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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
Key points
- Rh-negative mothers carrying Rh-positive fetuses can develop anti-D antibodies after sensitising events
- Sensitising events: delivery, APH, miscarriage/TOP >12 weeks, ectopic, ECV, amniocentesis, abdominal trauma
- Prevention: routine antenatal anti-D prophylaxis (RAADP) at 28 weeks for ALL Rh-negative women (unless known to be already sensitised)
- Postnatal anti-D: within 72 hours of delivery if baby is Rh-positive. Kleihauer test guides additional dosing
- HDFN: fetal anaemia → hydrops fetalis. Monitored by MCA Doppler peak systolic velocity. Treated with intrauterine transfusion
- Anti-D does NOT help once sensitisation has occurred (antibodies already present)
Overview
Rhesus (Rh) isoimmunisation occurs when an Rh-negative mother develops IgG anti-D antibodies following exposure to Rh-positive fetal red blood cells. These antibodies can cross the placenta in subsequent pregnancies and cause haemolysis of Rh-positive fetal red cells, leading to haemolytic disease of the fetus and newborn (HDFN). HDFN ranges from mild neonatal jaundice to severe fetal anaemia, hydrops fetalis, and intrauterine death. The introduction of anti-D immunoglobulin prophylaxis has dramatically reduced the incidence of HDFN.
Epidemiology
Approximately 15% of women in the UK are Rh-negative. Before anti-D prophylaxis, HDFN affected 1 in 200 pregnancies. With current prophylaxis protocols, the sensitisation rate has fallen to approximately 0.1–0.4%. Non-invasive fetal genotyping using cell-free fetal DNA in maternal blood can determine the fetal Rh status from 11–12 weeks, enabling targeted anti-D administration only to women carrying Rh-positive fetuses.
Clinical Features
Symptoms
Maternal: asymptomatic — sensitisation detected only on antibody screening
Fetal: hydrops fetalis (severe anaemia) — polyhydramnios, reduced fetal movements
Signs
Maternal: no clinical signs. Detected by indirect Coombs test (antibody screen)
Fetal USS: ascites, pleural/pericardial effusions, skin oedema, hepatomegaly (hydrops)
Neonatal: jaundice within 24 hours of birth (always pathological), anaemia, hepatosplenomegaly
Neonatal: kernicterus (bilirubin encephalopathy) if severe untreated hyperbilirubinaemia
Investigations
First-line
Blood group and Rh statusAt booking — identify Rh-negative women
Indirect Coombs test (antibody screen)At booking and 28 weeks. Detects circulating anti-D antibodies
Non-invasive fetal genotyping (cffDNA)Cell-free fetal DNA from maternal blood — determines fetal Rh status. Available from 11–12 weeks. Enables targeted anti-D
Second-line
Kleihauer testAfter potentially sensitising events and after delivery — quantifies volume of fetomaternal haemorrhage. Guides additional anti-D dosing
Serial anti-D antibody titresIf sensitised — rising titres indicate increasing risk. Refer to fetal medicine if antibody levels exceed critical threshold
Specialist
MCA Doppler peak systolic velocityNon-invasive monitoring for fetal anaemia in sensitised pregnancies. Raised PSV (>1.5 MoM) suggests moderate-severe anaemia
Cordocentesis / intrauterine transfusionFetal blood sampling and transfusion of O-negative packed cells if severe fetal anaemia confirmed
1
Routine antenatal anti-D prophylaxis (RAADP)
- Offer to ALL Rh-negative women at 28 weeks (single dose of 1,500 IU IM)
- Unless already sensitised (anti-D antibodies detected on screening)
- Unless fetal genotyping confirms fetus is Rh-negative (no anti-D needed)
2
Anti-D after sensitising events
- Give anti-D immunoglobulin (minimum 250 IU <12 weeks, 500 IU ≥12 weeks) within 72 hours of:
- Delivery of Rh-positive baby, threatened/actual miscarriage >12 weeks, ectopic pregnancy, TOP
- APH, ECV, amniocentesis/CVS, abdominal trauma, intrauterine death
- Perform Kleihauer test after 20 weeks to quantify FMH and calculate additional anti-D needed
3
Postnatal anti-D
- Cord blood: confirm baby is Rh-positive (and perform direct Coombs test)
- Give anti-D 500 IU IM within 72 hours if baby is Rh-positive
- Perform Kleihauer test to check for large FMH requiring additional anti-D
4
Management of sensitised pregnancies
- Serial anti-D antibody titres every 2–4 weeks
- MCA Doppler from 20 weeks to monitor for fetal anaemia
- Fetal medicine referral if titres rising or MCA PSV elevated
- Intrauterine transfusion if severe fetal anaemia (before 35 weeks)
- Planned delivery at 37–38 weeks or earlier if compromised
Complications
- Hydrops fetalis: Severe fetal anaemia causing oedema, ascites, effusions — high mortality without intervention
- Neonatal jaundice: Ongoing haemolysis — may require phototherapy or exchange transfusion
- Kernicterus: Bilirubin encephalopathy — irreversible neurological damage
- Intrauterine death: From severe untreated anaemia
UKMLA Exam Tips
- 1Anti-D at 28 weeks for ALL Rh-negative women (RAADP) — very commonly tested
- 2Anti-D must be given within 72 hours of sensitising events
- 3Kleihauer test quantifies FMH — guides ADDITIONAL anti-D dosing. Not diagnostic
- 4Anti-D has NO role once a woman is already sensitised — it only prevents new sensitisation
- 5MCA Doppler PSV is the non-invasive method for monitoring fetal anaemia in sensitised pregnancies
- 6Jaundice within 24 hours of birth is ALWAYS pathological — think haemolytic disease
- 7Non-invasive fetal genotyping (cffDNA) can determine fetal Rh status, enabling targeted anti-D
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