Discordant NIPT and ultrasound results from vanishing twin pregnancy

 

By Bowdoin Su, MD¹; Mitchell Nudelman, MD²; Melissa Stosic, MS¹; Zachary Demko, PhD¹; and Susan J. Gross, MD¹

¹Natera, San Carlos, CA; ²Bellegrove OBGYN, Bellevue, WA

The Case

In this case, the patient was a 35-year-old G2P1 who presented to her obstetrician for routine prenatal care at 9 weeks’ gestation. She had been referred by her infertility doctor after a successful in vitro fertilization-conceived pregnancy; two embryos were transferred. One week prior to being seen, ultrasound at another facility had revealed a “vanishing twin” pregnancy.

After discussing options for prenatal screening of chromosomal aneuploidies (because of her advanced maternal age), the patient chose noninvasive prenatal testing (NIPT). The PanoramaTM test (Natera, Inc.; San Carlos, CA), a single-nucleotide polymorphism (SNP)-based NIPT, was ordered 1 week later and reported, “Results are consistent with a possible triploid or vanishing twin pregnancy. Follow-up counseling and testing is recommended.”

At 13 weeks, the patient’s physician ordered a different NIPT (non-SNP-based, and counting-based). That NIPT reported a finding of a “normal male” fetus. At 17 weeks, the patient had another ultrasound. In contrast to the counting-based NIPT results, this ultrasound showed a normal female fetus.

Given the discrepancy between the 13-week counting-based NIPT (male) and the 17-week ultrasound (female), amniocentesis for definitive chromosomal studies was offered to the patient.

She declined, and at 39 weeks, delivered a phenotypically normal female baby. Peripheral blood revealed a 46,XX chromosomal complement.

Discussion

One in 30 live births is from a twin gestation pregnancy. Twins are even more common early in gestation-36% of first-trimester twin pregnancies result in one deceased (“vanishing”) twin.¹ Because a “vanished” twin often had a chromosomal aneuploidy, such pregnancies are acknowledged to be a source of false-positive NIPT results.

Several studies reporting on commercial experiences with NIPT using a counting method attribute 15% to 33% of false-positive calls to the phenomenon of vanishing twin pregnancies.^2,3 Multiple accounts have demonstrated that cell-free fetal DNA (cffDNA) from the demised twin can be detected 8 weeks or longer after demise.^4,5

Counting-based NIPT methods can determine gender early in gestation with high accuracy (>98%).^6,7 However, because such methods are based on counting total circulating DNA, they cannot distinguish the source of additional DNA sequences beyond the viable fetus, whether maternal or a vanishing twin. Thus, cffDNA from a genetically dissimilar deceased twin could be counted as part of the total DNA, and could lead to incorrect test results for the surviving fetus.

 

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