Maternal D alloimmunization (management): Clinical sciences

Maternal D alloimmunization management

Maternal D alloimmunization, also called isoimmunization, occurs when an Rh-negative pregnant patient produces antibodies against the Rh-D antigen on the surface of Rh-positive, fetal red blood cells. Maternal sensitization can develop following antepartum or intrapartum fetal-maternal bleeding if the fetus is Rh-positive, or after a blood transfusion with mismatched blood. In subsequent pregnancies with an Rh-positive fetus, maternal IgG anti-D antibodies can cross the placenta and attack the fetal red blood cells, causing hemolytic disease of the fetus and newborn characterized by anemia, jaundice, hydrops, and possibly fetal demise.

Your first step in evaluating a pregnant patient with a chief concern suggesting maternal D alloimmunization is to obtain a focused history. All pregnant patients are tested at the first prenatal visit for their ABO blood group, Rh-D type, and the presence of erythrocyte antibodies. Rh-negative individuals are rescreened at 28 weeks, and after delivery, before receiving anti-D immune globulin for prophylaxis. Patients with maternal D alloimmunization have an Rh-negative blood type and a positive anti-D antibody screen without having received anti-D immune globulin within the past 12 weeks.

Knowing the gestational age is helpful to guide the timing of fetal assessment and treatment when moderate to severe fetal anemia occurs. Finally, be sure to ask the patient at the initial prenatal visit if they had a previous pregnancy affected by alloimmunization and hemolytic disease.

If you suspect maternal D alloimmunization, your next step is to confirm the paternal Rh-D antigen status, whenever possible. If paternity is certain and paternal Rh status is negative, there’s no risk of Rh D-associated hemolytic disease and the patient can resume routine prenatal care.

However, in most cases, the paternal Rh status is either positive or unknown. In this situation, you should assess the paternal genotype using Rh-D antiserum or DNA testing. If unavailable, you should presume positive paternal Rh D status.

Here’s a clinical pearl! Testing for paternal genotype determines whether the father is heterozygous or homozygous for the erythrocyte D antigen. When the father is heterozygous, the fetus has a 50% chance of being Rh-negative and a 50% chance of being Rh-positive. If paternal genotype is homozygous for the D antigen, the fetus will always be Rh-positive.

Okay, back to genotype testing! If paternal genotype is either heterozygous or unknown, you should next assess the fetal Rh-D type. This is performed by 2nd trimester amniocentesis or maternal serum cell-free fetal DNA, which has an accuracy greater than 99%. If the fetus is Rh-D negative, the patient can resume routine prenatal care. Of note, in situations where determining fetal Rh-D type is not an option for availability or cost reasons, you should presume positive fetal Rh status.

On the other hand, if the fetus is Rh-D positive, your next step depends on whether the patient has a history of a previous pregnancy affected by hemolytic disease. Patients without a history of a previously affected fetus can be followed by assessing maternal anti-D antibody titers, which correlate with the severity of fetal anemia.

A maternal anti-D antibody titer that is 1-to-8 or less indicates a low likelihood of significant fetal harm. Reassess the titer every 2 to 4 weeks and begin screening for fetal anemia with Doppler ultrasound of fetal middle cerebral artery, or MCA, starting at 32 weeks gestation. These patients can be delivered between 37 and 38 weeks if the titer does not exceed 1-to-8.

A titer greater than 1-to-8 is considered critical because it’s associated with a significant risk of fetal hemolytic disease and hydrops. These patients warrant further assessment of fetal anemia using Doppler ultrasound of fetal MCA blood flow. Using the correct technique, a peak systolic velocity greater than 1.5 times the median is reliable for detecting a fetus with moderate or severe anemia.

Here’s another clinical pearl! With moderate to severe fetal anemia, peak systolic velocity is increased in the fetal MCA because of decreased blood viscosity and increased cardiac output!