Low fetal fraction in cell-free DNA testing is associated with adverse pregnancy outcome: Analysis of a subcohort of the TRIDENT-2 study

Ellis C. Becking, Soetinah A.M. Wirjosoekarto, Peter G. Scheffer, Julia V.M. Huiskes, Marinka J. Remmelink, Erik A. Sistermans, Caroline J. Bax, Janneke M. Weiss, Lidewij Henneman, Mireille N. Bekker*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
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Abstract

Objectives: To assess the association between low fetal fraction (FF) in prenatal cell-free DNA (cfDNA) testing and adverse pregnancy outcomes. Methods: We conducted a retrospective cohort study of participants of the TRIDENT-2 study (Dutch nationwide government-supported study offering cfDNA screening for fetal aneuploidies) who received a failed test result due to low FF (<4%) between April 2017 until February 2018. Outcome measures included pregnancy-induced hypertension (PIH), pre-eclampsia (PE), small for gestational age neonates (SGA), spontaneous preterm birth (sPTB), gestational diabetes mellitus (GDM), chromosomal aberrations, and congenital structural anomalies. Results: Test failure due to low FF occurred in 295 women (1.12% of tests performed). Information regarding pregnancy outcomes was available for 96.3% of these women. The incidence of PIH, PE, SGA, sPTB, and GDM was 11.2%, 4.1%, 7.3%, 5.1%, and 14.8%, respectively. The prevalence of chromosomal aberrations and congenital structural anomalies was 1.4% and 4.1%, respectively. Incidences of PIH, PE ≥ 34 weeks of gestation, GDM, and prevalence of aneuploidy and congenital structural anomalies were higher in women with low FF compared to the general Dutch obstetric population. Conclusion: Low FF is associated with adverse pregnancy outcomes. The value of FF in the prediction of these outcomes needs to be further established.

Original languageEnglish
Pages (from-to)1296-1304
Number of pages9
JournalPrenatal Diagnosis
Volume41
Issue number10
DOIs
Publication statusPublished - Sept 2021

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