Fetal red cell and platelet antigen genotyping: progress and pitfalls

Prior to the 1960s, haemolytic disease of the fetus and newborn (HDFN) caused 50% of all prenatal deaths.¹ However, the number of registered deaths and stillbirths attributed to HDFN fell from 46 deaths per 100,000 live births in 1953 to less than one death per 100,000 live births in 2005 in England and Wales.² The main reason for this decrease was the introduction of anti-D prophylaxis supported by developments in fetal monitoring and intervention such as intrauterine transfusion.

               This article highlights how advances in genetic testing have contributed further to the reduction in deaths associated with HDFN. First, in the management of the disease with early diagnosis of pregnancies at risk of HDFN due to antibodies against D, c and K, and second, in prevention, with a targeted approach to anti-D prophylaxis in D-negative mothers.

               Knowledge of whether or not the fetus has inherited paternal antigens is fundamental, not just to the cost-effective prevention and treatment of HDFN, but also in diagnosing fetal and neonatal alloimmune thrombocytopenia (FNAIT). Historically, the red cell antigen or human platelet antigen (HPA) status of the fetus was ascertained on samples obtained by chorionic villus sampling or amniocentesis. However, these invasive procedures are associated with a risk of miscarriage of approximately 0.35%.³