title: HLA associations and HLA sharing in recurrent miscarriage: A systematic review and meta-analysis.
abstract: OBJECTIVE
  The aim of this meta-analysis was to evaluate whether specific maternal HLA alleles and HLA sharing of couples are associated with the occurrence of recurrent miscarriage (RM).
  
  
  METHODS
  A systematic literature search was performed for studies that evaluated the association between HLA alleles, HLA sharing and RM. RM was defined as three or more consecutive unexplained miscarriages and a control group was included of women with at least one live birth and no miscarriages in their history. Meta-analyses were performed and the pooled odds ratio (OR) was calculated.
  
  
  RESULTS
  We included 41 studies. Selection bias was present in 40 studies and information bias in all studies. Meta-analyses showed an increased risk of RM in mothers carrying a HLA-DRB1*4 (OR 1.41, 95% CI 1.05-1.90), HLA-DRB1*15 (OR 1.57, 95% CI 1.15-2.14), or a HLA-E*01:01 allele (OR 1.47, 95% CI 0.20-1.81), and a decreased risk with HLA-DRB1*13 (OR 0.63, 95% CI 0.45-0.89) or HLA-DRB1*14 (OR 0.54, 95% CI 0.31-0.94). Pooling results for HLA sharing showed that HLA-B sharing (OR 1.39, 95% CI 1.11-1.75) and HLA-DR sharing (OR 1.57, 95% CI 1.10-1.25) were both associated with the occurrence of RM.
  
  
  CONCLUSIONS
  Although the present systematic review and meta-analysis demonstrates that specific HLA alleles and HLA sharing are associated with RM, a high degree of bias was present and therefore observed results should be interpreted carefully.
authors.affiliation: Department of Obstetrics, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands. Electronic address: t.meuleman@lumc.nl.
authors.forename: Tess
authors.initials: T
authors.lastname: Meuleman
authors.affiliation: Department of Obstetrics, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands.
authors.forename: Lisa E L O
authors.initials: LE
authors.lastname: Lashley
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands.
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Dekkers
authors.affiliation: Department of Obstetrics, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands.
authors.forename: Jan M M
authors.initials: JM
authors.lastname: van Lith
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands.
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.affiliation: Department of Obstetrics, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands.
authors.forename: Kitty W M
authors.initials: KW
authors.lastname: Bloemenkamp
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics / Q000276:immunology*; D000483:Alleles; D005260:Female; D056726:Genetic Association Studies; D015235:HLA-B Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006648:Histocompatibility; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D011247:Pregnancy; D012306:Risk; D015983:Selection Bias; D000097625:HLA-E Antigens
chemical_list: D015235:HLA-B Antigens; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens
keywords: HLA alleles; HLA sharing; Meta-analysis; Recurrent miscarriage; Systematic review