Association of Fetal Fraction of Cell-Free DNA and Hypertensive Disorders of Pregnancy

Abstract

Objective The objective of this study is to examine the relationship between fetal fraction and hypertensive disorders of pregnancy.

Study Design This is a retrospective cohort study of women with singleton pregnancies who had cell-free DNA (cfDNA) screening at 10 to 20 weeks of gestation. The primary outcome was the development of gestational hypertension (gHTN), preeclampsia (PEC), and PEC with severe features. Multinomial logistic regression was performed to assess the relationship between fetal fraction and pregnancy outcomes of interest while controlling for potential confounders.

Results Among 2,701 women meeting inclusion criteria, 387 (14.3%) were diagnosed with hypertensive disorders of pregnancy. First-trimester fetal fraction was significantly lower in women diagnosed with hypertensive disorders of pregnancy (10.9 vs. 12.4, p < 0.0001). An increased risk of gHTN and PEC, PEC with severe features with delivery > 34 weeks, and PEC with severe features with delivery ≤ 34 weeks was seen with lower first-trimester fetal fractions (odds ratio [OR]: 0.55, 95% confidence interval [CI] [0.36–0.83], p = 0.005; OR: 0.59, 95% CI [0.35–0.99], p = 0.048; and OR: 0.27, 95% CI [0.08–0.96], p = 0.044). The relationship between fetal fraction and hypertensive disorders of pregnancy was not statistically significant after adjusting for maternal age, race, body mass index, and chronic hypertension.

Conclusion Fetal fraction of cfDNA at 10 to 20 weeks of gestation was not associated with the development of hypertensive disorders of pregnancy.

Keywords

cell-free DNA - fetal fraction - pregnancy - hypertension - preeclampsia

Note

Findings of this article were presented as an oral presentation at the 21st International Society for Prenatal Diagnosis Conference in San Diego, CA, July 9–12, 2017.

• References

• 1 Hoffman B, Roberts S, Horsager R, Rogers V, Santiago-Muñoz P, Worley K. Hypertensive disorders. In: Williams Obstetrics, 24th ed. Ch. 40. New York: McGraw-Hill Education; 2014: 728-779
• 2 Wang E, Batey A, Struble C, Musci T, Song K, Oliphant A. Gestational age and maternal weight effects on fetal cell-free DNA in maternal plasma. Prenat Diagn 2013; 33 (07) 662-666
• 3 Gupta AK, Holzgreve W, Huppertz B, Malek A, Schneider H, Hahn S. Detection of fetal DNA and RNA in placenta-derived syncytiotrophoblast microparticles generated in vitro. Clin Chem 2004; 50 (11) 2187-2190
• 4 Huppertz B, Kingdom JC. Apoptosis in the trophoblast--role of apoptosis in placental morphogenesis. J Soc Gynecol Investig 2004; 11 (06) 353-362
• 5 Lo YM, Leung TN, Tein MS. , et al. Quantitative abnormalities of fetal DNA in maternal serum in preeclampsia. Clin Chem 1999; 45 (02) 184-188
• 6 Leung TN, Zhang J, Lau TK, Chan LY, Lo YM. Increased maternal plasma fetal DNA concentrations in women who eventually develop preeclampsia. Clin Chem 2001; 47 (01) 137-139
• 7 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
• 8 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
• 9 Sifakis S, Zaravinos A, Maiz N, Spandidos DA, Nicolaides KH. First-trimester maternal plasma cell-free fetal DNA and preeclampsia. Am J Obstet Gynecol 2009; 201 (05) 472.e1-472.e7
• 10 Papantoniou N, Bagiokos V, Agiannitopoulos K. , et al. RASSF1A in maternal plasma as a molecular marker of preeclampsia. Prenat Diagn 2013; 33 (07) 682-687
• 11 Kim MJ, Kim SY, Park SY, Ahn HK, Chung JH, Ryu HM. Association of fetal-derived hypermethylated RASSF1A concentration in placenta-mediated pregnancy complications. Placenta 2013; 34 (01) 57-61
• 12 Crowley A, Martin C, Fitzpatrick P. , et al. Free fetal DNA is not increased before 20 weeks in intrauterine growth restriction or pre-eclampsia. Prenat Diagn 2007; 27 (02) 174-179
• 13 Levine RJ, Qian C, Leshane ES. , et al. Two-stage elevation of cell-free fetal DNA in maternal sera before onset of preeclampsia. Am J Obstet Gynecol 2004; 190 (03) 707-713
• 14 Zhong XY, Holzgreve W, Hahn S. The levels of circulatory cell free fetal DNA in maternal plasma are elevated prior to the onset of preeclampsia. Hypertens Pregnancy 2002; 21 (01) 77-83
• 15 Yu H, Shen Y, Ge Q. , et al. Quantification of maternal serum cell-free fetal DNA in early-onset preeclampsia. Int J Mol Sci 2013; 14 (04) 7571-7582
• 16 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
• 17 Jakobsen TR, Clausen FB, Rode L, Dziegiel MH, Tabor A. Identifying mild and severe preeclampsia in asymptomatic pregnant women by levels of cell-free fetal DNA. Transfusion 2013; 53 (09) 1956-1964
• 18 Cotter AM, Martin CM, O'leary JJ, Daly SF. Increased fetal DNA in the maternal circulation in early pregnancy is associated with an increased risk of preeclampsia. Am J Obstet Gynecol 2004; 191 (02) 515-520
• 19 Farina A, Sekizawa A, Rizzo N. , et al. Cell-free fetal DNA (SRY locus) concentration in maternal plasma is directly correlated to the time elapsed from the onset of preeclampsia to the collection of blood. Prenat Diagn 2004; 24 (04) 293-297
• 20 Rolnik DL, O'Gorman N, Fiolna M, van den Boom D, Nicolaides KH, Poon LC. Maternal plasma cell-free DNA in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol 2015; 45 (01) 106-111
• 21 American College of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy. Report on Hypertension in Pregnancy. Washington, DC: 2013
• 22 Nygren AO, Dean J, Jensen TJ. , et al. Quantification of fetal DNA by use of methylation-based DNA discrimination. Clin Chem 2010; 56 (10) 1627-1635
• 23 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