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Effective management of foetal anaemia in Rh(D) alloimmunised pregnant women with intrauterine transfusion: a Systematic Review
Prescott, B., Jackson, D. E.
Hematology, transfusion and cell therapy. 2023
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Editor's Choice
Abstract
BACKGROUND Foetal anaemia is caused by a severe pregnancy complication, haemolytic disease of the foetus and newborn. Intrauterine transfusions (IUTs) are performed to treat foetal anaemia in alloimmunised pregnant women. If left untreated hydrops can develop thereby reducing the chance of survival. Survival rates have improved but the procedure is not without complications. Procedure-related complications can be associated with early gestational age, hence delaying IUT could improve outcomes. This review aims to determine the effectiveness and safety of IUTs by examining survival and mortality rates, procedure-related complications with associated foetal mortality and the influence of hydrops. STUDY DESIGN AND METHOD A systematic review was conducted by searching keywords in four scientific databases from January 2000 to April 2022. A meta-analysis was performed with the OpenMeta-Analyst software using an arcsine transformed proportion with the binary random-effects model and maximum likelihood method. RESULTS Fifteen studies were identified as eligible and used in the meta-analysis. The forest plots all showed statistically significant outcomes with heterogeneity of data. Results indicated a greater foetal survival rate with IUT to treat anaemic foetuses, a low foetal mortality rate, and low risk of procedure-related complications associated with foetal loss but a higher risk of foetal mortality when hydrops is present. CONCLUSION The findings of this systematic review and meta-analysis provide evidence that IUT is a safe and effective treatment for foetal anaemia in the absence of hydrops when experienced personnel perform the procedure to minimise the risk of procedure-related complications.
PICO Summary
Population
Rh(D) alloimmunised pregnant women (15 studies).
Intervention
Systematic review and meta-analysis to determine the effectiveness and safety of intrauterine transfusions (IUTs).
Comparison
Outcome
The forest plots all showed statistically significant outcomes with heterogeneity of data. Results indicated a greater foetal survival rate with IUT to treat anaemic foetuses, a low foetal mortality rate, and low risk of procedure-related complications associated with foetal loss but a higher risk of foetal mortality when hydrops is present.
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Maternal low and high hemoglobin concentrations and associations with adverse maternal and infant health outcomes: an updated global systematic review and meta-analysis
Young MF, Oaks BM, Rogers HP, Tandon S, Martorell R, Dewey KG, Wendt AS
BMC pregnancy and childbirth. 2023;23(1):264
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Editor's Choice
Abstract
BACKGROUND Growing evidence suggests low and high maternal hemoglobin (Hb) concentrations may have adverse consequences for maternal and child health. There remain questions on specific Hb thresholds to define anemia and high Hb as well as how cutoffs may vary by anemia etiology and timing of assessment. METHODS We conducted an updated systematic review (using PubMed and Cochrane Review) on low (< 110 g/L) and high (≥ 130 g/L) maternal Hb concentrations and associations with a range of maternal and infant health outcomes. We examined associations by timing of Hb assessment (preconception; first, second, and third trimesters, as well as at any time point in pregnancy), varying cutoffs used for defining low and high hemoglobin concentrations and performed stratified analyses by iron-deficiency anemia. We conducted meta-analyses to obtain odds ratios (OR) and 95% confidence intervals. RESULTS The updated systematic review included 148 studies. Low maternal Hb at any time point in pregnancy was associated with: low birthweight, LBW (OR (95% CI) 1.28 (1.22-1.35)), very low birthweight, VLBW (2.15 (1.47-3.13)), preterm birth, PTB (1.35 (1.29-1.42)), small-for-gestational age, SGA (1.11 (1.02-1.19)), stillbirth 1.43 (1.24-1.65)), perinatal mortality (1.75 (1.28-2.39)), neonatal mortality (1.25 (1.16-1.34), postpartum hemorrhage (1.69 (1.45-1.97)), transfusion (3.68 (2.58-5.26)), pre-eclampsia (1.57 (1.23-2.01)), and prenatal depression (1.44 (1.24-1.68)). For maternal mortality, the OR was higher for Hb < 90 (4.83 (2.17-10.74)) than for Hb < 100 (2.87 (1.08-7.67)). High maternal Hb was associated with: VLBW (1.35 (1.16-1.57)), PTB (1.12 (1.00-1.25)), SGA (1.17 (1.09-1.25)), stillbirth (1.32 (1.09-1.60)), maternal mortality (2.01 (1.12-3.61)), gestational diabetes (1.71 (1.19-2.46)), and pre-eclampsia (1.34 (1.16-1.56)). Stronger associations were noted earlier in pregnancy for low Hb and adverse birth outcomes while the role of timing of high Hb was inconsistent. Lower Hb cutoffs were associated with greater odds of poor outcomes; for high Hb, data were too limited to identify patterns. Information on anemia etiology was limited; relationships did not vary by iron-deficiency anemia. CONCLUSION Both low and high maternal Hb concentrations during pregnancy are strong predictors of adverse maternal and infant health outcomes. Additional research is needed to establish healthy reference ranges and design effective interventions to optimize maternal Hb during pregnancy.
PICO Summary
Population
Women during pregnancy or preconception (148 studies, n= 13,839,327).
Intervention
Updated systematic review on low (< 110 g/L) and high (≥ 130 g/L) maternal haemoglobin (Hb) concentrations and associations with adverse maternal and infant health outcomes.
Comparison
Outcome
Low maternal Hb at any time point in pregnancy was associated with: Low birthweight, very low birthweight (VLBW), preterm birth (PTB), small-for-gestational age (SGA), stillbirth, perinatal mortality, neonatal mortality, postpartum haemorrhage, transfusion, pre-eclampsia, and prenatal depression. For maternal mortality, the OR was higher for Hb < 90 (OR, 4.83; 95% CI [2.17, 10.74]) than for Hb < 100 (OR, 2.87; 95% CI [1.08, 7.67]). High maternal Hb was associated with: VLBW, PTB, SGA, stillbirth, maternal mortality, gestational diabetes, and pre-eclampsia. Stronger associations were noted earlier in pregnancy for low Hb and adverse birth outcomes while the role of timing of high Hb was inconsistent.
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Placental Transfusion Strategies in Preterm Infants in Low- and Middle-Income Countries: A Systematic Review and Network Meta-Analysis
Ramaswamy VV, Bandyopadhyay T, Abiramalatha T, Shaik NB, Pullattayil SAk, Jasani B, Hegde V, Trevisanuto D, Weiner GM
Neonatology. 2022;:1-16
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Editor's Choice
Abstract
INTRODUCTION Placental transfusion strategies in preterm newborns have not been evaluated in low- and middle-income countries (LMICs). The objective of this systematic review was to compare placental transfusion strategies in preterm newborns in LMICs, including delayed cord clamping (DCC) for various time intervals, DCC until cord pulsations stop, umbilical cord milking, and immediate cord clamping (ICC). METHODS Medline, Embase, CINAHL, and CENTRAL were searched from inception. Observational studies and randomized controlled trials (RCTs) were included. Two authors independently extracted data for Bayesian random-effects network meta-analysis (NMA) if more than 3 interventions reported an outcome or a pairwise meta-analysis was utilized. RESULTS Among newborns <34 weeks of gestation, NMA of 9 RCTs could not rule out benefit or harm for survival from DCC 30-60 s compared to ICC: relative risk (RR) (95% credible interval) 0.96 (0.78-1.12), moderate certainty, or any included strategy compared to each other (low to very low certainty). Among late preterm newborns, DCC 120 s might be associated with improved survival: RR (95% confidence interval) 1.11 (1.01-1.22), very low certainty. We could not detect differences in the risk of intraventricular hemorrhage grade > II and bronchopulmonary dysplasia for any included intervention (low to very low certainty). DCC 60 s and 120 s might improve the hematocrit level among all preterm newborns (very low certainty), and DCC 45 s may decrease the risk of receipt of inotropes among newborns <34 weeks of gestation (low certainty). CONCLUSIONS In LMICs, DCC for 60 s and 120 s might improve hematocrit level in preterm newborns, and DCC for 45 s may decrease the risk of receipt of inotropes in newborns <34 weeks, with no conclusive effect on survival.
PICO Summary
Population
Preterm newborns in low- and middle-income countries (9 studies).
Intervention
Delayed cord clamping (DCC) for various time intervals.
Comparison
DCC until cord pulsations stop. Umbilical cord milking. Immediate cord clamping (ICC).
Outcome
Network meta-analysis of 9 randomised controlled trials could not rule out benefit or harm for survival from DCC 30-60s compared to ICC: relative risk (RR), (95% credible interval) 0.96 (0.78 to 1.12), moderate certainty, or any included strategy compared to each other (low to very low certainty). Among late preterm newborns, DCC 120s might be associated with improved survival: RR (95% confidence interval) 1.11 (1.01 to 1.22), very low certainty. Differences were not detected in the risk of intraventricular hemorrhage grade > II and bronchopulmonary dysplasia for any included intervention (low to very low certainty). DCC 60s and 120s might improve the haematocrit level among all preterm newborns (very low certainty), and DCC 45 s may decrease the risk of receipt of inotropes among newborns <34 weeks of gestation (low certainty).
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Postpartum hemorrhage drills or simulations and adverse outcomes: a systematic review and Bayesian meta-analysis
Mendez-Figueroa H, Bell CS, Wagner SM, Pedroza C, Gupta M, Mulder I, Lee K, Blackwell SC, Bartal MF, Chauhan SP
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2022;:1-12
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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.
PICO Summary
Population
Postpartum haemorrhage patients (PPH), (18 studies with 355,060 deliveries).
Intervention
Systematic review and Bayesian meta-analysis to compare the rates of adverse outcomes with (PPH) before and after implementation of drills or simulation exercises.
Comparison
Outcome
The meta-analysis included 150,562 (42%) deliveries during the pre-intervention and 204,498 (57.6%) deliveries in the post-interventional period. 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).
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Predicting postpartum haemorrhage: A systematic review of prognostic models
Carr BL, Jahangirifar M, Nicholson AE, Li W, Mol BW, Licqurish S
The Australian & New Zealand journal of obstetrics & gynaecology. 2022
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Editor's Choice
Abstract
BACKGROUND Postpartum haemorrhage (PPH) remains a leading cause of maternal mortality and morbidity worldwide, and the rate is increasing. Using a reliable predictive model could identify those at risk, support management and treatment, and improve maternal outcomes. AIMS To systematically identify and appraise existing prognostic models for PPH and ascertain suitability for clinical use. MATERIALS AND METHODS MEDLINE, CINAHL, Embase, and the Cochrane Library were searched using combinations of terms and synonyms, including 'postpartum haemorrhage', 'prognostic model', and 'risk factors'. Observational or experimental studies describing a prognostic model for risk of PPH, published in English, were included. The Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist informed data extraction and the Prediction Model Risk of Bias Assessment Tool guided analysis. RESULTS Sixteen studies met the inclusion criteria after screening 1612 records. All studies were hospital settings from eight different countries. Models were developed for women who experienced vaginal birth (n = 7), caesarean birth (n = 2), any type of birth (n = 2), hypertensive disorders (n = 1) and those with placental abnormalities (n = 4). All studies were at high risk of bias due to use of inappropriate analysis methods or omission of important statistical considerations or suboptimal validation. CONCLUSIONS No existing prognostic models for PPH are ready for clinical application. Future research is needed to externally validate existing models and potentially develop a new model that is reliable and applicable to clinical practice.
PICO Summary
Population
Pregnant women (16 studies from eight different countries).
Intervention
Systematic review to identify and appraise existing prognostic models for post-partum haemorrhage (PPH) and ascertain suitability for clinical use.
Comparison
Various prognostic models for PPH, (e.g., based on prior hospital admissions for chronic diseases, based on medical history and clinical characteristics, using available antenatal and intrapartum variables, using prepartum fibrinogen levels).
Outcome
All studies were hospital settings. Models were developed for women who experienced vaginal birth (n= 7), caesarean birth (n= 2), any type of birth (n= 2), hypertensive disorders (n= 1) and those with placental abnormalities (n= 4). All studies were at high risk of bias due to use of inappropriate analysis methods or omission of important statistical considerations or suboptimal validation.
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Intravenous oxytocin regimens in patients undergoing cesarean delivery: a systematic review and network meta-analysis of cluster-based groups
Tantry TP, Karanth H, Anniyappa S, Shetty PK, Upadya M, Shenoy SP, Kadam D
Journal of anesthesia. 2022
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Editor's Choice
Abstract
Information on evaluations of different oxytocin regimens used to prevent post-partum hemorrhage during cesarean delivery is scarce, and there is a lack of statistically pooled results for comparative doses. In this review, we aimed to analyze the effectiveness of different oxytocin regimens used and rank them accordingly. We performed a meta-analysis of randomized controlled trials (RCTs) reporting the incidence of additional uterotonic (AUT) use or amount of blood loss during cesarean delivery, where different oxytocin regimens were compared. Cluster analysis was used to define different clusters of oxytocin therapy based on the identified variable regimens. During the frequentist network meta-analysis, all clusters were compared to bolus clusters of dose range 3-5 IU. Data from 33 RCTs (6741 patients) to 26 RCTs (5422 patients) were assessed for AUT use and blood loss, respectively. Pairwise meta-analysis revealed a significant reduction in the use of AUTs or blood loss was recorded for bolus-infusion combination regimens. The network meta-analysis found that combined bolus-infusion regimens of (i) 3-5 IU and 0.25-1 IU/min or (ii) 3-5 IU and < 0.25 IU/min had statistically significant results for lowest consumption of AUTs (Ranks 1 and 2, respectively); whereas with the latter's use, the lowest blood loss (Rank 2) was observed. In contrast, the dose range, > 5 IU regimen was associated with higher side effects (lowest rank). During cesarean delivery, a significant reduction in the use of AUTs or blood loss (Rank 2) was recorded for bolus-infusion combination regimens. High doses did not have enough evidence to draw meaningful conclusions.
PICO Summary
Population
Patients undergoing cesarean delivery (37 studies, n= >7,000).
Intervention
Different intravenous oxytocin regimens (bolus, infusion, or a combination).
Comparison
Outcome
During the frequentist network meta-analysis, all clusters were compared to bolus clusters of dose range 3-5 IU. Data from 33 randomised controlled trials (RCTs), (6,741 patients) to 26 RCTs (5,422 patients) were assessed for additional uterotonic (AUT) use and blood loss, respectively. Pairwise meta-analysis revealed a significant reduction in the use of AUTs or blood loss was recorded for bolus-infusion combination regimens. The network meta-analysis found that combined bolus-infusion regimens of (i) 3-5 IU and 0.25-1 IU/min or (ii) 3-5 IU and < 0.25 IU/min had statistically significant results for lowest consumption of AUTs (Ranks 1 and 2, respectively); whereas with the latter's use, the lowest blood loss (Rank 2) was observed. In contrast, the dose range, > 5 IU regimen was associated with higher side effects (lowest rank). During cesarean delivery, a significant reduction in the use of AUTs or blood loss (Rank 2) was recorded for bolus-infusion combination regimens.
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Non-Invasive Prenatal Fetal Blood Group Genotype and Its Application in the Management of Hemolytic Disease of Fetus and Newborn: Systematic Review and Meta-Analysis
Alshehri AA, Jackson DE
Transfusion medicine reviews. 2021
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Abstract
Hemolytic disease of fetus and newborn (HDFN) imposes great healthcare burden being associated with maternal alloimmunization against parental-inherited fetal red blood cell antigens causing fetal anemia or death. Noninvasive prenatal analysis (NIPT) provides safe fetal RHD genotyping for early identification of risk pregnancies and proper management guidance. We aimed to conduct systematic review and meta-analysis on NIPT's beneficial application, in conjunction with quantitative maternal alloantibody analysis, for early diagnosis of pregnancies at risk. Search for relevant articles was done in; PubMed/Medline, Scopus, and Ovid (January 2006April 2020), including only English-written articles reporting reference tests and accuracy data. Nineteen eligible studies were critically appraised. NIPT was estimated highly sensitive/specific for fetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons are optimum to increase accuracy. NIPT permits cost-effectiveness, precious resources sparing, and low emotional stress. Knowledge of parental ethnicity is important for correct NIPT result interpretations and quantitative screening. Cut-off titer ≥8-up-to-32 is relevant for anti-D alloantibodies, while, lower titer is for anti-K. Alloimmunization is influenced by maternal RHD status, gravida status, and history of adverse obstetrics. In conclusion, NIPT allows evidence-based provision of routine anti-D immunoprophylaxis and estimates potential fetal risks for guiding further interventions. Future large-scale studies investigating NIPT's non-RHD genotyping within different ethnic groups and in presence of clinically significant alloantibodies are needed.
PICO Summary
Population
Women whose pregnancy was at risk of haemolytic disease of foetus and new born (HDFN), (19 studies).
Intervention
Systematic review and meta-analysis on non-invasive prenatal analysis (NIPT) in conjunction with quantitative maternal alloantibody analysis.
Comparison
Outcome
NIPT was estimated highly sensitive/specific for foetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons were optimum to increase accuracy. NIPT permitted cost-effectiveness and was associated with low emotional stress. Knowledge of parental ethnicity was important for correct NIPT result interpretations and quantitative screening. Cut-off titre ≥8-up-to-32 was relevant for anti-D alloantibodies, while, lower titre was for anti-K. Alloimmunisation was influenced by maternal RHD status, gravida status, and history of adverse obstetrics.
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The Recognition of Excessive blood loss At ChildbirTh (REACT) Study: A two-phase exploratory, sequential mixed methods inquiry using focus groups, interviews, and a pilot, randomised crossover study
Hancock A, Weeks AD, Furber C, Campbell M, Lavender T
BJOG : an international journal of obstetrics and gynaecology. 2021
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Editor's Choice
Abstract
OBJECTIVES To explore how childbirth-related blood loss is evaluated and excessive bleeding recognised; and develop and test a theory of postpartum haemorrhage (PPH) diagnosis. DESIGN Two-phase, exploratory, sequential mixed methods design using focus groups, interviews and a pilot, randomised crossover study. SETTING Two hospitals in North West England. SAMPLE Women (following vaginal birth with and without PPH), birth partners, midwives and obstetricians. METHODS Phase 1 (qualitative): 8 focus groups and 20 one-to-one, semi-structured interviews were conducted with 15 women, 5 birth partners, 11 obstetricians, 1 obstetric anaesthetist and 19 midwives (n=51). Phase 2 (quantitative): 11 obstetricians and 10 midwives (n=21) completed two simulations of fast and slow blood loss using a high-fidelity childbirth simulator. RESULTS Responses to blood loss were described as automatic, intuitive reactions to the speed, nature and visibility of blood flow. Health professionals reported that quantifying volume was most useful after a PPH diagnosis, to validate intuitive decisions and guide on-going management. During simulations, PPH treatment was initiated at volumes at or below 200ml (fast mean blood loss 79.6ml, SD 41.1; slow mean blood loss 62.6ml, SD 27.7). All participants treated fast, visible blood loss, but only half treated slow blood loss, despite there being no difference in volumes (difference 18.2ml, 95% CI -5.6 to 42.2ml, p=0.124). CONCLUSIONS Experience and intuition, rather than blood loss volume, inform recognition of excessive blood loss after birth. Women and birth partners want more information and open communication about blood loss. Further research exploring clinical decision-making and how to support it is required.
PICO Summary
Population
Women following vaginal birth, birth partners, midwives and obstetricians in two centres in the UK (n= 51).
Intervention
Simulation of ‘slow blood loss followed by fast blood loss’ (n= 10).
Comparison
Simulation of ‘fast blood loss followed by slow blood loss’ (n= 11).
Outcome
This mixed methods study had a qualitative phase involving focus groups and interviews, and a quantitative phase consisting in a randomised crossover study. Responses to blood loss were described as automatic, intuitive reactions to the speed, nature and visibility of blood flow. Health professionals reported that quantifying volume was most useful after a postpartum haemorrhage (PPH) diagnosis, to validate intuitive decisions and guide on-going management. During simulations, PPH treatment was initiated at volumes at or below 200ml (fast mean blood loss 79.6ml, SD 41.1; slow mean blood loss 62.6ml, SD 27.7). All participants treated fast, visible blood loss, but only half treated slow blood loss, despite there being no difference in volumes (difference 18.2ml).
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9.
Tranexamic acid for prevention of bleeding in caesarean Delivery: an overview of systematic reviews
Hurskainen T, Deng MX, Etherington C, Burns J, Martin Calderon L, Moher D, Edwards W, Boet S
Acta anaesthesiologica Scandinavica. 2021
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Editor's Choice
Abstract
BACKGROUND Bleeding is the leading cause of maternal mortality in the world. Tranexamic acid reduces bleeding in trauma and surgery. Several systematic reviews of randomized trials have investigated tranexamic acid in the prevention of bleeding in caesarean delivery. However, the conclusions from systematic reviews are conflicting. This overview aims to summarize the evidence and explore the reasons for conflicting conclusions across the systematic reviews. METHODS A comprehensive literature search of Medline, Embase, and Cochrane Database of Systematic Reviews was conducted from inception to April 2021. Screening, data extraction, and quality assessments were performed by two independent reviewers. A Measurement Tool to Assess Reviews 2 and the Risk of Bias Assessment Tool for Systematic Reviews were used for study appraisal. A qualitative synthesis of evidence is presented. RESULTS Fourteen systematic reviews were included in our analysis. Across these reviews, there were 32 relevant randomized trials. A modest reduction in blood transfusions and bleeding outcomes was found by most systematic reviews. Overall confidence in results varied from low to critically low. All of the included systematic reviews were at high risk of bias. Quality of evidence from randomized trials was uncertain. CONCLUSIONS Systematic reviews investigating prophylactic tranexamic acid in caesarean delivery are heterogeneous in terms of methodological and reporting quality. Tranexamic acid may reduce blood transfusion and bleeding outcomes, but rigorous well-designed research is needed due to the limitations of the included studies. Data on safety and adverse effects is insufficient to draw conclusions.
PICO Summary
Population
Patients undergoing caesarean delivery (14 studies).
Intervention
Overview of systematic reviews on tranexamic acid for the prevention of bleeding.
Comparison
Outcome
A modest reduction in blood transfusions and bleeding outcomes was found by most systematic reviews. Overall confidence in results varied from low to critically low. All of the included systematic reviews were at high risk of bias. Quality of evidence from randomized trials was uncertain.
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10.
Tranexamic acid for the prevention of postpartum hemorrhage in women undergoing cesarean delivery: an updated meta-analysis
Bellos I, Pergialiotis V
American journal of obstetrics and gynecology. 2021
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Editor's Choice
Abstract
OBJECTIVE To assess the efficacy and safety of prophylactic tranexamic acid administration in comparison with standard uterotonic agents alone among women undergoing cesarean delivery. DATA SOURCES Medline, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov and Google Scholar were systematically searched from inception to June 30, 2021. STUDY ELIGIBILITY CRITERIA Randomized controlled trials comparing intravenous tranexamic acid administration to placebo in women undergoing cesarean delivery and receiving standard prophylactic uterotonic agents were held eligible. STUDY APPRAISAL AND SYNTHESIS METHODS The risk of bias of individual studies was appraised with the RoB-2 tool. Meta-analysis was conducted by fitting random-effects models using restricted maximum likelihood. Subgroup analysis was performed based on country, protocol availability, double-blinding, risk of bias, sample size and tranexamic acid dose. One-stage meta-analysis was performed as a sensitivity analysis. The credibility of outcomes was appraised with the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS Overall, 36 studies with 10,659 women were included. Tranexamic acid administration was associated with significantly lower total blood loss (Mean difference-MD: -189.44 ml, 95% confidence intervals-CI: -218.63; -160.25), lower hemoglobin drop (MD: 8.22%, 95% CI: 5.54; 10.90), decreased risk of blood loss >1000 ml (Odds ratio-OR: 0.37, 95% CI: 0.22; 0.60), transfusion requirement (OR: 0.41, 95% CI: 0.26; 0.65) and need of additional uterotonics (OR: 0.36, 95% CI: 0.25; 0.52). Subgroup analysis indicated a greater effect of tranexamic acid on total blood loss reduction in low-middle income countries. The outcomes remained stable by separately evaluating women at low bleeding risk. One-stage meta-analysis demonstrated similar outcomes with the primary analysis. The quality of evidence was judged to be moderate regarding total blood loss and hemoglobin percentage change and low for the other outcomes. CONCLUSIONS This meta-analysis suggests that prophylactic tranexamic acid administration is effective among women undergoing cesarean delivery in lowering postpartum blood loss and limiting hemoglobin drop. Further research is needed to test its efficacy in high-risk populations and to verify its safety profile.
PICO Summary
Population
Women undergoing caesarean delivery (36 studies, n= 10,659).
Intervention
Tranexamic acid.
Comparison
Standard uterotonic agents alone.
Outcome
Tranexamic acid administration was associated with significantly lower total blood loss (Mean difference (MD): -189.44 ml), lower haemoglobin drop (MD: 8.22%), decreased risk of blood loss >1000 ml, transfusion requirement and need of additional uterotonics. Subgroup analysis indicated a greater effect of tranexamic acid on total blood loss reduction in low-middle income countries. The outcomes remained stable by separately evaluating women at low bleeding risk. One-stage meta-analysis demonstrated similar outcomes with the primary analysis. The quality of evidence was judged to be moderate regarding total blood loss and haemoglobin percentage change and low for the other outcomes.