Abstract

BACKGROUND Heavy menstrual bleeding (HMB) detrimentally effects women. It is important to be able to compare treatments and synthesise data to understand which interventions are most beneficial, however, when there is variation in outcome reporting, this is difficult. OBJECTIVES To identify variation in reported outcomes in clinical studies of interventions for HMB. MATERIALS AND METHODS Searches were performed in medical databases and trial registries, using the terms 'heavy menstrual bleeding', menorrhagia*, hypermenorrhoea*, HMB, "heavy period "period", effective*, therapy*, treatment, intervention, manage* and associated MeSH terms. Two authors independently reviewed and selected citations according to pre-defined selection criteria, including both randomised and observational studies. The following data were extracted- study characteristics, methodology and quality, and all reported outcomes. Analysis considered the frequency of reporting. RESULTS There were 14 individual primary outcomes, however reporting was varied, resulting in 45 specific primary outcomes. There were 165 specific secondary outcomes. The most reported outcomes were menstrual blood loss and adverse events. CONCLUSIONS A core outcome set (COS) would reduce the evident variation in reporting of outcomes in studies of HMB, allowing more complete combination and comparison of study results and preventing reporting bias. WHAT IS NEW? This in-depth review of past research into heavy menstrual bleeding shows that there is the need for a core outcome set for heavy menstrual bleeding.

Abstract

Anemia in pregnancy is defined as a hemoglobin level of <11 g/dl, and is commonly due to iron deficiency. This systematic review was conducted to determine the prevalence and risk factors of anemia and iron deficiency among pregnant women in Malaysia. A systematic literature search was conducted in Google Scholar, PubMed, and Cochrane Library databases. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. Eight studies comprising a total number of 2,638 pregnant women were included in this review. Only two studies focused on iron deficiency, whereas the other six investigated anemia in pregnancy without specifying iron deficiency or any other nutritional cause for the anemia, signifying the lack of published literature on this important public health nutritional issue in Malaysia. The overall prevalence of anemia in pregnancy ranged from 19.3 to 57.4%, while the prevalence of iron deficiency was 31.6 to 34.6%. Factors that were significantly associated with anemia in pregnancy were extremes of reproductive age, late antenatal booking, non-compliance to hematinics, Indian ethnicity, being in the second or third trimester, low maternal educational level, low family income, and unemployment. The prevalence of anemia in pregnancy was found to be higher in rural compared to urban areas. Meanwhile, in terms of iron deficiency anemia, grandmultiparity, late antenatal booking and Indian ethnicity were significant determinants. It is certainly plausible that the anemia in pregnancy reported in these studies is not entirely secondary to iron deficiency and may be attributable to other nutritional deficiencies, emphasizing the importance of researching deeper into this subject. Nevertheless, in the meantime, focusing on iron supplementation in high-risk mothers with emphasis on compliance, seems to be the best option, in view of the high prevalence of iron deficiency found in this review.

Abstract

AIM: The shock index has been suggested as a screening tool for predicting postpartum hemorrhage (PPH); however, there is little comprehensive evidence regarding its predictive accuracy. This systematic review and meta-analysis aim to investigate the predictive accuracy of the shock index for severe PPH in high-income countries. METHODS A comprehensive search was conducted on MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science (from inception to June 2021). Studies assessing the predictive performance of the shock index for PPH in high-income countries were included. Two or more reviewers independently extracted the data and assessed the risk of bias and applicability concerns using the modified Quality Assessment of Diagnostic Accuracy Studies 2 tool. PPH requiring higher-level care, such as blood transfusions, were considered as primary analyses. We described the hierarchical summary receiver-operating characteristic curve for data synthesis. RESULTS Nine studies were included after the eligibility assessment. All studies were considered to either have a high risk of bias or high applicability concerns. The sensitivity of the four studies that defined severe PPH as PPH requiring blood transfusion ranged from 0.51 to 0.80, whereas their specificity ranged from 0.33 to 0.92. CONCLUSIONS This review shows that the predictive performance of the shock index for severe PPH is inconsistent. Therefore, the evidence for using the shock index alone as a screening tool for PPH in high-income countries is insufficient. STUDY REGISTRATION This review was prospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000044230).

Abstract

Birth asphyxia, with an estimated prevalence of 1 to 6 per 1,000 live births, may lead to multiorgan dysfunction due to impaired oxygen and/or blood supply to various organ systems, including the hemostatic system. Coagulopathy, a common complication of perinatal asphyxia, has been described since the 1960s. The aim of this study was to systematically review the literature for records on the use of hemostasis tests in the evaluation of coagulation disorders, in neonates who had suffered from perinatal hypoxia or asphyxia. We identified published studies by searching PubMed and Scopus, up until April 2022. The literature search retrieved 37 articles fulfilling the inclusion criteria of the review. According to the bibliography, thrombocytopenia is commonly associated with perinatal hypoxia/asphyxia. The thrombocytopenia is usually described as mild and platelets return to normal levels by the 10th day of life. Additionally, hypoxic neonates usually present with a hypocoagulable profile, as reflected by the prolongation of standard coagulation tests, including prothrombin time, activated partial thromboplastin time, and international normalized ratio, findings commonly associated with disseminated intravascular coagulation, and by the reduction of the levels of the physiologic inhibition of coagulation system. A few studies thus far using ROTEM/TEG in hypoxic neonates have come to the same conclusion as well; hypoxic newborns seem to be characterized by a hypocoagulable profile compared with healthy neonates. It should be emphasized, however, that standard coagulation tests provide only a rough estimation of the true bleeding or thrombotic risk of hypoxic neonates. On the contrary, viscoelastic methods seem to be more precise in the early detection of hemostasis disorders in the neonatal population. However, until now, there was uncertainty as to the most appropriate coagulation assays for diagnosis and management of coagulation derangement in neonates with perinatal hypoxia indicating the need for further research on this field.

Abstract

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.

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.

Abstract

BACKGROUND Congenital factor VII (FVII) deficiency is an inherited bleeding disorder, with heterogenous bleeding symptoms. Women with FVII deficiency face haemostatic challenges during menstruation, ovulation, and childbirth. This systematic review evaluated prevalence and management of bleeding symptoms associated with gynaecological and obstetric issues in women with FVII deficiency. METHODS Databases (BIOSIS Previews, Current Contents Search, Embase and Medline) were searched for studies reporting FVII deficiency and gynaecological or obstetric issues in women. Articles were screened using Joanna Briggs institute checklists and relevant data extracted. RESULTS 114 women were identified from 62 publications. 46 women had severe deficiency (FVII:C <5% or <5 IU/dL). Heavy menstrual bleeding (HMB) was the most common bleeding symptom, (n=94; 82%); Hospitalisation and urgent medical/surgical interventions for acute HMB episodes were required in 16 women (14%). Seven women reported ovarian bleeding (6%); other bleeding symptoms varied. Patient management was inconsistent and included haemostatic and hormonal treatments. Only four women (7%) reporting vaginal bleeding during pregnancy. Postpartum haemorrhage (PPH) occurred following 12/45 deliveries (27%) (five [42%] requiring blood transfusion) and was not necessarily prevented by prophylaxis (eight women). CONCLUSION Women with congenital FVII deficiency have an increased risk of HMB, ovarian bleeding and PPH, impacting quality of life. Recognition of a bleeding disorder as the cause is often delayed. Management of bleeding complications is heterogeneous due to lack of treatment guidelines. Harmonising severity classification of FVII deficiency may help standardise treatment strategies and development of specific guidelines for these women. FUNDING Novo Nordisk. Registered at PROSPERO (CRD42021218888).

Abstract

INTRODUCTION Cesarean rates are particularly high among Hispanic women in some regions of the United States, placing a disproportionate health burden on women and their newborns. This integrative review synthesized the literature on mode of birth (vaginal vs cesarean) and related childbirth complications (hemorrhage, surgical site infection, perineal trauma) among Mexican American women living in the United States. METHODS Four electronic databases, PubMed, Embase, CINAHL, and SCOPUS, were searched to identify studies meeting the inclusion criteria, research studies that included Mexican American women who were pregnant or postpartum. Results were limited to English language and publications that were peer-reviewed and published before May 2020. Covidence was used in article identification, screening, and assessment. Critical appraisal of the research was performed using the Quality Assessment Tool for Studies with Diverse Designs. RESULTS Ten articles met inclusion criteria. In some studies, Mexican American women born in the United States were more likely to have cesareans than women born in Mexico; in other studies, these findings were reversed. Mexican American women often had lower unadjusted cesarean rates compared with non-Hispanic white women, but adjusting for birth facility (some facilities perform more cesareans than others), sociodemographic, and risk factors often revealed Mexican American women have a higher adjusted risk for cesarean birth. Women with higher socioeconomic status had higher cesarean rates compared with women with lower socioeconomic status. In studies of birth outcome by level of acculturation, women who were US-oriented had higher rates of cesarean and more frequent perinatal complications. By ethnic subgroup, rates of cesarean and complications varied among Hispanic women. DISCUSSION Birth facility was associated with perinatal outcomes for Mexican American women; those who gave birth at higher-performing facilities had better outcomes when compared with women who gave birth at lower-performing facilities. After adjusting for pregnancy complications, Mexican American women had a greater risk for cesarean birth compared with non-Hispanic white women, a finding that may have clinical practice implications. Level of acculturation affected birth outcomes, but more research using precise instruments is needed.

Abstract

INTRODUCTION Iron deficiency anemia (IDA) is common among obstetric and gynecologic patients. This systematic review aimed to assess the comparative efficacy and safety of commonly used intravenous (IV) iron formulations, ferric carboxymaltose (FCM), and iron sucrose (IS) in the treatment of IDA in obstetric and gynecologic patients. METHODS We systematically searched PubMed, EMBASE, Cochrane CENTRAL, and Google Scholar for eligible randomized controlled trials (RCTs) comparing IV iron replacement using FCM and IS up to October 2019. The primary outcome was to compare the efficacy of FCM and IS, assessed by measuring serum hemoglobin (Hb) and ferritin levels before and after iron replacement. The secondary outcome was to compare the safety of FCM and IS, assessed by the incidence of adverse events during iron replacement. The meta-analysis was performed using RevMan 5.3. RESULTS We identified 9 RCTs with 910 patients (FCM group, n = 456; IS group, n = 454). Before iron replacement, FCM and IS group patients had similar baseline Hb (mean difference [MD], 0.04 g/dL; 95% confidence interval [CI], -0.07 to 015; I2 = 0%; P = 0.48) and ferritin levels (MD, -0.42 ng/mL; 95% CI, -1.61 to 0.78; I2 = 45%; P = 0.49). Following iron replacement, patients who received FCM had higher Hb (MD, 0.67; 95% CI, 0.25-1.08; I2 = 92%; P = 0.002) and ferritin levels (MD, 24.41; 95% CI, 12.06-36.76; I2 = 75%; P = 0.0001) than patients who received IS. FCM group showed a lower incidence of adverse events following iron replacement than IS group (risk ratio, 0.53; 95% CI, 0.35-0.80; I2 = 0%; P = 0.003). Serious adverse events were not reported in any group. CONCLUSION FCM group showed better efficacy in increasing Hb and ferritin levels and a favorable safety profile with fewer adverse events compared with IS group for IDA treatment among obstetric and gynecologic patients. However, this meta-analysis was limited by the small number of RCTs and high heterogeneity. TRIAL REGISTRATION The review was prospectively registered with the International Prospective Registry of Systematic Reviews (https://www.crd.york.ac.uk/prospero/, registration number CRD42019148905).

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.