(797) The disappearing act: diminishing Y chromosome cfDNA contribution in vanished twin pregnancies

Maternal blood samples were submitted to Sequenom Laboratories, a Labcorp subsidiary, for NIPS. Fetal fraction (FF) calculation is described in Kim et al¹. Chromosome Y fraction (YFF) is the proportion of the sample with cfDNA fragments mapping to unique regions of the Y chromosome. Sufficient chromosome Y detection is required for male sex reporting. Cases were identified via retrospective internal database search for reported fetal sex discrepancies between March 2015 and January 2022. Included cases had a vanished twin reported by the clinician, discordant fetal sex (male by NIPS, female by ultrasound), and submitted a repeat NIPS specimen.

Results:

49 cases met the above inclusion criteria. The average gestational age (GA) at initial screening was 11.7 weeks with repeat sampling 3.4 – 20.9 weeks later (mean & median: 9.6 weeks). The average FF and YFF at initial sampling were 9.9% and 2.3%, respectively, and 12.2% and 0.5% at resampling. YFF decreased in 96% of cases but was still detectable up to 14 weeks later. The average decrease in YFF was 0.2% per week.

Conclusion:

cfDNA contribution from a vanished twin is variable and influenced by the timing of the demise, reabsorption rates, and maternal physiology. Pre-test NIPS counseling in these pregnancies should include potential for sex discrepancy. In the absence of other fetal concerns repeat NIPS sampling at a later GA may be a reasonable first step in the context of a known vanished twin. The average change in YFF/week may guide time to resampling. Comparison of YFF to FF may be helpful in sex discrepant cases, particularly when early ultrasound data is limited.