Hemolytic disease of the fetus and newborn in the molecular era

Area of Science:

• Obstetrics and Gynecology
• Genetics
• Immunology

Background:

• Maternal-fetal red cell antigen incompatibility can cause alloimmunization, leading to hemolytic disease of the fetus and newborn (HDFN).
• Routine antenatal anti-D prophylaxis (RAADP) has substantially reduced HDFN incidence and mortality from RhD allosensitization.
• Advances in molecular diagnostics have improved the identification of pregnancies at risk for HDFN.

Purpose of the Study:

• To review molecular advancements in prenatal diagnostics for HDFN.
• To highlight the impact of non-invasive fetal RHD genotyping and targeted RAADP.
• To discuss the decreased need for invasive procedures in high-risk pregnancies.

Main Methods:

• Utilizing paternal molecular RHD zygosity testing to identify at-risk pregnancies.
• Employing non-invasive fetal molecular diagnostics using cell-free DNA (cff-DNA) in maternal plasma for fetal RHD detection.
• Integrating middle cerebral artery Doppler ultrasonography for predicting fetal anemia.

Main Results:

• Fetal RHD genotyping using cff-DNA has demonstrated increasing accuracy for fetal RHD detection.
• Targeted RAADP programs are being implemented in some countries based on mass screening of RhD-negative pregnant women.
• Non-invasive diagnostics, combined with Doppler ultrasonography, have significantly reduced the necessity for invasive diagnostic procedures.

Conclusions:

• Molecular advancements have revolutionized prenatal diagnostics for HDFN.
• Non-invasive fetal RHD genotyping enables precise risk assessment and targeted interventions.
• These innovations enhance maternal and fetal health outcomes by minimizing invasive procedures and optimizing prophylaxis strategies.