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1.
Antenatal and postpartum prevention of Rh alloimmunization: A systematic review and GRADE analysis
Hamel, C., Esmaeilisaraji, L., Thuku, M., Michaud, A., Sikora, L., Fung-Kee-Fung, K.
PloS one. 2020;15(9):e0238844
Abstract
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.
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2.
Clinical value of different anti-D immunoglobulin strategies for preventing Rh hemolytic disease of the fetus and newborn: A network meta-analysis
Xie X, Fu Q, Bao Z, Zhang Y, Zhou D
PLoS One. 2020;15(3):e0230073
Abstract
BACKGROUND Several anti-D immunoglobulin strategies exist for preventing Rh hemolytic disease of the fetus and newborn. This study systematically assessed the clinical value of those therapeutic strategies. METHODS The Web of Science, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for eligible studies that evaluated the value of different anti-D immunoglobulin strategies in preventing maternal anti-D antibody sensitization. Combined odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated. The network meta-analysis was conducted using Stata 14.2 and WinBUGS 1.4.3 software. RESULTS Twenty-four original studies involving 64860 patients were included. Among all therapeutic measures, injecting 300 mug anti-D immunoglobulin at 28 and 34 gestational weeks (antenatal 5/E) appeared to be the most effective measure for preventing maternal antibody sensitization (surface under the cumulative ranking curve [SUCRA] = 96.8%), while a single injection at 28 gestational weeks (SUCRA = 89.2%) was the second most effective. Administering no injection or a placebo (SUCRA = 0.0%) was the least effective intervention measure. CONCLUSION Among the therapeutic measures, antenatal 5/E appeared to be the best method for reducing the positive incidence of anti-D antibodies in the maternal serum; thus, it may be the most effective treatment for preventing fetal hemolytic disease.
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3.
First line treatments for newly diagnosed primary immune thrombocytopenia in children: a systematic review and network meta-analysis
Acero-Garces DO, Garcia-Perdomo HA
Current pediatric reviews. 2019
Abstract
BACKGROUND The first-line interventions in immune thrombocytopenia (ITP) consist in intravenous polyclonal immunoglobulins (IVIg), corticosteroids and anti-D immunoglobulin (anti-D). OBJECTIVE We aimed to compare the effectiveness and safety of first line treatments for newly-diagnosed primary ITP in children to increase the platelet count. METHODS We searched MEDLINE, EMBASE, LILACS, and the Cochrane Central register of Controlled Trials (CENTRAL); we included clinical trials. We performed the statistical analysis in R. RESULTS We included 12 studies for meta-analysis. Compared with IVIG 2g/kg, response rates were lower for prednisone 2mg/kg at 72 hours [RR 0.04 (95% CI 0.0 to 0.68)] and at 7 days [RR 0.23 (95% CI 0.08 to 0.67)]; at 48 hours, methylprednisolone 30mg/kg also showed lower response rates [RR 0.72 (95% CI 0.52 to 0.99)]. IVIG 2g/kg and 2.5g/kg had less adverse effects than Anti-D, methylprednisolone and IVIG 0.8g/kg. For rising platelet count, no statistical differences were found at 24 hours or at 7 days; at 48 hours, IVIG 2g/kg showed better results than Anti-D 75microg/kg [MD -58.84 (95% CI -87.02 to -25.66)]. At one month, platelet count with IVIG 2g/kg was higher than Anti-D 50 and 75microg/kg [-82.03 (95% CI -102.60 to -61.46) and -78.77 (95% CI -97.80 to -59.74), respectively], but lower than methylprednisolone 50mg/kg [MD 118 (95% CI 3.88 to 232.12)]. CONCLUSION The total platelet count rises higher in early and late phases with IVIG than Anti-D, but in long term it is higher with methylprednisolone. Additionally, IVIG causes less adverse effects than Anti-D and corticosteroids.
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4.
Efficacy and Safety of Anti-D Immunoglobulins versus Intravenous Immunoglobulins for Immune Thrombocytopenia in Children: Systematic Review and Meta-analysis of Randomized Controlled Trials
Lioger B, Maillot F, Ternant D, Passot C, Paintaud G, Bejan-Angoulvant T
The Journal of Pediatrics. 2018;204:225-233 e8.
Abstract
OBJECTIVES To compare the efficacy and safety of intravenous immunoglobulins (IVIG) and anti-D immunoglobulin (anti-D) in pediatric immune thrombocytopenia (ITP). STUDY DESIGN We conducted a systematic review and meta-analysis following PRISMA guidelines, including all randomized controlled trials that have assessed the efficacy and safety of anti-D and IVIG in children with ITP. We searched Medline, Embase, and Cochrane databases. Primary outcomes were the proportion of children achieving platelet count responses as defined in each study and bleeding response. Other safety outcomes included infusion reactions and hemolysis. RESULTS Eleven studies with 558 children were included. Anti-D was significantly inferior to IVIG at increasing platelet counts, both for thresholds of >20 x 10(9)/L at 24-72 hours (response rate ratio for anti-D vs IVIG 0.85, 95% CI 0.78-0.94) and >50 x 10(9)/L at 24-72 hours (response rate ratio for anti-D vs IVIG 0.75, 95% CI 0.61-0.92). Bleeding response was assessed in 4 studies, but some heterogeneity in reporting leads to unclear conclusion. General symptoms after anti-D infusion were less frequent than after IVIG (Peto OR 0.39, 95% CI 0.25-0.62). Hemolysis was more frequent after anti-D. The overall quality of the studies was low. CONCLUSIONS Compared with anti-D, IVIG led to a better response in terms of platelet count and may be preferred as a first-line treatment of ITP in children with acute hemorrhagic symptoms. However, the clinical significance of IVIG superiority on platelet count remains unclear.
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5.
Clinical effect of anti-D immunoglobulin in treatment of childhood immune thrombocytopenia: a meta analysis
Qin W, Huang SL, Li TT
Zhongguo Dang Dai Er Ke Za Zhi = Chinese Journal of Contemporary Pediatrics. 2017;19((10)):1070-1076.
Abstract
OBJECTIVE To investigate the clinical effect and safety of anti-D immunoglobulin (anti-D) in the treatment of children with newly diagnosed acute immune thrombocytopenia (ITP) through a Meta analysis. METHODS PubMed, EMBASE, Cohrane Library, Ovid, CNKI, and Wanfang Data were searched for randomized controlled trials (RCTs) published up to April 2017. Review Manager 5.3 was used for the Meta analysis. RESULTS Seven RCTs were included. The Meta analysis showed that after 72 hours and 7 days of treatment, the intravenous immunoglobulin (IVIG) group had a significantly higher percentage of children who achieved platelet count >20x109/L than the anti-D group (P<0.05). There were no significant differences in platelet count after 24 hours, 72 hours, and 7 days of treatment between the anti-D (50 mug/kg) group and the IVIG group (P>0.05), and there were also no significant differences in platelet count after 24 hours and 7 days of treatment between the 50 mug/kg and 75 mug/kg anti-D groups (P>0.05). The anti-D group had a significantly greater reduction in the hemoglobin level than the IVIG group after treatment, but did not need transfusion. No children in the anti-D group or the IVIG group experienced serious adverse reactions. CONCLUSIONS Intravenous injection of anti-D may have a similar effect as IVIG in improving platelet count in children with acute ITP, but it may be slightly inferior to IVIG in the rate of platelet increase after treatment. The anti-D dose of 50 mug/kg may have a similar effect as 75 mug/kg. The recommended dose of anti-D for treatment of ITP is safe.
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6.
Anti-D administration in pregnancy for preventing Rhesus alloimmunisation
McBain RD, Crowther CA, Middleton P
Cochrane Database of Systematic Reviews.. 2015;((9)):CD000020.
Abstract
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.
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7.
Intravenous immunoglobulin in the therapeutic armamentarium of systemic lupus erythematosus: a systematic review and meta-analysis
Sakthiswary R, D'Cruz D
Medicine. 2014;93((16):):e86.
Abstract
Prepared from the plasma of thousands of blood donors, therapeutic intravenous immunoglobulin (IVIg) mostly consists of human polyspecific immunoglobulin G (IgG). The use of IVIg in systemic lupus erythematosus (SLE) is still considered experimental without any clear indications.The purpose of this systematic review is, therefore, to evaluate the available evidence to determine the therapeutic role of IVIg in SLE.A comprehensive, computerised search was performed in the MEDLINE (Pubmed), Scopus, EMBASE, and Cochrane controlled trials.The study eligibility criteria were randomized controlled trials, and prospective and retrospective observational studies that examined the efficacy of IVIg in adult patients with SLE who were considered the participants.IVIg therapy was the mode of intervention in these patients.Data abstracted included the study design, study population, changes in the disease activity scores (Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure, and Lupus Activity Index-Pregnancy), steroid dose, complement levels, autoantibodies, and renal function. Thereafter, data analysis established statistical procedures for meta-analysis.Thirteen studies (including 3 controlled and 10 observational) were eligible for inclusion. There was significant reduction in the SLE disease activity scores with IVIg therapy with a standard mean difference of 0.584 (P=0.002, 95% confidence interval [CI] 0.221-0.947). In terms of rise in complement levels, the response rate was 30.9% (P=0.001, 95 CI 22.1-41.3). The effects of IVIg on other clinical outcome measures including anti-double-stranded DNA, antinuclear antibody, average steroid dose, and renal function could not be determined because of the limited numbers of trials.The limitations of this review were lack of well-designed controlled trials with adequate sample size on the use of IVIg in SLE.In conclusion, the use of IVIg is associated with significant reduction in SLE disease activity and improvement in complement levels.
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8.
Intramuscular versus intravenous anti-D for preventing Rhesus alloimmunization during pregnancy
Okwundu CI, Afolabi BB
Cochrane Database of Systematic Reviews. 2013;1:CD007885.
Abstract
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. Systematic Review
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9.
Anti-D administration in pregnancy for preventing Rhesus alloimmunisation
Crowther CA, Middleton P, McBain RD
Cochrane Database of Systematic Reviews. 2013;2:CD000020.
Abstract
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 g (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.
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10.
Anti-D administration after spontaneous miscarriage for preventing Rhesus alloimmunisation
Karanth L, Jaafar SH, Kanagasabai S, Nair NS, Barua A
Cochrane Database of Systematic Reviews.. 2013;3:CD009617.
Abstract
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 g 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.