E-Mail karger@karger.com Original Paper Fetal Diagn Ther DOI: 10.1159/000355655 Prenatal Detection of Fetal Triploidy from Cell-Free DNA Testing in Maternal Blood Kypros H. Nicolaides   a, b Argyro Syngelaki   a Maria del Mar Gil   a Maria Soledad Quezada   a Yana Zinevich   a   a  Harris Birthright Research Centre of Fetal Medicine, King’s College Hospital, and b  Department of Fetal Medicine, University College Hospital, London, UK weight and gestational age was below the 0.5th percentile. Conclusions: cfDNA testing by targeted sequencing and al- lelic ratio analysis of single nucleotide polymorphisms cov- ering chromosomes 21, 18, 13, X, and Y can detect diandric triploidy and raise the suspicion of digynic triploidy. © 2013 S. Karger AG, Basel Introduction Triploidy, in which the fetus has three copies of all chromosomes, affects about 1% of recognized concep- tions, but it is highly lethal and it is rarely observed in live births. The prevalence at 12 weeks’ gestation is about 1 in 2,000 and this falls to 1 in 250,000 by 20 weeks [1, 2]. There are two phenotypes of triploidy, depending on whether the origin of the extra haploid set is paternal (di- andric) or maternal (digynic) [3–6]. The digynic type is characterized by a small normal looking placenta, severe- ly growth-restricted fetus with pronounced wasting of the body and sparing of the head, normal fetal nuchal trans- lucency (NT) thickness and very low serum-free β-hCG and PAPP-A. In the diandric type, the placenta is en- larged and partially molar, the fetus is only mildly growth- restricted, the fetal NT tends to be high and maternal se- Key Words Non-invasive diagnosis · Prenatal diagnosis · Triploidy · Cell-free DNA Abstract Objective: To investigate potential performance of cell-free DNA (cfDNA) testing in maternal blood in detecting fetal triploidy. Methods: Plasma and buffy coat samples obtained at 11–13 weeks’ gestation from singleton pregnancies with diandric triploidy (n = 4), digynic triploidy (n = 4), euploid fetuses (n = 48) were sent to Natera, Inc. (San Carlos, Calif., USA) for cfDNA testing. Multiplex polymerase chain reaction amplification of cfDNA followed by sequencing of single nu- cleotide polymorphic loci covering chromosomes 13, 18, 21, X, and Y was performed. Sequencing data were analyzed us- ing the NATUS algorithm which identifies copy number for each of the five chromosomes. Results: cfDNA testing pro- vided a result in 44 (91.7%) of the 48 euploid cases and cor- rectly predicted the fetal sex and the presence of two copies each of chromosome 21, 18 and 13. In diandric triploidy, cfDNA testing identified multiple paternal haplotypes (indi- cating fetal trisomy 21, trisomy 18 and trisomy 13) suggest- ing the presence of either triploidy or dizygotic twins. In di- gynic triploidy the fetal fraction corrected for maternal Received: August 12, 2013 Accepted after revision: September 16, 2013 Published online: October 10, 2013 Prof. K.H. Nicolaides Harris Birthright Research Centre for Fetal Medicine King’s College Hospital Denmark Hill, London SE5 9RS (UK) E-Mail kypros  @  fetalmedicine.com © 2013 S. Karger AG, Basel 1015–3837/13/0000–0000$38.00/0 www.karger.com/fdt Downloaded by: UCL 82.23.63.209 - 2/17/2014 7:56:10 PM