Transfusion Antenatal Testing

Blood group and red cell antibody screening are routinely performed twice during all pregnancies. The first screening happens between 6 to 16 weeks, and the second, at 28 weeks.

Samples on patients who have developed significant red blood cell antibodies may be required more often than usual. The frequency of screening required, will be indicated on the antenatal report. This report will also state the number of blood samples required. 

The samples are required to monitor the strength (titre) of the antibodies concerned, and to identify pregnancies which may be at risk from Haemolytic Disease of the Foetus and Newborn (HDN). They also monitor the possible formation of additional allo-antibodies during the pregnancy. Patients who have developed red cell antibodies should be referred to an obstetrician.

The current guidelines state that pregnant people with anti-c, D, K or K related antibodies require a titre check every 4 weeks until the 28th week of pregnancy. And, thereafter, every 2 weeks until delivery.

Other specificities commonly implicated as causing HDN include anti-C, E, Fy(a) and Jk(a) - though there are many other, rarer, antibodies. Guidelines recommend testing these patients at booking, and at 28 weeks of pregnancy only. However further testing will be performed as required.

Anti-Le(a), Le(b), N, Lu(a), P1, H and A1 are not considered to be clinically significant as regards HDFN.

In some instances, a paternal sample may be requested. This is usually to determine the father’s phenotype and predict the likelihood of the foetus carrying the relevant red cell antigen. This indicates whether the possibility of HDN exists.

The red blood cell membrane contains numerous antigenic molecules which may induce the production of plasma antibodies. Currently, there are more than 600 known red cell antigens. Immunisation is caused by exposure to ‘foreign’ red cells via pregnancy or transfusion though some plasma antibodies are naturally occurring.

RhD Negative Women

Haemolytic Disease of the Foetus and Newborn (HDN) is a condition in which the life span of a neonate’s red cells is shortened by the action of antibodies from the mother that have crossed the placenta. 

The most common antibody involved in HDFN is anti-D. Anti-D can be produced when a Rh D negative mother is carrying a Rh D positive foetus and a feto-maternal haemorrhage (FMH) event occurs. This allows foetal red cells to enter the maternal circulation and stimulate the mother’s immune system. If immune anti-D is produced, it can then re-enter into the foetus, via the placenta, and cause HDN in current or subsequent pregnancies

The British Society for Haematology (BSH) guidelines for the use of anti-D immunoglobulin, for the prevention of HDFN (BCSH 2014) state that at least 500iu of anti-D immunoglobulin must be given to every D negative woman. There should be no preformed anti-D within 72 hours of an FMH event or delivery of a D positive baby. This dose will be sufficient to prevent sensitisation from a bleed of up to 4mL fetal red cells.

Prophylactic Anti-D

The National Institute for Clinical Excellence (NICE) issued guidelines in 2002 recommending that Routine Antenatal Anti-D Prophylaxis (RAADP) be offered to all non-sensitised pregnant women who are RhD Negative. 

Previously, Anti-D had been given only when a sensitising event occurred during pregnancy and, or at delivery - if the baby is RhD Positive. This had been successful in reducing the number of cases of HDN. However, a small number of cases still developed antibodies during pregnancy and the cause is thought to be hidden feto-maternal haemorrhages. 

A number of studies have shown that these can be further reduced by the administration of Anti-D at 28 to 30 weeks to cover these possible hidden bleeds in the last trimester. It should not be given before 28 weeks.  

Cell-free fetal DNA RhD screening

High-throughput non-invasive prenatal testing (NIPT) for fetal RHD genotype is recommended as a cost-effective option to guide antenatal prophylaxis with anti-D immunoglobulin. This will help reduce unnecessary use of a blood product in pregnant women, and conserve supplies by only using anti-D immunoglobulin for those who need it.

During pregnancy a small amount of cell-free fetal DNA is present in maternal blood. This DNA can be analysed for RHD exons 5 and 7 using real-time polymerase chain reaction to predict the baby’s D blood group to see if it differs from that of the mother.

Patients eligible for fetal RhD screening will be identified at antenatal booking by community and antenatal midwifery teams. Once identified the patients will be sent letter/email indicating that they can access fetal RhD screening service if they wish and consent will be obtained and recorded. Samples will be obtained by antenatal clinic and transported to the Blood Transfusion Laboratory for referral to NHS Blood and Transport, Filton.

This webpage was reviewed and updated by Mark Taplin, Blood Transfusion Manager, 22nd February 2024