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

Transfusion. 2008 May;48(5):941-52. doi: 10.1111/j.1537-2995.2007.01625.x. Epub 2008 Feb 1.


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.

Study design and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abruptio Placentae / mortality
  • Duffy Blood-Group System / immunology
  • Erythroblastosis, Fetal / blood
  • Erythroblastosis, Fetal / epidemiology*
  • Erythroblastosis, Fetal / immunology*
  • Exchange Transfusion, Whole Blood / statistics & numerical data
  • Female
  • Hepatitis B e Antigens / immunology
  • Humans
  • Infant, Newborn
  • Isoantibodies / blood*
  • Kell Blood-Group System / immunology
  • Kidd Blood-Group System / immunology
  • Mass Screening*
  • National Health Programs
  • Netherlands / epidemiology
  • Pregnancy
  • Pregnancy Complications, Hematologic / blood
  • Pregnancy Complications, Hematologic / epidemiology*
  • Pregnancy Complications, Hematologic / immunology*
  • Pregnancy Trimester, First / immunology
  • Rh-Hr Blood-Group System / blood
  • Rh-Hr Blood-Group System / immunology
  • Rho(D) Immune Globulin
  • Risk Factors
  • Seroepidemiologic Studies
  • Severity of Illness Index


  • Duffy Blood-Group System
  • Hepatitis B e Antigens
  • Isoantibodies
  • Kell Blood-Group System
  • Kidd Blood-Group System
  • RHO(D) antibody
  • Rh-Hr Blood-Group System
  • Rho(D) Immune Globulin
  • Rho(D) antigen
  • anti-c antibody