TY - JOUR
T1 - Association between low fetal fraction in cell-free DNA screening and fetal chromosomal aberrations
T2 - A systematic review and meta-analysis
AU - Becking, Ellis C.
AU - Schuit, Ewoud
AU - van Baar de Knegt, Sophie M. E.
AU - Sistermans, Erik A.
AU - Henneman, Lidewij
AU - Bekker, Mireille N.
AU - Scheffer, Peter G.
N1 - Funding Information: Erik A. Sistermans, Lidewij Henneman, and Mireille N. Bekker are all involved in the TRIDENT‐2 study (Dutch NIPT Consortium) supported by a grant from the Netherlands Organization for Health Research and Development (ZonMw, No. 543002001). Publisher Copyright: © 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.
PY - 2023/6
Y1 - 2023/6
N2 - 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], I2 of heterogeneity = 0%, n = 22 studies), trisomy 18 (OR 4.46 [3.07–6.47], I2 = 0%, n = 22 studies), monosomy X (OR 5.88 [2.34–14.78], I2 = 18%, n = 10 studies), and triploidy (OR 36.39 [9.83–134.68], I2 = 61%, n = 6 studies), but not trisomy 21 (OR 1.25 [0.76–2.03], I2 = 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], I2 = 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.
AB - 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], I2 of heterogeneity = 0%, n = 22 studies), trisomy 18 (OR 4.46 [3.07–6.47], I2 = 0%, n = 22 studies), monosomy X (OR 5.88 [2.34–14.78], I2 = 18%, n = 10 studies), and triploidy (OR 36.39 [9.83–134.68], I2 = 61%, n = 6 studies), but not trisomy 21 (OR 1.25 [0.76–2.03], I2 = 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], I2 = 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.
UR - http://www.scopus.com/inward/record.url?scp=85159638079&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/pd.6366
DO - https://doi.org/10.1002/pd.6366
M3 - Review article
C2 - 37143173
SN - 0197-3851
VL - 43
SP - 838
EP - 853
JO - Prenatal diagnosis
JF - Prenatal diagnosis
IS - 7
ER -