Impact of Co-Twin Demise on Circulating Cell-Free DNA (ccfDNA) Testing [10R]

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Abstract

INTRODUCTION:

Sequenom Laboratories' clinical validation data show high sensitivity and specificity in multifetal gestations. To date more than 16,000 such samples, have been analyzed in clinical practice. A small subset of NIPT results were reported as discordant with fetal outcome. Upon investigation co-twin demise could be identified as a possible cause for the discrepant results. Here we review these co-twin demise discordant results.

METHODS:

ccfDNA testing using massively parallel sequencing (MPS) on maternal blood was performed by Sequenom Laboratories.

RESULTS:

We report 37 discrepant NIPT results, 31 accompanied by ultrasound documented co-twin demise and six strongly suspected co-twin demise based on reported clinical findings. The majority of discrepancies were for fetal sex (26). Eleven patients with a co-twin demise were discrepant for trisomies 13, 16, 18, 21, 22, and 1p36 deletion. In two of these cases, one trisomy 21 and one 1p36 deletion, the genetic profile has stabilized at 12 and 15 weeks after the original result.

CONCLUSION:

Our cases demonstrate that residual ccfDNA from a demised twin may impact NIPT results by way of false positive or discrepant fetal sex results. Many variables confound the issue, such as embryo/fetus reabsorption rate, maternal ccfDNA clearance, and gestational age at demise and at NIPT testing. Evidence of loss is commonly seen in NIPT results 8 weeks or more after demise, illustrating the importance of reporting this clinical information to the testing laboratory. With an increased incidence of fetal mortality in multiple gestations, this biological factor is an important differential in discrepant NIPT cases.

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