title: Effect of screening for red cell antibodies, other than anti-D, to detect hemolytic disease of the fetus and newborn: a population study in the Netherlands.
abstract: BACKGROUND
  Hemolytic disease of the fetus and newborn (HDFN) is a severe disease, resulting from maternal red cell (RBC) alloantibodies directed against fetal RBCs. The effect of a first-trimester antibody screening program on the timely detection of HDFN caused by antibodies other than anti-D was evaluated.
  
  
  METHODS
  Nationwide, all women (1,002 in 305,000 consecutive pregnancies during 18 months) with alloantibodies other than anti-D, detected by a first-trimester antibody screen, were included in a prospective index-cohort study. In a parallel-coverage validation study, patients with HDFN caused by antibodies other than anti-D, that were missed by the screening program, were retrospectively identified.
  
  
  RESULTS
  The prevalence of positive antibody screens at first-trimester screening was 1,232 in 100,000; the prevalence of alloantibodies other than anti-D was 328 in 100,000, of which 191 of 100,000 implied a risk for occurrence of HDFN because the father carried the antigen. Overall, severe HDFN, requiring intrauterine or postnatal (exchange) transfusions, occurred in 3.7 percent of fetuses at risk: for anti-K in 11.6 percent; anti-c in 8.5 percent; anti-E in 1.1 percent; Rh antibodies other than anti-c, anti-D, or anti-E in 3.8 percent; and for antibodies other than Rh antibodies or anti-K, in none of the fetuses at risk. All affected children, where antibodies were detected, were promptly treated and healthy at the age of 1 year. The coverage validation study showed a sensitivity of the screening program of 75 percent. Five of 8 missed cases were caused by anti-c, with delay-induced permanent damage in at least 1.
  
  
  CONCLUSIONS
  First-trimester screening enables timely treatment of HDFN caused by antibodies other than anti-D, however, with a sensitivity of only 75 percent. A second screening at Week 30 of c- women will enhance the screening program. Severe HDFN, caused by antibodies other than anti-D, is associated with anti-K, anti-c, and to a lesser extent with other Rh-alloantibodies.
authors.affiliation: Sanquin Research, Amsterdam, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Koelewijn
authors.forename: T G M
authors.initials: TG
authors.lastname: Vrijkotte
authors.forename: C E
authors.initials: CE
authors.lastname: van der Schoot
authors.forename: G J
authors.initials: GJ
authors.lastname: Bonsel
authors.forename: M
authors.initials: M
authors.lastname: de Haas
mesh_terms: D000037:Abruptio Placentae / Q000401:mortality; D004375:Duffy Blood-Group System / Q000276:immunology; D004899:Erythroblastosis, Fetal / Q000097:blood / Q000453:epidemiology* / Q000276:immunology*; D005078:Exchange Transfusion, Whole Blood / Q000706:statistics & numerical data; D005260:Female; D006513:Hepatitis B e Antigens / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D007518:Isoantibodies / Q000097:blood*; D007626:Kell Blood-Group System / Q000276:immunology; D007667:Kidd Blood-Group System / Q000276:immunology; D008403:Mass Screening; D009313:National Health Programs; D009426:Netherlands / Q000453:epidemiology; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood / Q000453:epidemiology* / Q000276:immunology*; D011261:Pregnancy Trimester, First / Q000276:immunology; D012204:Rh-Hr Blood-Group System / Q000097:blood / Q000276:immunology; D018029:Rho(D) Immune Globulin; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D012720:Severity of Illness Index
chemical_list: D004375:Duffy Blood-Group System; D006513:Hepatitis B e Antigens; D007518:Isoantibodies; D007626:Kell Blood-Group System; D007667:Kidd Blood-Group System; C061961:RHO(D) antibody; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin; C026410:Rho(D) antigen; C051138:anti-c antibody