Maternal D alloimmunization (management): Clinical sciences

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Introduction0:00–1:00

Maternal D alloimmunization managementMaternal 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.

Focused history1:00–2:15

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.

Confirm paternal blood type2:15–2:37

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.

Assess paternal genotype2:37–3:31

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.

Paternal genotype heterozygous/unknown3:31–4:14

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.

Fetus Rh-D positive/negative history4:14–6:57

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!
Alright, when fetal assessment indicates the presence of mild fetal anemia, continue assessment of fetal wellbeing with serial MCA Doppler ultrasound studies starting at 32 weeks gestation and proceed with delivery at 37 to 38 weeks.
However, if severe fetal anemia is suspected, the next steps include percutaneous umbilical cord blood sampling, also known as PUBS, for fetal hematocrit determination and intrauterine fetal blood transfusion.
The goal is to prolong the pregnancy until the fetus reaches a gestational age when survival is possible. Administer maternal steroids to enhance fetal lung maturity, and schedule delivery by 32 to 34 weeks.
Okay, the final possibility here is an Rh-positive fetus in the current pregnancy and a maternal history of a previously affected fetus.

Fetus Rh-D positive/positive history6:57–7:54

In this case, you can go directly to assessing fetal anemia with a Doppler ultrasound of the fetal MCA. As before, mild fetal anemia is followed by serial MCA Doppler ultrasound starting at 32 weeks, with delivery at 37 to 38 weeks; while severe fetal anemia is managed with PUBS to confirm the fetal hematocrit followed by intrauterine fetal blood transfusion as appropriate.
Follow-up with serial MCA Doppler ultrasound studies, administer maternal steroids for fetal lung maturity, and deliver at 32 to 34 weeks..
Alright, let’s take a step back to the paternal Rh-D genotype assessment and talk about a different option. If the paternal Rh-D genotype is homozygous positive, and there is no history of a previously affected fetus, you don’t have to check the fetal Rh status, because all fetuses from this paternal lineage will be Rh-positive.

Paternal genotype homozygous/negative history7:54–9:24

Since maternal history is negative for a previously affected fetus, your next step is to assess maternal anti-D antibody titers.
A titer that is 1-to-8 or less is followed every 2-4 weeks, and delivery should be done at 37 to 38 weeks. If the anti-D antibody titer is greater than 1-to-8, as before, you’ll need to assess for fetal anemia with an MCA Doppler ultrasound and manage the pregnancy based on whether the anemia is mild or severe.
Mild fetal anemia is followed by serial MCA Doppler ultrasound starting at 32 weeks with delivery at 37 to 38 weeks, while severe fetal anemia is managed with PUBS, followed by intrauterine fetal blood transfusion if needed.
Maternal steroid administration to develop the fetal lungs, and delivery at 32 to 34 weeks are recommended.Finally, you might find that a paternal Rh-D genotype is homozygous positive and a maternal history that is positive for a previously affected fetus.

Paternal genotype homozygous/positive history9:24–9:56

Serial maternal antibody titers are not reliable to determine the degree of fetal anemia present. Instead, proceed with a Doppler ultrasound of the fetal middle cerebral artery, and manage the pregnancy based on whether mild or severe fetal anemia is suspected.
Alright, as a quick recap… If maternal D alloimmunization is suspected, confirm that the fetus is Rh-positive with paternal and fetal testing.

Review9:56–10:54

In the absence of a previously affected pregnancy, follow serial maternal anti-D antibody titers that are 1-to-8 or less.
When the titer is greater than 1-to-8, or if there is a positive history of a previously affected pregnancy, proceed with a Doppler ultrasound of the fetal middle cerebral artery to determine the degree of fetal anemia.
Affected pregnancies should undergo MCA Doppler ultrasound studies and scheduled delivery. But if fetal anemia becomes severe, perform percutaneous cord blood sampling and intrauterine fetal blood transfusion to prolong the pregnancy to viability.
Maternal steroids for fetal lung maturity and early delivery are