Open Access Articles- Top Results for Hemolytic disease of the newborn

Hemolytic disease of the newborn

Not to be confused with Hemorrhagic disease of the newborn.
File:1910 Erythroblastosis Fetalis.jpg
Classification and external resources
ICD-10 P55
ICD-9 773
DiseasesDB 5545
MedlinePlus 001298
eMedicine ped/959
NCI Hemolytic disease of the newborn
Patient UK Hemolytic disease of the newborn
MeSH D004899

Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis fetalis,[1] is an alloimmune condition that develops in a fetus, when the IgG molecules (one of the five main types of antibodies) produced by the mother pass through the placenta. Among these antibodies are some which attack the red blood cells in the fetal circulation; the red blood 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).


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 discoloration 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.[citation needed]


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 a foreign 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 antigen are:

  • Fetal-maternal hemorrhage can occur due to 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 have received a therapeutic blood transfusion. ABO blood group system and the D antigen of the Rhesus (Rh) 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. HDFN can also be caused by antibodies to a variety of other blood group system antigens, but Kell and Rh are the most frequently encountered.
  • 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 or IgG anti-A and anti-B antibodies early in life. Women of blood type O are more prone than women of types A and B to making IgG anti-A and anti-B antibodies, and these IgG antibodies are able to cross the placenta.[citation needed] For unknown reasons, the incidence of maternal antibodies against type A and B antigens of the IgG type that could potentially cause hemolytic disease of the newborn is greater than the observed incidence of "ABO disease." About 15% of pregnancies involve a type O mother and a type A, B, or AB child; only 3% of these pregnancies result in hemolytic disease due to A/B/O incompatibility. In contrast to antibodies to A and B antigens, Rhesus antibodies are generally not produced from exposure to environmental antigens.

Serological diagnoses

  • ABO system
  • Rhesus system
  • 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

Blood tests done on the mother


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 who are pregnant with a rhesus-positive infant are offered Rh immune globulin (RhIG) at 28 weeks during pregnancy, at 34 weeks, and within 48 hours after delivery to prevent sensitization to the D antigen. It works by binding any fetal red blood 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 can be difficult to distinguish from natural immunological responses that result in antibody production.

Complications and similar conditions

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.

In animals

File:Djaenisse moultea.JPG
Mule foal, 7-days-old, in the last stage of hemolytic disease; symptoms appeared only on Day 6

Hemolytic disease is a well-known condition in newborn foals, especially in Thoroughbreds and mules. Mares or jennies which have been sensitized by a previous pregnancy develop antibodies by fetal blood cells crossing the placental barrier. The iso-antibodies do not transcend the fetal barrier, but are present in colostrum. The Neonatal Fc receptor which in case of humans transfer the maternal antibody from mother through placenta to fetus, in this case is involved in transporting the IgG1 antibodies from mother animal's mammary gland into milk and then again from the ingested milk across the newborn intestine into the newborn animal's circulation.[2] The placenta of mammals can be of many varieties and unless it is hemochorial like humans and some rodents, the IgG of mother cannot directly cross the placenta and passively immunize the fetus. Horse (and also ruminants) have epitheliochorial placenta. Thus IgG1 will enter the bloodstream of the foal only after birth when colostrum immunoglobulins are exposed to FcRn in the newborn intestine, in the first days of life. Hence, hemolytic disease will develop only after birth : first to 4th day in foal [3] and 3 to 7 days in newborn mules. Affected animals show lethargy, recumbency, tachycardia, and progressive icterus of eye and mouth mucosae, which rapidly leads to death. The condition is also described in newborn pigs and other animals [4]

See also


  1. ^ "erythroblastosis fetalis" at Dorland's Medical Dictionary
  2. ^ Mayer, Balázs; Zolnai, Anna; Frenyó, László V.; Jancsik, Veronika; Szentirmay, Zoltán; Hammarström, Lennart; Kacskovics, Imre (1 November 2002). "Redistribution of the sheep neonatal Fc receptor in the mammary gland around the time of parturition in ewes and its localization in the small intestine of neonatal lambs". Immunology 107 (3): 288–296. PMC 1782797. PMID 12423304. doi:10.1046/j.1365-2567.2002.01514.x. 
  3. ^ The Merck Veterinary Manual, 3rd ed. Merck and co. Inc. Rahway, N.J., USA, 1967.
  4. ^ Hemolytic disease in animals

External links