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.

Abstract

INTRODUCTION Postpartum hemorrhage (PPH) has remained the leading cause of maternal mortality. While anemia is a leading contributor to maternal morbidity, molecular, cellular and anemia-induced hypoxia, clinical studies of the relationship between prenatal-anemia and PPH have reported conflicting results. Therefore, our objective was to investigate the outcomes of studies on the relationships between prenatal anemia and PPH-related mortality. MATERIALS AND METHODS Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, and the Cochrane Central Register of Controlled Trials) were searched for studies published before August 2019. Keywords included "anemia," "hemoglobin," "postpartum hemorrhage," and "postpartum bleeding." Only studies involving the association between anemia and PPH were included in the meta-analysis. Our primary analysis used random effects models to synthesize odds-ratios (ORs) extracted from the studies. Heterogeneity was formally assessed with the Higgins' I(2) statistics, and explored using meta-regression and subgroup analysis. RESULTS We found 13 eligible studies investigating the relationship between prenatal anemia and PPH. Our findings suggest that severe prenatal anemia increases PPH risk (OR = 3.54; 95% CI: 1.20, 10.4, p-value = 0.020). There was no statistical association with mild (OR = 0.60; 95% CI: 0.31, 1.17, p-value = 0.130), or moderate anemia (OR = 2.09; 95% CI: 0.40, 11.1, p-value = 0.390) and the risk of PPH. CONCLUSION Severe prenatal anemia is an important predictive factor of adverse outcomes, warranting intensive management during pregnancy. PROSPERO Registration Number: CRD42020149184; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=149184.

Abstract

BACKGROUND Postpartum anemia can negatively affect maternal health and interfere with early parenting. Thus, it is important to have clear, evidence-informed recommendations on its diagnosis and treatment. OBJECTIVE To compare global recommendations regarding the appropriate management of postpartum anemia and to highlight similarities and differences. METHODS Systematic searches were conducted in the databases PubMed, CINAHL, LILACS, TRIP database, and Scopus, and in the websites of health institutions and scientific societies. Search terms were related to anemia and the postpartum period. Two hundred and eighty papers were identified; the full texts of 30 sets of guidelines were reviewed, with seven being included in the final analysis. Recommendations were extracted through an evaluation of the evidence on the definition, screening, and diagnosis of anemia. The quality of the guidelines was assessed using the AGREE II instrument. RESULTS Two sets of guidelines have been elaborated by international organizations, and the rest were produced by professional associations within high-resource countries. The discrepancies found in the guidelines are important and affect the definition of anemia, the criteria for screening asymptomatic women, or the criteria guiding treatment. The quality of the guidelines commonly scored between 4 and 6 on a scale of 0 to 7. Recommendations with poor-quality evidence predominated over recommendations with high-quality evidence. CONCLUSIONS This review highlights the need to reach a consensus on the definition of postpartum anemia, to agree on what constitutes a problem for maternal health, and to provide recommendations that reach greater consensus on its diagnosis and treatment.

Abstract

BACKGROUND Infants born preterm (before 37 weeks' gestation) have poorer outcomes than infants at term, particularly if born before 32 weeks. Early cord clamping has been standard practice over many years, and enables quick transfer of the infant to neonatal care. Delayed clamping allows blood flow between the placenta, umbilical cord and baby to continue, and may aid transition. Keeping baby at the mother's side enables neonatal care with the cord intact and this, along with delayed clamping, may improve outcomes. Umbilical cord milking (UCM) is proposed for increasing placental transfusion when immediate care for the preterm baby is needed. This Cochrane Review is a further update of a review first published in 2004 and updated in 2012. OBJECTIVES To assess the effects on infants born at less than 37 weeks' gestation, and their mothers of: 1) delayed cord clamping (DCC) compared with early cord clamping (ECC) both with immediate neonatal care after cord clamping; 2) DCC with immediate neonatal care with cord intact compared with ECC with immediate neonatal care after cord clamping; 3) DCC with immediate neonatal care after cord clamping compared with UCM; 4) UCM compared with ECC with immediate neonatal care after cord clamping. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (10 November 2017), and reference lists of retrieved studies. We updated the search in November 2018 and added nine new trial reports to the awaiting classification section to be assessed at the next update. SELECTION CRITERIA Randomised controlled trials (RCTs) comparing delayed with early clamping of the umbilical cord (with immediate neonatal care after cord clamping or with cord intact) and UCM for births before 37 weeks' gestation. Quasi-RCTs were excluded. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Random-effects are used in all meta-analyses. Review authors assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS This update includes forty-eight studies, involving 5721 babies and their mothers, with data available from 40 studies involving 4884 babies and their mothers. Babies were between 24 and 36(+6) weeks' gestation at birth and multiple births were included. The data are mostly from high-income countries. Delayed clamping ranged between 30 to 180 seconds, with most studies delaying for 30 to 60 seconds. Early clamping was less than 30 seconds and often immediate. UCM was mostly before cord clamping but some were milked after cord clamping. We undertook subgroup analysis by gestation and type of intervention, and sensitivity analyses by low risk of selection and attrition bias.All studies were high risk for performance bias and many were unclear for other aspects of risk of bias. Certainty of the evidence using GRADE was mostly low, mainly due to imprecision and unclear risk of bias.Delayed cord clamping (DCC) versus early cord clamping (ECC) both with immediate neonatal care after cord clamping (25 studies, 3100 babies and their mothers)DCC probably reduces the number of babies who die before discharge compared with ECC (average risk ratio (aRR) 0.73, 95% confidence interval (CI) 0.54 to 0.98, 20 studies, 2680 babies (moderate certainty)).No studies reported on 'Death or neurodevelopmental impairment' in the early years'.DCC may make little or no difference to the number of babies with severe intraventricular haemorrhage (IVH grades 3 and 4) (aRR 0.94, 95% CI 0.63 to 1.39, 10 studies, 2058 babies, low certainty) but slightly reduces the number of babies with any grade IVH (aRR 0.83, 95% CI 0.70 to 0.99, 15 studies, 2333 babies, high certainty).DCC has little or no effect on chronic lung disease (CLD) (aRR 1.04, 95% CI 0.94 to 1.14, 6 studies, 1644 babies, high certainty).Due to insufficient data, we were unable to form conclusions regarding periventricular leukomalacia (PVL) (aRR 0.58, 95% CI 0.26 to 1.30, 4 studies, 1544 babies, low certainty) or maternal blood loss of 500 mL or greater (aRR 1.14, 95% CI 0.07 to 17.63, 2 studies, 180 women, very low certainty).We identified no important heterogeneity in subgroup or sensitivity analyses.Delayed cord clamping (DCC) with immediate neonatal care with cord intact versus early cord clamping (ECC) (one study, 276 babies and their mothers)There are insufficient data to be confident in our findings, but DCC with immediate neonatal care with cord intact may reduce the number of babies who die before discharge, although the data are also compatible with a slight increase in mortality, compared with ECC (aRR 0.47, 95% CI 0.20 to 1.11, 1 study, 270 babies, low certainty). DCC may also reduce the number of babies who die or have neurodevelopmental impairment in early years (aRR 0.61, 95% CI 0.39 to 0.96, 1 study, 218 babies, low certainty). There may be little or no difference in: severe IVH; all grades IVH; PVL; CLD; maternal blood loss ≥ 500 mL, assessed as low certainty mainly due to serious imprecision.Delayed cord clamping (DCC) with immediate neonatal care after cord clamping versus umbilical cord milking (UCM) (three studies, 322 babies and their mothers) and UCM versus early cord clamping (ECC) (11 studies, 1183 babies and their mothers)There are insufficient data for reliable conclusions about the comparative effects of UCM compared with delayed or early clamping (mostly low or very low certainty). AUTHORS' CONCLUSIONS Delayed, rather than early, cord clamping may reduce the risk of death before discharge for babies born preterm. There is insufficient evidence to show what duration of delay is best, one or several minutes, and therefore the optimum time to clamp the umbilical cord remains unclear. Whilst the current evidence supports not clamping the cord before 30 seconds at preterm births, future trials could compare different lengths of delay. Immediate neonatal care with the cord intact requires further study, and there are insufficient data on UCM.The nine new reports awaiting further classification may alter the conclusions of the review once assessed.

Abstract

OBJECTIVE To assess the efficacy, effectiveness, and safety of uterine balloon tamponade (UBT) for treating postpartum hemorrhage (PPH). DATA SOURCES Electronic databases from their inception to May 2019, and bibliographies. STUDY ELIGIBILITY CRITERIA Randomized controlled trials, non-randomized studies, and case series that reported on the efficacy, effectiveness, and/or safety of UBT in women with PPH. STUDY APPRAISAL AND SYNTHESIS METHODS The primary outcome was the success rate of UBT for treating PPH (number of UBT success cases/total number of women treated with UBT). For meta-analyses, we calculated pooled success rate for all studies, and relative risk (RR) with 95% confidence intervals (CIs) for studies that included a comparative arm. RESULTS Ninety-one studies, including 4,729 women, met inclusion criteria (6 randomized trials, 1 cluster randomized trial, 15 non-randomized studies, and 69 case series). The overall pooled UBT success rate was 85.9% (95% CI, 83.9-87.9). The highest success rates corresponded to uterine atony (87.1%) and placenta previa (86.8%), and the lowest to placenta accreta spectrum (66.7%) and retained products of conception (76.8%). The UBT success rate was lower in cesarean deliveries (81.7%) than in vaginal deliveries (87.0%). A meta-analysis of two randomized trials that compared UBT versus no-UBT in PPH due to uterine atony after vaginal delivery showed no significant differences between the study groups in the risk of surgical interventions or maternal death (RR 0.59, 95% CI 0.02-16.69). A meta-analysis of two non-randomized before-and-after studies showed that introduction of UBT in protocols for managing severe PPH significantly decreased the use of arterial embolization (RR 0.29, 95% CI 0.14-0.63). A non-randomized cluster study reported that use of invasive procedures was significantly lower in the perinatal network that routinely used UBT than that which did not use UBT (3.0/1000 vs 5.1/1000; p<0.01). A cluster randomized trial reported that the frequency of PPH-related invasive procedures and/or maternal death was significantly higher after UBT introduction than before UBT introduction (11.6/10,000 vs 6.7/10,000; p=0.04). Overall, the frequency of complications attributed to UBT use was low (≤6.5%). CONCLUSION UBT has a high success rate for treating severe PPH and appears to be safe. The evidence on UBT efficacy and effectiveness from randomized and non-randomized studies is conflicting, with experimental studies suggesting no beneficial effect in contrast with observational studies. Further research is needed to determine the most effective programmatic and health care delivery strategies on UBT introduction and use.

Abstract

BACKGROUND Postpartum hemorrhage (PPH) is responsible for about 25% of maternal deaths worldwide. Antifibrinolytic agents, mainly tranexamic acid, have been demonstrated to reduce blood loss in patients with established PPH Objective: The aim of this meta-analysis of randomized controlled trials (RCTs) was to evaluate the effectiveness of tranexamic acid administration in women with established primary PPH after vaginal delivery. DATA SOURCES The search was conducted using electronic databases from inception of each database through February 2018. Review of articles also included the abstracts of all references retrieved from the search. No restrictions for language or geographic location were applied. STUDY DESIGN Selection criteria included RCTs comparing the use of tranexamic acid in women with established primary PPH after vaginal delivery with control (either placebo or no treatment). Trials in women undergoing cesarean delivery and trials in prevention of PPH were excluded. The primary outcome was the incidence of hysterectomy. The summary measures were reported as summary relative risk (RR) with 95% of confidence interval (CI) using the random effects model of DerSimonian and Laird. TABULATION, INTEGRATION, AND RESULTS Two trials including 14 363 women with established primary PPH after vaginal delivery were analyzed. Women who received tranexamic acid soon after the diagnosis of PPH had a significantly lower incidence of hysterectomy (0.5 versus 0.8%; RR 0.63, 95% CI 0.42-0.94), compared to those who did not. The risk of thrombotic events was not increased in the tranexamic acid group. CONCLUSION In women with established PPH after vaginal delivery, use of tranexamic acid reduces the risk of hysterectomy and does not increase the risk of thrombotic events. We recommend 1 g plus a second dose of 1 g if bleeding continues after 30 min.