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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 -
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 -
The Cochrane Database of Systematic... May 2013Red blood cell alloimmunization in pregnancy can lead to fetal anaemia with potentially disastrous consequences. Traditional management involves the use of intrauterine... (Review)
Review
BACKGROUND
Red blood cell alloimmunization in pregnancy can lead to fetal anaemia with potentially disastrous consequences. Traditional management involves the use of intrauterine transfusion, which is associated with significant procedure-related risks. An alternative treatment that has been trialled is the use of immunoglobulin administered intravenously to the mother.
OBJECTIVES
The objective of this review was to assess the efficacy and safety of the use of intravenous immunoglobulin antenatally to women with severe fetal red blood cell alloimmunization.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group trials register (19 December 2012), and reference lists of articles.
SELECTION CRITERIA
Randomized trials assessing the antenatal use of intravenous immunoglobulin administered at any dose, frequency or duration with a control group (using any other, or no treatment) in the management of fetal red blood cell alloimmunization.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the available evidence.
MAIN RESULTS
There are no included studies.
AUTHORS' CONCLUSIONS
No information is available from randomized trials to indicate whether the antenatal use of intravenous immunoglobulin is effective in the management of fetal red blood cell alloimmunization. Several case series suggest a beneficial role in delaying the onset of fetal anaemia requiring invasive intrauterine transfusion.
Topics: Anemia, Hemolytic; Erythrocytes; Female; Fetal Diseases; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Pregnancy
PubMed: 23728672
DOI: 10.1002/14651858.CD008267.pub2 -
Transfusion Apr 2014Multiply transfused hypoproliferative thrombocytopenic (HT) patients with alloimmune transfusion refractoriness require specially selected platelets (PLTs).... (Review)
Review
BACKGROUND
Multiply transfused hypoproliferative thrombocytopenic (HT) patients with alloimmune transfusion refractoriness require specially selected platelets (PLTs). Cross-matching apheresis PLTs is a popular support option, avoiding requirements for large panels of typed donors for HLA-based selection. We undertook a systematic review of the utility of various cross-matching techniques on mortality reduction, prevention of hemorrhage, alloimmunization and refractoriness, and improvement in PLT utilization or count increments.
STUDY DESIGN AND METHODS
A systematic review to December 2012 was conducted of MEDLINE, EMBASE, and Cochrane databases along with a bibliographic search of pertinent references.
RESULTS
Of 146 retrieved citations, 20 met inclusion criteria. Eleven more were chosen from bibliographies, describing 29 unique cohorts. All but five enrolled transfusion-refractory, predominantly alloimmunized patients. Cross-match impact on mortality and hemorrhage could not be assessed from these studies. Two studies demonstrated durable corrected count increments and/or breadth of alloimmunization throughout cross-match support; none addressed development or persistence of refractoriness. In alloimmunized refractory patients and nonrefractory cohorts with greater than 25% alloimmunization, higher increments were seen with cross-match-compatible PLTs than incompatible or un-cross-matched units. In two nonrefractory, nonalloimmunized cohorts, the lack of utility of cross-match was reflected by test sensitivity of less than 20%. Comparison of cross-matched PLT success with that of HLA-identical units revealed inferior success rates for the former in one study and equivalent rates in another. No trend was observed regarding relative utility of the various commonly employed techniques.
CONCLUSION
Cross-matched PLTs are useful in increasing PLT counts in alloimmunized, transfusion-refractory HT patients, but data about their impact on hemorrhage and mortality are lacking.
Topics: Blood Grouping and Crossmatching; Blood Platelets; Cohort Studies; Histocompatibility; Humans; Platelet Transfusion; Predictive Value of Tests; Thrombocytopenia
PubMed: 24032995
DOI: 10.1111/trf.12395 -
The Cochrane Database of Systematic... Mar 2013During pregnancy, a Rhesus-negative (Rh-negative) woman may develop antibodies if her fetus is Rh-positive, which can cause fetal morbidity or mortality in following... (Review)
Review
BACKGROUND
During pregnancy, a Rhesus-negative (Rh-negative) woman may develop antibodies if her fetus is Rh-positive, which can cause fetal morbidity or mortality in following pregnancies, if untreated.
OBJECTIVES
To assess the effects of administering anti-D immunoglobulin (Ig) after spontaneous miscarriage in a Rh-negative woman, with no anti-D antibodies.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2012).
SELECTION CRITERIA
Randomised controlled trials (RCT) in Rh-negative women without antibodies who were given anti-D Ig following spontaneous miscarriage compared with no treatment or placebo treatment following spontaneous miscarriage as control.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and trial quality. Two review authors extracted data and checked it for accuracy.
MAIN RESULTS
We included one RCT, involving 48 women who had a miscarriage between eight to 24 weeks of gestation. Of the 19 women in the treatment group, 14 had therapeutic dilatation & curettage (D&C) and five had spontaneous miscarriage; of the 29 women in the control group, 25 had therapeutic D&C and four had spontaneous miscarriage. The treatment group received 300 µg anti-D Ig intramuscular injection and were compared with a control group who received 1 cc homogenous gamma globulin placebo.This review's primary outcomes (development of a positive Kleihauer Betke test (a test that detects fetal cells in the maternal blood; and development of RhD alloimmunisation in a subsequent pregnancy) were not reported in the included study.Similarly, none of the review's secondary outcomes were reported in the included study: the need for increased surveillance for suspected fetal blood sampling and fetal transfusions in subsequent pregnancies, neonatal morbidity such as neonatal anaemia, jaundice, bilirubin encephalopathy, erythroblastosis, prematurity, hypoglycaemia (low blood sugar) in subsequent pregnancies, maternal adverse events of anti-D administration including anaphylactic reaction and blood-borne infections.The included study did report subsequent Rh-positive pregnancies in three women in the treatment group and six women in the control group. However, due to the small sample size, the study failed to show any difference in maternal sensitisation or development of Rh alloimmunisation in the subsequent pregnancies.
AUTHORS' CONCLUSIONS
There are insufficient data available to evaluate the practice of anti-D administration in an unsensitised Rh-negative mother after spontaneous miscarriage. Thus, until high-quality evidence becomes available, the practice of anti-D Immunoglobulin prophylaxis after spontaneous miscarriage for preventing Rh alloimmunisation cannot be generalised and should be based on the standard practice guidelines of each country.
Topics: Abortion, Spontaneous; Female; Humans; Immunologic Factors; Pregnancy; Randomized Controlled Trials as Topic; Rh Isoimmunization; Rho(D) Immune Globulin
PubMed: 23543581
DOI: 10.1002/14651858.CD009617.pub2 -
The Cochrane Database of Systematic... Feb 2013During 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 (30 September 2012).
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 trial eligibility and risk of bias and extracted the data.
MAIN RESULTS
Two trials with moderate to high risk of bias, involving over 4500 women, compared anti-D prophylaxis with no anti-D during pregnancy. When women received anti-D at 28 and 34 weeks' gestation, risks of immunisation were not significantly different than for women not given antenatal anti-D: risk ratio (RR) of immunisation during pregnancy was 0.42 (95% confidence interval (CI) 0.15 to 1.17); after the birth of a Rh-positive infant the RR was 0.42 (95% CI 0.15 to 1.17); and within 12 months after birth of a Rh-positive infant the RR was 0.39 (95% CI 0.10 to 1.62).However, women receiving anti-D during pregnancy were significantly less likely to register a positive Kleihauer test (which detects fetal cells in maternal blood) in pregnancy (RR 0.60, 95% CI 0.41 to 0.88) and at the birth of a Rh-positive infant (RR 0.60, 95% CI 0.46 to 0.79). No data were available for the risk of Rhesus D alloimmunisation in a subsequent pregnancy. No significant differences were seen for neonatal jaundice, and no adverse effects were reported in either trial.
AUTHORS' CONCLUSIONS
The risk of Rhesus D alloimmunisation during or immediately after a first pregnancy is about 1%. Administration of 100 µg (500 IU) anti-D to women in their first pregnancy can reduce this risk to about 0.2% without, to date, any adverse effects. Although unlikely to confer benefit in the current pregnancy, fewer women may have Rhesus D antibodies in any subsequent pregnancy, but the effects of 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: 23450526
DOI: 10.1002/14651858.CD000020.pub2 -
Annals of Surgery Open : Perspectives... Sep 2023We aim to investigate the effects of genetically based HLA matching on patient and graft survival, and acute and chronic rejection after liver transplantation.
OBJECTIVE
We aim to investigate the effects of genetically based HLA matching on patient and graft survival, and acute and chronic rejection after liver transplantation.
BACKGROUND
Liver transplantation is a common treatment for patients with end-stage liver disease. In contrast to most other solid organ transplantations, there is no conclusive evidence supporting human leukocyte antigen (HLA) matching for liver transplantations. With emerging alternatives such as transplantation of bankable (stem) cells, HLA matching becomes feasible, which may decrease the need for immunosuppressive therapy and improve transplantation outcomes.
METHODS
We systematically searched the PubMed, Embase, and Cochrane databases and performed a meta-analysis investigating the effect of genetic HLA matching on liver transplantation outcomes (acute/chronic rejection, graft failure, and mortality).
RESULTS
We included 14 studies with 2682 patients. HLA-C mismatching significantly increased the risk of acute rejection (full mismatching: risk ratio = 1.90, 95% confidence interval = 1.08 to 3.33, = 0.03; partial mismatching: risk ratio = 1.33, 95% confidence interval = 1.07 to 1.66, = 0.01). We did not discern any significant effect of HLA mismatching per locus on acute rejection for HLA-A, -B, -DR, and -DQ, nor on chronic rejection, graft failure, or mortality for HLA-DR, and -DQ.
CONCLUSIONS
We found evidence that genetic HLA-C matching reduces the risk of acute rejection after liver transplantation while matching for other loci does not reduce the risk of acute rejection, chronic rejection, graft failure, or mortality.
PubMed: 37746594
DOI: 10.1097/AS9.0000000000000334 -
Haemophilia : the Official Journal of... Jul 2010Bernard Soulier syndrome (BSS) is a rare disorder of platelets, inherited mainly as an autosomal recessive trait. It is characterised by qualitative and quantitative... (Review)
Review
Bernard Soulier syndrome (BSS) is a rare disorder of platelets, inherited mainly as an autosomal recessive trait. It is characterised by qualitative and quantitative defects of the platelet membrane glycoprotein (GP) Ib-IX-V complex. The main clinical characteristics are thrombocytopenia, prolonged bleeding time and the presence of giant platelets. Data on the clinical course and outcome of pregnancy in women with Bernard Soulier syndrome is scattered in individual case reports. In this paper, we performed a systematic review of literature and identified 16 relevant articles; all case reports that included 30 pregnancies among 18 women. Primary postpartum haemorrhage was reported in 10 (33%) and secondary in 12 (40%) of pregnancies, requiring blood transfusion in 15 pregnancies. Two women had an emergency obstetric hysterectomy. Alloimmune thrombocytopenia was reported in 6 neonates, with one intrauterine death and one neonatal death. Bernard Soulier syndrome in pregnancy is associated with a high risk of serious bleeding for the mother and the neonate. A multidisciplinary team approach and individualised management plan for such women are required to minimise these risks. An international registry is recommended to obtain further knowledge in managing women with this rare disorder.
Topics: Adult; Bernard-Soulier Syndrome; Blood Transfusion; Female; Humans; Hysterectomy; Infant, Newborn; Platelet Count; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Thrombocytopenia, Neonatal Alloimmune; Young Adult
PubMed: 20070385
DOI: 10.1111/j.1365-2516.2009.02137.x -
The Cochrane Database of Systematic... Jan 2013Antibodies to the red cell Rhesus D (RhD) antigen can be produced during pregnancy in a RhD-negative mother carrying a RhD-positive fetus, in particular following... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antibodies to the red cell Rhesus D (RhD) antigen can be produced during pregnancy in a RhD-negative mother carrying a RhD-positive fetus, in particular following feto-maternal haemorrhage at birth or following any procedure that may cause feto-maternal haemorrhage. While the first baby is usually not harmed, these antibodies may cause haemolytic disease of the fetus/newborn (HDFN) in subsequent RhD-positive babies. RhD incompatibility is a major cause of HDFN.To reduce the risk of HDFN, anti-D is given to RhD-negative mothers at 28 or 30 weeks of pregnancy and within 72 hours of potential maternal exposure to fetal red cells. Anit-D is currently available in both intramuscular (IM) and intravenous (IV) preparations.
OBJECTIVES
To compare the efficacy and effectiveness of IM versus IV anti-D IgG in preventing RhD alloimmunization in RhD-negative pregnant women.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2012).
SELECTION CRITERIA
Randomized controlled trials, quasi-randomized trials and cluster-randomized trials comparing IM and IV anti-D for preventing RhD alloimmunization in RhD-negative pregnant women.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and assessed trial quality. Two review authors extracted data. Data were checked for consistency by both authors.
MAIN RESULTS
Two studies involving 447 (with sample sizes 14 and 432) RhD negative women were included. The studies compared IM and IV administration of anti-D prophylaxis. In both studies the women received a 1500 IU (300 microgram) dose of Rhophylac during week 28 of gestation. There was no incidence of RhD alloimmunization in either of the studies, as the sample size was insufficient for meaningful comparison of this uncommon outcome. One of the studies found that the mean anti-D IgG concentrations after IV and IM administration differed up to seven days (36.1 (2.6) ng/mL IV; 19.8 (8.7) ng/mL IM on day seven). However, from two to three weeks post-administration, the concentrations were similar for both routes of administration. None of the women involved in the studies developed antibodies against the RhD antigen.
AUTHORS' CONCLUSIONS
It appears that IM and IV administration of anti-D are equally effective. The number of included studies and the number of participants are not enough to assess whether there are any differences. Anti-D can be administered by IM or IV injection. The choice of IM or IV route of administration will depend on the available preparations, the dose to be administered and also on the patients' preferences. This review found insufficient information upon which to guide practice due to the limited number of included studies, small sample sizes and methodological limitations.
Topics: Administration, Intravenous; Female; Humans; Immunologic Factors; Injections, Intramuscular; Isoantibodies; Pregnancy; Randomized Controlled Trials as Topic; Rh Isoimmunization; Rho(D) Immune Globulin
PubMed: 23440818
DOI: 10.1002/14651858.CD007885.pub2 -
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