Fetal cell-free DNA testing can safely stop unnecessary monitoring for hemolytic disease of the fetus and newborn (HDFN), according to research published recently in Pregnancy.
These results show that when testing confirms a fetus does not carry the relevant antigen, continued antibody titer checks and ultrasound Doppler monitoring can be discontinued without increasing risk. This change could spare many expectant mothers from avoidable procedures, costs, and worry.
“[T]his study provides evidence that titers incorrectly suggest pregnancies are at risk of HDFN, leading to unnecessary downstream monitoring of alloimmunized pregnancies with additional titers and/or MCA-PSV Doppler,” explained this study’s authors. They continued, “Consequences of this unnecessary monitoring may include the financial and emotional burden to the patient, the cost to the healthcare system, and the potential risks of the patient undergoing unnecessary invasive procedures.”
Researchers reviewed 69 pregnancies affected by maternal antibodies between October 2022 and November 2023. All participants underwent fetal antigen cfDNA testing, and results were confirmed after birth by neonatal genotyping. The study found that 58% of fetuses were antigen positive, meaning at risk for HDFN, while 42% were antigen negative and therefore not at risk.
Read more about testing and diagnosis for HDFN
Surprisingly, antibody titers rose or reached critical levels at nearly identical rates in both groups, which was 70% among antigen-positive pregnancies and 69% among antigen-negative ones. These findings suggest that rising titers do not reliably indicate fetal risk and can lead to unnecessary follow-up testing.
Among antigen-negative pregnancies, 62% still underwent Doppler ultrasound monitoring to check for fetal anemia, even though no risk was present. One case (5.6%) produced a false-positive result, suggesting anemia that was not actually there. In contrast, 41% of antigen-positive pregnancies showed true signs of anemia, a significant difference that confirmed the accuracy of cfDNA testing (P = .009).
This study also highlighted that antibody titers vary between laboratories and often fail to match actual fetal outcomes. Investigators emphasized that relying on titers alone can cause emotional distress and financial strain, as well as prompt unnecessary invasive procedures such as amniocentesis.
Because cfDNA results matched neonatal outcomes in every case, researchers concluded that this testing provides a definitive answer about fetal antigen status. Ending serial titer checks and Doppler monitoring for antigen-negative pregnancies could reduce patient burden and healthcare costs while keeping care safe for those who truly need it.
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