2. William 2001

3. I. Fetal anemia II. Fetomaternal hemorrhage III. Isoimmunisation IV. Immune hydrops V. Management VI. Pervention VII. Large fetomaternal Hge

4. Normal fetal Hb% > 35 weeks = 17 gm/dL Fetal anemia = < 14 gm/dL Causes:  Placenta cut or torn  Fetal vessel perforation  Raising the neonate above the abdomen of his mother before clamping the cord Delayed clamping of the cord  ↑ of fetal Hb by 20%

5. Common in all pregnancies Rarely > 30mL = 0.3 – 0.6% Benefit in fetal karyotyping Keihauer – Batke test: Identify fetal RBCs by acid elusion  darker than maternal RBCs Rosette test: Maternal blood + anti D Ab+ indicator  fetal blood surrounded by Abs More accurate in hemoglobinopathy

6. Severe anemia  sinusoidal FHR not pathognomonic  evaluate immediately Chronic anemia may  normal FHR Significant acute /chronic Hge may  Neurological impairment due to: Hypotension  ↓ perfusion  Ischemia  CNS infarction Obstetric management may not improve CNS damage

7. Large fetal Hg may  fetal death in 5% and the cause may be unknown e.g. chorioangioma Placental abruption : usually  mild Hg except if traumatic Quantification of volume of blood loss:  influence management  Determine the dose of Anti D Ig

8. Fetal red cells = maternal Hct X maternal blood volume X % of fetal cells in Kleihauer - Batke test ÷ neonatal Hct Causes of fetal-to-maternal Hg:  Early abortion  Elective abortion

9.  Ectopic  Amniocentesis  Cordocentesis  Chorionic villous sampling  Antepartum trauma  Placental abruption  Fetal demise  Manual placental extraction  External version

11.  ABO blood group  CDE blood group  Other blood groups  Kell antigen  Other antigens

12. History: 1892 Ballantin  hydrops fetalis 1932 Anemia and reticulosis are present in hydrops fetalis 1940 Landsteiner & Weiner  Rh factor 1941 Levein  hydrops is caused by maternal isoimmunisation by Rh –ve fetus 1961 Anti Rh

13. - Fetal blood contain > 400 Ags most of them are insignificant - Most people inherit at least 1 Ag from their fathers that is lacking in their mothers - Isoimmunisation of an Rh –ve pregnant woman occur as a result of: Rh +ve fetus Blood transfusion

14. Isoimmunization is rare because:  Variable Ag amounts  Variable antigenicity  Maternal immune respond  ↓ placental passage  ABO incompitability  destruction of fetal RBCs

15. Not all isoimmunization  hydrops 2% of all women are isoimmunized 6 months postpartum % of isoimmunisation with Rh-ve ABO compatible fetus: 2% at delivery 7% 6 months postpartum 7% next pregnancy Total = 16%

16. ABO blood group incompatibility: - The most common cause of hemolytic disease of the neonate - 20% of all fetuses are ABO incompatible only 5% of them are clinically affected -  Mild anemia & ↑ reticulocytes - No erythtoplastosis - Treated by phototherapy

17. Difference from Rh incompatibility:  Affect 1 st baby  Milder ( Ig M does not pass placenta)  Rarely progressive  Affect African Americans Criteria of ABO incompatibility :  1 st day jaundice  Mother O, fetus A,B,or AB group  Anemia, ↑ reticulocytes

18. Management of ABO incompatibility: Same as Rh isoimmunization but:  No amniocentasis  No blood transfusion Because there is no hydrops CDE blood group: 5 types: c, C, e, E, D

19. - D is +ve if present and –ve if absent - D isoimmunisation is the most common isoimmunization - D –ve pregnant women are sensitized if their fetus is D +ve - CDE genes are inherited independent on other blood groups - They are located on chromosome 1

20. Geographic distribution of D +ve populations:  Native Americans and Chinese 95%  African Americans 92%  Caucasians 87%  Basque 76%

21. Other blood groups: % = 1 - ¼  Lewis blood group  mild jaundice starts weeks postpartum - 74% D, C, c, E & e antigens - Recently Rh isoimmunization is ↓ due to Anit D treatment - Now Rh = 40% Other Ags = 60%

22. Kell antigen: - Caucasian kell +ve = 91% - Isoimmunisation occur by pregnancy or blood transfusion -  Much earlier and more severe anemia which can not be predicted by:  Maternal titer  AF bilirubin = mild/moderate

23. - May  fetal death inspite of: Blood transfusion Normal AF bilirubin - Hemolysis ↓ due to: ↓ RBCs ↓ bilirubin - If maternal anti-Kell Ab titer ≥ 1 : 8  Cordiocentesis because AF bilirubin is out of proportion to anemia

24. Other antigens: Kid Ag: Jk a –ve = 25% Jk b –ve = 25% Jk a - b +ve = 50% Duffy Ag: Fy a – b –ve in some blacks C Ag: Most common Ag after D  Moderate to severe hemolysis

26.  Immune hydrops  Hyperbilirubinemia  Mortality  Identification of isoimmunization  Fetal Rh genotype

27. RBCs hemolysis by isoimmunization  Hyperplasia of BM  Hyperplasia of extramedulary sites: Liver Spleen Liver: Fatty degeneration Deposition of hemosidrine Large canaliculi with bile

28. Heart: HF Lungs: Hge - immature When fluid accumulate in subcutanous tissues  hydrops fetalis Definition: Abnormal fluid in ≥ 2 sites: Ascitis – oedema – pleural effusion

29. Placenta:  Enlarged cotyledons  Odemotus villi  Boggy Fetus:  Dystocia due to:  Hepatospleenomegaly  Odema

30. Heart: HF  hypoxia  capillary leakage Extramedulary hyperpleasia: Hepatic parynchemal distruction  portal HTN  umbilical vein HTN Liver disease:  ↓ protein  ↓ colloidal osmotic P

31. Study: Cordiocentesis in hydrops:  Hb = < 3.5 gm/dL  Plasma protein = < 2 SD  AF plasma protein ↑ The degree of anemia affect the degree of ascitis and made worse by ↓ plasma proteins

32. Capillary endothelial damage:  Capillary leakage  ↓ protein Study: ↑ Umbilical vein pressure is due to cardiac dysfunction and not portal HTN Sinusoidal FHR = impending death

33. Neonate:  Pale  Edematous  Limp  ↑ need for resuscitation  Dyspnea  Collapse  Hepatospleenomegaly  Petechiae  ecchymosis

34. Less affected fetuses are born normal  jaundice within hours If untreated  kernicterus = CNS damage affecting basal ganglia Mortality: Reduced dramatically due to:  D Ig  Blood transfusion  Induction of labor

35. Maternal serum Abs: Unbound to RBCs  disappear within 1 – 4 months  Indirect Coombs T Fetal serum Abs: Bound to RBCs  hemolysis  Direct Coombs test Neonatal blood group: Inaccurate because D-Ag may be coated with D-Ab

36. If maternal Abs are present:  Ig G or Ig M ? (Ig M can not pass the placenta) If Ig G  antibody titer: < critical value 1 : 16  repeat > critical value 1 : 16  evaluate Critical values for other Ags: Kell ≥ 1 : 8 C, E ≥ 1 : 32

37. The presence of Abs in the mother does not mean that:  The fetus is +ve  He will be affected Amnestic response: = ↑ Ab titer + Rh –ve fetus Because ½ of adult males are heterozygous for D Ag  ¼ of women at risk are Rh -ve

38. Estimation of fetal genotype: The father is tested for:  Blood group  Most likely arrangement of his CDE genes = presumed genotype based on the most common arrangement of genes in men of his race If the father is white:  94% chance to be heterozygous  47% chance of having D –ve fetus

40.  Amniotic fluid evaluation  Expanded Liley graph  Fetal blood sampling  Subsequent child development  Other methods to ↓ hemolysis  Delivery  Exchange transfusion  Prevention  Routine antepartum anti-D

41. ↑ Hemolysis  ↑ AF bilirubin  ↑ anemia Since AF bilirubin is very small  measured by a continuously recording spectrophotometer and is demonstrable as a change in absorbance at 450 nm ( ∆ OD 450 ) then the results are plotted on Liley graph (1961)

42. Zones of Liley graph: Zone 1 = mild anemia = 14 gm % Zone 2 = moderate/severe anemia = 13.9 – 8 gm % Zone 3 = severe anemia = < 8 gm % = death in 7 – 10 days

43. If the results are in zone 1 or 2: repeat in 1 – 2 weeks and draw a line between the 2 results: - If the trend of the line is:  Decreasing  Parallel to the lines of the graph = unaffected fetus or stable  repeat / 2 – 3 weeks until transfusion or delivery

44. - If the trend of the line is: - Rising within the zone - Rising to zone 3 = Unstable  Managed as zone 3 If the results are in zone 3: = Severe anemia  Immediate blood transfusion or delivery

45. Expanded Liley graph: Since Liley graph was made for fetuses > 27 week, expanded graph back to 18 – 20 weeks is inaccurate, because AF bilirubin < 25 weeks is high So, in cases of:  Hydrops < 25 weeks  Severe anemia < 25 weeks It’s better to do cordocentesis

46. Cordocentesis is risky # amniocentesis Advantages: blood typing Recently  amniocytes for Rh typing:  100% accurate  99.7% sensitivity  94% specificity  Also for C,E, Kell & other Ags

47. If fetus is Rh–ve  no further tests If amniocentesis  possible anemia U/S  hepatomegaly NST/BPP  fetal stress  immediate blood transfusion or delivery

48. Tests of cordocentesis:  Hb%  HTV  Indirect Coombs titer  Reticulocyte count Indications of IU blood transfusion:  Hb 2 gm/dL < mean of normal Hb in the fetuses in the same GA  HTV 30% = 2 SD < mean at all GAs

49. Methods of intrauterine blood transfusion: Intraperitoneal - intraumbilical Subsequent child development: 90% normal – delayed - abnormal Other methods to ↓ hemolysis:  Plasmapheresis  Large dose of promethazine  Corticosteroids for immunosuppresion  D +ve erythrocyte membrane capsules All are ineffective

50. Aim: = Delivery at or near term Monitor by fetal wellbeing tests If the fetus is very immature:  Intrauterine blood transfusion If near term:  deliver  If lungs are mature  induce labor  If compromised fetus  CS

51. If the mother is sensitized cord blood sample for:  Hb%  Direct Coombs test If overtly anemic  exchange blood transfusion by O –ve fresh blood If not overtly anemic  the need for blood transfusion is determined by:  The rate of bilirubin ↑  Maturity  Complications

52. By anti D Ig = 7S Ig G = 300 μg D Ab Given within 72 hours of delivery To none sensitized mothers only Given after: abortion, mole, ectopic, miscarrage Rate of sensitization without D Ig:  2% of spontaneous abortion  5% of elective abortion  6% of amniocentesis

53. At 28 weeks For all Rh –ve pregnant women ↓ isoimmunization from 1.8 % to 0.07% In the past : 2 nd injection 34 weeks ½ life of Ig : = 24 hours  Reduce titer by time  weak +ve indirect Coombs test

54. Now the 2 nd injection is given if:  Fetomaternal Hg occurs  Amniocentesis > 3 weeks from the 1 st injection The 2 nd dose is against:  15 mL of D +ve RBCs  30 mL of fetal blood

55. Sometimes Ab cross the placenta  Weakly +ve direct Coombs test Recognized by:  No anemia  No hyperbilirubinemia Risk of transmission of diseases:  HIV  inactivated by the factory  hepatitis  patients are excluded from donation  very low risk

56. Rarely 1 dose of Anti D Ig is insufficient = Very rare occur 1 : 1250 deliveries To avoid this all Rh –ve women should be tested after delivery by Kleihaure - Batke or rosette tests Number of ampoules: = fetal blood/15

57. D u antigen: A variant of D antigen: D u +ve & D u -ve Less antigenic Treated as Rh D –ve Maternal to fetal Hg: Very rarely an Rh –ve female fetus is sensitized inutero by her mother = Grandmother theory No need for Anti D prophylaxis