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The Cochrane Database of Systematic... Jan 2005Fetomaternal alloimmune thrombocytopenia occurs when the mother produces antibodies against a platelet alloantigen that the fetus has inherited from the father. A... (Review)
Review
BACKGROUND
Fetomaternal alloimmune thrombocytopenia occurs when the mother produces antibodies against a platelet alloantigen that the fetus has inherited from the father. A consequence of this can be a reduced number of platelets (thrombocytopenia) in the fetus, which can result in bleeding whilst in the womb or shortly after birth. In severe cases this bleeding may lead to long-lasting disability or death. Antenatal management of fetomaternal alloimmune thrombocytopenia centres on preventing severe thrombocytopenia in the fetus. Available management options include administration of intravenous immunoglobulins or corticosteroids to the mother or intrauterine transfusion of antigen compatible platelets to the fetus. All options are costly and need to be assessed in terms of potential risk and benefit to both the mother and an individual fetus.
OBJECTIVES
To determine the optimal antenatal treatment of fetomaternal alloimmune thrombocytopenia to prevent fetal and neonatal haemorrhage and death.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group trials register (February 2004), EMBASE (1980 to February 2004) and bibliographies of relevant publications and review articles.
SELECTION CRITERIA
Randomised controlled studies comparing any intervention, including corticosteroids with no treatment, or comparing any two interventions.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed eligibility, trial quality and extracted data.
MAIN RESULTS
One study met the inclusion criteria (54 pregnant women). This trial compared intravenous immunoglobulins plus corticosteroid (dexamethasone) with intravenous immunoglobulins alone. No significant differences were reported between the treatment and control groups, in any outcome measured: mean platelet count at birth (weighted mean difference (WMD) 14.10 x 10 9/l, 95% confidence interval (CI) -30.26 to 58.46), mean gestational age at birth (WMD -0.50 weeks, 95% CI -2.69 to 1.69), mean rise in platelet count from first to second fetal blood screen (WMD -3.50 x 10 9/l, 95% CI -24.62 to 17.62) and mean rise in platelet count from birth to first fetal blood screen (WMD 24.40 x 10 9/l (95% CI -14.17 to 62.97)). This trial had adequate methodological quality; however the method used to calculate sample size was inappropriate: therefore the power calculation was not sufficient to determine any significance in differences between the treatment groups.
AUTHORS' CONCLUSIONS
There are insufficient data from randomised controlled trials to determine the optimal antenatal management of fetomaternal alloimmune thrombocytopenia. Future trials should consider the dose of intravenous immunoglobulins, the timing of initial treatment, monitoring of response to treatment by fetal blood sampling, laboratory measures to define pregnancies with a high risk of intercranial haemorrhage, management of non-responders and long-term follow up of children.
Topics: Antigens, Human Platelet; Blood Transfusion, Intrauterine; Dexamethasone; Female; Fetal Diseases; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Platelet Transfusion; Pregnancy; Thrombocytopenia
PubMed: 15674934
DOI: 10.1002/14651858.CD004226.pub2 -
Influence of , , and genetic polymorphisms on disorders in transplant patients: a systematic review.Drug Metabolism and Personalized Therapy Dec 2021The glutathione-S-transferase (GST) enzymes are phase II isoenzymes responsible for protection against free radicals and xenobiotics. Since these proteins are described...
The glutathione-S-transferase (GST) enzymes are phase II isoenzymes responsible for protection against free radicals and xenobiotics. Since these proteins are described as polymorphic, polymorphisms in genes that encode them may alter enzymatic function and contribute to oxidative stress. In this context, such polymorphisms were already associated with several diseases and multiple therapeutic outcomes. A systematic review was performed to evaluate studies regarding the association between polymorphisms in three genes encoding enzymes of the GST family - , , and - and disorders in transplant patients. A total of 125 articles on which inclusion and exclusion criteria were applied were identified at PubMed database. Thirty-two studies met the target criteria and were included in the review. The mechanisms by which genotypes influence the development of disorders in transplant patients differ by disorder: they may participate in it by decreasing metabolism of drugs administered to patients undergoing transplantation, then exposing them to greater toxicity; by decreasing the repair ability against oxidative stress; or by encoding proteins that may be recognized as foreign, setting of an alloimmune reaction. Although some results are better established - such as null genotype's role in the development of toxicity events in transplant patients - others require further evidences, as influence on the development of pulmonary decline and posttransplant diabetes mellitus (PTDM). The importance of investigating these associations lies in a personalized medicine, in which the high-risk genotype patient has its treatment individualized and its care for prophylaxis and surveillance increased, potentially reducing this population's morbimortality.
Topics: Case-Control Studies; Genetic Predisposition to Disease; Genotype; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Polymorphism, Genetic; Risk Factors
PubMed: 34856092
DOI: 10.1515/dmpt-2021-0165 -
American Journal of Reproductive... Oct 2022The efficacy of lymphocyte immunotherapy (LIT) in the treatment of recurrent pregnancy loss (RPL) from alloimmunity has been debated for years. There is conflicting... (Meta-Analysis)
Meta-Analysis
PROBLEM
The efficacy of lymphocyte immunotherapy (LIT) in the treatment of recurrent pregnancy loss (RPL) from alloimmunity has been debated for years. There is conflicting evidence on the therapeutic role of LIT, since the etiology of most cases of RPL is previously classified as idiopathic.
METHOD OF STUDY
A systematic search of PubMed and Cochrane databases was done for randomized controlled trials that assessed the efficacy of paternal lymphocyte or third donor LIT among patients with primary or secondary RPL. The primary outcome was live birth rate after LIT. Random-effect meta-analysis was conducted using the software RevMan 5.4. Pre-planned subgroup analyses of source of lymphocytes, timing and frequency of administration, and concentration per immunization dose were conducted.
RESULTS
Data from eight trials showed a statistically significant benefit of LIT (RR = 1.45, 95% CI 1.05-2.01). The overall live birth rate is higher in the treatment group (65.6%) compared to placebo or no treatment (45.2%). Subgroup analysis based on source of lymphocytes revealed a trend towards benefit with paternal LIT but with wide confidence interval (RR = 1.34, 95% CI = .84-2.14). Multiple doses of immunotherapy before pregnancy and low dose (5×10 cells) LIT showed significant benefit. Sensitivity analysis involving studies with a low risk of bias demonstrated significant benefit of increased live birth rate among patients treated with LIT compared to those who received placebo or no treatment (RR = 1.97, 95% CI = 1.53-2.53).
CONCLUSION
LIT demonstrate benefit in improving pregnancy outcome of patients with RPL from alloimmunity.
Topics: Abortion, Habitual; Birth Rate; Female; Humans; Immunotherapy; Lymphocytes; Pregnancy; Pregnancy Outcome
PubMed: 35894648
DOI: 10.1111/aji.13605 -
Transplantation Reviews (Orlando, Fla.) Dec 2021Abdominal wall closure after intestinal, multivisceral or liver transplantation can be a major challenge. Different surgical techniques have been described to close... (Review)
Review
BACKGROUND
Abdominal wall closure after intestinal, multivisceral or liver transplantation can be a major challenge. Different surgical techniques have been described to close complex abdominal wall defects, but results remain variable. Two promising transplant techniques have been developed using either non-vascularized or vascularized donor rectus fascia. This systematic review aimed to evaluate the feasibility, safety, and effectiveness of the two techniques.
METHODS
A systematic review was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Human studies published between January 2000 and April 2020 were included. Methodological quality appraisal was done using an adapted 10-item standardized checklist.
RESULTS
The search resulted in 9 articles including 74 patients. Both techniques proved to be feasible and had similar results. After non-vascularized rectus fascia allotransplantation, there was a slightly higher rate of surgical site infections in the earlier reports. Overall, there were few complications, no fascial graft related rejections or deaths. The included articles scored low on quality appraisal, mostly due to the small number of cases and scarcely reported outcome parameters.
CONCLUSIONS
This systematic literature review reports two emerging new techniques for complex abdominal wall closure in transplant patients, with promising results. Standardized data collection in a prospective manner could give us more detailed information about short- and long-term outcomes. Preclinical animal studies are necessary for a thorough investigation of the mechanisms of graft integration, the risk of hernia development and the alloimmune response against the graft.
Topics: Abdominal Wall; Fascia; Graft Rejection; Humans; Liver Transplantation; Prospective Studies
PubMed: 34147948
DOI: 10.1016/j.trre.2021.100634 -
The Cochrane Database of Systematic... Oct 2009Idiopathic thrombocytopenic purpura (ITP) is a common hematologic disorder caused by immune-mediated thrombocytopenia. The magnitude of the maternal-fetal risk of ITP... (Review)
Review
BACKGROUND
Idiopathic thrombocytopenic purpura (ITP) is a common hematologic disorder caused by immune-mediated thrombocytopenia. The magnitude of the maternal-fetal risk of ITP during pregnancy is controversial. Labour management of pregnant women with ITP remains controversial. Management of ITP during pregnancy is complex because of the disparity between maternal and fetal platelet counts.
OBJECTIVES
To assess the effectiveness and safety of corticosteroids, intravenous immunoglobulin, vinca alkaloids, danazol, dapsone, and any other types of pharmacological treatments for the treatment of idiopathic thrombocytopenic purpura during pregnancy.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (February 2009), LILACS (1982 to 8 February 2009), ClinicalTrials.gov (8 February 2009), Current Controlled Trials (16 February 2009), Google Scholar (16 February 2009) and ongoing and unpublished trials cited in the reference lists of relevant articles.
SELECTION CRITERIA
Randomised controlled trials (RCTs) on any medical treatments for idiopathic thrombocytopenia purpura during pregnancy.
DATA COLLECTION AND ANALYSIS
Two review authors independently evaluated methodological quality and extracted trial data. Any disagreement was resolved by discussion or by consulting a third review author.
MAIN RESULTS
This review included one RCT in which 38 women (41 pregnancies) were randomised, with only 26 women (28 pregnancies) being analysed.This RCT comparing the effect of betamethasone (1.5 mg/day) with no medication found no statistically significant difference in neonatal thrombocytopenia (risk ratio (RR) 1.12, 95% confidence interval (CI) 0.62 to 2.05) and neonatal bleeding (RR 1.00, 95% CI 0.24 to 4.13). Review authors conducted an intention-to-treat analysis which showed similar findings: RR 1.18, 95% CI 0.57 to 2.45 and RR 1.05, 95% CI 0.24 to 4.61, respectively. Maternal death, perinatal mortality, postpartum haemorrhage and neonatal intracranial haemorrhage were not studied by this RCT.
AUTHORS' CONCLUSIONS
Current evidence indicates that compared to no medication, betamethasone did not reduce the risk of neonatal thrombocytopenia and neonatal bleeding in ITP during pregnancy. There is insufficient evidence to support the use of betamethasone for treating ITP. This Cohrane review does not provide evidence about other medical treatments for ITP during pregnancy. This systematic review also identifies the need for well-designed, adequately powered randomised clinical trials for this medical condition during pregnancy. Unless randomised clinical trials provide evidence of a treatment effect and the trade off between potential benefits and harms are established, policy-makers, clinicians, and academics should not use betamethasone for ITP in pregnant women. Any future trials on medical treatments for treating ITP during pregnancy should test a variety of important maternal, neonatal or both outcome measures, including maternal death, perinatal mortality, postpartum haemorrhage and neonatal intracranial haemorrhage.
Topics: Betamethasone; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Hematologic; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia, Neonatal Alloimmune
PubMed: 19821437
DOI: 10.1002/14651858.CD007722.pub2 -
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 -
Pharmacotherapy Jun 2006Intravenous immunoglobulin (IGIV) is used in the treatment of a wide variety of immune disorders. To our knowledge, no comprehensive or systematic review on the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intravenous immunoglobulin (IGIV) is used in the treatment of a wide variety of immune disorders. To our knowledge, no comprehensive or systematic review on the pharmacokinetics of IGIV has been published despite the availability of many published individual studies.
OBJECTIVE
To systematically review published studies of the pharmacokinetics of IGIV.
METHODOLOGY
We conducted a search of PubMed/MEDLINE from January 1966-September 2005 and EMBASE from January 1980-September 2005 for English-language articles on the pharmacokinetics of IGIV. This search was supplemented by a bibliographic review of all relevant articles.
RESULTS
Data elements extracted from these articles included study design, number of study subjects, indication for IGIV therapy, IGIV treatment regimen (formulation, dosage, and duration), pharmacokinetic parameters (clearance, volume of distribution, elimination rate constant, and half-life), analytic methodology, pharmacokinetic model, and blood sampling times. The United States Preventive Services Task Force rating scale was used to categorize the 50 pertinent citations identified in our literature search. According to the rating scale, 12 studies were level I (prospective, randomized, controlled studies), 3 were level II-1 (prospective, nonrandomized, controlled studies), 30 were level II-2 (prospective, nonrandomized, uncontrolled [cohort] studies), and 5 were level III (case reports or descriptive studies).
CONCLUSION
The pharmacokinetics of IGIV shows considerable intra- and interpopulation variability among patients with normal immunoglobulin levels, patients with primary immunodeficiency diseases, bone marrow transplant recipients, patients with immune deficiency due to chronic lymphocytic leukemia or multiple myeloma, very low birth weight neonates, neonates with suspected sepsis, high-risk infants in the neonatal intensive care unit, high-risk infants with cardiopulmonary disease, children with cryptogenic West or Lennox-Gastaut syndrome, women and infants with fetal alloimmune thrombocytopenia, and women with recurrent spontaneous abortions. Despite the large number of studies characterizing the pharmacokinetics of IGIV, major literature gaps include lack of information on IGIV clearance or area under the curve parameters and target serum immunoglobulin G concentrations. Further study is needed to rigorously characterize the pharmacokinetic properties of IGIV in a range of patient populations.
Topics: Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Immunoglobulins, Intravenous; Metabolic Clearance Rate
PubMed: 16716135
DOI: 10.1592/phco.26.6.813 -
American Journal of Medical Genetics.... May 2009Hydrops fetalis (HF) indicates excessive fluid accumulation within the fetal extravascular compartments and body cavities. HF is not a diagnosis in itself but a symptom,... (Review)
Review
Hydrops fetalis (HF) indicates excessive fluid accumulation within the fetal extravascular compartments and body cavities. HF is not a diagnosis in itself but a symptom, and the end-stage of a wide variety of disorders. In the era before routine immunization of Rhesus (Rh) negative mothers, most cases of hydrops were due to erythroblastosis from Rh alloimmunization, but nowadays, nonimmune hydrops fetalis (NIHF) is more frequent, representing 76-87% of all described HF cases. We performed a systematic review of the pertinent literature based on the QUality Of Reporting Of Meta-analyses (QUOROM) recommendations, using a QUOROM flowchart and QUOROM checklist. At initial screening 33,345 articles were retrieved. The various inclusion and exclusion criteria aimed at obtaining data that were as unbiased yet as complete as possible decreased the numbers dramatically, and eventually a total of 225 relevant NIHF articles were identified, describing 6,361 individuals. We established 14 different diagnostic categories and provide the pathophysiologic background of each, if known. All 6,361 patients were subclassified into one of the following diagnostic categories: Cardiovascular (21.7%), hematologic (10.4%), chromosomal (13.4%), syndromic (4.4%), lymphatic dysplasia (5.7%), inborn errors of metabolism (1.1%), infections (6.7%), thoracic (6.0%), urinary tract malformations (2.3%), extra thoracic tumors (0.7%), TTTF-placental (5.6%), gastrointestinal (0.5%), miscellaneous (3.7%), and idiopathic (17.8%).
Topics: Humans; Hydrops Fetalis
PubMed: 19334091
DOI: 10.1002/ajmg.a.32655 -
BMJ Sexual & Reproductive Health Jul 2022The aim of this review was to systematically review the outcome of routine anti-D administration among unsensitised rhesus (RhD)-negative individuals who have an... (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of this review was to systematically review the outcome of routine anti-D administration among unsensitised rhesus (RhD)-negative individuals who have an abortion. This review is registered with Prospero.
METHODS
A search for all published and ongoing studies, without restrictions on language or publication status, was performed using the following databases from their inception: EBM Reviews Ovid - Cochrane Central Register of Controlled Trials, MEDLINE Ovid (Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily), Embase.com, Popline and Google Scholar. Study types included: randomised controlled trials, controlled trials, cohort and case-control studies from 1971 onwards. The population included women who undergo an abortion (induced, incomplete, spontaneous or septic abortion), medical or surgical <12 weeks, and isoimmunisation in a subsequent pregnancy. The primary outcomes were: (1) development of a positive Kleihauer-Betke test and (2) development of Rh alloimmunisation in a subsequent pregnancy.
RESULTS
A total of 2652 studies were screened with 105 accessed for full-text review. Two studies have been included with high bias appreciated. Both studies found few women to be sensitised in forming antibodies after an abortion. The limited studies available and heterogeneity prevent the conduction of a meta-analysis.
CONCLUSIONS
Rh immunoglobulin has well-documented safety. However, it is not without risks and costs, is a possible barrier to delivering efficient services, and may have limited availability in some countries. The evidence base and quality of studies are currently limited. There is unclear benefit from the recommendation for Rh testing and immunoglobulin administration in early pregnancy. More research is needed as clinical practice guidelines are varied, based on expert opinions and moving away from testing and administration at time of abortion.
IMPLICATIONS
There is limited evidence surrounding medical benefit of Rh testing and immunoglobulin administration in early pregnancy. Further research is needed to define alloimmunisation and immunoglobulin benefit to update standards of care. Additionally, other factors should be considered in forming clinical policies and guidelines such as costs, feasibility and impact on access to care for patients.
Topics: Abortion, Induced; Abortion, Spontaneous; Cohort Studies; Female; Humans; Pregnancy; Rh Isoimmunization
PubMed: 34819315
DOI: 10.1136/bmjsrh-2021-201225 -
The Cochrane Database of Systematic... Dec 2021Bleeding disorders are uncommon but may pose significant bleeding complications during pregnancy, labour and following delivery for both the woman and the foetus. While... (Review)
Review
BACKGROUND
Bleeding disorders are uncommon but may pose significant bleeding complications during pregnancy, labour and following delivery for both the woman and the foetus. While many bleeding disorders in women tend to improve in pregnancy, thus decreasing the haemorrhagic risk to the mother at the time of delivery, some do not correct or return quite quickly to their pre-pregnancy levels in the postpartum period. Therefore, specific measures to prevent maternal bleeding and foetal complications during childbirth, are required. The safest method of delivery to reduce morbidity and mortality in these women is controversial. This is an update of a previously published review.
OBJECTIVES
To assess the optimal mode of delivery in women with, or carriers of, bleeding disorders.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the Cochrane Pregnancy and Childbirth Group's Trials Register as well as trials registries and the reference lists of relevant articles and reviews. Date of last search of the Group's Trials Registers: 21 June 2021.
SELECTION CRITERIA
Randomised controlled trials and quasi-randomised controlled clinical trials investigating the optimal mode of delivery in women with, or carriers of, any type of bleeding disorder during pregnancy were eligible for the review.
DATA COLLECTION AND ANALYSIS
No trials matching the selection criteria were eligible for inclusion.
MAIN RESULTS
No trials matching the selection criteria were eligible for inclusion.
AUTHORS' CONCLUSIONS
The review did not identify any randomised controlled trials investigating the safest mode of delivery and associated maternal and foetal complications during delivery in women with, or carriers of, a bleeding disorder. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials, case studies) to decide upon the optimal mode of delivery to ensure the safety of both mother and foetus. Given the ethical considerations, the rarity of the disorders and the low incidence of both maternal and foetal complications, future randomised controlled trials to find the optimal mode of delivery in this population are unlikely to be carried out. Other high quality controlled studies (such as risk allocation designs, sequential design, and parallel cohort design) are needed to investigate the risks and benefits of natural vaginal and caesarean section in this population or extrapolation from other clinical conditions that incur a haemorrhagic risk to the baby, such as platelet alloimmunisation.
Topics: Blood Coagulation Disorders; Cesarean Section; Female; Fetus; Humans; Infant; Labor, Obstetric; Pregnancy; Pregnancy Complications, Hematologic
PubMed: 34881425
DOI: 10.1002/14651858.CD011059.pub4