Fetal Haemolytic Disease

Maternal antibodies develop against fetal red blood cells IgG antibodies cross the placenta Haemolysis, anaemia, high-output cardiac failure & death

Usually a problem with subsequent pregnancies but may occur in the index pregnancy

Causes ABO – does not usually cause significant haemolytic disease. Anti-Kell – causes fetal bone marrow aplasia. Rhesus – D antigen anti-D c antigen anti-c E antigen anti-E

Incidence Approx 17% of the population is Rh-ve 10% of women at risk of developing anti-D. Incidence 1/1000 pregnancies

Predisposing Factors Miscarriage and ectopic pregnancy Invasive procedures ECV Abdominal trauma Antepartum haemorrhage Labour and birth

Initial exposure Small IgM response Subsequent exposure Large IgG response

IgG crosses placenta Forms antigen-antibody complex on red cell Red cells phagocytosed Anaemia and haemolysis

Anaemia Fetal hypoxia Hepatic and cardiac dysfunction Oedema, ascites, pericardial & pleural effusions - HYDROPS

Haemolysis Increased bilirubin Jaundice postnatally Kernicterus

Prevention Anti-D after any sensitizing episode after 12 weeks Consider routine prophylaxis

Management Check antibodies at booking and 3rd trimester If antibodies present – check antibody levels every 4 weeks to 28 weeks and then 2-weekly to term <4IU/ml – severe disease rare 4-15IU/ml – moderate risk >15IU/ml – 50% risk of severe anaemia

Check paternal genotype D antigen autosomal dominant Father DD – fetus Rh positive Father d/D – 50% chance that fetus will be Rh+ve

Anti-D for sensitising events after 12 weeks. If anti-D antibodies present do not give more anti-D. Serial measurements of Anti-D levels. Observe for signs of fetal anemia – if anemic transfuse or deliver.

Amniocentesis cordocentesis Measurement of blood velocity in middle cerebral artery. Hyperkinetic circulation correlates with fetal anaemia and need for further treatment.

Intrauterine Transfusion (IUT) Given to the fetus to prevent hydrops fetalis and fetal death. Can be done as early as 17 weeks, although preferable to wait until 20 weeks Severely affected fetus, transfusions done every 1 to 4 weeks until the fetus is mature enough to be delivered safely. Amniocentesis may be done to determine the maturity of the fetus's lungs before delivery is scheduled. After multiple IUTs, most of the baby’s blood will be D negative donor blood, therefore, the Direct Antiglobulin test will be negative, but the Indirect Antiglobulin Test will be positive. After IUTs, the cord bilirubin is not an accurate indicator of rate of hemolysis or of the likelihood of the need for post-natal exchange transfusion.

Intrauterine Transfusion An intrauterine fetal blood transfusion is done in the hospital. The mother may have to stay overnight after the procedure. The mother is sedated, and an ultrasound image is obtained to determine the position of the fetus and placenta. After the mother's abdomen is cleaned with an antiseptic solution, she is given a local anesthetic injection to numb the abdominal area where the transfusion needle will be inserted. Medication may be given to the fetus to temporarily stop fetal movement. Ultrasound is used to guide the needle through the mother's abdomen into the fetus's abdomen or an umbilical cord vein. A compatible blood type (usually type O, Rh-negative) is delivered into the fetus's abdominal cavity or into an umbilical cord blood vessel. The mother is usually given antibiotics to prevent infection. She may also be given tocolytic medication to prevent labor from beginning, though this is unusual.

Intrauterine Transfusion Increasingly common and relatively safe procedure since the development of high resolution ultrasound particularly with colour Doppler capability. MCA Doppler velocity as a reliable non-invasive screening tool to detect fetal anemia. The vessel can be easily visualized with color flow Doppler as early as 18 weeks’ gestation. In cases of fetal anemia, an increase in the fetal cardiac output and a decrease in blood viscosity contribute to an increased blood flow velocity

Intrauterine Transfusion The risk of these procedures is now largely dependent on the prior condition of the fetus and the gestational age at which transfusion is commenced.

Intrauterine Transfusion Titer greater than 32 for anti-D and 8 for anti-K OR four fold increase in titer indicates need for analysis of amniotic fluid. Amniocentesis Perform at 28 wks if HDN in previous child Perform at 22 wks if previous child severely affected Perform if maternal antibody increases before 34th wk. High values of bilirubin in amniotic fluid analyses by the Liley method or a hemoglobin concentration of cord blood below 10.0 g/mL. Type fetus -recent development in fetal RhD typing involves the isolation of free fetal DNA in maternal serum. In the United Kingdom, this technique has virtually replaced amniocentesis for fetal RhD determination in the case of a heterozygous paternal phenotype Maternal plasma exchange may be instituted if the fetus is too young for intrauterine transfusion.

Liley Graph

Selection of Blood CPD, as fresh as possible, preferably <5 days old. A hematocrit of 80% or greater is desirable to minimize the chance of volume overload in the fetus. The volume transfused ranges from 75-175 mL depending on the fetal size and age. CMV negative Hemoglobin S negative IRRADIATED O negative, lack all antigens to which mom has antibodies and Coomb’s compatible.