High Fetal Fraction on First Trimester Cell-Free DNA Aneuploidy Screening and Adverse Pregnancy OutcomesFunding None.
20. Juni 2019
25. Juni 2019
31. Juli 2019 (online)
Objective To test the hypothesis that high fetal fraction (FF) on first trimester cell-free deoxyribonucleic acid (cfDNA) aneuploidy screening is associated with adverse perinatal outcomes.
Study Design This is a single-institution retrospective cohort study of women who underwent cfDNA screening at <14 weeks' gestation and delivered a singleton infant between July 2016 and June 2018. Women with abnormal results were excluded. Women with high FF (≥95th percentile) were compared with women with normal FF (5th–95th percentiles). Outcomes investigated were preterm birth, small for gestational age, and hypertensive disorders of pregnancy.
Results A total of 2,033 women met inclusion criteria. The mean FF was 10.0%, and FF >16.5% was considered high (n = 102). Women with high FF had a greater chance of delivering a small for gestational age infant <fifth percentile, with an adjusted odds ratio of 2.4 (95% confidence interval: 1.1–4.8, p = 0.039). There was no significant association between high FF and either preterm birth or hypertensive disorders of pregnancy.
Conclusion Women with a high FF in the first trimester are at increased risk of delivering a small for gestational age infant <fifth percentile. Further investigation into the clinical implications of a high FF is warranted.
Keywordsaneuploidy screening - cell-free DNA - fetal fraction - adverse pregnancy outcomes - fetal growth restriction
This study was presented as poster abstract (no. 901) at SMFM's 39th Annual Pregnancy Meeting, Las Vegas, NV, February 11–16, 2019.
- 1 Lo YM, Corbetta N, Chamberlain PF. , et al. Presence of fetal DNA in maternal plasma and serum. Lancet 1997; 350 (9076): 485-487
- 2 Huppertz B, Kingdom JC. Apoptosis in the trophoblast--role of apoptosis in placental morphogenesis. J Soc Gynecol Investig 2004; 11 (06) 353-362
- 3 Taglauer ES, Wilkins-Haug L, Bianchi DW. Review: cell-free fetal DNA in the maternal circulation as an indication of placental health and disease. Placenta 2014; 35 (Suppl): S64-S68
- 4 Sekizawa A, Jimbo M, Saito H. , et al. Increased cell-free fetal DNA in plasma of two women with invasive placenta. Clin Chem 2002; 48 (02) 353-354
- 5 Illanes S, Parra M, Serra R. , et al. Increased free fetal DNA levels in early pregnancy plasma of women who subsequently develop preeclampsia and intrauterine growth restriction. Prenat Diagn 2009; 29 (12) 1118-1122
- 6 Sekizawa A, Jimbo M, Saito H. , et al. Cell-free fetal DNA in the plasma of pregnant women with severe fetal growth restriction. Am J Obstet Gynecol 2003; 188 (02) 480-484
- 7 Farina A, LeShane ES, Romero R. , et al. High levels of fetal cell-free DNA in maternal serum: a risk factor for spontaneous preterm delivery. Am J Obstet Gynecol 2005; 193 (02) 421-425
- 8 Jakobsen TR, Clausen FB, Rode L, Dziegiel MH, Tabor A. High levels of fetal DNA are associated with increased risk of spontaneous preterm delivery. Prenat Diagn 2012; 32 (09) 840-845
- 9 Thurik FF, Lamain-de Ruiter M, Javadi A. , et al. Absolute first trimester cell-free DNA levels and their associations with adverse pregnancy outcomes. Prenat Diagn 2016; 36 (12) 1104-1111
- 10 van Boeckel SR, Davidson DJ, Norman JE, Stock SJ. Cell-free fetal DNA and spontaneous preterm birth. Reproduction 2018; 155 (03) R137-R145
- 11 Dugoff L, Barberio A, Whittaker PG, Schwartz N, Sehdev H, Bastek JA. Cell-free DNA fetal fraction and preterm birth. Am J Obstet Gynecol 2016; 215 (02) 231.e1-231.e7
- 12 Leung TN, Zhang J, Lau TK, Hjelm NM, Lo YM. Maternal plasma fetal DNA as a marker for preterm labour. Lancet 1998; 352 (9144): 1904-1905
- 13 Phillippe M. Cell-free fetal DNA--a trigger for parturition. N Engl J Med 2014; 370 (26) 2534-2536
- 14 Kim SK, Hannum G, Geis J. , et al. Determination of fetal DNA fraction from the plasma of pregnant women using sequence read counts. Prenat Diagn 2015; 35 (08) 810-815
- 15 ACOG practice bulletin no. 204: fetal growth restriction. Obstet Gynecol 2019; 133 (02) e97-e109
- 16 Getahun D, Ananth CV, Kinzler WL. Risk factors for antepartum and intrapartum stillbirth: a population-based study. Am J Obstet Gynecol 2007; 196 (06) 499-507
- 17 Oken E, Kleinman KP, Rich-Edwards J, Gillman MW. A nearly continuous measure of birth weight for gestational age using a United States national reference. BMC Pediatr 2003; 3 (01) 6
- 18 Krishna I, Badell M, Loucks TL, Lindsay M, Samuel A. Adverse perinatal outcomes are more frequent in pregnancies with a low fetal fraction result on noninvasive prenatal testing. Prenat Diagn 2016; 36 (03) 210-215
- 19 Caramelli E, Rizzo N, Concu M. , et al. Cell-free fetal DNA concentration in plasma of patients with abnormal uterine artery Doppler waveform and intrauterine growth restriction--a pilot study. Prenat Diagn 2003; 23 (05) 367-371
- 20 Alberry MS, Maddocks DG, Hadi MA. , et al. Quantification of cell free fetal DNA in maternal plasma in normal pregnancies and in pregnancies with placental dysfunction. Am J Obstet Gynecol 2009; 200 (01) 98.e1-98.e6
- 21 Poon LC, Musci T, Song K, Syngelaki A, Nicolaides KH. Maternal plasma cell-free fetal and maternal DNA at 11-13 weeks' gestation: relation to fetal and maternal characteristics and pregnancy outcomes. Fetal Diagn Ther 2013; 33 (04) 215-223
- 22 Stein W, Müller S, Gutensohn K, Emons G, Legler T. Cell-free fetal DNA and adverse outcome in low risk pregnancies. Eur J Obstet Gynecol Reprod Biol 2013; 166 (01) 10-13
- 23 Contro E, Bernabini D, Farina A. Cell-free fetal DNA for the prediction of pre-eclampsia at the first and second trimesters: a systematic review and meta-analysis. Mol Diagn Ther 2017; 21 (02) 125-135
- 24 Bender WR, Koelper NC, Sammel MD, Dugoff L. Association of fetal fraction of cell-free DNA and hypertensive disorders of pregnancy. Am J Perinatol 2019; 36 (03) 311-316
- 25 Quezada MS, Francisco C, Dumitrascu-Biris D, Nicolaides KH, Poon LC. Fetal fraction of cell-free DNA in maternal plasma in the prediction of spontaneous preterm delivery. Ultrasound Obstet Gynecol 2015; 45 (01) 101-105
- 26 Wataganara T, Bui T-H, Choy KW, Leung TY. Debates on fetal fraction measurement and DNA-based noninvasive prenatal screening: time for standardisation?. BJOG 2016; 123 (Suppl. 03) 31-35