1. Fetal transfusion and neonatal exchange transfusion – trends, indications and methods
A/Prof Helen Liley
Newborn Medicine – Mater Mothers’ Hospital
Mater Research – The University of Queensland
Australia

2. Haemolytic disease of the fetus and newborn can have diverse outcomes, including lifethreatening hydrops and brain damage due to kernicterus. In many parts of the world, the severe adverse outcomes have gone from being common to being a rare occurrence. Nevertheless, the global burden of disease from haemolytic disease and other causes of fetal anaemia remains high.

3. Levine: Rh antigen cause of HDN
Darrow: fetal red cells stimulate Ab in mother, then Ab X placenta and destroys baby’s cells:
propose Ab to fetal Hb
DIAGNOSIS AND TREATMENT
Early delivery, exchange transfusion
1961: Liley chart: disease assessment
1963: Liley intrauterine transfusion
PREVENTION Antenatal immunoprophylaxis
DIAGNOSIS
Rh proteins and genes sequenced
Louyse Bourgeois describes twins with hydrops and kernicterus
1609
1932
1938
1940
1941
1943
1960s
1970s
1980s
1990s
Diamond et al:
Hydrops and kernicterus were different aspects of same disease: erythroblastosis fetalis .
Cause then unknown.
PREVENTION Rh Ig experiments
Gorman, Freda, Pollock (USA)
Clarke, Finn
(UK)
TREATMENT
Intravascular intrauterine transfusion
Landsteiner and Weiner discover “Rhesus factor”
Fisher and Race: describe CDE system for Rh
ASSESSMENT
MCA Doppler
There have been many landmarks in the understanding of the pathophysiology, diagnosis, treatment and prevention of haemolytic disease of the fetus and newborn, and it now stands as one of the finest examples of how a common lifethreatening and disabling disease can be prevented and managed. Rh haemolytic disease was the first and pioneering example of intrauternine diagnosis and treatment. Immunoprophylaxis using RhD immunoglobulin was one of the first and most successful forms of immunotherapy. The use of non-invasive techniques to diagnose fetal anaemia and to perform fetal blood typing have also been critical breakthroughs in improving outcomes.

4. Mater Mothers’ Hospital, Brisbane, Australia

5. Mater Mothers’ Hospital
>10,000 births per year Referral centre for fetal management of haemolytic disease
79 bed Neonatal Intensive and Special Care Service

6. 2003-2016 162 fetal transfusions for 80 fetuses
124 intrauterine transfusions for Rh or other haemolytic disease of the fetus and newborn
38 for other reasons
48 exchange transfusions in 48 babies
40 for RhD, other Rh or Kell HDFN
2 ABO
6 other (e.g. pyruvate kinase deficiency, hereditary spherocytosis, twin-twin transfusion syndrome)

7. Intrauterine transfusion for haemolytic disease
The maternal fetal medicine specialists at our hospital perform an average of about 12 intrauterine transfusions per year, and while the number fluctuates from year to year, there is no particular trend towards an increase or decrease over the last 14 years. This graph shows the number of transfusions per year and number of fetuses transfused per year for , in this case for infants with haemolytic disease.

8. Intrauterine transfusion – for causes other than haemolytic disease
There is also a steady incidence of intrauterine transfusions for other causes of fetal anaemia, mostly parvovirus.
All but 6 were for fetal anaemia due to parvovirus

9. Exchange transfusions
Interestingly, while exchange transfusion has been fairly uncommon over the last 14 years, the incidence remained fairly steady until 2013, then we haven’t done an exchange transfusion since.

10. Potential causes of decrease in exchange transfusions
effective RhD immunoprophylaxis
Patient blood management
Extended cross-matching for girls and women of childbearing potential
trends to smaller family size
improved screening
effective intrauterine treatment
early use of intensive phototherapy for severe neonatal jaundice.
We don’t know the exact reasons, but these I think are among the most likely. The incidence of haemolytic disease is gradually declining in Australia, for a variety of reasons

11. NHMRC, 1999 RECOMMENDATIONS
625 IU: delivery, sensitising events + assess fetomaternal haemorrhage
250 IU: sensitising events < 12wk events
Antenatal prophylaxis 28w and 34w: best practice (reduces anti-D Ab formation from 1.8% to 0.14%*):
however could not be justified in view of supply situation
Strategy for self sufficiency:
Additional funding to increase anti D plasma collection
license minidose 250IU (May 2001)
Supplement with imported anti-D, WinRho (Oct 2002)
Guideline review 2001:
Staged introduction of routine antenatal prophylaxis
Education regarding appropriate use
© Commonwealth of Australia 2003
*Bowman JM, Chown B, Lewis M et al. Rh-immunization during pregnancy: antenatal prophylaxis. Can Med Assoc J 1978; 118: 623.

12. Where are we now ?

13. Graph showing individual state contributions and total trends
Stopped recruitment for primary immunisation in 2013 as sufficient supply
However within 2 years targets revised again.
Now just short of target.
Why steady decrease? What to do about it?

14. The future Careful management of RhD IgG supply
Non-invasive fetal blood typing (fetal DNA in maternal circulation) => target RhD IgG to mothers with RhD positive fetuses
Continue successful intrauterine management of affected fetuses
Intensive phototherapy for affected infants.