Could Anti-Coagulant Medication Obscure NIPS Results?

BACKGROUND AND PURPOSE:

  • ‘No result’ or ‘no call’ will be reported in a small number of NIPS studies
    • Often due to low fetal fraction (FF) of <4%
    • Other causes include obesity
    • Low molecular weight heparin (LMWH) has been suggested as a factor, but limited data
  • Burns et al. (Prenatal Diagnosis, 2017) identified maternal characteristics and comorbidities associated with a failed cell-free DNA (cfDNA) test due to a low FF, including the effects of enoxaparin

METHODS:

  • Retrospective cohort study
  • Participants: Women with singleton pregnancies who had NIPS screening
  • FF performed using 2 different techniques
    • Methylation techniques initially
    • Switched over to multivariable model using whole genome low coverage massively parallel sequencing
    • FF threshold remained at 4%
  • Multivariable logistic regression was performed to identify maternal characteristics associated with no NIPS result secondary to low FF

RESULTS:

  • 2,890 women were eligible for the study
  • 33 (1.2%) had a failed NIPS
    • 6% were due to low FF
    • 18% of women on enoxaparin had a failed NIPS
  • A failed screening result due to low FF was associated with
    • Obesity (adjusted odds ratio [aOR] of 1.11, CI 1.05–1.18, p= 0.0003)
    • Treatment with enoxaparin (aOR 37.5, 11.19–125.87, p< 0.0001)
  • Hypertension was not significantly associated with a failed NIPS after adjusting for BMI, anticoagulation therapy, and gestational age at screening (aOR 1.34, CI 0.33–5.41, p = 0.681)

CONCLUSION:

  • A failed cfDNA test due to low FF was associated with enoxaparin therapy and obesity
  • The authors suggest the following mechanisms for failure rate and LMWH
    • Heparin has been shown to decrease trophoblast apoptosis which would impact the ‘fetal’ cfDNA fraction which originates from the placenta
  • Further research is needed to determine the mechanism by which anticoagulation therapy alters cfDNA test functionality and identify approaches to improve test performance in these women

Learn More – Primary Sources:

The association between anticoagulation therapy, maternal characteristics, and a failed cfDNA test due to a low fetal fraction