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HDN
Classification & external resources

ICD-10	P55.
ICD-9	773
DiseasesDB	5545
MedlinePlus	001298
eMedicine	ped/959

Hemolytic disease of the newborn, also known as HDN or Erythroblastosis fetalis, is an alloimmune condition that develops in a fetus, when the IgG antibodies that have been produced by the mother and have passed through the placenta include ones which attack the red blood cells in the fetal circulation. The red cells are broken down and the fetus can develop reticulocytosis and anemia. This fetal disease ranges from mild to very severe, and fetal death from heart failure (hydrops fetalis) can occur. When the disease is moderate or severe, many erythroblasts are present in the fetal blood and so these forms of the disease can be called erythroblastosis fetalis (or erythroblastosis foetalis).

Contents 1 Symptoms 2 Causes 3 Serological diagnoses 4 Diagnosis 5 Treatment 6 Complications 7 Similar conditions 8 References 9 See also 10 External links

Hemolysis leads to elevated bilirubin levels. After delivery bilirubin is no longer cleared (via the placenta) from the neonate's blood and the symptoms of jaundice (yellowish skin and yellow discolouration of the whites of the eyes) increase within 24 hours after birth. Like any other severe neonatal jaundice, there is the possibility of acute or chronic kernicterus.

Profound anemia can cause high-output heart failure, with pallor, enlarged liver and/or spleen, generalized swelling, and respiratory distress. The prenatal manifestations are known as hydrops fetalis; in severe forms this can include petechiae and purpura. The infant may be stillborn or die shortly after birth.

Antibodies are produced when the body is exposed to an antigen foreign to the make-up of the body. If a mother is exposed to an alien antigen and produces IgG (as opposed to IgM which does not cross the placenta), the IgG will target the antigen, if present in the fetus, and may affect it in utero and persist after delivery. The three most common models in which a woman becomes sensitized toward (i.e., produces IgG antibodies against) a particular blood type are:

• Fetal-maternal hemorrhage can occur due to trauma, abortion, childbirth, ruptures in the placenta during pregnancy, or medical procedures carried out during pregnancy that breach the uterine wall. In subsequent pregnancies, if there is a similar incompatibility in the fetus, these antibodies are then able to cross the placenta into the fetal bloodstream to attach to the red blood cells and cause hemolysis. In other words, if a mother has anti-RhD (D being the major Rhesus antigen) IgG antibodies as a result of previously carrying a RhD-positive fetus, this antibody will only affect a fetus with RhD-positive blood.

• The woman may receive a therapeutic blood transfusion with an incompatible blood type. ABO blood group system and Rhesus blood group system typing are routine prior to transfusion. Suggestions have been made that women of child bearing age or young girls should not be given a transfusion with Rhc-positive blood or Kell₁-positive blood to avoid possible sensitization, but this would strain the resources of blood transfusion services, and it is currently considered uneconomical to screen for these blood groups.

• The third sensitization model can occur in women of blood type O. The immune response to A and B antigens, that are widespread in the environment, usually leads to the production of IgM anti-A and IgM anti-B antibodies early in life. On rare occasions, IgG antibodies are produced. In contrast, Rhesus antibodies are generally not produced from exposure to environmental antigens.

• ABO system
  • ABO hemolytic disease of the newborn can range from mild to severe, but generally it is a mild disease.
    • anti-A antibodies
    • anti-B antibodies

• Rhesus system (the Rh d antigen and Rh d antibodies do not exist)
  • rhesus D hemolytic disease of the newborn (often called Rh disease) is the most common form of severe HDN. The disease varies from mild to severe.
  • rhesus E hemolytic disease of the newborn is a mild condition
  • rhesus c hemolytic disease of the newborn can range from a mild to severe disease - is the third most common form of severe HDN
  • rhesus e hemolytic disease of the newborn - rare
  • rhesus C hemolytic disease of the newborn - rare
  • antibody combinations (ie anti-Rhc and anti-RhE antibodies occurring together) - can be severe

• Kell system
  • anti-Kell hemolytic disease of the newborn
    • anti-K ₁ antibodies - disease ranges from mild to severe - over half of the cases are caused by multiple blood transfusions - is the second most common form of severe HDN
    • anti-K ₂ ,anti-K ₃ and anti-K ₄ antibodies - rare

• Other blood group antibodies (Kidd, Lewis, Duffy, MN, P and others).

The diagnosis of HDN is based on history and laboratory findings:

Blood tests done on the newborn baby

• Biochemistry tests for jaundice
• Peripheral blood morphology shows increased reticulocytes. Erythroblasts (also known as nucleated red blood cells) occur in moderate and severe disease.

• Positive direct Coombs test (might be negative after fetal interuterine blood transfusion)

Blood tests done on the mother

• Positive indirect Coombs test

Before birth, options for treatment include intrauterine transfusion or early induction of labor when pulmonary maturity has been attained, fetal distress is present, or 35 to 37 weeks of gestation have passed. The mother may also undergo plasma exchange to reduce the circulating levels of antibody by as much as 75%.

After birth, treatment depends on the severity of the condition, but could include temperature stabilization and monitoring, phototherapy, transfusion with compatible packed red blood, exchange transfusion with a blood type compatible with both the infant and the mother, sodium bicarbonate for correction of acidosis and/or assisted ventilation.

Rhesus-negative mothers who have had a pregnancy with/are pregnant with a rhesus-positive infant are given Rh immune globulin (RhIG) at 28 weeks during pregnancy and within 72 hours after delivery to prevent sensitization to the D antigen. It works by binding any fetal red cells with the D antigen before the mother is able to produce an immune response and form anti-D IgG. A drawback to pre-partum administration of RhIG is that it causes a positive antibody screen when the mother is tested which is indistinguishable from immune reasons for antibody production.

Complications of HDN could include kernicterus, hepatosplenomegaly, inspissated (thickened or dried) bile syndrome and/or greenish staining of the teeth, hemolytic anemia and damage to the liver due to excess bilirubin.

Similar conditions include acquired hemolytic anemia, congenital toxoplasma and syphilis infection, congenital obstruction of the bile duct and cytomegalovirus infection.

• Geifman-Holtzman, O; Wojtowycz M, Kosmas E, and Artal R (1997). "Female allo-immunization with antibodies known to cause hemolytic disease". Obstetrics and Gynecology 89 (2): 272-275. ISSN 0029-7844. 
• Mollison, PL; Engelfriet CP and Contreras M (1997). Blood Transfusion in Clinical Medicine, 10th edition, Oxford, UK: Blackwell Science. ISBN 0-86542-881-6. 

• Coombs test
• Hemolytic anemia
• Hematology
• Exchange transfusion

• Blood Groups and Red Cell Antigens: Hemolytic disease of the newborn

v • d • e Hemolytic disease of the newborn (HDN)
ABO HDN • Anti-Kell HDN • Rhesus c HDN • Rhesus D HDN • Rhesus E HDN

v • d • e Certain conditions originating in the perinatal period (P, 760-779)
Maternal factors and complications	Umbilical cord prolapse - Nuchal cord - Chorioamnionitis
Length of gestation and fetal growth	Small for gestational age - Large for gestational age - Premature birth - Postmature birth
Birth trauma	Cephalhematoma - Brachial plexus lesion (Erb's palsy, Klumpke paralysis)
Respiratory and cardiovascular	Intrauterine hypoxia - Infant respiratory distress syndrome - Transient tachypnea of the newborn - Meconium aspiration syndrome - Pneumomediastinum - Wilson-Mikity syndrome - Bronchopulmonary dysplasia
Haemorrhagic and haematological	Hemorrhagic disease of newborn - Hemolytic disease of the newborn - Rh disease - Hydrops fetalis - Kernicterus - Neonatal jaundice
Digestive system	Ileus - Necrotizing enterocolitis
Integument and temperature regulation	Erythema toxicum
Other disorders	Periventricular leukomalacia - Congenital hypertonia - Congenital hypotonia - Congenital rubella syndrome