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.     

Outdoor and indoor cadmium distributions near an abandoned smelting works and their relations to human exposure

The relationship of measured or modelled Cd concentrations in soil, house dust and available to plants with human urinary Cd concentrations were assessed in a population living around a Cd/Pb/Zn smelter in the UK. Modelled air concentrations explained 35% of soil Cd variation indicating the smelter contributed to soil Cd loads. Multi-variate analysis confirmed a significant role of biological and life-style factors in determining urinary Cd levels. Significant correlations of urinary Cd with soil, house dust and modelled plant available Cd concentrations were not, however, found. Potential reasons for the absence of clear relationships include limited environmental contact in urban populations; the role of undefined factors in determining exposure; and the limited spatial scope of the survey which did not sample from the full pollution gradient. Further, the absence of any significant relationship indicates that environmental measures provide limited advantage over atmospheric model outputs for first stage human exposure assessment.     

Mobilization of arsenic in aquifers from the Datong Basin,China: Evidence from geochemical and iron isotopic data

Iron isotope compositions of various Fe pools in aquifer sediments were measured at a known As-contaminated site in the Datong Basin, China. The δ⁵⁶Fe values of HCl-extracted poor-crystalline Fe(III) range widely from ?0.41‰ to 0.36‰. We interpret the low Fe(II)/Fe_Extractable ratios (<50%) and the negative correlation between Fe(II)/Fe_Extractable and δ⁵⁶Fe values in HCl-extracted poor-crystalline Fe to be best explained by redox cycling of Fe induced by microbial Fe(III) reduction. However, the high Fe(II)/Fe_Extractable ratios (?70%) and positive correlation between Fe(II)/Fe_Extractable and δ⁵⁶Fe values for HCl-extracted poor-crystalline Fe indicates production of sulfides (FeSs). The δ⁵⁶Fe values of crystalline Fe(III) extracted by reductant appears to be comparatively small varying from ?0.01‰ to 0.24‰, which is consistent with the δ⁵⁶Fe values for ferric oxides/hydroxides having undergone microbial Fe(III) reduction. The Fe isotope composition of various Fe pools shows the transformation between crystalline Fe(III) and poor-crystalline crystalline Fe(III) and the secondary Fe(II) phases has already occurred or is occurring in aquifer sediments. More importantly, there is a significant difference in the As concentrations in crystalline Fe(III) oxides/hydroxides and HCl-extracted Fe phases. The concentrations of As range from 1.6 to 29.9 mg kg^?1 and from 0.6 to 3.0 mg kg^?1, for crystalline Fe(III) and HCl-extracted Fe phases respectively. Accordingly, the transformation of Fe minerals induced by microbial Fe(III) reduction can contribute to the mobilization of As. This study is the first to examine the Fe isotope compositions in high As aquifer sediments; the results show that the Fe isotope would be an important tool in demonstrating the enrichment of As in groundwater.     

Prenatal exclusion of homocystinuria (cystathionine β-synthase deficiency) by assay of phytohaemagglutinin-stimulated fetal lymphocytes

Homocystinuria due to cystathionine β-synthase deficiency was excluded in a fetus at 23 weeks' gestation by demonstrating activity of the enzyme in fetal lymphocytes after stimulation by phytohaemagglutinin. Fetal blood sampling was carried out because two determinations of enzyme activity on cultured amniotic cells gave low, not fully diagnostic values.     

The recovery of selenious acid aerosols on glass fiber filters

Previous workers have shown that selenium is only partially trapped on a filter during air sampling. In some cases, these losses have been attributed to volatilization of selenium dioxide. Our results demonstrate that selenium dioxide, in the presence of moist air, is completely recovered (apparently as selenious acid aerosols) and that the previous shortfalls must be due to other selenium species as yet unidentified. Selenious acid aerosols in our study were formed by volatilizing selenium dioxide (approximately 3 mg) into a stream of moist ambient air (relative humidity, greater than 50%), and trapped on glass fiber filters using a high-volume air sampler. Selenium(IV) was ultrasonically extracted from the filter with water and analyzed by atomic absorption spectrometry. Selenious acid aerosols were trapped on the filters with high efficiency (105 +/- 5 percent) using a 50 minute sampling period. With an extended sampling period (24 hours) the recovery was 103 +/- 6 percent.     

Future directions in air-quality science,policy, and education

On February 12-15, 2001, more than 200 scientists, engineers, decision makers, and educators participated in a conference on the "Future Directions in Air Quality Research: Ecological, Atmospheric, Regulatory/Policy, and Educational Issues." Important perspectives are summarized from the keynote addresses of noted scientists and educators, as well as managers in government, industry, and public interest groups. Observations and recommendations are provided to stimulate further thought about how to increase opportunities to make greater use of scientific knowledge in air-quality decision making and to ensure that decisions are effective, economically viable, health and ecologically sound, and socially acceptable. Recommendations are given regarding ways in which communications between scientists and policy makers should be structured so as to make appropriate and effective use of scientists and the knowledge they can provide in policy-making fora.