Antenatal screening for fetal trisomies using microarray-based cell-free DNA testing: A systematic review and meta-analysis

Objective

To evaluate the test accuracy of non-invasive prenatal testing (NIPT) for fetal trisomy 21, 18, and 13 using cell-free (cf) DNA analysis in maternal plasma with microarray quantitation.

Method

Systematic review and meta-analysis. Searches in MEDLINE, Pre-MEDLINE, EMBASE, Web of Science, and the Cochrane Library to 09.07.2018.

Results

Five studies analyzing 3074 samples, including 187 trisomy 21, 43 trisomy 18, and 19 trisomy 13 cases, were identified. Risk of bias was high in all studies, introduced particularly by exclusions from analysis and by the role of the sponsor. Sensitivity of microarray-based cfDNA testing was 99.5% (95%CI 96.3%-99.9%) for trisomy 21, 97.7% (95%CI 87.9%-99.6%) for trisomy 18, and 100% (95%CI 83.2%-100%) for trisomy 13. Specificity was 100% (95% CI 99.87%-100%) for trisomy 21, 99.97% (95%CI 99.81%-99.99%) for trisomy 18, and 99.97% (95%CI 99.81%-99.99%) for trisomy 13. Pooled test failure rate was 1.1%. A direct comparison of microarray- and sequencing-based cfDNA found equivalent test accuracy.

Conclusion

Included studies suggest that NIPT using microarray-based cfDNA testing has high sensitivity and specificity for detecting fetal trisomy 21, 18, and 13. However, the evidence base is small and at high risk of bias.     

Association between low fetal fraction in cell-free DNA screening and fetal chromosomal aberrations: A systematic review and meta-analysis

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.     

A review of concepts and criteria for assessing agroecosystem health including a preliminary case study of southern Ontario

The model of agroecosystem health has been advocated as an appealing guideline for agricultural research. Yet, some ambiguity remains in how the concept can be defined and how the general criteria for assessing the health of an agroecosystem at a particular scale can be selected. This paper reviews the literature from various disciplines pertinent to the concept of agroecosystem health. It focuses on assessing the applicability of assorted concepts, norms, and criteria to agroecosystem health assessment, and develops a general definition of agroecosystem health. A classification scheme is proposed which scattered while potentially useful concepts in the literature are discussed, using southern Ontario as a case study to further illustrate the usefulness of the conceptual framework in studying agroecosystem health. Agroecosystem health can be characterized from four different perspectives that are related to agroecosystem structure, function, organization, and dynamics. Given the complexity of agroecosystems, the health of the systems at different scales cannot be fully captured from one perspective only. Criteria, such as resource availability, diversity, and accessibility, are some of the existing concepts capable of depicting the structural state of agroecosystem health. Concepts including productivity, efficiency, and effectiveness appear very useful for assessing the functional performance of agroecosystems. As any agroecosystem interacts actively with its external environments and changes over time, such characteristics are not necessarily captured by structural or functional criteria. Organizational criteria, such as autonomy and self-dependence, are useful to characterize the organizational nature inherent to agroecosystem health. Stability and resilience on the other hand are two appealing concepts capable of revealing the temporal dimension of agroecosystem health. Numerous empirical studies that are used to illustrate how these concepts developed in different disciplines of agricultural research can be potentially employed to facilitate the assessment of agroecosystem health. It is argued that any holistic investigation of the health of an agroecosystem needs to examine biophysical, economic, and human conditions of the system and to evaluate these conditions from perspectives pertinent to system structure, function, organization, and dynamics.     

The benefits and limitations of cell-free DNA screening for 22q11.2 deletion syndrome

Cell-free DNA testing is increasingly being used to screen pregnant women for fetal aneuploidy. This technology may also identify microdeletion syndromes, including 22q11.2 deletion syndrome, the most common microdeletion syndrome, and the 22q11.2 duplication syndrome. The purpose of this paper is to provide an overview of the 22q11.2 deletion syndrome, to review the early experience with cell-free DNA screening for this deletion and to consider the potential benefits that may be associated with prenatal detection of the deletion. © 2016 John Wiley & Sons, Ltd.     

Noninvasive screening by cell-free DNA for 22q11.2 deletion: Benefits,limitations, and challenges

Cell-free DNA (cfDNA) testing for fetal aneuploidy is one of the most important technical advances in prenatal care. Additional chromosome targets beyond common aneuploidies, including the 22q11.2 microdeletion, are now available because of this clinical testing technology. While there are numerous potential benefits, 22q11.2 microdeletion screening using cfDNA testing also presents significant limitations and pitfalls. Practitioners who are offering this test should provide comprehensive pretest and posttest prenatal counselling. The discussion should include the possibility of an absence of a result, as well as the risk of possible discordance between cfDNA screening results and the actual fetal genetic chromosomal constitution. The goal of this review is to provide an overview of the cfDNA testing technologies for 22q11.2 microdeletions screening, describe the current state of test validation and clinical experience, review “no results” and discordant findings based on differing technologies, and discuss management options.