Conditions · Obstetrics and gynecology
Rh alloimmunisation in pregnancy !
An RhD-negative mother makes antibodies against her RhD-positive baby's red cells. They can cause severe fetal anaemia, but it is largely preventable.
Updated 2026-11-01
Structures involved
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In embryology
Why it happens
- Fetal hydrops: immune and nonimmune
- Rh incompatibility
- Blood groups, transfusion and transfusion reactions
- Immunoglobulins (antibodies)
- Heme breakdown and bilirubin
What it is
Formation of maternal antibodies against the RhD antigen of fetal red blood cells after exposure to RhD-positive blood. In later pregnancies, these IgG antibodies cross the placenta and destroy fetal red cells, causing haemolytic disease of the fetus and newborn.
Who gets it
RhD-negative blood is less frequent in Latin American mestizo and Indigenous populations than in people of European ancestry, but the problem persists in Colombia where anti-D immunoglobulin is not given after every sensitising event. Routine prophylaxis has made it rare in high-income countries.
Causes
- Fetomaternal haemorrhage of RhD-positive fetal blood into an RhD-negative mother, mostly at delivery
- Sensitising events: miscarriage, abortion, ectopic pregnancy, amniocentesis, abdominal trauma, external cephalic version, placental abruption, antepartum bleeding
- Transfusion of incompatible blood
- Other red-cell antibodies (Kell, c, E) cause a similar disease
Risk factors
- RhD-negative mother with an RhD-positive partner
- Previous pregnancy or loss without anti-D immunoglobulin prophylaxis
- Invasive procedures or trauma during pregnancy
- Manual removal of the placenta or caesarean delivery
- Lack of blood group typing in antenatal care
Pathophysiology
The first exposure produces mainly IgM, which does not cross the placenta, so the first pregnancy is usually spared. In later pregnancies with an RhD-positive fetus, memory cells rapidly produce IgG that crosses the placenta, coats fetal red cells and leads to their destruction in the fetal spleen. The result is fetal anaemia, extramedullary haematopoiesis, high-output heart failure and, in severe cases, hydrops fetalis. ABO incompatibility between mother and fetus partly protects by clearing fetal cells quickly.
Symptoms and signs
- No symptoms in the mother; detected by antenatal blood tests
- Fetal signs on ultrasound: increased middle cerebral artery flow, enlarged liver or spleen, polyhydramnios
- Hydrops fetalis in severe cases: skin oedema, ascites, pleural and pericardial effusions
- In the newborn: early jaundice, pallor, hepatosplenomegaly
Diagnosis
- Clinical
- Every pregnant woman has her ABO and RhD group and an antibody screen at the first visit. In RhD-negative women, the partner's blood group and the history of sensitising events are recorded.
- Tests
- Indirect antiglobulin (Coombs) test for maternal anti-D antibodies and serial titres; partner genotyping or cell-free fetal DNA in maternal blood to know the fetal RhD status; Kleihauer-Betke or flow cytometry to measure fetomaternal haemorrhage; in the newborn, direct Coombs test, haemoglobin and bilirubin.
- Imaging
- Doppler ultrasound of the fetal middle cerebral artery peak systolic velocity, a non-invasive way to detect fetal anaemia, plus ultrasound surveillance for hydrops; cordocentesis confirms the fetal haematocrit and allows transfusion.
Differential diagnosis
- ABO haemolytic disease of the newborn
- Other causes of fetal hydrops (infection such as parvovirus B19, heart disease, chromosomal abnormalities, alpha-thalassaemia)
- Alloimmunisation to other red-cell antigens (Kell, c, E, Duffy)
- Neonatal jaundice from other causes (G6PD deficiency, spherocytosis, sepsis)
Goal of treatment
Prevent sensitisation in RhD-negative women, and in women already sensitised detect fetal anaemia early and correct it so that the baby can be born as close to term as is safe.
Treatment
- Medical
- Anti-D immunoglobulin for non-sensitised RhD-negative women: routinely around 28 weeks, within 72 hours of birth when the newborn is RhD-positive, and after any sensitising event; the amount after delivery is adjusted to the size of the fetomaternal haemorrhage.
- Follow-up
- For sensitised women: serial antibody titres and, once titres reach the critical level, fetal middle cerebral artery Doppler every one to two weeks.
- Procedure
- Intrauterine transfusion of compatible red cells into the umbilical vein for severe fetal anaemia, in specialised fetal medicine centres.
- Procedure
- Planned delivery, usually before term in affected pregnancies, with neonatal team present.
- Medical
- Newborn care: phototherapy, exchange transfusion or top-up transfusion; this part belongs to neonatal care.
Complications
- Fetal anaemia and hydrops fetalis
- Intrauterine fetal death
- Neonatal hyperbilirubinaemia and kernicterus
- Late anaemia of the newborn
- Complications of invasive fetal procedures (bleeding, preterm birth, fetal loss)
- Disease is usually more severe in each subsequent affected pregnancy
Prognosis
Prophylaxis prevents most cases. Once a woman is sensitised, anti-D no longer helps and every RhD-positive pregnancy is at risk; with Doppler surveillance and intrauterine transfusion in experienced centres, survival of anaemic fetuses is high, though hydrops worsens outcome.
Prevention
- Blood group and antibody screening of every pregnant woman
- Anti-D immunoglobulin at 28 weeks, after birth and after every sensitising event
- Avoiding transfusion of RhD-positive blood to RhD-negative girls and women of childbearing age
Test yourself
Think of the answer, then tap the question to see it.
Why is the first RhD-positive pregnancy of an RhD-negative woman usually unaffected?
The first response is mainly IgM, which does not cross the placenta; IgG appears in later pregnancies.
When is anti-D immunoglobulin given to a non-sensitised RhD-negative woman?
Around 28 weeks, within 72 hours after birth of an RhD-positive baby, and after any sensitising event.
Which non-invasive test detects fetal anaemia?
Doppler measurement of the peak systolic velocity in the fetal middle cerebral artery.
What does the Kleihauer-Betke test measure?
The amount of fetal blood in the maternal circulation, to adjust the anti-D dose after a fetomaternal haemorrhage.
Is anti-D useful in a woman who already has anti-D antibodies?
No; it only prevents sensitisation. Sensitised women need titre and Doppler surveillance.
Related conditions
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Rh incompatibility (MedlinePlus (U.S. National Library of Medicine), 2024).
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