**4.5 Challenge associated with use of anti-D immunoglobulin for the prevention of haemolytic disease of the foetus and newborn**

Alloantibody-D are produced in a woman of child bearing age either as a result of Rhesus D incompatible transfusion (deliberate or erroneous transfusion of D positive donor red cells to Rhesus D negative women) or as a result of prior Rhesus D incompatibility between the mother and the developing foetus. These sensitizations are often as a result of fetomaternal haemorrhage during pregnancy or during delivery. This is often associated with D positive red cells entering into the maternal circulation to sensitise the mother to produce these immune antibody D. This immune D is an IgG class antibody and can potentially cross the placenta in subsequent D positive pregnancies to cause D HDFN. If a Rhesus D negative woman is married to Rh D positive men who are either homozygous or heterozygous for blood group antigen D, there is a 100 and 50% chance respectively of potentially carrying a Rhesus D positive foetus. In such pregnancies the risk of sensitization of the mother during the first pregnancy as a result of fetomaternal haemorrhage (during pregnancy or delivery) of D positive foetal red cell into maternal circulation is high. The recommend that prophylaxis be provided as soon as possible and always within 72h of the following potentially sensitising event taking place in Rh D negative pregnant women (Amniocentesis, chorionic villus biopsy and cordocentesis, APH, PV bleed during pregnancy, ECV, Abdo trauma (sharp/blunt, open/closed, ectopic pregnancy, evacuation of molar, pregnancy, IUFD, intrauterine intervention during pregnancy (transfusion, surgery, insertion of shunts and laser), miscarriages, TOP, delivery (normal, instrument or C/S) and intraoperative cell salvage) to prevent sensitization and anti-D-related HDFN in subsequent pregnancy. Evidence-based best practice in most developed countries is to prevent this sensitization from taking place by the implementation of the Routine Antenatal Anti-D Prophylaxis (RAADP) programme. This program is alloimmunization prevention where all Rh D negative women are universally offered anti prophylaxis during pregnancy (28 weeks gestation) and following the delivery of a Rhesus positive baby. The implementation of this program has significantly reduced the number of residual alloimmunization from 16% to less than 0.1% [123]. The justification for this implementation is based of scientific evidence that 92% of women who develop an alloantibody-D during pregnancy do so at or after 28 weeks gestation [124, 125].

This implementation has significantly reduced the number of women who are sensitised and by extension the number of D HDFN. However, in countries like Nigeria and some other developing countries where this policy has not been implemented, a significant 14% of unfortunate foetuses are born dead while 50% of those who are born alive suffer from brain injury and neonatal death [126]. This cases of preventable death of Nigerian and African children is a humanitarian emergency that require urgent attention and good will by the Nigerian, African government and people of good will across to globe. Rho(D) immune globulin (RhIG) is a medication that can be given to non-sensitised Rhesus D negative pregnant women to prevent Rh D sensitization. The medication is often administered intramuscularly

**127**

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

part of their HDFN prevention program recommend the following [92].

**4.6 Unaffordability due to high cost of prophylactic anti-D**

the best possible health care delivery.

In Nigeria and many countries in Africa, these recommendations and best practices are not being implemented. Government in these countries will need to rise up to their responsibilities by implementing these recommendations to prove the sincerity of their resolve to offer their people particularly Rhesus negative women

Anti-D related HDFN often result from the transplacental passage of maternal allo-antibodies directed against foetal red cell antigens inherited from the father affects the foetus or neonate. Majority of the mothers becomes sensitised following small feto-maternal haemorrhages during pregnancy and at delivery of the first Rh D-positive infant. These antibodies can potentially cause HDFN in successive Rh D-positive infants. Implementation of universal access to prophylactic anti-D given during antenatal and post-partum period following the delivery of a Rh D positive baby can help prevent primary Rh D immunisation and risk of HDFN in subsequent pregnancies [129]. It is recommended that routine antenatal anti-D prophylaxis (RAADP) is offered to all non-sensitised pregnant women who are Rh D negative to reduce the risk of sensitization and by extension D-related HDFN [130]. The World Health Organisation (WHO) recommends that antenatal prophylaxis with anti-D immunoglobulin should be given to non-sensitised Rh-negative pregnant women at 28 and 34 weeks of gestation to prevent Rh D alloimmunization. It is estimated that single dose of anti-D can cost around US\$ 50 (500 IU) to US\$ 87 (1500 IU), depending on the brand and local taxes. Therefore, the cost of antenatal prophylaxis for two 500 IU doses could be as much as US\$ 100 per woman. Additional costs will include screening for blood typing in settings where Rh blood tests are not

or intravenously and has a half-life of 12 weeks. Rho(D) immune globulin used for prophylaxis is a human derived fractionated plasma product produced from blood donors who have high levels of anti-D Ig either due to previous sensitization or intentional immunisation of Rh D negative men to produced immune D. This product is significantly virally tested (HBsAg, anti-HIV and HCV RNA) and includes viral inactivation steps in order to further reduce the risk of viral transmission. There is still a small unquantifiable possibility of transmitting prion particularly vCJD or other infectious agents. Product safety data submitted by manufacturers to National Institute of Health and Clinical Excellence technical appraisal guidance 156 (National Institute for Health and Clinical Excellence [127]) indicates a very low rate of adverse event (less than one non-serious per 80,000 doses of anti-D administered) [89]. There is no evidence till date to suggest that prophylactic anti-D administered to Rhesus D negative women during pregnancy is harmful to the foetus. Child birth or delivery is a potential sensitising event that can potentially expose the mother to the Rhesus D positive cells of the baby. Following delivery in these women, the cord blood is tested for ABO, Rh D group and DAT. If the infant is Rhesus D positive, the mother sample taken within 72 h is tested for fetomaternal haemorrhage (flow cytometry of Kleihauer-Betke test). These tests quantify the number of foetal cells that has entered the maternal circulation and thus facilitates the determination of the optimal dosage of prophylactic anti-D to be administered. As a general rule 125iu of anti-D is required to clear 1 ml of foetal cells from maternal circulation. A dose of 300 μg or 1500 IU is often sufficient to prevent alloimmunization after delivery in 99% of cases [128]. If the D-type of a newborn or stillborn is unknown or cannot be determined, a dose of anti-D prophylaxis should be administered. However, if the infant is found Rhesus D negative, prophylaxis will not be required. Evidenced-based best practices in most developed countries as

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

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

or intravenously and has a half-life of 12 weeks. Rho(D) immune globulin used for prophylaxis is a human derived fractionated plasma product produced from blood donors who have high levels of anti-D Ig either due to previous sensitization or intentional immunisation of Rh D negative men to produced immune D. This product is significantly virally tested (HBsAg, anti-HIV and HCV RNA) and includes viral inactivation steps in order to further reduce the risk of viral transmission. There is still a small unquantifiable possibility of transmitting prion particularly vCJD or other infectious agents. Product safety data submitted by manufacturers to National Institute of Health and Clinical Excellence technical appraisal guidance 156 (National Institute for Health and Clinical Excellence [127]) indicates a very low rate of adverse event (less than one non-serious per 80,000 doses of anti-D administered) [89]. There is no evidence till date to suggest that prophylactic anti-D administered to Rhesus D negative women during pregnancy is harmful to the foetus. Child birth or delivery is a potential sensitising event that can potentially expose the mother to the Rhesus D positive cells of the baby. Following delivery in these women, the cord blood is tested for ABO, Rh D group and DAT. If the infant is Rhesus D positive, the mother sample taken within 72 h is tested for fetomaternal haemorrhage (flow cytometry of Kleihauer-Betke test). These tests quantify the number of foetal cells that has entered the maternal circulation and thus facilitates the determination of the optimal dosage of prophylactic anti-D to be administered. As a general rule 125iu of anti-D is required to clear 1 ml of foetal cells from maternal circulation. A dose of 300 μg or 1500 IU is often sufficient to prevent alloimmunization after delivery in 99% of cases [128]. If the D-type of a newborn or stillborn is unknown or cannot be determined, a dose of anti-D prophylaxis should be administered. However, if the infant is found Rhesus D negative, prophylaxis will not be required. Evidenced-based best practices in most developed countries as part of their HDFN prevention program recommend the following [92].

In Nigeria and many countries in Africa, these recommendations and best practices are not being implemented. Government in these countries will need to rise up to their responsibilities by implementing these recommendations to prove the sincerity of their resolve to offer their people particularly Rhesus negative women the best possible health care delivery.
