Should vanishing twin pregnancies be systematically excluded from cell‐free fetal DNA testing?

• Published in: Prenatal diagnosis Vol. 41; no. 10; pp. 1241 - 1248
• Main Authors: Balaguer, Nuria, Mateu‐Brull, Emilia, Serra, Vicente, Simón, Carlos, Milán, Miguel
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.09.2021; Wiley Subscription Services, Inc
• Subjects: Algorithms; Aneuploidy; Chromosomes; Clinical medicine; Contaminants; Deoxyribonucleic acid; DNA; DNA sequencing; DNA testing; Fetal resorption; Fetuses; Pregnancy; Sex; Trisomy
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.5817

Objective To demonstrate the feasibility of cell‐free DNA (cfDNA) testing in vanishing twin (VT) pregnancies in routine clinical practice. Methods Our study included 24 874 singleton and 206 VT consecutive pregnancies. Cell‐free DNA was analyzed by massively parallel sequencing. Both aneuploidy analysis (chromosomes 13,18, 21, X, and Y) and fetal fraction estimation were performed according to an Illumina algorithm. Contaminant DNA contribution from the demised co‐twin was studied in detail. Results VT pregnancies exhibited a higher prevalence of screen‐positive cases (5.8% vs 2.5%), sex discrepancies (10.2% vs 0.05%), and false positive rates (FPR) (2.6% vs 0.3%) than singleton pregnancies. However, their incidence was significantly lower in tests performed after the 14th week (screen‐positive cases: 3.1%; sex discrepancies: 7.8%; and FPR: 0.8%). Among the 12 cases in which cfDNA was performed at two time points, fading of contaminating cfDNA was observed in four cases with a sex discrepancy and in one false positive for trisomy 18, resulting in a final correct result. Conclusions Our data suggest VT pregnancies could be included in cfDNA testing as long as it is applied after the 14th week of pregnancy. However, future studies to validate our findings are needed before including VT cases in routine clinical practice. Once established, unnecessary invasive procedures could be avoided, mitigating negative emotional impact on future mothers.