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Journal of Clinical Medicine Apr 2023Neonatal hemochromatosis (NH) is an uncommon, severe disorder that results in fetal loss or neonatal death due to liver failure. NH is currently regarded as the... (Review)
Review
Neonatal hemochromatosis (NH) is an uncommon, severe disorder that results in fetal loss or neonatal death due to liver failure. NH is currently regarded as the phenotypic expression of gestational alloimmune liver disease (GALD). The diagnosis of NH-GALD is rarely prenatally established. In addition to providing a systematic review of the prenatal features that are identifiable using ultrasound (US) and MRI, we suggest a prenatal diagnosis algorithm for use in suspected NH during the first affected pregnancy. From a total of 586 database entries identified in PubMed, Google Scholar, and ResearchGate, we selected 18 studies published from 1993 to 2021 that reported maternal medical and obstetric history, prenatal ultrasound findings, and postpartum outcomes. We investigated the ultrasound and MRI features of these studies, along with the outcome due to this condition. A total of 74 cases were identified. The main reported prenatal US finding was fetal growth restriction (FGR) (33%), followed by oligohydramnios (13%) and hydrops fetalis (13%), with 13% cases described as uneventful. Other rare prenatal findings were fetal anemia, ascites, and abnormal fetal liver and spleen. Most pregnancies ended with fetal/perinatal death or therapeutic interruption of pregnancy. Favorable evolution with treatment (ensanguine transfusion and intravenous immunoglobulin (IVIG)) was reported for only 7% of fetuses. Using T2-weighted MRI, fetal extrahepatic siderosis confirmed prenatally in two cases and postnatally in 11 cases. IVIG treatment throughout subsequent pregnancies was found to significantly improve fetal prognosis. MRI should be indicated in selected cases of oligohydramnios, fetal hydrops, fetal hepatomegaly, ascites, or unexplained FGR or anemia after ruling out all other more frequently encountered conditions. MRI can be used to detect iron overload in the liver and extrahepatic siderosis.
PubMed: 37048762
DOI: 10.3390/jcm12072679 -
Hematology, Transfusion and Cell Therapy Feb 2024The clinical manifestation of foetal anaemia caused by maternal Kell alloantibodies differs from that caused by non-Kell alloantibodies. Severe anaemia develops in the... (Review)
Review
The role of measuring peak systolic velocity of the middle cerebral artery blood flow and anti-K1 titre during pregnancy to detect foetuses with severe anaemia, foetal hydrops, and the requirement of intrauterine transfusion: A systematic review and meta-analysis.
The clinical manifestation of foetal anaemia caused by maternal Kell alloantibodies differs from that caused by non-Kell alloantibodies. Severe anaemia develops in the foetus in the early weeks of gestation; therefore, proper management and early intervention are important. A systematic review and meta-analysis was performed to determine whether the anti-K1 titre can determine the sequelae of Kell alloimmunised pregnancies. Prospective and retrospective cohort studies were used to conduct a systematic review following a comprehensive literature search, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Studies were screened based on a defined set of inclusion and exclusion criteria. A total of 5143 potential articles were identified. Ten studies were used in the meta-analysis of pregnancy outcomes for a specific anti-K1 titre cut-off. The meta-analysis identified statistical significance for intrauterine transfusion (ARD: 0.351; 95 % CI: 0.593-0.109; p-value = 0.004), hydrops (ARD: 0.808; 95 % CI: 1.145-0.472; p-value <0.001), intrauterine foetal death (ARD: 0.938; 95 % CI:1.344 to -0.533; p-value <0.001) and intrauterine transfusion for Doppler middle cerebral artery >1.5 MoM (ARD: 0.381; 95 % CI:1.079 to -0.317; p-value = 0.285). It was concluded that there is no correlation between anti-K1 titre and Kell sensitised pregnancy outcomes, but monitoring the anti-K1 titre is important to manage the pregnancy and it helps clinicians determine the need for intrauterine transfusions. Doppler middle cerebral artery peak systolic velocity is strongly correlated with foetal anaemia and is an efficient routine method for determining the need for intrauterine transfusions in pregnancies affected by anti-K1.
PubMed: 38429195
DOI: 10.1016/j.htct.2024.02.002 -
The Cochrane Database of Systematic... Sep 2015During pregnancy, a Rhesus negative (Rh-negative) woman may develop antibodies when her fetus is Rhesus positive (Rh-positive). These antibodies may harm Rh-positive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
During pregnancy, a Rhesus negative (Rh-negative) woman may develop antibodies when her fetus is Rhesus positive (Rh-positive). These antibodies may harm Rh-positive babies.
OBJECTIVES
To assess the effects of antenatal anti-D immunoglobulin on the incidence of Rhesus D alloimmunisation when given to Rh-negative women without anti-D antibodies.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised trials in Rh-negative women without anti-D antibodies given anti-D after 28 weeks of pregnancy, compared with no treatment, placebo or a different regimen of anti-D.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.
MAIN RESULTS
We included two trials involving over 4500 women, comparing anti-D prophylaxis with no anti-D during pregnancy in this review. Overall, the trials were judged to be at moderate to high risk of bias. The quality of the evidence for pre-specified outcomes was also assessed using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach.In regards to primary review outcomes, there did not appear to be a clear difference in the risks of immunisation when women who received anti-D at 28 and 34 weeks' gestation were compared with women who were not given antenatal anti-D: risk ratio (RR) for incidence of Rhesus D alloimmunisation during pregnancy was 0.42 (95% confidence interval (CI) 0.15 to 1.17, two trials, 3902 women; GRADE: low quality evidence); at birth of a Rh-positive infant the RR was 0.42 (95% CI 0.15 to 1.17, two trials, 2297 women); and within 12 months after birth of a Rh-positive infant the average RR was 0.39 (95% CI 0.10 to 1.62, two trials, 2048 women; Tau²: 0.47; I²: 39%; GRADE: low quality evidence). Neither of the trials reported on incidence of Rhesus D alloimmunisation in subsequent pregnancies.Considering secondary outcomes, in one trial, women receiving anti-D during pregnancy were shown to be less likely to register a positive Kleihauer test (which detects fetal cells in maternal blood) in pregnancy (at 32 to 25 weeks) (RR 0.60, 95% CI 0.41 to 0.88; 1884 women; GRADE: low quality evidence) and at the birth of a Rh-positive infant (RR 0.60, 95% CI 0.46 to 0.79; 1189 women; GRADE: low quality evidence). No clear differences were seen for neonatal jaundice (RR 0.26, 95% CI 0.03 to 2.30; 1882 infants; GRADE: very low quality evidence). Neither of the trials reported on adverse effects associated with anti-D treatment.
AUTHORS' CONCLUSIONS
Existing studies do not provide conclusive evidence that the use of anti-D during pregnancy benefits either mother or baby in terms of incidence of Rhesus D alloimmunisation during the pregnancy or postpartum, or the incidence of neonatal morbidity (jaundice) (low to very low quality evidence). However women receiving anti-D may be less likely to register a positive Kleihauer test in pregnancy and at the birth of a Rh-positive infant (low quality evidence). Fewer women who receive anti-D during pregnancy may have Rhesus D antibodies in a subsequent pregnancy, with benefits for the baby, however this needs to be tested in studies of robust design.
Topics: Female; Humans; Immunologic Factors; Pregnancy; Pregnancy Trimester, Third; Randomized Controlled Trials as Topic; Rh Isoimmunization; Rho(D) Immune Globulin
PubMed: 26334436
DOI: 10.1002/14651858.CD000020.pub3 -
Asian Journal of Transfusion Science 2022Repeated allogeneic blood transfusions in thalassemia major patients stimulate the patient's immune system to generate antibodies against foreign erythrocyte antigens.... (Review)
Review
BACKGROUND
Repeated allogeneic blood transfusions in thalassemia major patients stimulate the patient's immune system to generate antibodies against foreign erythrocyte antigens. This study was carried out to systematically review the findings of available studies about the prevalence of alloantibodies and autoantibodies, as well as the type of causative antigens among transfusion-dependent thalassemia patients in Iran.
METHODS
Electronic search was conducted on Medline, PubMed, Cochrane, EMBASE, ScienceDirect, and Persians databases. All relevant articles published from January 1990 to July 2018 were included. Abstracts of conference booklets which that been published in the last 5 years were also included in the meta-analysis. The search language was restricted to English and Persian. The quality of studies was evaluated according to a checklist developed by authors, and Cochrane Risk of Bias Assessment Tool was used to evaluate the risk of bias.
RESULTS
Twenty-three relevant articles met all the inclusion criteria. The prevalence of alloimmunization was 13%. Our study showed that anti-D (25%) and anti-K (25%) were most prevalent among Iranian β-thalassemia patients. Data analysis shows the autoantibody prevalence to be 1% among 3787 patients. Meta-regression revealed that the prevalence of alloantibodies increases with each year as the average age of the study population increases.
CONCLUSION
The prevalence of red blood cell (RBC) alloantibodies in transfused Iranian β-thalassemia patients was high. Appropriate preventive strategies such as RBC phenotyping for patients before beginning transfusion and using extended RBC donor-recipient matching, specifically for Rh and Kell system, could be implemented to avoid complications in thalassemia patients.
PubMed: 36199396
DOI: 10.4103/ajts.AJTS_39_20 -
Transfusion Medicine Reviews Apr 2016Optimal selection of blood donors is critical for ensuring the safety of blood products. The current selection process is concerned principally with the safety of the... (Meta-Analysis)
Meta-Analysis Review
Optimal selection of blood donors is critical for ensuring the safety of blood products. The current selection process is concerned principally with the safety of the blood donor at the time of donation and of the recipient at the time of transfusion. Recent evidence suggests that the characteristics of the donor may affect short- and long-term transfusion outcomes for the transfused recipient. We conducted a systematic review with the primary objective of assessing the association between blood donor characteristics and red blood cell (RBC) transfusion outcomes. We searched MEDLINE, EMBASE, and Cochrane Central databases and performed manual searches of top transfusion journals for all available prospective and retrospective studies. We described study characteristics, methodological quality, and risk of bias and provided study-level effect estimates and, when appropriate, pooled estimates with 95% confidence intervals using the Mantel-Haenszel or inverse variance approach. The overall quality of the evidence was graded using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. From 6121 citations identified by our literature search, 59 studies met our eligibility criteria (50 observational, 9 interventional). We identified the evaluation of association of 17 donor characteristics on RBC transfusion outcome. The risk of bias and confounding of the included studies was high. The quality of evidence was graded as very low to low for all 17 donor characteristics. Potential associations were observed for donor sex with reduced survival at 90 days and 6 months in male recipients that receive donated blood from females (hazard ratio 2.60 [1.09, 6.20] and hazard ratio 2.40 [1.10, 5.24], respectively; n = 1), Human Leukocyte Antigen - antigen D Related (HLA-DR) selected transfusions (odds ratio [OR] 0.39 [0.15, 0.99] for the risk of transplant alloimmunization, n = 9), presence of antileukocyte antibodies (OR 5.84 [1.66, 20.59] for risk of transfusion-related acute lung injury, n = 4), and donor RBC antigens selection (OR 0.20 [0.08, 0.52] for risk of alloimmunization, n = 4). Based on poor quality evidence, positive antileukocyte antibodies, female donor to male recipients, HLA-DR selected RBC transfusion, or donor RBC antigen selection may affect RBC transfusion outcome. Our findings that donor characteristics may be associated with transfusion outcomes warrant establishing vein-to-vein data infrastructure to allow for large robust evaluations. PROSPERO registration number: CRD42013006726.
Topics: Age Factors; Bias; Blood Donors; Donor Selection; Erythrocyte Transfusion; Evidence-Based Medicine; Female; HLA Antigens; Hospital Mortality; Humans; Isoantibodies; Male; Observational Studies as Topic; Research Design; Sex Factors; Survival Analysis; Treatment Outcome; Viremia
PubMed: 26920039
DOI: 10.1016/j.tmrv.2016.01.002 -
Ultrasound in Obstetrics & Gynecology :... Dec 2019To evaluate the performance of fetal middle cerebral artery peak systolic velocity (MCA-PSV) ≥ 1.5 multiples of the median (MoM) for the prediction of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the performance of fetal middle cerebral artery peak systolic velocity (MCA-PSV) ≥ 1.5 multiples of the median (MoM) for the prediction of moderate-severe anemia, in untransfused and transfused fetuses.
METHODS
A systematic search was performed to identify relevant observational studies reported in the period 2008-2018 that evaluated the performance of MCA-PSV, using a threshold of 1.5 MoM for the prediction of fetal anemia. Diagnosis of fetal anemia by blood sampling was the reference standard. A hierarchical summary receiver-operating characteristics (hSROC) curve was constructed using random-effects modeling. Subgroup and meta-regression analyses, according to the number of previous intrauterine transfusions, were performed.
RESULTS
Twelve studies and 696 fetuses were included in the meta-analysis. The area under the hSROC curve (AUC) for moderate-severe anemia was 83%. Pooled sensitivity and specificity (95% CI) were 79% (70-86%) and 73% (62-82%), respectively, and positive and negative likelihood ratios were 2.94 (95% CI, 2.13-4.00) and 0.272 (95% CI, 0.188-0.371). When considering only untransfused fetuses, prediction improved, achieving an AUC of 87%, sensitivity of 86% (95% CI, 75-93%) and specificity of 71% (95% CI, 49-87%). A decline in sensitivity for the prediction of moderate-severe anemia by MCA-PSV ≥1.5 MoM was observed (estimate, -5.5% (95% CI, -10.7 to -0.3%), P = 0.039) as the number of previous transfusions increased.
CONCLUSIONS
MCA-PSV ≥ 1.5 MoM for the prediction of moderate-severe anemia in untransfused fetuses shows moderate accuracy (86% sensitivity and 71% specificity), which declines with increasing number of intrauterine transfusions. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Anemia; Blood Flow Velocity; Blood Transfusion, Intrauterine; Female; Fetal Diseases; Fetus; Gestational Age; Humans; Middle Cerebral Artery; Observational Studies as Topic; Predictive Value of Tests; Pregnancy; Sensitivity and Specificity; Severity of Illness Index; Ultrasonography, Doppler, Color
PubMed: 30932276
DOI: 10.1002/uog.20273 -
Blood Mar 2017Several strategies can be used to manage fetal or neonatal alloimmune thrombocytopenia (FNAIT) in subsequent pregnancies. Serial fetal blood sampling (FBS) and... (Review)
Review
Several strategies can be used to manage fetal or neonatal alloimmune thrombocytopenia (FNAIT) in subsequent pregnancies. Serial fetal blood sampling (FBS) and intrauterine platelet transfusions (IUPT), as well as weekly maternal IV immunoglobulin infusion (IVIG), with or without additional corticosteroid therapy, are common options, but optimal management has not been determined. The aim of this systematic review was to assess antenatal treatment strategies for FNAIT. Four randomized controlled trials and 22 nonrandomized studies were included. Pooling of results was not possible due to considerable heterogeneity. Most studies found comparable outcomes regarding the occurrence of intracranial hemorrhage, regardless of the antenatal management strategy applied; FBS, IUPT, or IVIG with or without corticosteroids. There is no consistent evidence for the value of adding steroids to IVIG. FBS or IUPT resulted in a relatively high complication rate (consisting mainly of preterm emergency cesarean section) of 11% per treated pregnancy in all studies combined. Overall, noninvasive management in pregnant mothers who have had a previous neonate with FNAIT is effective without the relatively high rate of adverse outcomes seen with invasive strategies. This systematic review suggests that first-line antenatal management in FNAIT is weekly IVIG administration, with or without the addition of corticosteroids.
Topics: Adult; Disease Management; Female; Fetal Diseases; Humans; Immunoglobulins, Intravenous; Infant, Newborn; Intracranial Hemorrhages; Mothers; Pregnancy; Prenatal Care; Steroids; Thrombocytopenia, Neonatal Alloimmune; Treatment Outcome; Young Adult
PubMed: 28130210
DOI: 10.1182/blood-2016-10-739656 -
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 -
The Cochrane Database of Systematic... Aug 2017Bleeding 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: 16 February 2017.
SELECTION CRITERIA
Randomised controlled trials and all types of 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 results from randomised controlled trials were found.
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: Adult; Blood Coagulation Disorders; Cesarean Section; Delivery, Obstetric; Female; Fetus; Heterozygote; Humans; Pregnancy; Pregnancy Complications, Hematologic
PubMed: 28776324
DOI: 10.1002/14651858.CD011059.pub3