Association between fetal fraction of cell-free DNA and adverse pregnancy outcomes.
Cell-free DNA
Fetal fraction
Non-invasive prenatal test
Pregnancy outcomes
Pregnancy-induced hypertensive diseases
Journal
Archives of gynecology and obstetrics
ISSN: 1432-0711
Titre abrégé: Arch Gynecol Obstet
Pays: Germany
ID NLM: 8710213
Informations de publication
Date de publication:
05 Mar 2024
05 Mar 2024
Historique:
received:
16
11
2023
accepted:
16
02
2024
medline:
5
3
2024
pubmed:
5
3
2024
entrez:
5
3
2024
Statut:
aheadofprint
Résumé
To determine the association between fetal fraction (FF) levels in cell-free fetal DNA (cffDNA) testing and adverse pregnancy outcomes. This retrospective cohort study, conducted at a single center, involved 2063 pregnant women with normal 1st and 2nd trimester non-invasive prenatal test (NIPT) results between 2016 and 2021. Pregnancy outcomes were examined by determining the < 4% and < 5th percentile (3.6%) cut-off values for low fetal fraction (LFF). Pregnancy outcomes were also examined by dividing the FF into population-based quartiles. Adverse pregnancy outcomes were pregnancy-induced hypertensive diseases (PIHD), gestational diabetes mellitus (GDM), spontaneous preterm birth (PTB), intrahepatic cholestasis of pregnancy (ICP), small for gestational age (SGA), large for gestational age (LGA), low birth weight (LBW), macrosomia, and 1st and 5th minutes low APGAR scores (< 7). PIHD was significantly higher in LFF (< 4% and < 5th percentile) cases (p = 0.015 and p < 0.001, respectively). However, in population-based quartiles of FF, PIHD did not differ significantly between groups. Composite adverse maternal outcomes were significantly higher in the FF < 4% group (p = 0.042). When analyzes were adjusted for maternal age, BMI, and gestational age at NIPT, significance was maintained at < 4%, < 5th percentile LFF for PIHD, and < 4% LFF for composite adverse maternal outcomes. However, there was no significant relationship between LFF with GDM, ICP and PTB. Additionally, there was no significant association between low APGAR scores, SGA, LGA, LBW, macrosomia, and LFF concerning neonatal outcomes. Our study showed that LFF in pregnant women with normal NIPT results may be a predictor of subsequent PIHD.
Identifiants
pubmed: 38441603
doi: 10.1007/s00404-024-07443-z
pii: 10.1007/s00404-024-07443-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW et al (1997) Presence of fetal DNA in maternal plasma and serum. Lancet Lond Engl 350:485–487. https://doi.org/10.1016/S0140-6736(97)02174-0
doi: 10.1016/S0140-6736(97)02174-0
Practice Bulletin No. 163: Screening for fetal aneuploidy. Obstet Gynecol. 2016;127:e123–37. https://doi.org/10.1097/AOG.0000000000001406
Alberry M, Maddocks D, Jones M, Abdel Hadi M, Abdel-Fattah S, Avent N et al (2007) Free fetal DNA in maternal plasma in anembryonic pregnancies: confirmation that the origin is the trophoblast. Prenat Diagn 27:415–418. https://doi.org/10.1002/pd.1700
doi: 10.1002/pd.1700
pubmed: 17286310
Zhou Y, Zhu Z, Gao Y, Yuan Y, Guo Y, Zhou L et al (2015) Effects of maternal and fetal characteristics on cell-free fetal DNA fraction in maternal plasma. Reprod Sci Thousand Oaks Calif 22:1429–1435. https://doi.org/10.1177/1933719115584445
doi: 10.1177/1933719115584445
Grömminger S, Erkan S, Schöck U, Stangier K, Bonnet J, Schloo R et al (2015) The influence of low molecular weight heparin medication on plasma DNA in pregnant women. Prenat Diagn 35:1155–1157. https://doi.org/10.1002/pd.4668
doi: 10.1002/pd.4668
pubmed: 26248743
İleri̇ A, Karaca SY, İleri̇ H, Gölbaşi H, Yildirim AGŞ, Kutbay YB, et al. Effect of levothyroxine sodium ıntake on the fetal fraction in non-ınvasive prenatal testing: a cross-sectional study. J Clin Obstet Gynecol. 2022;32:106–10. https://doi.org/10.5336/jcog.2022-90002 .
İleri A, Yıldırım Karaca S, İleri H, Karaca İ, Gölbaşı H, Özer M et al (2023) The effect of progesterone supplementation in women with threatened miscarriage on fetal fraction in non-invasive prenatal testing: a matched case-control study. J Gynecol Obstet Hum Reprod 52:102662. https://doi.org/10.1016/j.jogoh.2023.102662
doi: 10.1016/j.jogoh.2023.102662
pubmed: 37659577
Kuhlmann-Capek M, Chiossi G, Singh P, Monsivais L, Lozovyy V, Gallagher L et al (2019) Effects of medication intake in early pregnancy on the fetal fraction of cell-free DNA testing. Prenat Diagn 39:361–368. https://doi.org/10.1002/pd.5436
doi: 10.1002/pd.5436
pubmed: 30740743
Peng XL, Jiang P (2017) Bioinformatics approaches for fetal DNA fraction estimation in noninvasive prenatal testing. Int J Mol Sci 18:453. https://doi.org/10.3390/ijms18020453
doi: 10.3390/ijms18020453
pubmed: 28230760
pmcid: 5343987
Hestand MS, Bessem M, van Rijn P, de Menezes RX, Sie D, Bakker I et al (2019) Fetal fraction evaluation in non-invasive prenatal screening (NIPS). Eur J Hum Genet EJHG 27:198–202. https://doi.org/10.1038/s41431-018-0271-7
doi: 10.1038/s41431-018-0271-7
pubmed: 30254213
Scheffer PG, Wirjosoekarto SAM, Becking EC, Weiss MM, Bax CJ, Oepkes D et al (2021) Association between low fetal fraction in cell-free DNA testing and adverse pregnancy outcome: a systematic review. Prenat Diagn 41:1287–1295. https://doi.org/10.1002/pd.6028
doi: 10.1002/pd.6028
pubmed: 34350596
pmcid: 9292009
Hahn S, Rusterholz C, Hösli I, Lapaire O (2011) Cell-free nucleic acids as potential markers for preeclampsia. Placenta 32(Suppl):S17-20. https://doi.org/10.1016/j.placenta.2010.06.018
doi: 10.1016/j.placenta.2010.06.018
pubmed: 21257079
Lazar L, Rigó J, Nagy B, Balogh K, Makó V, Cervenak L et al (2009) Relationship of circulating cell-free DNA levels to cell-free fetal DNA levels, clinical characteristics and laboratory parameters in preeclampsia. BMC Med Genet 10:120. https://doi.org/10.1186/1471-2350-10-120
doi: 10.1186/1471-2350-10-120
pubmed: 19930583
pmcid: 2789064
Al Nakib M, Desbrière R, Bonello N, Bretelle F, Boubli L, Gabert J et al (2009) Total and fetal cell-free DNA analysis in maternal blood as markers of placental insufficiency in intrauterine growth restriction. Fetal Diagn Ther 26:24–28. https://doi.org/10.1159/000236355
doi: 10.1159/000236355
pubmed: 19816026
Dugoff L, Barberio A, Whittaker PG, Schwartz N, Sehdev H, Bastek JA (2016) Cell-free DNA fetal fraction and preterm birth. Am J Obstet Gynecol 215(231):e1-7. https://doi.org/10.1016/j.ajog.2016.02.009
doi: 10.1016/j.ajog.2016.02.009
Chan N, Smet M-E, Sandow R, da Silva CF, McLennan A (2018) Implications of failure to achieve a result from prenatal maternal serum cell-free DNA testing: a historical cohort study. BJOG Int J Obstet Gynaecol 125:848–855. https://doi.org/10.1111/1471-0528.15006
doi: 10.1111/1471-0528.15006
Clapp MA, Berry M, Shook LL, Roberts PS, Goldfarb IT, Bernstein SN (2020) Low fetal fraction and birth weight in women with negative first-trimester cell-free DNA screening. Am J Perinatol 37:86–91. https://doi.org/10.1055/s-0039-1700860
doi: 10.1055/s-0039-1700860
pubmed: 31739367
Gerson KD, Truong S, Haviland MJ, O’Brien BM, Hacker MR, Spiel MH (2019) Low fetal fraction of cell-free DNA predicts placental dysfunction and hypertensive disease in pregnancy. Pregnancy Hypertens 16:148–153. https://doi.org/10.1016/j.preghy.2019.04.002
doi: 10.1016/j.preghy.2019.04.002
pubmed: 31056151
pmcid: 10066927
Adiyaman D, Konuralp Atakul B, Kuyucu M, Toklu G, Golbasi H, Koc A, et al. Can fetal fractions in the cell-free DNA test predict the onset of fetal growth restriction? J Perinat Med. 2020:/j/jpme.ahead-of-print/jpm-2020-0010/jpm-2020-0010.xml. https://doi.org/10.1515/jpm-2020-0010 .
Krishna I, Badell M, Loucks TL, Lindsay M, Samuel A (2016) Adverse perinatal outcomes are more frequent in pregnancies with a low fetal fraction result on noninvasive prenatal testing. Prenat Diagn 36:210–215. https://doi.org/10.1002/pd.4779
doi: 10.1002/pd.4779
pubmed: 26783737
Yuan X, Zhou L, Zhang B, Wang H, Yu B, Xu J (2020) Association between low fetal fraction of cell free DNA at the early second-trimester and adverse pregnancy outcomes. Pregnancy Hypertens 22:101–108. https://doi.org/10.1016/j.preghy.2020.07.015
doi: 10.1016/j.preghy.2020.07.015
pubmed: 32777709
Benn P, Valenti E, Shah S, Martin K, Demko Z (2018) Factors associated with informative redraw after an initial no result in noninvasive prenatal testing. Obstet Gynecol 132:428–435. https://doi.org/10.1097/AOG.0000000000002728
doi: 10.1097/AOG.0000000000002728
pubmed: 29995728
Magee LA, Brown MA, Hall DR, Gupte S, Hennessy A, Karumanchi SA et al (2022) The 2021 International Society for the Study of Hypertension in pregnancy classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens 27:148–169. https://doi.org/10.1016/j.preghy.2021.09.008
doi: 10.1016/j.preghy.2021.09.008
pubmed: 35066406
International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010;33:676–82. https://doi.org/10.2337/dc09-1848 .
Ovadia C, Seed PT, Sklavounos A, Geenes V, Di Ilio C, Chambers J et al (2019) Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet Lond Engl 393:899–909. https://doi.org/10.1016/S0140-6736(18)31877-4
doi: 10.1016/S0140-6736(18)31877-4
Villar J, Cheikh Ismail L, Victora CG, Ohuma EO, Bertino E, Altman DG et al (2014) International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. Lancet Lond Engl 384:857–868. https://doi.org/10.1016/S0140-6736(14)60932-6
doi: 10.1016/S0140-6736(14)60932-6
Crowley A, Martin C, Fitzpatrick P, Sheils O, O’Herlihy C, O’Leary JJ et al (2007) Free fetal DNA is not increased before 20 weeks in intrauterine growth restriction or pre-eclampsia. Prenat Diagn 27:174–179. https://doi.org/10.1002/pd.1645
doi: 10.1002/pd.1645
pubmed: 17191257
Levine RJ, Qian C, Leshane ES, Yu KF, England LJ, Schisterman EF et al (2004) Two-stage elevation of cell-free fetal DNA in maternal sera before onset of preeclampsia. Am J Obstet Gynecol 190:707–713. https://doi.org/10.1016/j.ajog.2003.12.019
doi: 10.1016/j.ajog.2003.12.019
pubmed: 15042003
Poon LCY, Musci T, Song K, Syngelaki A, Nicolaides KH (2013) 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 33:215–223. https://doi.org/10.1159/000346806
doi: 10.1159/000346806
pubmed: 23466432
Kim MJ, Kim SY, Park SY, Ahn HK, Chung JH, Ryu HM (2013) Association of fetal-derived hypermethylated RASSF1A concentration in placenta-mediated pregnancy complications. Placenta 34:57–61. https://doi.org/10.1016/j.placenta.2012.11.001
doi: 10.1016/j.placenta.2012.11.001
pubmed: 23187089
Braunthal S, Brateanu A (2019) Hypertension in pregnancy: pathophysiology and treatment. SAGE Open Med 7:2050312119843700. https://doi.org/10.1177/2050312119843700
doi: 10.1177/2050312119843700
pubmed: 31007914
pmcid: 6458675
Morano D, Rossi S, Lapucci C, Pittalis MC, Farina A (2018) Cell-free DNA (cfDNA) fetal fraction in early- and late-onset fetal growth restriction. Mol Diagn Ther 22:613–619. https://doi.org/10.1007/s40291-018-0353-9
doi: 10.1007/s40291-018-0353-9
pubmed: 30056492
Stein W, Müller S, Gutensohn K, Emons G, Legler T (2013) Cell-free fetal DNA and adverse outcome in low risk pregnancies. Eur J Obstet Gynecol Reprod Biol 166:10–13. https://doi.org/10.1016/j.ejogrb.2012.09.006
doi: 10.1016/j.ejogrb.2012.09.006
pubmed: 23021026
Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH (2018) The pathophysiology of gestational diabetes mellitus. Int J Mol Sci 19:3342. https://doi.org/10.3390/ijms19113342
doi: 10.3390/ijms19113342
pubmed: 30373146
pmcid: 6274679
Golbasi H, Bayraktar B, Golbasi C, Omeroglu I, Adiyaman D, Sever B et al (2022) Can sonographic imaging of the fetal pancreas predict perinatal outcomes in gestational diabetes mellitus? J Perinat Med 50:1189–1197. https://doi.org/10.1515/jpm-2022-0050
doi: 10.1515/jpm-2022-0050
pubmed: 35607725