Fergus Perry Scott1,2, Melody Menezes3, Ricardo Palma-Dias4,5, Debbie Nisbet4,6, Philip Schluter7,8, Fabricio da Silva Costa3,9, Andrew Cameron McLennan1,10. 1. a Sydney Ultrasound for Women , Bondi Junction , Australia. 2. b Department of Obstetrics and Gynaecology , University of New South Wales , Sydney , Australia. 3. c Monash Ultrasound for Women , The Epworth Centre , Richmond , Australia. 4. d Women's Ultrasound Melbourne , Parkville , Australia. 5. e Pregnancy Research Centre, Department of Obstetrics and Gynaecology , University of Melbourne , Melbourne , Australia. 6. f Department of Medicine and Radiology , University of Melbourne , Melbourne , Australia. 7. g School of Health Sciences , University of Canterbury , Christchurch , New Zealand. 8. h School of Nursing, Midwifery and Social Work , University of Queensland , Brisbane , Australia. 9. i Department of Obstetrics and Gynaecology, Monash University , Clayton , Australia. 10. j Discipline of Obstetrics, Gynaecology and Neonatology, University of Sydney , Sydney , Australia.
Abstract
INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. DISCUSSION: 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%.
INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. DISCUSSION: 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%.
Entities:
Keywords:
Cell-free DNA; NIPT; fetal fraction; test accuracy
Authors: Liesbeth Vossaert; Qun Wang; Roseen Salman; Anne K McCombs; Vipulkumar Patel; Chunjing Qu; Michael A Mancini; Dean P Edwards; Anna Malovannaya; Pengfei Liu; Chad A Shaw; Brynn Levy; Ronald J Wapner; Weimin Bi; Amy M Breman; Ignatia B Van den Veyver; Arthur L Beaudet Journal: Am J Hum Genet Date: 2019-11-27 Impact factor: 11.025