Neonatal alloimmune neutropenia (NAIN) and hemolytic disease of the fetus and newborn (HDFN) are rare blood-related conditions that can occur in pregnancy, putting the fetus and newborn at risk.
In both cases, the mother’s immune system creates antibodies that attack her baby’s blood cells, causing them to break down. This can have mild to severe consequences for fetuses and newborns, with early diagnosis and timely treatment important factors to increase the likelihood of positive outcomes.
What is HDFN?
Hemolytic disease of the fetus and newborn (HDFN) is an immune-mediated red blood cell 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.
What is fetal neonatal alloimmune neutropenia?
NAIN is a rare white blood cell disorder that is found in less than 0.1% of newborns. It affects the neutrophils, which help fight infection, in the fetus and newborn. It occurs when the mother develops antibodies against the baby’s human neutrophil antigens (HPAs) that have been inherited from the father and are not present in the mother. The mother’s immune system perceives them as foreign and releases antibodies as a defense mechanism, which then cross the placenta.
The breakdown of neutrophils leads to neutropenia, which lowers the body’s ability to prevent or fight infection. In utero, this is not an issue, but newborns with neutropenia may require antibiotics or a drug containing granulocyte-colony stimulating factor to boost the production of neutrophils. A low absolute neutrophil count (ANC) can last a few weeks to 6 months in newborns.
Symptoms of NAIN can vary from none to unexplained fever, tiny blood spots under the skin (petechiae), mild skin infections, umbilical cord site infections (omphalitis) or more severe infections, including sepsis, meningitis and pneumonia.
Fetal neonatal alloimmune neutropenia vs HDFN
As rare blood-related disorders that can occur in pregnancy as the result of a maternal/fetal incompatibility, NAIN and HDFN have a number of similarities and distinct differences.
Similarities
Both conditions:
- Occur in pregnancy
- Involve the mother’s immune system attacking her baby’s blood cells
- Reoccur in subsequent pregnancies
- Are diagnosed by blood tests
- Require close monitoring and timely treatment
Additionally, maternal immunization can occur in first pregnancies, leading to NAIN. While possible, cases of HDFN are less common in first pregnancies.
Differences
- NAIN is caused by an incompatibility in maternal/fetal neutrophil antigen; HDFN is caused by Rh incompatibility or ABO incompatibility.
- NAIN is not part of prenatal screening; HDFN is often included in standard prenatal screening programs.
- Most often, NAIN has no long-term affect on the baby; HDFN can lead to severe jaundice and anemia.
- NAIN affects the baby’s white blood cells, whereas HDFN affects the baby’s red blood cells.
- NAIN is not a risk during pregnancy; HDFN can be life-threatening if diagnosis and medical intervention are delayed.
- NAIN is treated with antibiotics and a drug containing ganulocyte-colony stimulating factor; HDFN can require blood transfusions, intravenous immunoglobulin and phototherapy.
- NAIN is diagnosed through Neutrophil Antigen Genotyping, as well as the Neutrophil Antibody Identification and HLA Antibody Screen; HDFN is diagnosed through a direct Coombs test to detect maternal anti-D antibodies that have already bound to fetal RBC.
