Factors affecting cell-free DNA fetal fraction and the consequences for test accuracy

• DOI: 10.1080/14767058.2017.1330881
• Publication Date: 2017-05-18T04:28:36Z
• Authors: Fergus Perry Scott; Melody Menezes; Ricardo Palma-Dias; Debbie Nisbet; Philip Schluter; Fabricio da Silva...; Andrew Cameron Mc...
• Keywords: Adult; 610; Clinical sciences; Gestational Age; 2729 Obstetrics and Gynaecology; Body Mass Index; Cell-free DNA; 03 medical and health sciences; 0302 clinical medicine; fetal fraction; Pregnancy; Humans; Pregnancy-Associated Plasma Protein-A; Chorionic Gonadotropin, beta Subunit, Human; Placenta Growth Factor; Retrospective Studies; Science & Technology; Obstetrics & Gynecology; Paediatrics; test accuracy; Aneuploidy; Perinatology; 3. Good health; and Child Health; Female; 2735 Pediatrics; Life Sciences & Biomedicine; Cell-Free Nucleic Acids; NIPT; Biomarkers; Maternal Serum Screening Tests

Biological factors are known to influence the fetal fraction (FF) of cell-free DNA and may also influence the accuracy of non-invasive prenatal testing.NIPT from 5267 mixed risk women across three specialist clinics in Australia were analyzed. Multivariable regression analysis was used to determine whether maternal characteristics, ultrasound, and placental biomarkers affect FF and test accuracy.FF ranged from 4% to 37% (mean 11.6%). Body mass index (BMI), gestation, and placental biomarkers were found to be significant factors associated with FF. For each unit increase in BMI, the logarithmically transformed FF, (lnFF), mean value decreased by 0.027. Each week increases in gestation, lnFF increased by 0.023. Each unit increase in free BhCG, PAPPA, and PlGF, the lnFF increased by 0.065, 0.050, and 0.17, respectively. There was no significant association between FF with either maternal age or nuchal translucency. The false-positive cases and one false-negative case did not have lower FF than the true-positive cases.The fetal fraction in maternal plasma cfDNA increased with gestational age, serum pregnancy-associated plasma protein A (PAPP-A), β-hCG, and PlGF and decreased with increasing maternal BMI. There was no significant correlation between low FF and test accuracy, when FF was above 4%.