Prevention And Management Of Alloimmunisation

Clinical description

Screening for alloimmunization is important as 4% of Malawians are Rh-negative. The most common type of Rh incompatibility occurs when a Rh-negative pregnant mother is exposed to Rh-positive fetal red blood cells secondary to fetomaternal hemorrhage during the course of pregnancy from miscarriage, trauma, [1] invasive obstetric procedures, or normal delivery. In 90% of cases, sensitization occurs during delivery.

Once produced, maternal Rh Immunoglobulin G (IgG) antibodies persist for life and may cross freely from the placenta to the fetal circulation, where they form antigen-antibody complexes with Rh-positive fetal erythrocytes and eventually are destroyed, resulting in a fetal alloimmune-induced hemolytic anemia. [2] The binding of maternal Rh antibodies produced after sensitization with fetal Rh-positive erythrocytes results in fetal autoimmune hemolysis.

The fetus may have red blood cell antigens (i.e. ABO, Rhesus, Kell, Kid, Duffy) that the mother does not.

Although the Rh blood group systems consist of many antigen subtypes (e.g., D, C, c, E, e), the D antigen is the most common; therefore, it most commonly is involved in Rh incompatibility. When ≥ 0.1 ml of fetal blood leaks into the maternal circulation, there is a risk that the maternal immune system will form antibodies against the foreign antigen. This is known as alloimmunisation and can occur in pregnancy > 7 wks gestation (including ectopic pregnancy), chorionic villus sampling, cordocentesis, amniocentesis, APH, external cephalic version, abdominal trauma and delivery. Once sensitized, it takes approximately 1 month for Rh antibodies in the maternal circulation to equilibrate in the fetal circulation.

Therefore, most firstborn infants with Rh-positive blood type are not affected unless immunized during a previous blood transfusion, because the short period from first exposure of Rh-positive fetal erythrocytes to the birth of the infant is insufficient to produce a significant maternal IgG antibody response. A small percentage will follow sensitization very early in the pregnancy. Maternal antibodies cross the placenta and form antigen- antibody complexes in subsequent pregnancies. Manifestations of alloimmunisation include hydrops fetalis, icterus gravis neonatorum and congenital anaemia.

Signs and symptoms

History Ask about gravidity, parity, previous abortions and/or miscarriages, history of transfusions and blood group of pregnant woman and her partner Exam/InvestigationsSend blood for Hb, blood group, Direct Coombs test, syphilis test and HIV; ultrasound (US) for dating, serial US to diagnose and/or monitor.

• All Rh-negative mothers should be tested for antibodies 3 times during pregnancy: at their 1stantenatal

visit, at 28 weeks gestation, and at delivery.

• All potentially-affected infants of Rh-negative mothers should be tested for Rh type and antibodies

from the umbilical cord at the time of delivery.

Preventive Management Prevention of Rh alloimmunisation

• Give Rh immunoglobulin immediately after a sensitizing event* (give 150 μg at <20 weeks)
• Give Rh immunoglobulin 300 μg (1500 IU) at 20 wks gestation or
• Give Rh immunoglobulin 300 μg (1500 IU) within 72 hrs of delivery if infant is Rh positive.
• If the RhIG is not administered during the recommended immediate postpartum period, it

should still be given up to 28 days postpartum.

*Sensitizing events include vaginal bleeding early in pregnancy, abortion/miscarriage, ectopic pregnancy, molar, pregnancy, chorionic villus sampling, amniocentesis, blunt trauma to the abdomen, fetal death**, bleeding from placenta previa, manual removal of placenta, or external cephalic version. Rh Ig should be protective against sensitization for 12 weeks.

** Give Rh Ig at time that fetal death is diagnosed rather than waiting until time of delivery.

Clinical description

Minimization of fetomaternal haemorrhage

• Avoid manual removal of placenta
• Immediate clamping of cord and keep cord of fetus long (for possible transfusion)

Treatment

Manifestations of alloimmunization occur after delivery because the bilirubin of in utero haemolysis is cleared by the maternal liver, but after birth this assistance is not available leading to the risk of icterus causing brain damage. A life-threatening condition in infants affected is erythroblastosis fetalis, characterized by severe hemolytic anemia and jaundice. The most severe form of erythroblastosis fetalis is hydrops fetalis, characterized by high output cardiac failure, edema, ascites, pericardial effusion, and extramedullary hematopoiesis. An affected fetus requires referral to the pediatricians.

Treatment for sensitized maternal patient (positive Coombs test in Rh negative woman)

• Refer to Specialist for Consultation
• Conservative management: perform monthly US for fetal weight and to look for features of hydrops fetalis

(i.e. edema or accumulation of fluid in fetal compartments); if latter are present, then deliver if viable.

• If available, perform US for middle cerebral artery (MCA) Doppler, which can detect fetal anemia, using a

threshold value of 1.5 multiples of the median (MoM) to predict moderate-severe fetal hemoglobin. This should begin at 16 to 18 weeks gestation and continue weekly.

• If severe fetal anemia, consider delivery if viable.
• Perform caesarean delivery for severely affected and/or preterm fetus. If < 34 weeks EGA, give antenatal

corticosteroids (i.e. dexamethasone) prior to delivery if possible.

• Transfuse newborn with Hb ≤ 12 g/dL and/or positive direct Coombs and/or bilirubin ≥ 5 mg.
• In the 7 to 10 days prior to delivery, oral phenobarbital may be considered to improve hepatic maturity

and enhance conjugation of bilirubin.

Intrapartum: timing of delivery is on a case-by-case basis in consultation with a Specialist, but it is reasonable to proceed with induction of labor at 37-38 weeks gestation, or earlier if fetal lung maturity is documented.

Postpartum: women with pregnancies affected by alloimmunization should be counseled that future pregnancies are generally more severely affected.

Blood group in all pregnant women Rhesus negative Coombs test Rhesus positive Unsensitised Sensitised Routine antenatal anti-D prophylaxis (RAADP) If father Rh positive

• Give Rh immunoglobulin 300 μg (1500IU) at 28 weeks • Antibody titer at booking visit
• Give Rh immunoglobulin 300 μg (1500IU) within 72hrs of • Monitor antibody titers 4-weekly until 28

delivery weeks and 2-weekly until delivery Antenatal sensitizing events • 3-4 weekly growth scans and assess for fetal

• Give 150 μg Rh immunoglobulin for events occurring < 20 hydrops

weeks • Weekly MCA Doppler USS from 16-18

• Give 300 μg Rh immunoglobulin for events occurring ≥20 weeks

weeks, administer 300mg Rh immunoglobulin • If severe anemia, deliver preterm by C/S.

Give dexamethasone if < 34 weeks.

NB: If non-viable pregnancy, give anti-D within 72 hours of

• At delivery, perform blood group, direct

diagnosis regardless of timing of delivery.

Coombs test and bilirubin level for the infant If recurrent APH after 20 weeks, administer Anti-D at least 6 weekly.