Association between low fetal fraction in cell-free DNA screening and fetal chromosomal aberrations: A systematic review and meta-analysis |
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| Authors: | Ellis C Becking Ewoud Schuit Sophie M E van Baar de Knegt Erik A Sistermans Lidewij Henneman Mireille N Bekker Peter G Scheffer |
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| Institution: | 1. Department of Obstetrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;2. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
Cochrane Netherlands, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;3. Department of Human Genetics, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands |
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| Abstract: | Objective To perform a systematic review and meta-analysis of the available literature on low fetal fraction (LFF) in cell-free DNA (cfDNA) screening and the risk of fetal chromosomal aberrations. Method We searched articles published between January 2010 and May 2021 in PubMed and EMBASE databases. Risk of bias was assessed using QUADAS-2. Results Twenty-seven studies met the inclusion criteria, comprising data of 243,700 singleton pregnancies. Compared to normal fetal fraction, LFF was associated with a higher risk of trisomy 13 (OR 5.99 3.61–9.95], I 2 of heterogeneity = 0%, n = 22 studies), trisomy 18 (OR 4.46 3.07–6.47], I 2 = 0%, n = 22 studies), monosomy X (OR 5.88 2.34–14.78], I 2 = 18%, n = 10 studies), and triploidy (OR 36.39 9.83–134.68], I 2 = 61%, n = 6 studies), but not trisomy 21 (OR 1.25 0.76–2.03], I 2 = 36%, n = 23 studies). LFF was also associated with a higher risk of various other types of fetal chromosomal aberrations (OR 4.00 1.78–9.00], I 2 = 2%, n = 11 studies). Meta-analysis of proportions showed that absolute rates of fetal chromosomal aberrations ranged between 1% and 2% in women with LFF. A limitation of this review is the potential risk of ascertainment bias because of differences in outcome assessment between pregnancies with LFF and those with normal fetal fraction. Heterogeneity in population characteristics or applied technologies across included studies may not have been fully addressed. Conclusion An LFF test result in cfDNA screening is associated with an increased risk of fetal trisomy 13, trisomy 18, monosomy X, and triploidy, but not trisomy 21. Further research is needed to assess the association between LFF and other specific types of fetal chromosomal aberrations. |
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