scholarly journals Fetal/neonatal alloimmune thrombocytopenia: a systematic review of impact of HLA-DRB3*01:01 on fetal/neonatal outcome

2020 ◽  
Vol 4 (14) ◽  
pp. 3368-3377
Author(s):  
Jens Kjeldsen-Kragh ◽  
Dean A. Fergusson ◽  
Mette Kjaer ◽  
Lani Lieberman ◽  
Andreas Greinacher ◽  
...  
Keyword(s):  
Systematic Review ◽  
Prospective Studies ◽  
Retrospective Studies ◽  
Neonatal Outcome ◽  
Meta Analysis ◽  
Severe Thrombocytopenia ◽  
Platelet Antigen ◽  
Human Platelet Antigen ◽  
Neonatal Thrombocytopenia ◽  
Alloimmune Thrombocytopenia

Abstract 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−.

A Screening and Intervention Program Reducing Mortality and Serious Morbidity Associated with Neonatal Alloimmune Thrombocytopenia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1232-1232
Author(s):  
Jens Kjeldsen-Kragh ◽  
Mette K. Killie ◽  
Geir Tomter ◽  
Elzbieta Golebiowska ◽  
Helene Pedersen ◽  
...  
Keyword(s):  
Platelet Count ◽  
Intervention Program ◽  
Human Platelet ◽  
Fetal Brain ◽  
University Hospital ◽  
Severe Thrombocytopenia ◽  
Platelet Antigen ◽  
Human Platelet Antigen ◽  
Alloimmune Thrombocytopenia

Abstract Background: Neonatal alloimmune thrombocytopenia (NAIT) is most frequently caused by antibodies against the human platelet antigen (HPA) 1a. The objective of the present study was to identify HPA 1a negative women, and to offer them an intervention program aimed to reduce morbidity and mortality of NAIT. Methods: A total of 100,448 pregnant women were HPA 1 typed. The HPA 1a negative women were screened for anti-HPA 1a, which was quantified when present. Immunized women were referred to a university hospital for clinical follow-up, including ultrasonographic examination of the fetal brain. Caesarean section was performed 2–4 weeks prior to term with platelets from HPA 1bb donors reserved for immediate transfusion if petechiae were present and/or if platelet count was < 35 × 109/L. Results: Of all women typed 2.1% were HPA 1a negative. Anti-HPA 1a was detected in 210 of 1,990 HPA 1a negative women. A total of 170 pregnancies in 154 HPA 1a negative women were managed according to the intervention program. These women gave birth to 161 HPA 1a positive children of whom 55 had severe thrombocytopenia (<50 × 109/L) including two with ICH. There were no intrauterine deaths. In 13 previously published prospective studies comprising 131,465 women of whom 2,290 were HPA 1a negative, there were 10 cases with severe NAIT-related complications (3 intrauterine deaths and 7 neonates with ICH), which are significantly higher than in our study (p < 0.05). Conclusions: The screening and intervention program seems to reduce mortality and serious morbidity associated with NAIT.

scholarly journals Systematic review and meta-analysis of anakinra, sarilumab, siltuximab and tocilizumab for COVID-19

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-215266 ◽  
Author(s):  
Fasihul A Khan ◽  
Iain Stewart ◽  
Laura Fabbri ◽  
Samuel Moss ◽  
Karen Robinson ◽  
...  
Keyword(s):  
Systematic Review ◽  
Prospective Studies ◽  
Retrospective Studies ◽  
Meta Analysis ◽  
Ordinal Scale ◽  
Current Evidence ◽  
Immunomodulatory Agents ◽  
Registration Number ◽  
Interleukin Inhibitors ◽  
Survival Risk

BackgroundThere is accumulating evidence for an overly activated immune response in severe COVID-19, with several studies exploring the therapeutic role of immunomodulation. Through systematic review and meta-analysis, we assess the effectiveness of specific interleukin inhibitors for the treatment of COVID-19.MethodsElectronic databases were searched on 7 January 2021 to identify studies of immunomodulatory agents (anakinra, sarilumab, siltuximab and tocilizumab) for the treatment of COVID-19. The primary outcomes were severity on an Ordinal Scale measured at day 15 from intervention and days to hospital discharge. Key secondary endpoints included overall mortality.Results71 studies totalling 22 058 patients were included, 6 were randomised trials. Most studies explored outcomes in patients who received tocilizumab (60/71). In prospective studies, tocilizumab was associated with improved unadjusted survival (risk ratio 0.83, 95% CI 0.72 to 0.96, I2=0.0%), but conclusive benefit was not demonstrated for other outcomes. In retrospective studies, tocilizumab was associated with less severe outcomes on an Ordinal Scale (generalised OR 1.34, 95% CI 1.10 to 1.64, I2=98%) and adjusted mortality risk (HR 0.52, 95% CI 0.41 to 0.66, I2=76.6%). The mean difference in duration of hospitalisation was 0.36 days (95% CI −0.07 to 0.80, I2=93.8%). There was substantial heterogeneity in retrospective studies, and estimates should be interpreted cautiously. Other immunomodulatory agents showed similar effects to tocilizumab, but insufficient data precluded meta-analysis by agent.ConclusionTocilizumab was associated with a lower relative risk of mortality in prospective studies, but effects were inconclusive for other outcomes. Current evidence for the efficacy of anakinra, siltuximab or sarilumab in COVID-19 is insufficient, with further studies urgently needed for conclusive findings.PROSPERO registration numberCRD42020176375.

scholarly journals An Updated Systematic Review and Meta-Analysis of the Obstetric Consequences of Female Genital Mutilation/Cutting

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
R. C. Berg ◽  
J. Odgaard-Jensen ◽  
A. Fretheim ◽  
V. Underland ◽  
G. Vist
Keyword(s):  
Systematic Review ◽  
Prospective Studies ◽  
Retrospective Studies ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Previous Systematic Review ◽  
Genital Mutilation ◽  
Meta Analyses ◽  
Female Genital ◽  
Made In

In our recent systematic review inObstetrics and Gynecology Internationalof the association between FGM/C and obstetric harm we concluded that FGM/C significantly increases the risk of delivery complications. The findings were based on unadjusted effect estimates from both prospective and retrospective studies. To accommodate requests by critics, we aimed to validate these results through additional analyses based on adjusted estimates from prospective studies. We judged that 7 of the 28 studies included in our original systematic review were prospective. Statistical adjustments for measured confounding factors were made in eight studies, including three prospective studies. The adjusted confounders differed across studies in number and type. Results from meta-analyses based on adjusted estimates, with or without data from retrospective studies, consistently pointed in the same direction as our earlier findings. There were only small differences in the sizes or the level of statistical significance. Using GRADE, we assessed that our confidence in the effect estimates was very low or low for all outcomes. The adjusted estimates generally show similar obstetric harms from FGM/C as unadjusted estimates do. Thus, the current analyses confirm the findings from our previous systematic review. There are sufficient grounds to conclude that FGM/C, with respect to obstetric circumstances, involves harm.

scholarly journals POS0522 PREVALENCE OF BRONCHIECTASIS IN RHEUMATOID ARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 494.2-495
Author(s):  
L. Martin ◽  
L. Prisco ◽  
W. Huang ◽  
G. Mcdermott ◽  
N. Shadick ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Random Effects ◽  
Study Design ◽  
Prospective Studies ◽  
Retrospective Studies ◽  
Meta Analysis ◽  
Ct Imaging ◽  
Research Support ◽  
Exclusion Criteria

Background:Bronchiectasis is a known extra-articular manifestation of rheumatoid arthritis (RA) and can lead to decreased quality of life as well as increased risk for infection and mortality. Understanding the burden of bronchiectasis in RA may lead to a better understanding of pathogenesis and improved management. We performed a systematic review and meta-analysis to determine the prevalence of bronchiectasis in RA.Objectives:We investigated the prevalence of RA-related bronchiectasis (RA-BR) using a systematic review and meta-analysis.Methods:We followed the PRISMA-P 2015 guideline for systematic reviews and registered this analysis (ID#199080) on PROSPERO. We queried PubMed and EMBASE databases using the search strategy “rheumatoid arthritis; AND; bronchiectasis” as of July 31, 2020. The inclusion and exclusion criteria were assessed for study eligibility by two independent abstractors. Exclusion criteria included: (1) non-primary literature (i.e., review articles, editorials); (2) case reports involving less than 5 patients; (3) published in a language other than English; (4) did not relate to both RA and bronchiectasis; and (5) studies not involving humans (e.g., mouse models). After the initial screen, we conducted a full text review to verify that inclusion criteria were met: (1) reported frequency of RA-BR and denominator of all RA patients in the study sample. Data including type of study design, method of RA-BR detection, and RA characteristics were extracted by two independent abstractors. We performed meta-analyses using random effects models to estimate prevalence of RA-BR among RA overall and restricted to retrospective or prospective studies.Results:Out of a total of 208 studies, 37 studies were identified that reported frequency of RA-BR among RA. The included studies had heterogeneous methods to identify RA-BR that were based on either clinical or research chest computed tomography (CT) imaging and had varying methods to adjudicate images. Some studies focused on patients with respiratory symptoms or suspected RA-associated interstitial lung disease (RA-ILD). There were a total of 8,646 patients with RA, and 612 were identified as having RA-BR. The pooled overall prevalence of RA-BR in the random effects meta-analysis was 18.2% (95%CI 13.3-23.7%, Figure 1). Among prospective studies (n=24), the prevalence of RA-BR in the meta-analysis was 20.7% (95% CI 14.7-27.4%). Among retrospective studies (n=13) reporting RA-BR, the prevalence was 14.5% (95% CI 7.2-23.7%). Prevalence was lowest in retrospective studies where RA-BR was identified through clinical care (e.g., two large retrospective studies that investigated 4,000 and 1,129 RA patients reported RA-BR prevalence of 0.6% and 2.7%, respectively). The two largest prospective studies that incorporated a research protocol performing chest CT imaging on all enrolled patients investigated 150 and 332 patients with RA and reported a RA-BR prevalence of 8.0% and 9.6%, respectively. Smaller studies of both study design types generally reported higher prevalence of RA-BR.Figure 1.Pooled prevalence of RA-related bronchiectasis in RA among all studies identified (n=37).Conclusion:The prevalence of RA-BR in this systematic review and meta-analysis was 18.2%, emphasizing that bronchiectasis is a common extra-articular feature of RA. However, some studies may have identified subclinical RA-BR through research imaging or RA-BR may have been secondary to RA-ILD. Future studies should standardize methods to identify RA-BR cases and investigate the natural history and clinical course given the relatively high prevalence that we report.Disclosure of Interests:Lily Martin: None declared, Lauren Prisco: None declared, Weixing Huang: None declared, Gregory McDermott: None declared, Nancy Shadick Consultant of: Consultant < 5K Bristol-Myers Squibb, Grant/research support from: BMS Amgen Lilly, Mallinckrodt, and Sanofi, Tracy Doyle Consultant of: Boehringer Ingelheim (<5K), Grant/research support from: Bristol Myers Squibb and Genentech, Jeffrey Sparks Consultant of: Bristol-Myers Squibb, Gilead, Inova Diagnostics, Optum, and Pfizer, Grant/research support from: Bristol-Myers Squibb

scholarly journals The Natural History of Fetomaternal Alloimmunization to the Platelet-Specific Antigen HPA-1a (PlA1, Zwa) as Determined by Antenatal Screening

Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2280-2287 ◽  
Author(s):  
Lorna M. Williamson ◽  
Gerald Hackett ◽  
Janet Rennie ◽  
Christopher R. Palmer ◽  
Caroline Maciver ◽  
...  
Keyword(s):  
Specific Antigen ◽  
Blood Platelet ◽  
Severe Thrombocytopenia ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Platelet Antigen ◽  
Human Platelet Antigen ◽  
Cerebral Ultrasound ◽  
Neonatal Thrombocytopenia ◽  
Definition Of

Abstract Immunization against the human platelet antigen (HPA)-1 alloantigen is the most common cause of severe fetal and neonatal thrombocytopenia. Fetal therapy has substantial risks and its indications need better definition. Of 24,417 consecutive pregnant women, 618 (2.5%) were HPA-1a negative of whom 385 entered an observational study. All were HLA-DRB3*0101 genotyped and screened for anti–HPA-1a. Their partners and neonates were HPA-1 genotyped and the latter were assessed by cord blood platelet counts and cerebral ultrasound scans. Anti–HPA-1a was detected in 46 of 387 pregnancies (12.0%; 95% CI 8.7%-15.2%). All but one were HLA-DRB3*0101 positive (odds ratio 140; 95% CI 19-1035;P< .00001). One baby died in utero, and of 26 HPA-1a–positive babies born to women with persistent antenatal antibodies, 9 were severely thrombocytopenic (8 with a count <10 × 109/L, 1 with a large porencephalic cyst), 10 were mildly thrombocytopenic, whereas 7 had normal platelet counts. Severe thrombocytopenia was significantly associated with a third trimester anti–HPA-1a titer ≥ 1:32 (P = .004), but was not observed in babies of women with either transient or postnatal-only antibodies. HPA-1a alloimmunization complicates 1 in 350 unselected pregnancies, resulting in severe thrombocytopenia in 1:1,200. HPA-1a and HLA-DRB3*0101 typing combined with anti–HPA-1a titration allows selection of the majority of pregnancies at risk of severe thrombocytopenia.

scholarly journals The Natural History of Fetomaternal Alloimmunization to the Platelet-Specific Antigen HPA-1a (PlA1, Zwa) as Determined by Antenatal Screening

Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2280-2287 ◽  
Author(s):  
Lorna M. Williamson ◽  
Gerald Hackett ◽  
Janet Rennie ◽  
Christopher R. Palmer ◽  
Caroline Maciver ◽  
...  
Keyword(s):  
Specific Antigen ◽  
Blood Platelet ◽  
Severe Thrombocytopenia ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Platelet Antigen ◽  
Human Platelet Antigen ◽  
Cerebral Ultrasound ◽  
Neonatal Thrombocytopenia ◽  
Definition Of

Immunization against the human platelet antigen (HPA)-1 alloantigen is the most common cause of severe fetal and neonatal thrombocytopenia. Fetal therapy has substantial risks and its indications need better definition. Of 24,417 consecutive pregnant women, 618 (2.5%) were HPA-1a negative of whom 385 entered an observational study. All were HLA-DRB3*0101 genotyped and screened for anti–HPA-1a. Their partners and neonates were HPA-1 genotyped and the latter were assessed by cord blood platelet counts and cerebral ultrasound scans. Anti–HPA-1a was detected in 46 of 387 pregnancies (12.0%; 95% CI 8.7%-15.2%). All but one were HLA-DRB3*0101 positive (odds ratio 140; 95% CI 19-1035;P< .00001). One baby died in utero, and of 26 HPA-1a–positive babies born to women with persistent antenatal antibodies, 9 were severely thrombocytopenic (8 with a count <10 × 109/L, 1 with a large porencephalic cyst), 10 were mildly thrombocytopenic, whereas 7 had normal platelet counts. Severe thrombocytopenia was significantly associated with a third trimester anti–HPA-1a titer ≥ 1:32 (P = .004), but was not observed in babies of women with either transient or postnatal-only antibodies. HPA-1a alloimmunization complicates 1 in 350 unselected pregnancies, resulting in severe thrombocytopenia in 1:1,200. HPA-1a and HLA-DRB3*0101 typing combined with anti–HPA-1a titration allows selection of the majority of pregnancies at risk of severe thrombocytopenia.

scholarly journals Daily sodium consumption and CVD mortality in the general population: systematic review and meta-analysis of prospective studies

2014 ◽  
Vol 18 (4) ◽  
pp. 695-704 ◽  
Author(s):  
Rosana Poggio ◽  
Laura Gutierrez ◽  
María G Matta ◽  
Natalia Elorriaga ◽  
Vilma Irazola ◽  
...  
Keyword(s):  
Systematic Review ◽  
Relative Risk ◽  
General Population ◽  
Prospective Studies ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Random Effects Models ◽  
Meta Regression ◽  
Cvd Mortality

AbstractObjectiveThe purpose of the present study was to determine whether elevated dietary Na intake could be associated with CVD mortality.DesignWe performed a systematic review and meta-analysis of prospective studies representing the general population. The adjusted relative risks and their 95 % confidence intervals were pooled by the inverse variance method using random-effects models. Heterogeneity, publication bias, subgroup and meta-regression analyses were performed.SettingsMEDLINE (since 1973), Embase (since 1975), the Cochrane Library (since 1976), ISI Web of Science, Google Scholar (until September 2013) and secondary referencing were searched for inclusion in the study.SubjectEleven prospective studies with 229 785 participants and average follow-up period of 13·37 years (range 5·5–19 years).ResultsHigher Na intake was significantly associated with higher CVD mortality (relative risk=1·12; 95 % CI 1·06, 1·19). In the sensitivity analysis, the exclusion of studies with important relative weights did not significantly affect the results (relative risk=1·08; 95 % CI 1·01, 1·15). The meta-regression analysis showed that for every increase of 10 mmol/d in Na intake, CVD mortality increased significantly by 1 % (P=0·016). Age, hypertensive status and length of follow-up were also associated with increased CVD mortality.ConclusionsHigher Na intake was associated with higher CVD mortality in the general population; this result suggests a reduction in Na intake to prevent CVD mortality from any cause.

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