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# 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

Tap one to see what it is and open it in 3D.

- [Body of uterus](https://durgical.com/en/anatomy/body-of-uterus/)

## In embryology

- [Prenatal diagnosis: ultrasound, serum screening, cell-free DNA, CVS, amniocentesis](https://durgical.com/en/embryology/prenatal-diagnosis-ultrasound-serum-screening-cell-free-dna-cvs-amniocentesis/)

## Why it happens

- [Fetal hydrops: immune and nonimmune](https://durgical.com/en/general-pathology/fetal-hydrops-immune-and-nonimmune/)
- [Rh incompatibility](https://durgical.com/en/physiology/rh-incompatibility/)
- [Blood groups, transfusion and transfusion reactions](https://durgical.com/en/physiology/blood-groups-transfusion-and-transfusion-reactions/)
- [Immunoglobulins (antibodies)](https://durgical.com/en/biochemistry/enzymes/immunoglobulins/)
- [Heme breakdown and bilirubin](https://durgical.com/en/biochemistry/pathways/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](https://durgical.com/en/anatomy/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](https://durgical.com/en/anatomy/liver/) or spleen, polyhydramnios
- Hydrops fetalis in severe cases: [skin](https://durgical.com/en/anatomy/skin/) oedema, ascites, pleural and pericardial effusions
- In the newborn: early jaundice, pallor, hepatosplenomegaly

## Red flags

- Rising antibody titre above the critical level for the laboratory
- Middle cerebral artery peak systolic velocity above the threshold for moderate or severe anaemia
- Signs of hydrops on ultrasound
- Reduced fetal movements or an abnormal (sinusoidal) fetal heart rate pattern
- Jaundice in the first 24 hours of life

## 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](https://durgical.com/en/anatomy/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.

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## Related conditions

- [Neonatal jaundice](https://durgical.com/en/conditions/neonatal-jaundice/)
- [Ectopic pregnancy](https://durgical.com/en/conditions/ectopic-pregnancy/)
- [Placental abruption](https://durgical.com/en/conditions/placental-abruption/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Rh incompatibility](https://medlineplus.gov/ency/article/001600.htm) (MedlinePlus (U.S. National Library of Medicine), 2024).

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Source: https://durgical.com/en/conditions/rh-alloimmunisation-in-pregnancy/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/rh-alloimmunisation-in-pregnancy/