OBJECTIVES: To study the incidence of red cell immunization and to evaluate the use of low-risk invasive procedures in the management of alloimmunized during pregnancy. DESIGN: A 14-year retrospective study of all immunized mothers and their newborns. Population. All reported alloimmunizations between the years 1992 and 2005 in our catchment area were examined. METHODS: Background factors, maternal antibody classification, antibody titers, anti-D quantitation, procedures and maternal treatments instituted during pregnancy, fetal outcome and treatment of the newborn were evaluated. RESULTS: There were 78,145 deliveries in the region. Alloimmunization during pregnancy was detected in 0.4% of all pregnancies, excluding ABO immunizations. A significant alloimmunization (titer level > or =8) was detected in 0.16%. Anti-D immunizations were responsible for 60% of significant immunizations followed by anti-Fy(a) in 10%, anti-c in 7% and anti-K in 4%. Maternal plasma exchange and high-dose intravenous immunoglobulin were used as low-risk invasive treatments in 12 cases. Delivery was in > or =38 weeks in 93% of cases. Twenty-nine newborns were treated with exchange transfusions (ETs) after delivery, whereof 21/29 were due to anti-D, seven due to anti-c and anti-E and in one case anti-Fy(a). No deaths occurred due to severe alloimmunization. CONCLUSION: Anti-D still accounts for the most severe immunizations and for most of the cases where ET was necessary. Low-risk invasive techniques to evaluate and treat pregnancies complicated by alloimmunization seem possible and accurate, avoiding invasive procedures that may exacerbate the immunization during pregnancy.