BACKGROUND Neonatal thrombocytopenia (NT) occurs in 0.5 to 0.9% of unselected Caucasian newborns. However, the prevalence of this complication in other populations is unknown. In this study the prevalence/causes of NT was determined in Brazilian newborns, a population characterized by admixture among Indigenous, Africans, and Caucasians. STUDY DESIGN A prospective study was carried out in a 3-year period, to determine the prevalence and causes of thrombocytopenia in cord blood samples. Genotyping for HPA 1-5 systems was performed in pairs of mother/neonates with and without thrombocytopenia. All mothers with genotypic mismatches from each group were tested for HPA-specific antibody using the MAIPA technique to identify alloimmunization. RESULTS Platelet counts <100 x 10(9)/L were detected in 1.5% of 9,332 unselected newborns. In 0.15%, platelet count was <50 x 10(9)/L. Clinically significant bleeding was rare. Underlying diseases were present in 48% of the thrombocytopenic cases. HPA 1-5 system genotype mismatches occurred in 50% of gestations, but did not predict the risk for thrombocytopenia. Notably, mismatched genotypes for HPA-5 were slightly increased in the thrombocytopenic group. The presence of anti-HPA-5b antibodies was observed in 0.05% of unselected pregnancies, but increased to 12% among mothers of neonates with thrombocytopenia and mismatched genotype (N = 51). CONCLUSIONS Neonatal thrombocytopenia is common among Brazilian newborns at rates comparable with those described among Caucasians. These data suggest that screening for genotypic HPA mismatch, followed by an HPA-specific immunoassay system, particularly for the HPA-5 system, among mothers of newborns with thrombocytopenia in our population would allow the identification of pregnancies at risk of alloimmune thrombocytopenia.