title: Strategy for managing maternal variant RHD alleles in Rhesus D negative obstetric populations during fetal RHD genotyping.
abstract: OBJECTIVE
  Fetal RHD screening programs that aim to reduce unnecessary antenatal anti-D prophylaxis are being introduced into clinical practice. Strategies to manage women serologically typed as Rhesus D negative who have maternal RHD variants are needed. This study describes maternal RHD allelic variants detected in nonselected and alloimmunised Rhesus D negative obstetric populations and explores a mathematical approach to identify these variants.
  
  
  METHODS
  Fetal RHD status was defined by testing cell-free fetal DNA in maternal plasma. Women at risk of an RHD variant were identified by selection for C and E haplotypes or by recognition of low polymerase chain reaction cycle threshold on fetal RHD typing. Maternal RHD alleles were defined by SNP profiling or sequencing.
  
  
  RESULTS
  The prevalence of RHD variants in nonselected and alloimmunised groups was 1% (6/603) and 5.5% (6/110), respectively (p < 0.001). An inverse association between RHD cycle threshold values and gestational age was described by a linear model (p < 0.001). Standard residual values with a Z score threshold of -3.00 would have detected all maternal variants with one (1/713) false positive.
  
  
  CONCLUSIONS
  The prevalence of maternal RHD variants was significantly higher in alloimmunised cases. The causative mechanism for this needs further investigation. Mathematical modeling simplifies the detection of maternal RHD variants.
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Brisbane, Queensland, Australia.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Hyland
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Gardener
authors.forename: Helen
authors.initials: H
authors.lastname: O'Brien
authors.forename: Glenda
authors.initials: G
authors.lastname: Millard
authors.forename: Kristen
authors.initials: K
authors.lastname: Gibbons
authors.forename: Anne
authors.initials: A
authors.lastname: Tremellen
authors.forename: Gorka
authors.initials: G
authors.lastname: Ochoa-Garay
authors.forename: Robert L
authors.initials: RL
authors.lastname: Flower
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Hyett
mesh_terms: D000483:Alleles; D004247:DNA / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D014644:Genetic Variation; D060005:Genotyping Techniques; D005865:Gestational Age; D006801:Humans; D011247:Pregnancy; D012203:Rh Isoimmunization / Q000235:genetics* / Q000517:prevention & control; D012204:Rh-Hr Blood-Group System / Q000097:blood / Q000235:genetics*
chemical_list: D012204:Rh-Hr Blood-Group System; D004247:DNA