Rh NEGATIVE PREGNANCY

1. Rh NEGATIVE PREGNANCY DR.ARCHANAVIKRAM

2. Introduction Landsteiner and S.Weiner – discovered Rhesus system in Rhesus monkeys.

4. There are 5 Rhesus antigens – D, C,c,E and e. • Out of which D antigen is most powerful antigen. • Other antigens like Kell and Duffy antigens. • Anti- kell is very serious.

5. The individual having the antigen on the human red cells is called Rh positive and in whom it is not present is called Rh negative. Incidence :In India 5% to 10% • South India 5% • North India 10% • In general 60% of Rh Positive men are heterozygous and 40% are homozygous

6. . Mechanism of antibody formation in the mother • Antibody formation occurs by iso immunization, which is defined as the production of immune antibodies in an individual in response to an antigen derived from another individual of the same species provided first one lacks the antigen. • This occurs in two stages Sensitisation Immunisation • In ABO - blood groups naturally occurring anti-A, anti-B antibodies are present in the serum.

7. But in Rh group there is no such naturally occurring antibodies. • when Rh positive fetal red cells enter mother’s blood, they remain in the circulation for their remaining life span. • removed by the reticulo-endothelial tissues and are broken down with liberation of antigen which triggers the iso immunization. • Since it takes as long as 6 months for detectable antibodies to develop the immunization in 1st pregnancy is unlikely. • If the feto-maternal bleed is less than 0.1 ml the anti body production sufficient to produce iso immunization is unlikely

8. ERYTHROBLASTOSIS FETALIS

9. The main effect of Rh antibodies is on the baby in the form of hemolytic disease of the new born. • The effected fetal cells are rapidly removed from the circulation by the RE system. Depending upon the degree of agglutination and destruction of the fetal red cells various types of fetal hemolytic diseases appear. • They are Congenital anemia of new born Icterus gravis Neonatorum Hydrops fetalis

10. Congenital anemia of new born: It is the mildest form where hemolysis is going on slowly. The destruction of the red cells continues up to six weeks after which the antibodies are not available for hemolysis. So the neonate may require blood transfusion for its survival. • Icterus gravis Neonatorum: The baby is born alive without evidence of jaundice but soon develops it with in 24 hrs of birth. If Bilirubin level rises to the critical level of 20 mg/100ml then Bilirubin crosses the blood brain barrier to damage the basal nuclei of the brain producing clinical manifestations of Kernicterus and may require exchange transfusion.

11. Hydropsfetalis: • Excessive destruction of the fetal RBC leads to severe anemia, tissue anoxaemia and metabolic acidosis. • These have got adverse effects on the fetal heart, brain and on the placenta. • Hyperplasia of the placental tissue occurs in an effort to increase the transfer of oxygen. • there is damage to the liver leading to hypoproteinemia - generalized oedema, ascites and hydrothorax. • Fetal death occurs sooner or later due to cardiac failure. • Baby is either still born or macerated and even if it is born alive dies soon after.

14. Affection in the mother • Increased incidence of pre-eclampsia, Polyhydramnios • Big size of the baby • Hypofibrinogenemia due to prolonged retention of dead fetus. • Maternal syndrome or mirror syndrome with generalized oedema proteinurea and pruritis. • Repeated still births • Repeated abortions.

15. Feto maternal hemorrhage • Amount of antibody production varies with the amount of fetal RBCs entered into maternal circulation. • Quantity tests for FMH is done by 1.Kleihuer-Betke test 2.Flow cytometry

16. Management – Rh negative women who are sensitized • Assess accurately gestational age by USG • Blood group and typing of partners • Assess Antibody titer – by Indirect Coomb’s test – every 2-4 weeks • Amniocentesis – at a critical titer 1:16 to assess the hemolytic anemia

17. Amniocentesis • To determine the amount of bilirubin which is produced by fetal hemolysis and is secreted by secretions from fetal body. • Spectrophotometricanalysis is used to find out level of bilirubin in amniotic fluid. • Bilirubin causes shift of optical density from linearity. Shift is greatest at 450 nanometer. • Degree of shift at 450 nm called Delta OD [OD 450] indicates degree of hemolysis.

18. Liley’s Chart • Delta OD at 450 should be plotted in Liley chart.[used between 27 to 41 weeks] • I t has X axis –indicates gestation in weeks and Y axis about Delta OD. • It has 3 zones called Low, Mid and High Zone. • Delta OD may fall either of the zones and gives approximate time for time of delivery. • This chart also helpful in preventing iatrogenic preterm delivery.

20. Low zone indicates - mild anemia - • Mid zone –mild to severe anemia • High zone – severe anemia and impending fetal death within 7-10 days.

21. Low zone • Like a normal pregnancy deliver at 38 weeks • Do regular ultrasound and may have to repeat amniocentesis. • Fetal well being tests – NST, CTG, Biophysical profile, Doppler study.

22. Mid and High Zone • High mid and High zone will require CORDOCENTESIS – to assess fetal hemoglobin, hematocrit , platelets and group and type, reticulocyte count fetal transfusion through umbilical vein and delivery. Transfusion of O negative fresh blood if hematocrit is less than 30%.

23. Transfusion • 1. Intra peritoneal • 2. Intra vascular – umbilical vein • Transfusion can be given till fetal hematocrit becomes normal till the risk of prematurity is crossed.

24. Non Invasive tests • A] Ultrasound – to determine hydropic changes like 1. scalp edema 2. Anasarca 3. Effusions 4. Hepato and spleenomegaly 5. Umbilicalomegaly 6. Placentomegaly B] Doppler Velocimetry– Assess peak systolic velocity in middle cerebral artery, aorta, vena cava and umbilical vein. It will be increased in severe anemia. C] CTG – NST D] Biophysical profile

25. Delivery • Low Zone & Low Mid Zone - – Deliver at 38 weeks. • High mid zone High Zone – Deliver at 34 weeks electively by cesarean section . • Arrange adequate amount of O negative fresh blood for the newborn. • Inform the neonatologist prior to the delivery. • Higher tertiary centers is ideal place for delivery.

26. 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.

27. Rh D Immune Globulin and the Prevention of Rh D Alloimmunization • antibody-mediated immune suppression • the amount of Rh D immune globulin necessary to prevent alloimmunization varies according to the size of fetomaternal hemorrhage: • 300 µg of Rh D immune globulin for exposure to 10 mL of fetal blood • 20 µg of Rh D immune globulin for exposure to 1 mL of fetal erythrocytes • 10 µg of Rh D immune globulin for 1 mL of whole fetal blood

28. Postpartum Alloimmunization Prophylaxis • administration of Rh D immune globulin • a dose of 300 µg • within 72 hours of delivery • if for some reason Rh D immune globulin prophylaxis does not occur within 72 hours after exposure, susceptible Rh D-negative women should be treated up to 14 to 28 days.

29. Management of the Unsensitized Rh-Negative Pregnant Woman • obtaining another antibody screen before administration of Rh D immune globulin, in • After delivery, another antibody screen is routinely performed. If negative and the newborn is Rh D positive or weak D positive, women should be given 300 µg of Rh D immune globulin including antepartum prophylaxis

30. Management of the Unsensitized Rh-Negative Pregnant Woman • because a small number of deliveries (0.1% to 1.0%) result in a fetomaternal hemorrhage greater than 30 mL : • a screen for “excessive” fetomaternal hemorrhage should be performed routinely • use the erythrocyte rosette test • If positive :the volume of fetal red cells in the maternal circulation can be calculated by using the Kleihauer-Betke test ,if >30 ml : • an additional 10 µg of Rh D immune globulin should be administered for each additional milliliter of fetal blood.

31. Management of the Unsensitized Rh-Negative Pregnant Woman

32. Management of the Unsensitized Rh-Negative Pregnant Woman • First-trimester complications result in fetomaternal hemorrhage sufficient to alloimmunization : • spontaneous miscarriage, • elective abortion • ectopic abortion • women with threatened first-trimester miscarriage • only occasionally is associated with alloimmunization

33. Management of the Unsensitized Rh-Negative Pregnant Woman • patient who has antepartum bleeding or suffers an unexplained second- or third-trimester fetal death: • should receive Rh D immune globulin prophylaxis • be evaluated for the possibility of massive fetomaternal hemorrhage.

34. Management of the Unsensitized Rh-Negative Pregnant Woman • Several procedures also may result in fetomaternal hemorrhage sufficient to cause alloimmunization : • chorionic villus sampling (CVS) • amniocentesis • external cephalic version.

35. Management of the Unsensitized Rh-Negative Pregnant Woman • For first-trimester pregnancy complications and procedures : • 50 µg of Rh D immune globulin is protective. • Beyond 12 weeks, a full 300-µg dose is indicated, even in the absence of detectable hemorrhage.