High-throughput non-invasive prenatal testing for fetal RHD genotype

2 Current practice

During pregnancy, small amounts of fetal blood can enter the maternal circulation (an event called fetomaternal haemorrhage). The presence of fetal D‑positive cells in the maternal circulation, after fetomaternal haemorrhage, can cause a mother who is rhesus‑D (D) negative to produce antibodies against the D antigen on the fetal blood cells (anti‑D), a process called sensitisation.

If sensitisation happens, the immune response is quicker and much greater when the mother is exposed during a later pregnancy to D antigen from a D‑positive fetus. The anti‑D produced by the mother can cross the placenta and cause haemolytic disease of the fetus and newborn. This can cause severe fetal anaemia, leading to fetal heart failure, fluid retention and swelling (hydrops), and intrauterine death.

Routine antenatal anti‑D prophylaxis (RAADP) for all women who are D‑negative is the current practice in most NHS maternity services. Confirming the blood group of a baby born to a D‑negative mother by taking a cord blood sample is routine postpartum clinical practice.

The NICE technology appraisal guidance on routine antenatal anti-D prophylaxis for women who are rhesus D negative recommends that all pregnant women who are D‑negative are offered prophylactic anti‑D immunoglobulin in the third trimester. This is generally offered at the 28-week antenatal appointment, but a 2‑dose regime may be offered at 28 and 34 weeks. The NICE technology appraisal guidance and NICE diagnostic guidance should be read together.

The British Committee for Standards in Haematology's guideline on the use of anti-D immunoglobulin for the prevention of haemolytic disease of the fetus and newborn also recommends that all D‑negative pregnant women who are not known to be sensitised to D antigen have anti‑D immunoglobulin after:

The NICE diagnostics guidance states that about 40% of D‑negative women carry a D‑negative fetus and do not need anti‑D immunoglobulin if the rhesus‑D status of the fetus can be determined. A small number of organisations have already implemented high-throughput NIPT for fetal RHD genotype into routine practice to target this group of women and prevent unnecessary prophylactic treatment.