Although hemolytic disease of the fetus and newborn (HDFN) associated with the presence of irregular red blood cell (RBC) antibodiesAntibody A protein made by the immune system that recognizes and attacks foreign substances, such as bacteria, or in HDFN, fetal red blood cells carrying incompatible antigens. is rare, the clinical manifestations can be quite serious, according to a retrospective study published recently in the journal Children.
HDFN is an immune hemolytic disorder that is caused by blood groupBlood group A classification of blood based on inherited markers found on red blood cells. The ABO and Rh blood groups are most common in HDFN. incompatibility between a pregnant patient and the fetus, with the disease associated with neonatal anemiaAnemia A condition that occurs when the body doesn’t have enough healthy red blood cells to carry oxygen to its tissues. In HDFN, anemia occurs when maternal antibodies destroy fetal red blood cells. and jaundiceJaundice A common symptom of HDFN, jaundice is caused by excess bilirubin and is characterized by a yellow tint to the skin or eyes.. To date, more than 40 blood group systems and 350 RBC group antigensAntibody A protein made by the immune system that recognizes and attacks foreign substances, such as bacteria, or in HDFN, fetal red blood cells carrying incompatible antigens. have been identified, with all exhibiting immunogenic potential—that is, the ability to generate an immune response in the body.
Common vs uncommon types of HDFN
The most common type of HDFN is ABO incompatibility, which is followed by Rhesus (RhRh factor A protein or antigen found on red blood cells. When an Rh-negative mother carries an Rh-positive fetus, her immune system may make antibodies that attack the fetus' red blood cells.) incompatibility. However, HDFN can occur in other, less common RBC group systems, including Kell, Kidd and MNS. In fact, the diagnosis of irregular antibodies outside of the ABO group necessitates the use of specialized laboratory tests, which causes such cases to be frequently overlooked or misdiagnosed. This, in turn, can lead to “unnecessary testing, adverse outcomes, and an increased economic burden.”
Advancements in diagnostic techniques have led to the detection and recognition of more cases of HDFN associated with irregular antibodies. It is becoming increasingly more evident that HDFN can be associated with very serious complications, including prolonged or aplastic anemia.
Read more about HDFN testing and diagnosis
Recognizing that limited research is available on the maternal factors, clinical features and outcomes of HDFN linked to irregular antibodies, the investigators sought to evaluate the maternal conditions, clinical characteristics and prognosis among individuals with HDFN caused by irregular antibodies. They used patients with ABO-HDFN as the reference.
Study methods and outcome
All children who were admitted to Peking University Third Hospital between Jun. 1, 2009, and Dec. 31, 2022, with a definite diagnosis of HDFN were assessed.
Patients with irregular antibodies were matched in a 1:3 ratio to patients with ABO-HDFN. All participants were divided into one of two groups, according to the type of RBC antibodies they exhibited:
- ABO incompatibility group, which comprised newborns with ABO-HDFN
- Irregular antibodyAntibody A protein made by the immune system that recognizes and attacks foreign substances, such as bacteria, or in HDFN, fetal red blood cells carrying incompatible antigens. group, which included newborns with Rh or another rare blood group incompatibility form of HDFN (n=32)
Children with the verified Rh incompatibility form of HDFN were further divided into one of the following two subgroups:
- RhD subgroup, in whom hemolysis (destruction of RBCs) was induced by Rh anti-D
- Non-RhD subgroup, in whom hemolysis was induced by other Rh antibodies
Results of the study showed that compared with the ABO incompatibility group, those in the irregular antibody group exhibited statistically significant earlier development of jaundice, higher rates of direct antiglobulin testDirect antiglobulin test A blood test used to detect antibodies attached to red blood cells. It helps confirm HDFN in newborns. positivity, earlier and more severe anemia, greater use of enhanced phototherapyPhototherapy A treatment that uses special blue light to help newborns break down bilirubin and prevent kernicterus., higher rates of blood transfusions/blood exchange and lengthier hospital stays (P <.05 for all).
In addition, compared with the non-RhD subgroup, those in the RhD subgroup demonstrated a significantly earlier occurrence of jaundice, along with significantly higher rates of spleen and liver enlargement (P <.05 for both).
Patients were also grouped into a single irregular antibody group and a multiple irregular antibodies group. Those in the multiple irregular antibodies group exhibited significantly higher rates of phototherapy, blood transfusions and blood exchange compared with those in the single irregular antibody group (P <.05 for all).
“It is important to pay attention to the screening of irregular antibodies during pregnancy, to strengthen monitoring, and to provide intrauterine treatment and early intervention if necessary,” the authors concluded.
