1. Red Cell Alloimmunization in Pregnancy Case Presentation
Michael McNamara, DO, FACOG
Sanford Maternal Fetal Medicine

2. Allo-Immunization in Pregnancy
Objectives
Understand the problem of red cell alloimmunization during pregnancy
Diagnosis of red cell alloimmunization
Surveillance and treatment of patient with red cell alloimmunization

3. Disclaimer
No conflicts to disclose

4. Red Cell Alloimmunization
Maternal immune system makes antibodies against fetal red cell antigen (paternal origin)
Common etiology for immune hydrops
Incidence 6.7/1000 (2002 data)
Most commonly due to Rh disease, D antigen

5. Etiology Mom exposed to foreign red cell antigen
Fetal blood (paternal origin)
Blood transfusion (most often Kell)
Mom develops antibodies
Antibodies IgG or IgM
IgG small enough to pass through placenta
Attacks (destroys) fetal red blood cells
Fetal anemia, subsequent hydrops

6. Anemia Results in release of erythroblasts into fetal circulation
Increased cardiac output
Tissue hypoxia
Hydrops (fluid in two or more fetal compartments)
Ascites
Skin edema
Pleural effusions
Pericardial effusions
Polyhydramnios
Seen when fetal hemoglobin 7-10 g/dL below normal

7. Hydrops

8. Rh Alloimmunization D antigen on short arm of chromosome 1
Absence (Rh-) homozygous
15% Caucasian European
30% Spanish from Basque region of Spain
8% African American, Hispanic (Mexican, South American)
< 1% native American, Eskimo, Chinese, Japanese

9. Rh and Rhogam Prevention of Alloimmunization
Blood type incompatability
Passive immunization
300 ug protects against 30 ml fetal blood
Given 28 weeks and following delivery (if fetus Rh +)
Quantify amount (Rhogam) based on testing of amount of fetal blood in maternal blood

10. Kleihauer-Betke Test

11. Evaluation of Red Cell Alloimmunization
Maternal antibody titers
Fetus
Ultrasound

12. Antibody Titers Degree that Mom is responding to fetal antigen
Critical titer – titer with significant risk for fetal hydrops
Usually between 1:8 and 1:32 for D antibodies
Use same for other red cell antibodies except Kell

13. Fetal Evaluation Paternal testing Chorionic villus sampling
Amniocentesis
Cell free DNA
Fetal blood typing

14. Ultrasound Hydrops – abnormal fluid in two or more compartments
Pleural effusion, pericardial effusion, ascites, skin edema, polyhydramnios
Doppler studies
Middle cerebral artery (MCA)doppler studies

15. Fetal Surveillance
Titers checked monthly to 24 weeks, then every two weeks for critical titer
Once critical titer is reached (titers checked monthly until 24 weeks and then every 2 weeks) further evaluation needed
Amniocentesis
Umbilical vein sampling
Ultrasound

16. Surveillance Amniocentesis (serial) Cord Sampling
Monitor bilirubin in amniotic fluid
Amount (OD 450) vs gestational age
Plot on Liley graph (curve) to see if fetus anemic
Cord Sampling
1-2% of fetal loss
50% chance for increasing hemolytic response

17. Liley Curve

18. Surveillance Ultrasound
Middle cerebral artery Doppler blood flow (MCA)
Anemia increases blood flow (velocity), less cells
Plot the peak systolic velocity against gestational age
1.5 multiples of the median (MoM) or greater suspect for fetal anemia, needing fetal blood sampling, transfusion

19. MCA Peak Systolic Velocity

20. MCA Doppler

21. MCA Dopplers Non invasive Sensitivity 88%
Negative predictive value of 89%

22. Management Identify titer-1st episode usually no consequence for fetus
Paternal status / fetal status
Titers monthly until 24 weeks, every two weeks thereafter
Critical titer – MCA Dopplers every 1-2 weeks
Abnormal MCA – fetal umbilical vein sampling, transfusion

23. Next Pregnancy High risk if previous pregnancy
Fetal loss due to hydrops
Fetal transfusion
Neonatal exchange transfusion

24. Case 34 year old Gravid 2, para 1 Presented in consult at 19+ weeks
D antibody titer of 1:64
Previous cesarean x 1
Drug use history, currently on suboxone

25. Fetus Fetus with D antigen? Father not available for screening
Normal anatomy except echogenic focus in heart (soft marker for trisomy 21)
Normal MCA Doppler
Mom desired amniocentesis for karyotype and assess fetal Rh status

26. Patient
Normal karyotype
Fetal + D antigen
Normal MCA doppler

27. Graph for MCA Doppler

28. Patient
33+5 weeks
Ultrasound showing elevated MCA peak systolic velocity Doppler at 2.0 MoM
Fetal ascites, polyhydramnios of 30.5 cm

29. Fetal weight graph

30. Gestational Age, MCA Dopplers
Doppler (MoM)
20+5
< 1.0
23+5
1.1
25+2
28+5
1.13
30+5
1.11
32+5
1.24
33+5
2.0

32. Patient Admitted, antenatal steroids
Delivery at 33+6 weeks repeat cesarean
Earlier in pregnancy, consideration for umbilical vein sampling and RBC transfusion
Uneventful post operative course