Rh incompatibility

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 10 Aug 2025

Last updated: 16 Feb 2024

Rhesus (Rh) incompatibility is a condition where an Rh-negative mother carrying an Rh-positive fetus can produce antibodies against paternally derived Rh antigens on fetal red blood cells. These antibodies can cross the placenta, and destroy fetal red blood cells. It is a leading cause of haemolytic disease of the fetus and newborn, also known as erythroblastosis fetalis.

Effective immunoprophylaxis of Rh-negative at-risk mothers is key to primary prevention.

Intrauterine fetal transfusion is a life-saving treatment for severely affected fetuses.

Survival rates are more than 90%.

Definition

Rh incompatibility occurs in an Rh-negative mother carrying an Rh-positive fetus. If the mother is exposed to the paternally derived Rh antigens on fetal red blood cells (RBCs) she can become sensitised and produce immunoglobulin G (IgG) antibodies, usually against the RhD antigen. These maternally derived antibodies can then freely cross the placenta, binding to and destroying fetal RBCs. This is a leading cause of haemolytic disease of the fetus and newborn (HDN or HDFN, also known as erythroblastosis fetalis), which involves progressive fetal anaemia, and, if untreated, may ultimately lead to hydrops fetalis (collection of fluid in serous compartments) and death.[1][2]

History and exam

Key diagnostic factors

presence of risk factors

Full details

Risk factors

history of an RhD-positive fetus in an RhD-negative mother
fetomaternal haemorrhage
invasive fetal procedures
placental trauma
abortion
multiparity
omission of Rh immunoprophylaxis
external cephalic version
molar pregnancy
ectopic pregnancy

Full details

Diagnostic investigations

1st investigations to order

maternal blood type
maternal serum Rh antibody screen

Full details

Investigations to consider

maternal serum antibody titre
paternal blood type
paternal zygosity
fetal ultrasound
Doppler velocimetry of fetal middle cerebral artery (peak systolic velocity)
fetal blood typing (from amniocentesis or maternal circulation)
direct assessment of fetal anaemia
rosette test
Kleihauer-Betke test/flow cytometry

Full details

Treatment algorithm

INITIAL

unsensitised RhD-negative mother

sensitised RhD-negative mother

ACUTE

neonate with erythroblastosis

Contributors

Authors

Andrew D. Hull, MD, FRCOG, FACOG

Professor of Clinical Obstetrics, Gynecology, and Reproductive Sciences

Director, UC San Diego Maternal-Fetal Care and Genetics

Division of Maternal-Fetal Medicine

Department of Obstetrics, Gynecology, and Reproductive Sciences

University of California San Diego

La Jolla

Disclosures

ADH declares that he has no competing interests.

Acknowledgements

Dr Andrew D. Hull would like to gratefully acknowledge Dr Karen Fung-Kee-Fung and Dr Felipe Moretti, previous contributors to this topic.

Disclosures

KFKF is an author of a reference cited in this topic. KFKF and FM declare that they have no competing interests.

Peer reviewers

Alan Cameron, MD

Honorary Professor of Medicine

University of Glasgow

Glasgow

Disclosures

AC is an author of several references cited in this topic.

Liakat Ali Parapia, MD, FRCP

Consultant Hematologist

Bradford Teaching Hospitals NHS Trust

Yorkshire Clinic

Bingley

Bradford

Disclosures

LAP declares that he has no competing interests.

Kenneth J. Moise, Jr., MD

Professor of Obstetrics and Gynecology

Texas Children's Fetal Center

Baylor College of Medicine/Texas Children's Hospital

Houston

Disclosures

KJM declares that he has no competing interests.

Peer reviewer acknowledgements

BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.

Disclosures

Peer reviewer affiliations and disclosures pertain to the time of the review.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

American Congress of Obstetrics and Gynecology. ACOG practice bulletin no. 181: prevention of Rh D alloimmunization. Obstet Gynecol. 2017 Aug;130(2):e57-70. Abstract

Fung KFK, Eason E. No. 133: prevention of Rh alloimmunization. J Obstet Gynaecol Can. 2018 Jan;40(1):e1-10. Abstract

American Congress of Obstetrics and Gynecology. ACOG practice bulletin no. 192: management of alloimmunization during pregnancy. Obstet Gynecol. 2018 Mar;131(3):e82-90. Abstract

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 Feb;24(1):8-20.Full text Abstract

Mari G, Deter RL, Carpenter RL, et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. N Engl J Med. 2000 Jan 6;342(1):9-14.Full text Abstract

Visser GHA, Thommesen T, Di Renzo GC, et al. FIGO/ICM guidelines for preventing Rhesus disease: a call to action. Int J Gynaecol Obstet. 2021 Feb;152(2):144-7.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Non-immune fetal hydrops
- Parvovirus infection
- Non-RhD haemolytic disease
More Differentials
Guidelines
- Ectopic pregnancy and miscarriage: diagnosis and initial management
- Prophylactic use of RhD immunoglobulin in pregnancy care
More Guidelines
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Rh incompatibility

Summary

Definition

History and exam

Key diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Treatment algorithm

unsensitised RhD-negative mother

sensitised RhD-negative mother

neonate with erythroblastosis

Contributors

Authors

Andrew D. Hull, MD, FRCOG, FACOG

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Alan Cameron, MD

Disclosures

Liakat Ali Parapia, MD, FRCP

Disclosures

Kenneth J. Moise, Jr., MD

Disclosures

Peer reviewer acknowledgements

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice