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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
Key points
- Rh-negative unsensitized patients need antibody screening and Rh(D) immune globulin prophylaxis
- Give Rh(D) immune globulin at 28 weeks and within 72 hours postpartum if infant Rh-positive
- Also give after sensitizing events such as bleeding, miscarriage, ectopic, procedures, trauma, external cephalic version
- Rh(D) immune globulin prevents sensitization but does not treat established alloimmunization
- Sensitized pregnancies are monitored with antibody titers and fetal MCA Doppler
Overview
Rh isoimmunization occurs when an Rh-negative patient forms anti-D antibodies after exposure to Rh-positive fetal RBCs. In subsequent antigen-positive pregnancies, maternal IgG causes fetal hemolysis, anemia, hydrops, and neonatal hyperbilirubinemia.
Epidemiology
Routine prophylaxis has made severe Rh hemolytic disease uncommon in the US. Sensitization risk rises with delivery, miscarriage, ectopic pregnancy, bleeding, invasive procedures, trauma, abruption, and external cephalic version.
Clinical Features
Symptoms
Unsensitized Rh-negative pregnancy is asymptomatic
Antepartum bleeding or trauma is a sensitizing event
Severe fetal anemia may cause decreased fetal movement
Prior affected pregnancy raises recurrence risk
Neonatal jaundice or anemia may occur
Signs
Positive maternal anti-D antibody screen = sensitization
Fetal hydrops: ascites, skin edema, effusions, placentomegaly
Elevated MCA peak systolic velocity suggests fetal anemia
Neonatal pallor, hepatosplenomegaly, jaundice
Kleihauer-Betke may show fetomaternal hemorrhage
Investigations
First-line
ABO/Rh type and antibody screenFirst prenatal visit; repeat at 24-28 weeks in unsensitized Rh-negative patients
Infant Rh testing after deliveryDetermines postpartum prophylaxis need
Kleihauer-Betke or flow cytometryQuantifies fetomaternal hemorrhage for additional dosing
Second-line
Serial antibody titersUsed once sensitization present until critical threshold
Paternal/fetal antigen testingAssesses whether fetus is at risk
MCA DopplerPeak systolic velocity >1.5 MoM suggests moderate-severe fetal anemia
Specialist
CordocentesisDirect fetal hemoglobin assessment when severe anemia suspected
Intrauterine transfusionTreatment for severe fetal anemia before delivery
Management
ACOG Guidance on Prevention of Rh D Alloimmunization and USPSTF Rh Screening Recommendations1
Unsensitized Rh-negative patient
- Rh(D) immune globulin at 28 weeks
- Rh(D) immune globulin within 72 hours postpartum if infant Rh-positive or unknown
- Give after miscarriage, ectopic, abortion, bleeding, trauma, invasive testing, external cephalic version, or abruption
- Dose depends on gestational age and fetomaternal hemorrhage volume
2
Already sensitized patient
- Rh(D) immune globulin is not useful once anti-D antibodies are present
- Serial titers until critical threshold
- MCA Doppler surveillance for fetal anemia
- Intrauterine transfusion for severe fetal anemia when appropriate
3
Neonatal management
- Direct antiglobulin test, hemoglobin, and bilirubin monitoring
- Phototherapy, IVIG, or exchange transfusion depending on severity
- Monitor for late anemia
Complications
- Fetal anemia: Maternal IgG-mediated hemolysis
- Hydrops fetalis: High-output heart failure with edema/effusions
- Stillbirth: Severe untreated anemia
- Neonatal hyperbilirubinemia: Risk of kernicterus
- Recurrence: Subsequent antigen-positive pregnancies often more severe
USMLE Step 2 CK Exam Tips
- 1Rh-negative unsensitized patient at 28 weeks = Rh(D) immune globulin
- 2Rh-negative mother + Rh-positive infant = Rh(D) immune globulin within 72 hours
- 3Rh(D) immune globulin prevents sensitization; it does not treat anti-D antibodies
- 4Positive antibody screen → serial titers and MCA Doppler
- 5MCA velocity rises because anemic fetal blood is less viscous
- 6Bleeding/trauma/procedure/ectopic/miscarriage in Rh-negative pregnancy = Rh(D) immune globulin
- 7Hydrops from Rh disease = fetal anemia causing high-output failure
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