Rh incompatibility

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

Evidence last reviewed: 23 Apr 2026

Topic last updated: 13 May 2026

Rhesus (Rh) incompatibility is a condition where an Rh-negative mother carrying an Rh-positive fetus can produce antibodies against paternally derived RhD antigens on fetal red blood cells (Rh alloimmunization/sensitization). These antibodies can cross the placenta, and destroy fetal red blood cells. It is a leading cause of hemolytic disease of the fetus and newborn.

Sensitization of the Rh-negative mother is most likely to occur during labor. Once sensitized, the risk of hemolytic disease of the fetus and newborn will be higher in subsequent pregnancies. Effective immunoprophylaxis of Rh-negative at-risk mothers is key to primary prevention.

Intrauterine fetal transfusion and/or early delivery are lifesaving treatments for severely affected fetuses.

Survival rates are more than 90%.

Definition

The nomenclature used to describe proteins found on the surface of red blood cells is complex and there are many subtypes. This topic specifically addresses the RhD antigen and its impact in pregnancy.[1] 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 sensitized and produce immunoglobulin G (IgG) antibodies against their RhD erythrocyte antigen.[1] These maternally derived antibodies can then freely cross the placenta, binding to and destroying fetal RBCs. This is a leading cause of hemolytic disease of the fetus and newborn (previously also known as erythroblastosis fetalis), which may clinically manifest as anemia, hyperbilirubinemia, kernicterus, fetal hydrops (collection of fluid in serous compartments), and may lead to fetal or neonatal death.[2][3][4]

History and exam

Key diagnostic factors

presence of risk factors

Full details

Risk factors

history of an rhesus D (RhD)-positive fetus in an RhD-negative mother
fetomaternal hemorrhage
invasive fetal procedures
placental trauma
abortion
multiparity
omission of rhesus D (RhD) immunoprophylaxis
external cephalic version
molar pregnancy
ectopic pregnancy

Full details

Diagnostic tests

1st tests to order

maternal blood type
maternal serum antibody screen

Full details

Tests to consider

maternal serum antibody titer
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 anemia
rosette test
Kleihauer-Betke test/flow cytometry

Full details

Treatment algorithm

INITIAL

unsensitized RhD-negative mother

sensitized RhD-negative mother

ACUTE

neonate with hemolytic disease of the newborn

Contributors

Authors

Andrea Shields, MD

Associate Professor of Obstetrics and Gynecology

Program Director Maternal Fetal Medicine Fellowship

Division of Maternal Fetal Medicine

University of Connecticut School of Medicine

Farmington, CT

Disclosures

AS declares that she has no competing interests.

Kristen Elmezzi, DO

Maternal Fetal Medicine Fellow

Division of Maternal Fetal Medicine

University of Connecticut School of Medicine

Farmington, CT

Disclosures

KE declares that she has no competing interests.

Acknowledgements

Dr Andrea D. Shields and Dr Kristen Elmezzi would like to gratefully acknowledge Dr Andrew D. Hull, 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. ADH, 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, TX

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

Brennand J, Cameron A. Fetal anaemia: diagnosis and management. Best Pract Res Clin Obstet Gynaecol. 2008 Feb;22(1):15-29. 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

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

Whyte RK, Jefferies AL; Canadian Paediatric Society, Fetus and Newborn Committee. Red blood cell transfusion in newborn infants. Paediatr Child Health. 2014 Apr;19(4):213-22.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
- Nonimmune fetal hydrops
- Parvovirus infection
- Non-RhD hemolytic disease
More Differentials
Guidelines
- Guideline for the investigation and management of red cell antibodies in pregnancy
- ACOG clinical practice update: Rh D immune globulin administration after abortion of pregnancy loss at less than 12 weeks of gestation
More Guidelines
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Rh incompatibility

Summary

Definition

History and exam

Key diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

unsensitized RhD-negative mother

sensitized RhD-negative mother

neonate with hemolytic disease of the newborn

Contributors

Authors

Andrea Shields, MD

Disclosures

Kristen Elmezzi, DO

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