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Although RhD blood group antigens were discovered in the 1930s, haemolytic disease of the newborn (HDN) resulting from RhD isoimmunisation remained a common cause of fetal and neonatal morbidity and mortality for another 30 years. In 1969, routine anti-D immunoprophylaxis was introduced for RhD negative women who had delivered a RhD positive baby.1 This policy was extended in 1976 to RhD negative women who had suffered a miscarriage or undergone a termination, and in 1981 to include women who had undergone other potentially sensitising events (e.g. invasive prenatal diagnosis and other intrauterine procedures). By 1991, neonatal mortality resulting from haemolytic disease had fallen to 1.6/100,000 births (from 46/100,000 births before 1969), and the rate of maternal isoimmunisation had dropped from 16% to 2%.1,2 Routine antenatal prophylaxis resulted in a further fall in the sensitisation rate to less than 0.3%.2 Approximately 15% of women in the UK are RhD negative (the incidence being higher in white women than other groups)3 and 40% of babies born to such women will be RhD negative, and therefore not at risk of HDN.4 As a result, it is estimated that 40,000 pregnant women receive antenatal anti-D immunoglobulin unnecessarily each year—could this be about to change?
Prenatal diagnosis of fetal RhD status from maternal peripheral blood was first reported in 1994.5 Since 2001, the technology has been available to guide clinical management of women who are already isoimmunised, by allowing early determination of the baby's RhD status without an invasive procedure. In 2010, Denmark introduced routine screening for fetal RhD6 and in 2011, the Netherlands adopted a nationwide fetal screening programme to target antenatal and postnatal immunoprophylaxis.7 A recent prospective multicentre UK trial demonstrated that the technology for mass RhD genotyping of cell-free fetal DNA is sufficiently accurate from 11 weeks' gestation.8 Data from a pilot implementation study indicate that a policy of offering a cell-free fetal DNA test is acceptable to women and health care professionals.4 It is predicted that the introduction of tests for fetal Rh status would result in a 30% reduction in the use of anti-D immunoglobulin and that combined with other savings, such as a reduction in costly tests for fetomaternal haemorrhage, would be cost neutral.8
Anti-D immunoglobulin is a blood product prepared from plasma taken from RhD negative donors who have been immunised against the anti-D antigen. Although blood donors are carefully screened for transmissible infections there is always a small risk of transmission of blood-borne infections.3 No blood product is without risk and all preparations of anti-D immunoglobulin carry a small risk of localised or generalised allergic reactions. It therefore makes sense to avoid administering anti-D immunoglobulin unnecessarily. The introduction of maternal blood testing for fetal RhD status beyond 11 weeks' gestation would represent a significant advance in personalised obstetric care by allowing both routine and post-sensitisation antenatal anti-D to be directed only to those women carrying RhD positive fetuses. At less than £20 per test, it looks like good value but a final decision from the National Institute for Health and Care Excellence is not expected until 2016.