Grand Rounds

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

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

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)

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

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