Medical advances in prenatal screening and early diagnosis and treatment in recent decades have led to hemolytic disease of the fetus and newborn (HDFN) becoming significantly less prevalent worldwide.
However, although now considered to be a rare red blood cell disease, HDFN cases still occur, and they can vary from mild to severe, with worst outcomes including fetal mortality and stillbirth. Early detection of at-risk pregnancies remains a key contributor to positive outcomes.
While more research is needed, several common risk factors have been identified in severe cases. These include red cell antibody specificity, ethnicity and geographic location.
What is HDFN?
Hemolytic disease of the fetus and newborn (HDFN) is an immune-mediated red blood cell (RBC) disorder that occurs when a baby’s RBCs break down quickly, which is called hemolysis. HDFN is caused by a mismatch between a mother’s and her baby’s blood type (A, B, AB, or O) or Rhesus (Rh) factor (Rh-positive or Rh-negative) during pregnancy. Numerous antibodies to RBC antigens can be linked to HDFN, such as those from the ABO and Rh blood group systems.
In the United States, according to a study of HDFN from 1996 to 2010, cases of HDFN correspond with a live birth prevalence of 1695 per 100,000 live births. Among newborns with HDFN, 0.6% of cases were severe.
Severe HDFN risk factors
Red cell alloantibody specificities
HDFN is a red blood cell (RBC) disorder that can be activated during pregnancy when maternal and fetal blood types are incompatible. The two main RBC incompatibilities are ABO and Rh-D, with other antigens including Rh-c, Rh-E, other Rh antigens, as well as the rarer Kell, Duffy and Kidd antigens.
Severity differs according to the antigen, with Rh-D is the most common and is shown to have the highest risk for fetal mortality and morbidity. Other antigens lead to milder versions of HDFN, which require less medical intervention and have better outcomes. Different ethnicities experience HDFN differently.
According to a study of babies affected by HDFN in the United States from 1996 to 2010, Rh alloimmunization were more likely to require medical interventions and more likely to be delivered by cesarean.
Learn more about HDFN causes and risk factors
Ethnicity
Asian and Black populations have shown to have different experiences with HDFN, with different antigens leading to severe HDFN than in a White population. For example, in the Chinese population, non-RhD alloantibodies including anti-E, anti-c, and anti-M have been reported to cause severe HDFN.
Geography
High-income countries have greater resources for prenatal screening, preventative measures and specialized treatment, prenatally and postnatally. This has meant a reduction in severe cases of HDFN. Inversely, severe cases of HDFN in lower-income countries have worse outcomes.
Severe HDFN outcomes
Regardless of the red cell alloantibody specificity responsible, if severe HDFN is left untreated or diagnosed at a later stage, outcomes for the fetus or newborn can become dire. Prognosis can be poor in utero, with a high risk of fetal anemia, hydrops fetalis and fetal death. Post-delivery, the neonate can suffer from hyperbilirubinemia (jaundice) and kernicterus, with the risk of permanent brain damage.
