**4.1 Absence of universal access to prophylactic anti-D through the routine antenatal anti-D prophylaxis (RAADP) program**

RAADP or routine antenatal anti-D prophylaxis is a recommended treatment option for all Rhesus D negative pregnant women who are not known to be sensitised previously to the RhD antigen. The D antigen is the most immunogenic and most clinically relevant of the Rhesus antigens. A mother who is RhD negative and married to a homozygous or heterozygous D positive husband has a 100 and 50% chance respectively of carrying a D positive baby. During such pregnancies as a result of feto maternal haemorrhage (FMH) following potentially sensitising events [abdominal trauma, abortion or termination of pregnancy, antepartum haemorrhage (APH), amniocentesis, chorionic villus sampling, external cephalic version (ECV) and miscarriages] during pregnancy, small amounts of foetal blood can enter into the maternal circulation. The foetal RhD-positive cells can irreversibly sensitise the mother to produce alloantibody D. The risk of sensitisation occurring is dependent on a number of factors; ABO blood group of the developing foetus (there is a higher risk if there is ABO compatibility between mum and baby), dose of foetal cells entering the maternal circulation, immune competence of the mother and type of pregnancy (risk is significantly higher in the first decreasing in the subsequent pregnancies. The antibody produced is immune IgG antibody that is a low molecular weight antibody and can potentially cross the placenta barrier. The maternal immune anti-D are small molecular weight IgG immunoglobulin and can pass through the placenta in subsequent D positive pregnancy and destroy the foetal red cells with increased production of bilirubin a product of red cell breakdown (HDFN). While in womb the mother manages the bilirubin on behalf of the baby by production of glucoronyl transferase enzyme which break down (conjugate) the bilirubin to water soluble forms that can be excreted in the urine. However, after delivery, the excess bilirubin released from the breakdown of the foetal red cells leads to jaundice. With the baby's liver poorly developed and not producing enough glucoronyl transferase enzyme to conjugate the bilirubin to excretable form, the level can potentially rise above the blood brain barrier and cause kernicterus (permanent brain damage) with attendant neurodevelopmental problems (cerebral palsy, deafness neuromotor and speech delay). Routine antenatal anti-D prophylaxis (RAADP) is a program under which Rhesus D negative non-sensitised pregnant women are universally offered anti-D prophylaxis at 28–34 weeks' gestation with the aim of preventing the sensitization of Rh D-negative women and by extension prevent anti-D HDFN in subsequent pregnancy [89]. The aim of the RAADP programme is the reduction in the incidence of anti-D related HDFN; improve the survival of the children delivered by Rhesus D negative women, reduce the incidence of disability and health-related quality of life of children and mortality in children delivered by Rhesus D negative women who would have developed anti-D related-HDFN if mothers were not offered prophylaxis. The RAADP program is based on offering either two doses of at least 500IU at 28- and 34-weeks' gestation or a single dose of at least 1500IU at 28 weeks gestation followed by a further dose of at least 1500IU within 72 h of delivery of a Rh D positive baby. The dose offered post-delivery is dependent on the result of feto maternal haemorrhage testing result (flow cytometry of Kleihauer testing). Both methods quantify in millilitres the amount of foetal red cells that has entered maternal circulation to facilitate the administration of adequate dose of prophylactic anti-D. As a general rule 1 25 IU of anti-D is administered to clear 1 ml of foetal red cells from maternal circulation. The introduction of anti-D prophylaxis using Rhesus D immunoglobulin

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*Distribution of Clinically Relevant Blood Group Antigens among Nigerians…*

(given intramuscular or intravenous administration) has led to a significant fall in the number of women becoming sensitised and by extension reduced the incidence and severity of this condition. The anti D immunoglobulin used as prophylaxis is prepared from plasma of male Rhesus D negative donors who have high levels of plasma anti-D due to deliberate or intentional immunisation with D positive red cells. Anti D is also administered to Rhesus D negative women following a potentially sensitising events during pregnancy. The anti-D facilitates the clearance of foetal red cells from the maternal circulation to prevents active immunisation, thus preventing the production of alloantibody D. Prior to the availability and widespread use of anti-D prophylaxis for Rhesus negative pregnant women, the incidence of Rh D sensitization among Rhesus D negative women following two deliveries of D positive and ABO-compatible, infants was approximately 16% and haemolytic disease of the foetus and newborn (HDFN) due to immune anti-D was a significant cause of morbidity and mortality [90]. Following the implementation of anti-D prophylaxis, the rate of sensitization has declined significantly to approximately 2%. With the implementation of RAADP by providing anti-D prophylaxis in the 3rd trimester between 28 and 34 weeks gestation, there has been a further remarkable reduction in the sensitisation rate to 0.17–0.28% [91]. Mortality from D-related HDFN related has also declined significantly from 46/100,000 births to 1.6/100,000 births [89]. Evidence from best practice implementation in England and Wales indicates that RAADP has reduced the incidence of sensitisation and hence of HDFN [92]. Conservative estimate indicates that it cost £2–£3.5 million for England and Wales to provide RAADP to all her Rh D-negative pregnant women. The Nigerian government can learn from this evidence-based best practice by implementing RAADP program for her population of Rhesus D negative pregnant population with the hope of reducing sensitization, incidence and severity of anti-D

**4.2 Absence of facility for foetal genotype testing for D, K and other clinically** 

Rhesus D grouping is relevant for blood donors, transfusion recipients and for women of child bearing age including pregnant women. This is because the Rh blood group antigens particularly D is significantly immunogenic. Rh D negative individuals often lack the D antigens on their red cells and can potentially be sensitised when exposed to D antigen positive red cells during pregnancy and blood transfusion. Such antibodies are often capable of causing a haemolytic transfusion reaction (HTR) and haemolytic disease of the foetus and newborn (HDFN). Since the introduction of prophylactic anti-D and implementation of evidence based best practice of careful management and monitoring of D negative pregnant women for all the potentially sensitising events that occur during pregnancy, the prevalence of HDFN because of Rh D incompatibility between the mother and baby has declined significantly [90]. In order to prevent Rhesus D negative women who are not previously sensitised from developing alloantibody D, these women are offered prophylactic anti-D during pregnancy under the Routine Antenatal Anti-D Prophylaxis program between 28 and 34 weeks' gestation. The half-life of the administered anti-D is 12 weeks. The anti-D prevents the mother from being sensitised by micro foetal maternal haemorrhage that can occur as a result of potentially sensitising events that occur during pregnancy. These women should have a fetomaternal haemorrhage testing following any potentially sensitising events that occur after from 20 weeks' gestation. This test quantifies the amount of foetal red cells that entered the maternal circulation to allow for the administration of adequate dose of anti-D to clear the fotal cells and prevent them from

*DOI: http://dx.doi.org/10.5772/intechopen.90372*

related HDFN and mortality in Nigeria.

**relevant red cell antigens**

*Distribution of Clinically Relevant Blood Group Antigens among Nigerians… DOI: http://dx.doi.org/10.5772/intechopen.90372*

(given intramuscular or intravenous administration) has led to a significant fall in the number of women becoming sensitised and by extension reduced the incidence and severity of this condition. The anti D immunoglobulin used as prophylaxis is prepared from plasma of male Rhesus D negative donors who have high levels of plasma anti-D due to deliberate or intentional immunisation with D positive red cells. Anti D is also administered to Rhesus D negative women following a potentially sensitising events during pregnancy. The anti-D facilitates the clearance of foetal red cells from the maternal circulation to prevents active immunisation, thus preventing the production of alloantibody D. Prior to the availability and widespread use of anti-D prophylaxis for Rhesus negative pregnant women, the incidence of Rh D sensitization among Rhesus D negative women following two deliveries of D positive and ABO-compatible, infants was approximately 16% and haemolytic disease of the foetus and newborn (HDFN) due to immune anti-D was a significant cause of morbidity and mortality [90]. Following the implementation of anti-D prophylaxis, the rate of sensitization has declined significantly to approximately 2%. With the implementation of RAADP by providing anti-D prophylaxis in the 3rd trimester between 28 and 34 weeks gestation, there has been a further remarkable reduction in the sensitisation rate to 0.17–0.28% [91]. Mortality from D-related HDFN related has also declined significantly from 46/100,000 births to 1.6/100,000 births [89]. Evidence from best practice implementation in England and Wales indicates that RAADP has reduced the incidence of sensitisation and hence of HDFN [92]. Conservative estimate indicates that it cost £2–£3.5 million for England and Wales to provide RAADP to all her Rh D-negative pregnant women. The Nigerian government can learn from this evidence-based best practice by implementing RAADP program for her population of Rhesus D negative pregnant population with the hope of reducing sensitization, incidence and severity of anti-D related HDFN and mortality in Nigeria.
