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Ultrasound in Obstetrics & Gynecology :... Mar 2023To analyze outcomes of singleton pregnancies with idiopathic polyhydramnios through a systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To analyze outcomes of singleton pregnancies with idiopathic polyhydramnios through a systematic review and meta-analysis.
METHODS
Electronic databases, including MEDLINE, OVID, EBSCO, Cochrane collection and Science Citation Index, were searched from 1946 to 2019. Gray literature and tables of contents of relevant journals were also screened. Prospective and retrospective studies with a control group were included. Two authors independently reviewed the abstracts retrieved from the literature search. Inclusion criteria were: studies documented in English, singleton pregnancy and idiopathic polyhydramnios determined by amniotic fluid volume assessment on ultrasound. Exclusion criteria were: maternal diabetes, fetal structural or chromosomal anomaly, alloimmunization and intrauterine fetal infection.
RESULTS
Twelve studies met the inclusion criteria, giving a total of 2392 patients with idiopathic polyhydramnios and 160 135 patients with normal amniotic fluid volume. Pregnancies complicated by idiopathic polyhydramnios were at a higher risk of neonatal death (odds ratio (OR), 8.68 (95% CI, 2.91-25.87)), intrauterine fetal demise (OR, 7.64 (95% CI, 2.50-23.38)), neonatal intensive care unit admission (OR, 1.94 (95% CI, 1.45-2.59)), 5-min Apgar score < 7 (OR, 2.21 (95% CI, 1.34-3.62)), macrosomia (OR, 2.93 (95% CI, 2.39-3.59)), malpresentation (OR, 2.73 (95% CI, 2.06-3.61)) and Cesarean delivery (OR, 2.31 (95% CI, 1.79-2.99)).
CONCLUSIONS
This study suggests that pregnancies complicated by idiopathic polyhydramnios are at increased risk of adverse outcome. Future investigations should aim to determine an amniotic fluid volume threshold above which antenatal fetal surveillance is appropriate in the management of these pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Polyhydramnios; Pregnancy Outcome; Retrospective Studies; Prospective Studies; Amniotic Fluid
PubMed: 35723677
DOI: 10.1002/uog.24973 -
Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape.BMC Pregnancy and Childbirth Jan 2023Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past...
BACKGROUND
Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past decades. Considering improvements in HDFN care, the objectives of this systematic literature review were to assess the prenatal treatment landscape and outcomes of Rh(D)- and K-mediated HDFN in mothers and fetuses, to identify the burden of disease, to identify evidence gaps in the literature, and to provide recommendations for future research.
METHODS
We performed a systematic search on MEDLINE, EMBASE and clinicaltrials.gov. Observational studies, trials, modelling studies, systematic reviews of cohort studies, and case reports and series of women and/or their fetus with HDFN caused by Rhesus (Rh)D or Kell alloimmunization. Extracted data included prevalence; treatment patterns; clinical outcomes; treatment efficacy; and mortality.
RESULTS
We identified 2,541 articles. After excluding 2,482 articles and adding 1 article from screening systematic reviews, 60 articles were selected. Most abstracted data were from case reports and case series. Prevalence was 0.047% and 0.006% for Rh(D)- and K-mediated HDFN, respectively. Most commonly reported antenatal treatment was intrauterine transfusion (IUT; median frequency [interquartile range]: 13.0% [7.2-66.0]). Average gestational age at first IUT ranged between 25 and 27 weeks. weeks. This timing is early and carries risks, which were observed in outcomes associated with IUTs. The rate of hydrops fetalis among pregnancies with Rh(D)-mediated HDFN treated with IUT was 14.8% (range, 0-50%) and 39.2% in K-mediated HDFN. Overall mean ± SD fetal mortality rate that was found to be 19.8%±29.4% across 19 studies. Mean gestational age at birth ranged between 34 and 36 weeks.
CONCLUSION
These findings corroborate the rareness of HDFN and frequently needed intrauterine transfusion with inherent risks, and most births occur at a late preterm gestational age. We identified several evidence gaps providing opportunities for future studies.
Topics: Female; Humans; Pregnancy; Erythroblastosis, Fetal; Hydrops Fetalis; Hemolysis; Blood Transfusion, Intrauterine; Fetus
PubMed: 36611144
DOI: 10.1186/s12884-022-05329-z -
PloS One 2020Existing systematic reviews of Rh immunoprophylaxis include only data from randomized controlled trials, have dated searches, and some do not report on all domains of...
BACKGROUND
Existing systematic reviews of Rh immunoprophylaxis include only data from randomized controlled trials, have dated searches, and some do not report on all domains of risk of bias or evaluate the certainty of the evidence. Our objective was to perform an updated review, by including new trials, any comparative observational studies, and assessing the certainty of the evidence using the GRADE framework.
METHODS
We searched MEDLINE, Embase and the Cochrane Library from 2000 to November 26, 2019. Relevant websites and bibliographies of systematic reviews and guidelines were searched for studies published before 2000. Outcomes of interest were sensitization and adverse events. Risk of bias was evaluated with the Cochrane tool and ROBINS-I. The certainty of the evidence was performed using the GRADE framework.
RESULTS
Thirteen randomized trials and eight comparative cohort studies were identified, evaluating 12 comparisons. Although there is some evidence of beneficial treatment effects (e.g., at 6-months postpartum, fewer women who received RhIg at delivery compared to no RhIg became sensitized [70 fewer sensitized women per 1,000 (95%CI: 67 to 71 fewer); I2 = 73%]), due to very low certainty of the evidence, the magnitude of the treatment effect may be overestimated. The certainty of the evidence was very low for most outcomes often due to high risk of bias (e.g., randomization method, allocation concealment, selective reporting) and imprecision (i.e., few events and small sample sizes). There is limited evidence on prophylaxis for invasive fetal procedures (e.g. amniocentesis) in the comparative literature, and few studies reported adverse events.
CONCLUSION
Serious risk of bias and low to very low certainty of the evidence is found in existing RCTs and comparative observational studies addressing optimal effectiveness of Rh immunoprophylaxis. Guideline development committees should exercise caution when assessing the strength of the recommendations that inform and influence clinical practice in this area.
Topics: Female; GRADE Approach; Humans; Immunologic Factors; Postnatal Care; Pregnancy; Prenatal Care; Randomized Controlled Trials as Topic; Rh Isoimmunization; Rh-Hr Blood-Group System
PubMed: 32913362
DOI: 10.1371/journal.pone.0238844 -
Journal of Obstetrics and Gynaecology... Dec 2021Noninvasive fetal rhesus D (RhD) blood group genotyping may prevent unnecessary use of anti-D immunoglobulin (RhIG) in non-alloimmunized RhD-negative pregnancies and can... (Review)
Review
OBJECTIVE
Noninvasive fetal rhesus D (RhD) blood group genotyping may prevent unnecessary use of anti-D immunoglobulin (RhIG) in non-alloimmunized RhD-negative pregnancies and can guide management of alloimmunized pregnancies. We conducted a systematic review of the economic literature to determine the cost-effectiveness of this intervention over usual care.
DATA SOURCES
Systematic literature searches of bibliographic databases (Ovid MEDLINE, Embase, and Cochrane) until February 26, 2019, and auto-alerts until October 30, 2020, and of grey literature sources were performed to retrieve all English-language studies.
STUDY SELECTION
We included studies done in serologically confirmed non-alloimmunized or alloimmunized RhD-negative pregnancies, comparing costs and effectiveness of the intervention versus usual care.
DATA EXTRACTION AND SYNTHESIS
Two reviewers extracted data from the eligible studies and assessed their methodological quality (risk of bias) using the Quality of Health Economic Studies (QHES) and Drummond tools. We narratively synthesized findings. Our review included 8 economic studies that evaluated non-invasive fetal RhD genotyping followed by targeted RhIG prophylaxis in non-alloimmunized pregnancies. Five studies further considered a subsequent alloimmunized pregnancy. The cost-effectiveness of the intervention versus usual care (e.g., universal RhIG or prophylaxis conditional on results of paternal testing) for non-alloiummunized pregnancies was inconsistent. Two studies indicated greater benefits and lower costs for the intervention, and another 2 suggested a trade-off. In 4 studies, the intervention was less effective and costlier than alternatives. Three studies were determined to be of high quality by both tools. Two of these studies favoured the intervention, and one assessed benefits in quality-adjusted life-years. No study clearly examined the cost-effectiveness of repetitive use of fetal genotyping in multiple non-alloimmunized or alloimmunized pregnancies. The cost of genotyping was the most influential parameter.
CONCLUSION
The cost-effectiveness of noninvasive fetal RhD genotyping for non-alloimmunized pregnancies varies between studies. Potential savings from targeted management of alloimmunized pregnancies requires further research.
Topics: Cost-Benefit Analysis; Female; Fetal Blood; Genotype; Humans; Pregnancy; Prenatal Diagnosis; Rh Isoimmunization; Rh-Hr Blood-Group System
PubMed: 34390866
DOI: 10.1016/j.jogc.2021.07.014 -
Journal of Medicine and Life Jul 2023The D antigen of the Rh blood group is considered clinically significant due to its ability to cause hemolytic transfusion reactions and hemolytic disease in the fetus... (Meta-Analysis)
Meta-Analysis Review
The D antigen of the Rh blood group is considered clinically significant due to its ability to cause hemolytic transfusion reactions and hemolytic disease in the fetus and newborn. This systematic review discusses the prevalence of RhD variants among pregnant women and the importance of including RhD genotyping for prenatal testing to detect RhD variants and prevent anti-D alloimmunization. A comprehensive literature search was conducted using scientific search engines, including PubMed and MEDLINE databases, with the keywords 'anti-D alloimmunization', 'RhD variant', and 'pregnant women.' The review adhered to the PRISMA guidelines. Meta-analysis was performed using MedCalc version 20. A significance level of p≤0.05 was considered statistically significant for all two-tailed tests. The meta-analysis included four articles that met the inclusion criteria. The total prevalence of RhD positivity (RhD+) was 61% (95% CI:34%-85%). The prevalence ranged from 22% to 82%, indicating a high degree of heterogeneity between studies (I2=98.71%, p<0.0001). The overall prevalence of D variants was 15% (95% CI, 9%-23%) with a prevalence of 0.05% to 100%, showing a high degree of heterogeneity between studies (I2=99.89%, p<0.0001). Anti-D alloimmunization could occur in pregnant women with some types of RhD variants. All four studies focused on molecular testing of samples showing inconsistent or weak results with at least two anti-D antibodies using serological methods.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Pregnant Women; Fetus; Prevalence
PubMed: 37900088
DOI: 10.25122/jml-2023-0004 -
Vox Sanguinis Sep 2022There is a varied prevalence of red cell alloimmunization being reported from different parts of India. This study aimed to estimate the overall prevalence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
There is a varied prevalence of red cell alloimmunization being reported from different parts of India. This study aimed to estimate the overall prevalence of alloimmunization in India by performing a systematic review of the literature and to establish the most suitable antigen-matching strategy to reduce the red blood cell (RBC) alloimmunization rate among transfusion recipients.
MATERIALS AND METHODS
A systematic search of all the original articles published in English on RBC alloimmunization among transfusion recipients from India in MEDLINE, SCOPUS, CINAHL and Google Scholar bibliographic databases was conducted. After screening the articles as per inclusion/exclusion criteria, data extraction was done independently by two sets of investigators. Meta-analysis was performed by the binary random-effects model using the restricted maximum likelihood method.
RESULTS
A total of 44 studies on RBC alloimmunization, with a cumulative sample size of 309,986 patients, were grouped into hospital-based and multiply-transfused patients, which yielded a prevalence of 0.5 (95% confidence interval; 0.3-0.8) and 4.8 (95% confidence interval; 3.9-5.7) per 100 patients, respectively. As many as 1992 alloantibodies were identified among the 1846 alloimmunized patients. The most common antibody identified was anti-E (127; 31.99%), followed by anti-c (75; 18.89%) in multiply-transfused patients.
CONCLUSION
The rate of alloimmunization was 0.5 per 100 patients tested for antibodies and 4.8 per 100 patients receiving transfusion. Considering E- and c-antigen-matched red cells along with ABO and RhD matching may significantly reduce the overall occurrence of alloimmunization among Indian population who are transfusion-dependent.
Topics: Blood Group Antigens; Blood Transfusion; Erythrocytes; Humans; India; Isoantibodies
PubMed: 35608911
DOI: 10.1111/vox.13296 -
Pathogens (Basel, Switzerland) Jun 2022In this systematic review, we evaluate the efficacy and safety of blood components treated with pathogen reduction technologies (PRTs). We searched the Medline, Embase,... (Review)
Review
In this systematic review, we evaluate the efficacy and safety of blood components treated with pathogen reduction technologies (PRTs). We searched the Medline, Embase, Scopus, Ovid, and Cochrane Library to identify RCTs evaluating PRTs. Risk of bias assessment and the Mantel-Haenszel method for data synthesis were used. We included in this review 19 RCTs evaluating 4332 patients (mostly oncohematological patients) receiving blood components treated with three different PRTs. Compared with standard platelets (St-PLTs), the treatment with pathogen-reduced platelets (PR-PLTs) does not increase the occurrence of bleeding events, although a slight increase in the occurrence of severe bleeding events was observed in the overall comparison. No between-groups difference in the occurrence of serious adverse events was observed. PR-PLT recipients had a lower 1 and 24 h CI and CCI. The number of patients with platelet refractoriness and alloimmunization was significantly higher in PR-PLT recipients compared with St-PLT recipients. PR-PLT recipients had a higher number of platelet and RBC transfusions compared with St-PLT recipients, with a shorter transfusion time interval. The quality of evidence for these outcomes was from moderate to high. Blood components treated with PRTs are not implicated in serious adverse events, and PR-PLTs do not have a major effect on the increase in bleeding events. However, treatment with PRTs may require a greater number of transfusions in shorter time intervals and may be implicated in an increase in platelet refractoriness and alloimmunization.
PubMed: 35745493
DOI: 10.3390/pathogens11060639 -
Vox Sanguinis Nov 2022Sickle cell disease (SCD) patients are commonly treated with red blood cell (RBC) transfusion. Pretransfusion tests commonly involve limited serological antibody... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Sickle cell disease (SCD) patients are commonly treated with red blood cell (RBC) transfusion. Pretransfusion tests commonly involve limited serological antibody testing. RBC alloimmunization to RBC antigens is a frequently encountered complication seen in chronically transfused patients. Genetic factors such as the human leukocyte antigen (HLA) are known to influence and regulate immune responses. HLAs are highly polymorphic and play an essential role in regulating immune responses, including RBC alloimmunization. The aim of this study was to conduct a systematic review and meta-analysis to evaluate the association between HLA Class II allelic polymorphisms with the possible risk of developing RBC alloantibodies.
MATERIALS AND METHODS
Four databases were systematically searched for relevant studies between the years 2000 and 2021 following the PRISMA guidelines. Four articles met the eligibility and quality criterion, and three alleles, HLA-DRB1*04, HLA-DRB1*15 and HLA-DQB1*03, that were found to be potentially associated with an increased risk in alloantibody formation were included.
RESULTS
The primary outcome measure was alloimmunization by RBC antigen exposure in multiply transfused SCD patients. The total estimate of alloimmunization of the SCD patients was 2.33 (95% CI, 1.58-3.44), demonstrating susceptibility to RBC alloantibody formation. Heterogeneity between the studies was insignificant, suggesting the differences associated with random sampling errors. The results showed that SCD patients carry an increased risk of producing RBC alloantibodies.
CONCLUSION
A strategy to prevent RBC alloimmunization is genotyping for genetically susceptible SCD patients receiving multiple transfusions. Early identification of genetic variants that can potentially increase the risk of RBC alloimmunization could aid in the screening process and selection of phenotypically matched RBC units.
Topics: Humans; Isoantibodies; Anemia, Sickle Cell; Erythrocytes; Erythrocyte Transfusion; Anemia, Hemolytic, Autoimmune; Immunity
PubMed: 36102140
DOI: 10.1111/vox.13351 -
Blood Advances Jul 2020The most common, severe cases of fetal and neonatal alloimmune thrombocytopenia among whites are caused by antibodies against human platelet antigen 1a (HPA-1a). The... (Meta-Analysis)
Meta-Analysis
The most common, severe cases of fetal and neonatal alloimmune thrombocytopenia among whites are caused by antibodies against human platelet antigen 1a (HPA-1a). The aims of this systematic review and meta-analysis are to determine the association between maternal HLA-DRB3*01:01 and: (1) HPA-1a-alloimmunization and (2) neonatal outcome in children born of HPA-1a-immunized women. A systematic literature search identified 4 prospective and 8 retrospective studies. Data were combined across studies to estimate pooled odds ratios (ORs) and the associated 95% confidence intervals (CIs). The population represented by the prospective studies was more than 150 000. In the prospective studies, there were 64 severely thrombocytopenic newborns (platelet count <50 × 109/L) of whom 3 had intracranial hemorrhage. The mothers of all 64 children were HLA-DRB3*01:01+. The number of severely thrombocytopenic children born of HPA-1a-alloimmunized women in the retrospective studies was 214; 205 of whom were born of HLA-DRB3*01:01+ women. For HLA-DRB3*01:01- women, the OR (95% CI) for alloimmunization was 0.05 (0.00-0.60), and for severe neonatal thrombocytopenia 0.08 (0.02-0.37). This meta-analysis demonstrates that the risk of alloimmunization and of having a child with severe thrombocytopenia are both very low for HPA-1a- women who are HLA-DRB3*01:01-.
Topics: Child; Female; Fetus; HLA-DRB3 Chains; Humans; Infant, Newborn; Prospective Studies; Retrospective Studies; Thrombocytopenia, Neonatal Alloimmune
PubMed: 32717028
DOI: 10.1182/bloodadvances.2020002137 -
Journal of Plastic, Reconstructive &... Feb 2022Acute rejection remains a vexing problem in vascularized composite allotransplantation (VCA). Available immunosuppressive regimens are successful at minimizing... (Review)
Review
BACKGROUND
Acute rejection remains a vexing problem in vascularized composite allotransplantation (VCA). Available immunosuppressive regimens are successful at minimizing alloimmune response and allowing VCA in humans. However, repeated rejection episodes are common, and systemic side effects of the current standard regimen (Tacrolimus, MMF, Prednisone) are dose limiting. Novel immunomodulatory approaches to improve allograft acceptance and minimize systemic toxicity are continuously explored in preclinical models. We aimed to systematically summarize past and current approaches to help guide future research in this complex field.
METHODS
We conducted a systematic review of manuscripts listed in the MEDLINE and PubMed databases. For inclusion, articles had to primarily investigate the effect of a therapeutic approach on prolonging the survival of a skin-containing preclinical VCA model. Non-VCA studies, human trials, anatomical and feasibility studies, and articles written in a language other than English were excluded. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.
RESULTS
The search retrieved 980 articles of which 112 articles were ultimately included. The majority of investigations used a rat model. An orthotopic hind limb VCA model was used in 53% of the studies. Cell and drug-based approaches were investigated 58 and 52 times, respectively. We provide a comprehensive review of immunomodulatory strategies used in VCA preclinical research over a timeframe of 44 years.
CONCLUSION
We identify a transition from anatomically non-specific to anatomical models mimicking clinical needs. As limb transplants have been most frequently performed, preclinical research focused on using the hind limb model. We also identify a transition from drug-based suppression therapies to cell-based immunomodulation strategies.
Topics: Animals; Graft Rejection; Humans; Immunomodulation; Immunosuppressive Agents; Rats; Skin; Tacrolimus; Vascularized Composite Allotransplantation
PubMed: 34895853
DOI: 10.1016/j.bjps.2021.11.003