Fetal fraction in maternal plasma cell‐free DNA at 11–13 weeks' gestation: relation to maternal and fetal characteristics

• Published in: Ultrasound in obstetrics & gynecology 2013-01, Vol.41 (1), p.26-32
• Main Authors: Ashoor, G., Syngelaki, A., Poon, L. C. Y., Rezende, J. C., Nicolaides, K. H.
• Format: Article
• Language: English
• Subjects: Adult; Alleles; Biological and medical sciences; cell‐free DNA; Chromosome aberrations; DNA - blood; Female; Fetal Blood - chemistry; fetal fraction; first‐trimester screening; Gynecology. Andrology. Obstetrics; Humans; Male; Maternal Serum Screening Tests - standards; Medical genetics; Medical sciences; non‐invasive prenatal testing; Pregnancy; Pregnancy Trimester, First - blood; Risk Factors; Sequence Analysis, DNA - methods; trisomy 21
• ISSN: 0960-7692; 1469-0705
• DOI: 10.1002/uog.12331

Objective To examine the possible effects of maternal and fetal characteristics on the fetal fraction in maternal plasma cell‐free (cf) DNA at 11–13 weeks' gestation and estimate the proportion of pregnancies at high risk of non‐invasive prenatal testing (NIPT) failure because the fetal fraction is less than 4%. Methods In 1949 singleton pregnancies at 11–13 weeks' gestation cf‐DNA was extracted from maternal plasma. Chromosome‐selective sequencing of non‐polymorphic and polymorphic loci, where fetal alleles differ from maternal alleles, was used to determine the proportion of cf‐DNA that was of fetal origin. Multivariable regression analysis was used to determine significant predictors of the fetal fraction among maternal and fetal characteristics. Results The fetal fraction decreased with increased maternal weight, it was lower in women of Afro‐Caribbean origin than in Caucasians and increased with fetal crown–rump length, serum pregnancy‐associated plasma protein‐A, serum free β‐human chorionic gonadotropin, smoking and trisomy 21 karyotype. The median fetal fraction was 10.0% (interquartile range, 7.8–13.0%) and this decreased with maternal weight from 11.7% at 60 kg to 3.9% at 160 kg. The estimated proportion with fetal fraction below 4% increased with maternal weight from 0.7% at 60 kg to 7.1% at 100 kg and 51.1% at 160 kg. Conclusions Fetal fraction in maternal plasma cf‐DNA is affected by maternal and fetal characteristics.Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.