One Seminar on rh negative pregnancy.pptx

Rh negative pregnancy

1. Rh Isoimmunisation and recent development PRESENTED BY— MODERATOR— DR ABHIJIT NATH DR SANGHAMITRA DAS PGT ASSISTANT PROFESSOR

2. Isoimmunization: Production of antibodies in response to an antigen derived from another individual of the same species. Rh isoimmunization: Maternal antibody production in response to fetal red blood cell Rh antigen , when mother is Rh - ve and fetus is Rh + ve . Antibodies once produced , remains throughout the life.

3. Inheritance of Rh group Father Mother Father Homozygous Rh + ve Rh — ve Heterozygous Rh+ve DD dd Dd Dd Dd FETAL BLOOD GROUP Dd dd

4. Pathogenesis of Rh isoimmunization Normally foetal red cells carrying Rh antigen do not mix with maternal blood. However some circulating foetal RBC can enter maternal circulation stimulating an immune response due to IgM or complete antibody which being a bigger molecule cannot cross the placenta and does not affect the fetus . The first immune response in the mother is the formation of IgM antibodies . Subsequent antigen exposure leads to an increased response and IgG formation in the mother. IgG being a tiny molecule which cross the placenta and destroy the fetal red blood cells (RBC) leading to reticulocytosis , anemia, heart failure and hydrops . There is no effect on the Rh – ve fetus due to absence of Rh antigen on red cell surface.

5. The first child is not affected because… Feto -maternal hemorrhage occurs late in pregnancy or during delivery and antibody response slowly (over 2–6 months) The initial maternal immunoglobulin M (IgM) antibody are formed, which do not cross the placenta.( molecular weight that is too large to cross the placenta )

6. Factors deciding maternal response ( why all Rh – ve mother do not get immunised)… Size of inoculum of feto -maternal haemorrhage : As RhD antigen is very potent , a volume of 0.1 ml blood can stimulate the production of antibodies. Magnitude of mother’s response : only one third woman are non responders. Concurrent ABO incompatibility between mother and fetus : the risk of sensitisation is less if it is incompatible with mother’s blood group. When ABO incompatible fetal red cell enter the mother’s blood, they quickly combine with naturally occurring anti A and anti B agglutinins and are neutralised and cleared by them

7. Risk of isoimmunization and after anti D after 1 st Rh positive pregnancy ABO COMPATIBLE (80%) 16% ABO INCOMPATIBLE (20%) 1.5 – 2% POSTPARTUM ANTI D ONLY 2% ANTI AND POSTPARTUM ANTI D 0.1%

8. Factors predisposing to feto -maternal haemorrhage and sensitization Spontaneous abortions Induced abortions (medical Termination of pregnancy) Ectopic pregnancy Molar pregnancy Threatened abortion: (only if the bleeding repeated, heavy or associated with abdominal pain). Invasive prenatal testing( amniocentesis, chorion villus sampling & cordocentesis) Antepartum hemorrhage Intrauterine fetal demise Manual removal of placenta External cephalic version Following vaginal and cesarean delivery

9. PREVENTION OF RH IMMUNIZATION

10. CURRENT RECOMMENDATIONS FOR IMMUNOPROPHYLAXIS DURING PREGNANCY Prophylactic anti D should be offered to unsensitized RhD negative woman at 28 weeks of gestation . Following birth , if the infant is Rh positive all Rh negative mother who are known to be sensitized should receive anti D immunoglobulin within 72 hours of delivery .( LEVEL A evidence grade IA recommendation ACOG 2017). As the half life of anti D lasts for 24 days and protective effect is about 6 weeks, post partum anti D is required despite antepartum prophylaxis. Although risk of alloimmunization is low, RhD immunoglobulin should be considered in cases of 1 st trimester misscarrige , specially in late 1 st trimester. ( Level C evidence ). This is the new change. Earlier anti D was not prescribed in 1 st trimester abortions. Dose prior to 20 weeks is 50 ug or 250 IU.

11. Contd …. Should be given to all cases of ectopic pregnancies with Rh negative status of the woman Should be given to all cases of MTP with Rh – ve woman , either medical or surgical. Following delivery of IUD fetus Rh negative woman with continual uterine bleeding, eg. Placenta previa. They should be given a minimum dose of 250 IU if <20weeks and 500 IU if >20 weeks . When in doubt, it is better to give anti D as it causes no harm. But not giving in indicated cases may have serious consequences. Woman undergoing ligation( Tubal Ligation or BLT) should also be given as they can come back for tubal recanalization later on.

12. EARLY PREGNANCY LATE PREGNANCY THREATENED ABORTION MISCARRIGES MTP(MEDICAL OR SURGICAL) ECTOPIC PREGNANCY MOLAR PREGNANCY INVASIVE PROCEDURES(CVS) ABDOMINAL TRAUMA MULTIFETAL REDUCTION OTHER UTERINE PROCEUDERS LATE MISCARRIGES AMNIOCENTESIS CORDOCENTESIS APH ECV MROP IUD ROUTINELY AT 28 WEEKS AFTER DELIVERY WITHIN 72 HRS INDICATIONS OF ANTI D IMMUNOPROPHYLAXIS

13. SCREENING AND QUANTIFICATION OF FETO-MATERNAL HAEMORHHAGE ROSETTE TEST KLEIHAUER BETKE TEST Kleihauer – Betke test : it is screening test should be performed within 2 hours of delivery to identify the amount of fetal–maternal hemorrhage. Fetal erythrocyte contain Hb F which is more resistant to acidic solution ( citric acid phosphate buffer ) or alcohol denaturation than adult Hb A , so after exposure to acid only fetal cells remain, The acid is able to elute adult hemoglobin, but not fetal hemoglobin, from the red blood cells. As a result, on subsequent staining the fetal cells appear rose pink in color, while adult red blood cells appear as “ ghosts ’. Should be performed before administration of anti-D  

14. DETERMINATION OF VOLUME OF FMH AND DOSE OF ANTI D TO BE GIVEN 1 ST METHOD VOLUME OF FMH = PERCENTAGE OF FETAL RBC x 50 NO. OF VIALS OF ANTI D REQUIRED = VOLUME OF FMH / 30 ALTERNATE METHOD FMH OF 4ML FOETAL BLOOD= 80 FOETAL RBC/ 50 LOWER POWER FIELD = DOSE OF ANTI D REQUIRED EVERY 10 ug OF ANTI D REQUIRED FOR 0.5ml OF FOETAL RBC OR 1ml OF WHOLE FOETAL BLOOD

15. EFFECTS OF RH ISOIMMUNIZATION FOETAL EFFECTS IMMUNE HYDROPS ICTERUS GRAVIS NEONATRUM CONGENITAL HAEMOLYTIC ANAEMIA MATERNAL EFFECTS PRE-ECLAMPSIA POLYHYDROMNIS MACROSOMIC FETUS COAGULOPATHY HYPOFIBRINOGENEMIA PPH

16. 1. IMMUNE HYDROPS This is the most serious form of Rh hemolytic disease (HDFN). Of all cases of fetal hydrops: 90% are due to a non‐immune cause 10% have an immune etiology There is increased extramedullary hematopoiesis in spleen and liver causing there dysfunction Cardiomegaly and pulmonary hemorrhage. Fluid collection in fetal thorax, abdominal cavity and skin is the hallmark of hydrops . Placenta is large, oedematous, boggy with large prominent cotyledons and oedematous villi Ascites, hepatomegaly and splenomegaly may lead to severe dystocia. Anaemia <7g/dl

17. 2.CONGENITAL ANEMIA OF NEWBORN: mildest form( Hb: 9-10 g/dl) About 50% extramedullary hematopoiesis leading to liver and spleen enlargement 3.ICTERUS GRAVIS NEONATORUM: moderate(Hb:7-12 g/dl) about 25-30% unconjugated hyperbilirubinemia critical level of 20mg/100ml bilirubin: kernicterus DEPOSITION OF BILLIRUBIN IN CNS AND 8 TH CRANIAL NERVE Features: loss of moros reflex, posturing, poor feeding bulging anterior fontanelle high pitched cry, seizures sensorineural hearing loss

18. USG FINDINGS :: Fetal drops, fetal ascites , scalp and skin edema , pericardial and pleural effusion , and hepatosplenomegaly. Maternal X Ray :: BUDDHA POSITION

19. MANAGEMENT OF PATIENT FOUND TO BE RH NEGATIVE

20. Detailed history Husband blood group In primigravida : previous history of blood transfusion In a parous woman: a detailed obstetric history. History of fetal affection in the form of stillbirth or neonatal death due to severe jaundice following one or two uneventful births is quite suggestive. Previous history of hydrops fetalis History of receiving anti-D immunoglobulin in previous pregnancies Current pregnancy sensitizing events In Rh negative isoimmunization there is progressive worsening obstetric history with 1 st baby being usually normal

21. INVESTIGATIONS Blood group and Rh of the husband: If Negative : No further testing as the baby will be also Rh – ve and the pregnancy will be managed as normal. If positive : consult with a pathologist to determine the paternal genotyping (homozygous or heterozygous) → homozygous of Rh antigen → fetus is likely to be affected 100 → heterozygous of Rh antigen → fetus is affected only in 50% cases.

22. Cell-free fetal DNA : Non-invasive prenatal determination of fetal Rh D , from maternal blood samples one at 14 weeks using a conventional PCR for Y chromosome , it can be used to prevent unnecessary prophylaxis. → if an antigen-negative fetus is found, no further testing is warranted .

23. Indirect coomb's test or Rh antibody titer T he maternal serum is incubated with Rh-positive erythrocytes and Coomb’s serum (antiglobulin antibodies). The red cells will agglutinate if Rh antibodies are present in the maternal plasma .

24. MANAGEMENT According to Maternal indirect Coomb's test if: Rh-negative unsensitized pregnant woman( indirect coomb’s test negative) Rh-negative sensitized pregnant woman( indirect coomb’s test positive)  

25.   Group 1: Management of the Rh-negative, unsensitized pregnant woman( Coomb’s test negative) The goal during pregnancy is to keep her from becoming sensitized. If the ICT is negative, the mother is not yet sensitized . The test is to be performed at 1 st antenatal checkup. If negative, the test is repeated at 28 and 34 weeks of gestation in a primigravida and monthly in a multigravida after 28 weeks. Administer anti D 300 ug at 28 weeks . If ICT is persistently negative , the pregnancy can be continued up to 40 weeks. She is not allowed to go beyond the EDD . At delivery , early cord clamping is done and cord blood to be send for Hb, bilirubin and Direct Coomb’s test .

26. Group 2: Management of the Rh-negative, sensitized pregnant woman( Coomb’s test positive) Indirect Coombs’ test (ICT) positive at any ANC visit. estimation of ( Anti-D antibody) titer If the ICT is positive, it should be repeated in dilution to find out the antibody titre. The CRITICAL TITRE is 1:16 If the titre is >1:16 , repeat every 2 weekly( from 28 weeks until delivery or when there is rising titer) The titer < 1:16, expectant management until 38 weeks . If it becomes ≥1:16, investigate for fetal anemia every week by MCA Doppler at 1-2 week interval

27. MIDDLE CEREBRAL ARTERY PEAK SYSTOLIC VELOCITY (MCA-PSV) Doppler measurement of peak systolic velocity in foetal middle cerebral artery is an appropriate non invasive method to monitor pregnancies complicated by red cell alloimmunization.( Level A recommendation ACOG 2017) The PSV of middle cerebral artery is increased due to hypoxia , brain sparing high cardiac output, and decreases in blood viscosity due to haemolysis and anaemia. MCA PSV DEGREE OF ANAEMIA 1- 1.29 MOM Mild anaemia 1.29- 1.5 MOM Moderate anaemia >1.5 MOM Severe anaemia

28. Doppler study : Middle cerebral artery (MCA)-peak systolic velocity (PSV) is the mainstay to assess fetal anemia. Begin serial MCA Doppler assessments at 18 weeks of gestation Repeat Middle cerebral artery (MCA)-peak systolic velocity (PSV) at 1- to 2-week interval.

29. If MCA-PSV: ≤1.5 MoM for gestational age , follow the same protocol for antenatal monitoring and delivery, Evaluated every 2 weeks from at least 32 weeks until delivery for fetal well-being (nonstress tests, modified biophysical profile ,Doppler assessment.) A MCA-PSV >1.5 MoM for gestational age : predicts moderate to severe fetal anemia. indication for (cordocentesis and intrauterine fetal transfusion for a fetal hematocrit of less than 30%).

30. Amniocentesis: it is invasive and increases the risk of sensitization . By using The spectrophotometry ;In presence of bilirubin there is a “ deviation bulge ” at Δ OD450 is plotted in Liley’s chart and accordingly the management is decided. Indications: 1. antibody titre >1:16 2. past history of isoimmunization 3. heterozygosity of father to know fetal affection Timing: In primigravida and without past history it is performed at 30-32 weeks and again after 3-4 weeks. In Previous Rh immunized baby it should be performed 10 weeks before the last stillbirth or fetal affection as fetal anemia occurs earlier. However it should not be done before 20 weeks.

31. INTERPRETATION ZONE 1 :: Fetus has mild disease or not affected and pregnancy can be taken to term ZONE 2 :: Fetus is at moderate risk. It is divided into lower zone 2 and upper zone 2. expected Hb in lower zone 2 is 11g/dl to 13.9g/dl expected Hb in upper zone 2 is 8g/dl to 10.9g/dl amniocentesis should be repeated in 2 weeks and If the value rises cordocentesis to be done. if hematocrit is <30% ,intrauterine transfusion is indicated to raise hematocrit to 45% . fetus likely to require delivery at 34 weeks. ZONE 3 :: fetus is severely affected and Hb is <8g/dl without intervention fetus will die in 7-10 days if pregnancy is >34 weeks delivery is indicated if pregnancy is <34 weeks urgent cordocentesis is done to know Hb, hematocrit and blood group. in the same setting intrauterine transfusion is done to increase the hematocrit to 40%

32. USG GUIDED CORDOCENTESIS Indication: Elevated peak systolic MCA Doppler velocities (>1.5 MOM). Benefits : to detect fetal blood grouping, Rh type hematocrit (accurate Assessment of fetal anemia) direct Coomb’s test reticulocyte count total bilirubin level Fetal hematocrit value <15% is associated with hydrops

33. Time and mode of delivery   Time: In mild affection , the pregnancy may be continued up to 38 weeks and then termination is to be done. In severe affection : terminate the pregnancy around 34 weeks after maternal steroid administration.

34. Mode of delivery   : Vaginal delivery: Amniotomy is quite effective, if termination is done near term. Vaginal prostaglandin gel (PGE2) could be used to make the cervix ripe. Cesarean section : In cases when termination has to be done prematurely (34–37 weeks), the cervix will be unfavorable and considering the severity of affection and urgency of termination.  

35. Fetal blood transfusion is lifesaving in a severely anemic fetus (hematocrit <30%, Hb<10 gm/dL) that is too premature . the aim is to restore hemoglobin levels preventing hydrops or death. It can be started at 18 weeks and repeated at intervals of 1–3 weeks up to 32–34 weeks.it performed only in fetal medicine units.  

36. Care during delivery to minimize the risk of feto -maternal hemorrhage During labor Not to give prophylactic ergometrine during second stage of labor. Gentle handling of the uterus during the third stage. If the manual removal of the placenta is required, it should be performed gently During cesarean delivery To avoid blood spillage into the peritoneal cavity. To avoid routine manual removal of the placenta. Early cord clamping .

37. Summary of Recommendations and Conclusions ::: ACOG UPDATES(2017)

38. Level A:: The following recommendations are based on good and consistent scientific evidence.. Prophylactic anti-D immune globulin should be offered to unsensitized Rh D-negative women at 28 weeks of gestation. Following birth, if the infant is confirmed to be Rh D positive, all Rh D-negative women who are not known to be sensitized should receive anti-D immune globulin within 72 hours of delivery

39. Level B The following recommendations are based on limited or inconsistent scientific evidence.. Administration of Rh D immune globulin is recommended with all invasive diagnostic procedures such as chorionic villus sampling or amniocentesis in Rh D-negative women when the fetuses could be Rh D positive.

40. Level C The following recommendations are based primarily on consensus and expert opinion.. External cephalic version (regardless of success) is associated with a 2–6% risk of fetal–maternal hemorrhage, and anti-D immune globulin is indicated for unsensitized Rh D-negative patient. It is reasonable to administer anti-D immune globulin to Rh D-negative women who are suspected of molar pregnancy and who undergo uterine evacuation. Although the risk of alloimmunization is low, the consequences can be significant, and administration of Rh D immune globulin should be considered in cases of spontaneous first-trimester miscarriage, especially those that are later in the first trimester

41. Because of the higher risk of alloimmunization, Rh D-negative women who have instrumentation for their miscarriage should receive Rh D immune globulin prophylaxis Rh D immune globulin should be given to Rh D-negative women who have pregnancy termination, either medical or surgical . Administration of Rh D immune globulin for all cases of ectopic pregnancy in Rh D-negative women is recommended. Anti-D immune globulin is recommended for Rh D-negative women who experience antenatal hemorrhage after 20 weeks of gestation . Anti-D immune globulin should be administered to Rh D-negative women who have experienced abdominal trauma . Anti-D immune globulin should be administered to Rh D-negative women who experience fetal death in the second or third trimester.

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