DR. RAZAQ MASHA, FRCOG Consultant, Ob/Gyn Dept. Rh IMMUNIZATION DR. RAZAQ MASHA, FRCOG Consultant, Ob/Gyn Dept.

Rh IMMUNIZATION Rh haemolytic disease (RHD) is a common condition and affects 1 in 250 live births in Europe and North America although it is much less frequent in other parts of the world such as Asia, where the Rh-negative blood group is uncommon.

TRANSPLACENTAL HAEMORRHAGE (TPH) The Rh antigen is limited to the red cell surface and maternal Rh immunization, can, therefore, only take place if fetal red cells cross the placental barrier into the maternal circulation. Occasional breaks in continuity will occur in the placental barrier, during the stress of labour, with consequent admixture of small quantities of maternal and fetal blood. Kleihauer test – citric-phostphate buffer- an elution technique which is capable of detecting very small THP’s of the order of 0.1 ml of fetal blood.

DELIVERY: The placenta is subjected to maximal trauma during delivery and it has been deduced that TPH would mainly occur during delivery rather than during the course of pregnancy.

ABORTION: TPH occurs after abortion. The risk is greater with induced as compared with spontaneous abortion TPH of 0.2 ml of fetal blood has been recorded in about 5 percent of abortion.

THE NATURAL HISTORY OF Rh IMMUNIZATION The process by which the body responds to an antigen by producing the appropriate antibody is called immunization and there are two types of immunity: a) Humoral immunity – associated with free antibody b) Cellular immunity – cell bound antibody Rhesus antibodies are humoral antibodies or free antibody 1 gm – large, unable to cross the placenta 1gG – small, able to cross the placeta and attach itself to Rh positive red cells leading to haemolytic anaemia

IMMUNE RESPONSES ARE: a) Primary – first response to an antigen b) Secondary For the D-antigen, the primary response appears after several weeks and is IgM. When exposed to the D- antigen for the second time a secondary immune response takes place. If already primed, antibody will appear within a few days or if antibody is already present, the strength will increase rapidly and the antibody will change its character to IgG. Generally, the quantity of antigen required to produce a secondary immune response is very much smaller than that required to initiate the primary immune response.

THE IMMUNIZING PREGNANCY: The first pregnancy is usually unaffected by RHD because TPH’s of sufficient magnitude to induce primary immunization do not usually take place until delivery. Only about 5 percent of all Rh-negative mothers form antibodies.

Reasons: A TPH of sufficient magnitude to induce primary immunization may not take place. 50 percent of individuals do not produce Rh antibodies even after a massive TPH Reduced chance of immunization if there are no complications of delivery. Vast majority of TPH’s after delivery are small and are in the order of about 0.1 ml of fetal blood, but about 0.2% of mothers have larger bleeds of 30 ml or more. The risk of Rh immunization is proportional to the size of the TPH.

ABO INCOMPATIBILITY When the mother and the baby are ABO incompatible such as an O mother and an A baby any fetal red cell (Group A) entering the maternal circulation (Group O) is destroyed, in an exactly similar way to that occurring in an ABO incompatible blood transfusion.

PREGNANCY: TPH does occur during pregnancy but is much less common than following delivery. Most of the bleeds occur in the last trimester when the placenta is degenerating and the barrier may become a little more pervious.

COMPLICATIONS: Anything which damages the placenta is liable to increase the risk of TPH. The incidence and magnitude of TPH is therefore increased in:  Caesarean section  Complicated and difficult deliveries  External version  Toxaemia  Hypertension  Amniocentesis

ABORTIONS: Rh IMMUNOGLOBULIN Abortions with a gestational age above 14 weeks carry a risk of inducing immunization. Rh IMMUNOGLOBULIN The prevention of RHD is dependent on the fact that, D-positive TPH’s can be neutralized by passively administered anti-D antibody (Rh immunoglobulin) take together with the realization that Rh priming is usually due to a TPH occurring at delivery in the preceeding D-positive pregnancy.

FAILURE RATE: About 1 percent of Rh-negative women become immunized after two D-positive pregnancies despite treatment with Rh immunoglobulin a) Those already primed, even though overt antibody is undetectable by present techniques. b) Large TPH’s before delivery e.g. epileptic or eclamptic patients. c) Extreme sensitivity to the D-antigen: thus small bleeds will produce primary response. d) Large TPHs after delivery more than the amount that can be taken care of by standard dose of immunoglobulin. e) Failure to give the immunoglobulin – patients who slip through the net.

AMNIOCENTESIS AND AMNIOTIC FLUID ANALYSIS. When erythroblastosis fetalis is severe, the amniotic fluid becomes bright yellow from the bilirubin derived from fetal haemolysis. Amniotic fluid bilirubin concentration can be quantified by spectrophotometry by assessing the change in optical density at 450nm ( OD 450) Amniocentesis is started after 24 weeks under continuous ultrasound control.

COMPLICATIONS FOLLOWING INTRAUTERINE TRANSFUSION: 1. Premature labour 2. Pre-labour ruptured membrane 3. Fetal haemorrhage 4. Fetal bradycardia 5. Failure to obtain a sample 6. Increase in maternal Iso immunization by inducing feto-maternal haemorrhage

MANAGEMENT OF RED BLOOD CELL ISOIMMUNIZATION Pregnancies complicated by clinically relevant maternal RBC antibodies are managed in regional blood transfusion centers and fetal medicine units. These centres maintain expertise in the diverse clinical presentation of these cases, follow them non-invasively and perform invasive tests or therapy as the case requires.

Cont. a) Maternal antibody quantification b) Paternal blood group genotyping c) Fetal blood group genotyping d) Ultrasound assessment e) Amniotic fluid spectrophotometry f) Fetal blood sampling g) Fetal blood transfusion

ULTRASOUND ASSESSMENT: The severely anaemic fetus is readily identifiable on scan by the detection of skin oedema, ascites, pleural or pericardial effusions, cardiomegaly and an oedematous placenta. Fetal heart rate changes have been noted with severe anaemia. A sinusoidal pattern with the loss of normal baseline variability of the CTG is highly suggestive of severe aneamia.