Physiology · Blood, hemostasis and basic immunity

Rh incompatibility !

Mechanism
For completeness

An Rh-negative mother can make antibodies against her Rh-positive baby's red cells. In a later pregnancy they cross the placenta and destroy the baby's cells.

Updated 2026-11-01

Also called: Hemolytic disease of the fetus and newborn, Erythroblastosis fetalis, RhD alloimmunization

See it in 3D: Spleen · Liver

Key points

The first pregnancy is usually spared: sensitization mainly occurs at delivery, and the primary response is slow and mostly IgM, which does not cross the placenta.
Other sensitizing events: miscarriage, ectopic pregnancy, abdominal trauma, amniocentesis, antepartum bleeding, mismatched transfusion.
Anti-D immunoglobulin given to the RhD-negative mother clears fetal RhD-positive cells before her immune system responds; it prevents sensitization but cannot reverse it.
Fetal effects: anemia → extramedullary hematopoiesis, erythroblasts in blood, high-output heart failure and hydrops.
After birth, the liver cannot clear the bilirubin load → severe unconjugated jaundice and risk of kernicterus.
ABO incompatibility (group O mother, A or B baby) is more common but milder, and it partly protects against Rh sensitization.

What it is

Rh incompatibility arises when an RhD-negative mother carries an RhD-positive fetus. Fetal cells entering her blood, mostly at delivery, sensitize her and she makes anti-D. In later pregnancies these IgG antibodies cross the placenta, coat fetal red cells and cause hemolytic disease of the fetus and newborn, from mild jaundice to fetal hydrops.

How it works, step by step

Fetal RhD-positive red cells cross into the RhD-negative mother's circulation (fetomaternal hemorrhage).
Her immune system sees RhD as foreign → primary response, then memory B cells.
In a later RhD-positive pregnancy, small leaks trigger a fast secondary response of anti-D IgG.
IgG crosses the placenta via the neonatal Fc receptor → coats fetal red cells.
Fetal spleen macrophages remove coated cells → hemolysis and anemia; marrow, liver and spleen expand red cell production.
Severe anemia → hypoxia, heart failure, low albumin from liver crowding → generalized edema (hydrops fetalis).
During pregnancy the placenta clears bilirubin; after birth the immature liver is overwhelmed → jaundice in the first 24 h.

Clinical notes

Indirect Coombs test (mother's serum) detects anti-D during pregnancy; direct Coombs test (baby's cells) detects antibody already bound.
Jaundice in the first 24 hours of life is never physiological: think of hemolysis such as Rh or ABO disease.
Fetal anemia is followed by Doppler of the middle cerebral artery: anemic blood is less viscous and flows faster.

Test yourself

Think of the answer, then tap the question to see it.

Why is the first RhD-positive pregnancy of an RhD-negative mother usually unaffected?

Most fetal cells enter her blood at delivery, too late to harm that baby, and the first response is slow and mostly IgM, which does not cross the placenta.

How does ABO incompatibility between mother and fetus lower the risk of Rh sensitization?

If the mother has anti-A or anti-B against the fetal group, those antibodies destroy fetal cells entering her blood before her immune system can respond to RhD.

Why does the newborn with Rh disease become jaundiced only after birth?

Before birth, unconjugated bilirubin crosses the placenta and the mother's liver clears it. After birth, the newborn's immature liver, with low UGT1A1 activity, cannot handle the hemolysis load.

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See it in 3D

The structures of Durgical's 3D anatomy where it happens.

Neonatal jaundice

In Biochemistry

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Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: Rh incompatibility (MedlinePlus (U.S. National Library of Medicine), 2024); 18.6 Blood Typing (OpenStax (Rice University), 2022); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 36). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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