title: The controversy about controls for fetal blood group genotyping by cell-free fetal DNA in maternal plasma.
abstract: OBJECTIVE
  Fetal blood group genotyping using cell-free fetal DNA from maternal plasma is routinely performed in alloimmunized women and has been introduced for targeted antenatal anti-D prophylaxis. The necessity to control for extraction of fetal DNA in these tests is questioned by many. This review describes the various types of controls for preventing false-negative results and discusses their value.
  
  
  RESULTS
  Polymorphic markers like short tandem repeats, insertion/deletion polymorphisms or single nucleotide polymorphisms can be used as a fetal DNA control in pregnancies in which a Y-chromosome marker is not applicable, but workload is considerable and more than 99% coverage is only reached on platforms allowing high level of multiplexing. Recently, the universal fetal marker RASSF1A has been introduced, enabling the demonstration of fetal DNA after methylation-sensitive digestion of maternal DNA. The analysis of recently published noninvasive fetal blood group genotyping studies showed that false-negative results were only encountered in studies lacking a control for the presence of fetal DNA, albeit at a low frequency of 0.1-0.2%.
  
  
  CONCLUSIONS
  Because of the potentially severe consequences of false-negative results in alloimmunized women, a blood group antigen-negative result should in these cases only be issued if fetal DNA is demonstrated. However, the low frequency of false-negative results makes it acceptable to perform screening studies without a fetal marker.
authors.affiliation: Department of Experimental Immunohaematology, Sanquin Research Amsterdam and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Scheffer
authors.forename: Masja
authors.initials: M
authors.lastname: de Haas
authors.forename: C Ellen
authors.initials: CE
authors.lastname: van der Schoot
mesh_terms: D001789:Blood Group Antigens / Q000235:genetics*; D001788:Blood Grouping and Crossmatching / Q000379:methods* / Q000592:standards; D004247:DNA / Q000097:blood*; D005188:False Negative Reactions; D005260:Female; D005333:Fetus; D005838:Genotype; D006801:Humans; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*
chemical_list: D001789:Blood Group Antigens; D004247:DNA