Non-invasive prenatal testing (NIPT) is used to detect if a fetus is at risk of developing a range of genetic fetal disorders or abnormalities, including hemolytic disease of the fetus and newborn (HDFN).
Testing can be done as early as 10 weeks into the pregnancy and can also predict the sex of the fetus. NIPT tests were previously given only to pregnant women at high risk but are now recommended by The American College of Obstetricians and Gynecologists (ACOG) for all pregnant women.
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.
Medical advances in recent decades have resulted in the early detection of the risk of HDFN during pregnancy via prenatal blood typing, leading to preventative measures and reinforced prenatal care. If the pregnant RhD-negative mother becomes alloimmunized, close monitoring of the fetus will ensure prompt medical intervention if HDFN develops. Early detection and timely treatment have lead to improved outcomes for fetuses and newborns with HDFN.
What is NIPT?
NIPT is genetic screening conducted on a maternal blood sample, using advances in next-generation sequencing, that looks for congenital abnormalities and conditions in the fetus’s DNA. Several different kinds of NIPT exist, covering a variety of chromosomal disorders, including Down syndrome, Edwards syndrome, Patau syndrome and disorders related to the sex chromosomes, such as Turner syndrome and Klinefelter syndrome.
Unlike NIPTs that determine whether there is a risk of the fetus having these conditions, invasive genetic tests which are higher risk–such as amniocentesis or chorionic villus sampling (CVS)–are used to accurately diagnose conditions in the fetus. If a risk is confirmed non-invasively, the next step would be to confirm it with an invasive test. As a result, counseling is offered prior to and following NIPTs to help pregnant couples make informed choices.
NIPT and benefits for HDFN risk detection
In addition to prenatal blood typing, a NIPT has recently been developed to detect fetal antigen genotypes to more accurately identify fetuses at risk for HDFN.
Currently, RhD-negative women at risk of having an RhD-positive fetus routinely receive Rho(D) immunoglobulin and are closely monitored throughout their pregnancy, particularly following alloimmunization. However, in approximately 40% of RhD-negative women pregnant with an RhD-negative fetus, this intervention is not necessary.
If the fetus is negative for the antigen, it is not at risk for HDFN and the Rho(D) immunoglobulin injections can be avoided. This new NIPT tests for the genotype of fetal antigens RhD, C, c, E, K, and Fya, which provides greater accuracy than testing only for RhD antigens. Possible as early as 10 weeks of pregnancy, this next-generation sequencing-based fetal antigen NIPT offers higher sensitivity and specificity in identifying fetuses at risk of HDFN.
