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O&G TopicsAntenatal care — fetal medicine and immunohaematology

O&G · Antenatal care — fetal medicine and immunohaematology

Rh(D) alloimmunisation and anti-D prophylaxis

Also known as RhD alloimmunisation · Rhesus isoimmunisation · Anti-D prophylaxis · Haemolytic disease of the fetus and newborn · HDFN · Routine antenatal anti-D prophylaxis · RAADP

Exam-exhaustive FRANZCOG reference on Rh(D) alloimmunisation and anti-D prophylaxis — the pathophysiology of maternal sensitisation, the NBA/RANZCOG 2024 anti-D schedule (625 IU at 28 and 34 weeks, 625 IU within 72 hours of birth, 250 IU for events under 12 weeks), sensitising events, fetomaternal haemorrhage quantification by Kleihauer and flow cytometry, and management of the alloimmunised pregnancy with serial MCA-PSV Doppler (above 1.5 MoM = fetal blood sampling with intrauterine transfusion) and intrauterine transfusion. RANZCOG-primary, globally tagged to MRCOG and ABOG.

high14 referencesUpdated 26 July 202615 min readVerification in progress

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FRANZCOGMRCOGABOGFRCSCMRCPI

Red flags

  • A titre at or above the critical level (typically 1:16 by IAT for anti-D or anti-c) is the trigger for serial MCA-PSV — not for repeating the titre
  • In a previously affected pregnancy, maternal titres are non-predictive — go straight to serial MCA-PSV from 16 to 18 weeks
  • MCA-PSV above 1.5 multiples of the median means fetal blood sampling with intrauterine transfusion ready, not a repeat scan next week
  • Give the postpartum 625 IU within 72 hours — do not wait for the Kleihauer-Betke result
  • Anti-D is prevention; once the woman is sensitised, more anti-D does nothing — escalate to MCA-PSV surveillance and fetal therapy referral
  • Anti-K causes erythroid suppression as well as haemolysis — use a lower threshold for MCA-PSV surveillance
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Practise this topic9 MCQs with explanations

Target exams

FRANZCOGMRCOGABOGFRCSCMRCPI

Red flags

  • A titre at or above the critical level (typically 1:16 by IAT for anti-D or anti-c) is the trigger for serial MCA-PSV — not for repeating the titre
  • In a previously affected pregnancy, maternal titres are non-predictive — go straight to serial MCA-PSV from 16 to 18 weeks
  • MCA-PSV above 1.5 multiples of the median means fetal blood sampling with intrauterine transfusion ready, not a repeat scan next week
  • Give the postpartum 625 IU within 72 hours — do not wait for the Kleihauer-Betke result
  • Anti-D is prevention; once the woman is sensitised, more anti-D does nothing — escalate to MCA-PSV surveillance and fetal therapy referral
  • Anti-K causes erythroid suppression as well as haemolysis — use a lower threshold for MCA-PSV surveillance
One-line fellowship answer

Rh(D) alloimmunisation is the maternal IgG response to fetal RhD-positive red cells that crosses the placenta and destroys fetal erythrocytes — prevented by anti-D immunoglobulin (ANZ: 625 IU IM at 28 and 34 weeks, 625 IU within 72 hours of an RhD-positive birth, 250 IU for sensitising events under 12 weeks and 625 IU for events over 12 weeks), and, once sensitised, managed by serial middle cerebral artery peak systolic velocity Doppler with fetal blood sampling and intrauterine transfusion when the MCA-PSV rises above 1.5 multiples of the median.[4][14]

It is the antenatal booking visit. A 29-year-old G2P1, blood group A RhD-negative, is in front of you. Her first baby was RhD-positive and healthy; she had anti-D then. This time her booking antibody screen is positive for anti-D at a titre of 1:32. The registrar asks you: "Do we just give more anti-D?" No. Anti-D is prevention; once a woman is sensitised it does nothing. The whole game now is detecting fetal anaemia non-invasively and transfusing before hydrops. This topic is the script for both halves — preventing sensitisation, and managing it when prevention has failed.[2][8]

Overview and definition

Rh(D) alloimmunisation is two diseases separated by a moment of prevention. Untreated, it is haemolytic disease of the fetus and newborn (HDFN) — maternal IgG crosses the placenta, coats fetal RhD-positive red cells, and triggers extravascular haemolysis that can end in hydrops, stillbirth, or kernicterus. Treated with anti-D immunoglobulin, it is a preventable success story of modern obstetrics.[6]

Three terms the examiner separates for you: [2]

  • Sensitisation — the asymptomatic event. Maternal B-cells meet fetal RhD antigen and form anti-D. No fetal harm yet, and anti-D given now cannot reverse it.
  • Alloimmunisation — the established state. Anti-D is present on the maternal screen. Future pregnancies are at risk.
  • HDFN — the fetal and neonatal disease. Maternal IgG haemolyses fetal cells, causing anaemia, hydrops, and neonatal jaundice.[2]

The distinction matters because anti-D is prevention, not treatment. Once anti-D appears on the screen, you stop giving prophylactic anti-D and start surveillance.[2][8]

The numbers that frame the topic

~15%RhD-negative prevalence (Caucasian)lower in Asian populations
~6 / 1000 birthsResidual RhD alloimmunisationthe post-prophylaxis rate
13 to 16% → 0.5 to 1.8%Postpartum anti-D effectsensitisation fall after postpartum prophylaxis
→ 0.14 to 0.2%Plus antenatal prophylaxisfurther reduction with RAADP
[2] [6]
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References14ShowHide
  1. [1]Mari G, Deter RL, Carpenter RL, et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses N Engl J Med, 2000.PMID 10620643
  2. [2]Moise KJ Jr Management of rhesus alloimmunization in pregnancy Obstet Gynecol, 2008.PMID 18591322
  3. [3]Moise KJ Jr, Argoti PS Management and prevention of red cell alloimmunization in pregnancy: a systematic review Obstet Gynecol, 2012.PMID 23090532
  4. [4]Mari G, Norton ME, Stone J, et al. Society for Maternal-Fetal Medicine (SMFM) Clinical Guideline #8: the fetus at risk for anemia—diagnosis and management Am J Obstet Gynecol, 2015.PMID 25824811
  5. [5]Qureshi H, Massey E, Kirwan D, et al. BCSH guideline for the use of anti-D immunoglobulin for the prevention of haemolytic disease of the fetus and newborn Transfus Med, 2014.PMID 25121158
  6. [6]Practice Bulletin No. 181: Prevention of Rh D Alloimmunization Obstet Gynecol, 2017.PMID 28742673
  7. [7]de Winter DP, Kaminski A, Tjoa ML, Oepkes D Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape BMC Pregnancy Childbirth, 2023.PMID 36611144
  8. [8]Savoia HF, Parakh A, Kane SC How I manage pregnant patients who are alloimmunized to RBC antigens Blood, 2025.PMID 38743880
  9. [9]Zimmerman R, Carpenter RJ Jr, Durig P, Mari G Longitudinal measurement of peak systolic velocity in the fetal middle cerebral artery for monitoring pregnancies complicated by red cell alloimmunisation: a prospective multicentre trial with intention-to-treat BJOG, 2002.PMID 12135209
  10. [10]Okwundu CI, Afolabi BB Intramuscular versus intravenous anti-D for preventing Rhesus alloimmunization during pregnancy Cochrane Database Syst Rev, 2013.PMID 23440818
  11. [11]Pilgrim H, Lloyd-Jones M, Rees A Routine antenatal anti-D prophylaxis for RhD-negative women: a systematic review and economic evaluation Health Technol Assess, 2009.PMID 19210896
  12. [12]Saramago P, Yang H, Llewellyn A, et al. High-throughput, non-invasive prenatal testing for fetal Rhesus D genotype to guide antenatal prophylaxis with anti-D immunoglobulin: a cost-effectiveness analysis BJOG, 2018.PMID 29415334
  13. [13]Moise KJ Jr, Markham KB, Spinella PC, et al. A Clinical Practice Guideline for the Management of Pregnancy Alloimmunized to Red Blood Cell Antigens JAMA Netw Open, 2025.PMID 41284292
  14. [14]Glazebrook B, Akers C, Bielby L, Bastin K, Von Wielligh K, Daly J Quality audit of the guidelines for the use of RhD immunoglobulin in obstetrics: Are we getting it right? Aust N Z J Obstet Gynaecol, 2020.PMID 32424867

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