 67%, p = .005), and experience shorter surgical time (50 vs 55 min, p = .026). The rate of postpartum hemorrhage for those receiving interrupted magnesium sulfate infusion (9.9%) and continuous magnesium sulfate infusion (10.2%) was similar, falling within the non-inferiority margin (absolute difference 0.3%, 95% CI -7.8 to 8.4%, p = .88). There were no significant differences in the secondary outcomes. CONCLUSION: Interrupted magnesium sulfate infusion is non-inferior to continued magnesium sulfate infusion for rates of postpartum hemorrhage in women with preeclampsia with severe features undergoing cesarean delivery.

Calculated blood loss at cesarean delivery in patients with preeclampsia with severe features on magnesium sulfate.

INTRODUCTION: Magnesium sulfate decreases the risk of eclampsia in patients with severe preeclampsia. There is a theoretical risk that magnesium sulfate increases the risk of intrapartum hemorrhage. We evaluated whether there was a quantitative difference in blood loss in patients receiving magnesium sulfate at the time of cesarean delivery (CD) compared to those who were not. MATERIALS AND METHODS: A retrospective cohort study was performed using a database of patients with preeclampsia with severe features or eclampsia. The primary outcome was calculated estimated blood loss (cEBL) compared between patients who received magnesium sulfate during CD and those who did not. cEBL was derived through a validated equation by multiplying the patient's blood volume by percent of blood volume loss. Secondary outcomes were hematocrit change, visual EBL (vEBL), hemorrhage, cEBL >1500mL, Apgar <7 at 5 min, and NICU admission. Exclusion criteria were incomplete records or negative cEBL, as well as blood transfusion prior to collection of a postpartum hematocrit. RESULTS: We identified 124 patients with preeclampsia with severe features or eclampsia at time of CD. There were 57 (46%) that received magnesium sulfate during CD and 67 (54%) in which magnesium was stopped during the CD. The mean differences for hematocrit value (0.8, 95% confidence interval (CI) -0.3 to 1.8) and cEBL (108, 95% CI -102 to 318) were not significantly different after adjusting for obesity and history of CD. CONCLUSION: Magnesium sulfate administration for seizure prevention in patients with preeclampsia with severe features at the time of CD does not appear to be associated with an increase in the cEBL.