Affiliation:
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
3. Cochrane Netherlands University Medical Center Utrecht Utrecht University Utrecht The Netherlands
4. Department of Human Genetics Amsterdam UMC Location Vrije Universiteit Amsterdam Amsterdam The Netherlands
5. Amsterdam Reproduction & Development Research Institute Amsterdam UMC Amsterdam The Netherlands
Abstract
AbstractObjectiveTo 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.MethodWe searched articles published between January 2010 and May 2021 in PubMed and EMBASE databases. Risk of bias was assessed using QUADAS‐2.ResultsTwenty‐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.ConclusionAn 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.
Subject
Genetics (clinical),Obstetrics and Gynecology
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献