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.     

Host-plant-mediated competition via induced resistance: interactions between pest herbivores on potatoes.

Plant-mediated competition among insect herbivores occurs when one species induces changes in plant chemistry, nutrition, or morphology that render plants resistant to attack by others. We explored plant-mediated interspecific interactions between the potato leafhopper (Empoasca fabae) and the Colorado potato beetle (Leptinotarsa decemlineata), two important pests on potatoes. Leafhoppers colonize fields in advance of beetles, and thus the possibility exists that previous feeding by leafhoppers induces changes in potato plants that have adverse consequences for beetles. The consequences of leafhopper-induced resistance for beetle performance were studied in the greenhouse, field cages, and in large open-field plots. Potato plants were exposed to four densities of leafhoppers (none, low, moderate, and high), and visible feeding symptoms were measured as percentage leaf curling, chlorosis, and necrosis. The oviposition preference, performance, and survivorship of Colorado potato beetles were then measured on the four categories of induced plants in field-cage and greenhouse settings. In open field plots, survival on the four categories of induced plants was determined by placing cohorts of beetle adults onto plants and measuring the densities of resulting eggs, larvae, and emerging Fl adults. Leafhopper-induced symptoms on potato plants were density dependent, with the percentage of curled, chlorotic, and necrotic leaves increasing with leafhopper density. Previous feeding by leafhoppers adversely affected oviposition and larval performance of beetles. Fewer egg masses were deposited on plants that incurred high levels of leafhopper feeding. Similarly, larval development was delayed and emerging adult beetles weighed less when fed induced foliage from the high leafhopper-density treatment. Beetles survived less well in the field on plants experiencing moderate and high levels of leafhopper feeding as evidenced by lower densities of eggs, larvae, and emerging F1 adults. Overall, leafhoppers and beetles competed through feeding-induced changes in plant quality. Notably, the asymmetric interaction took place at a large spatial scale in open field plots and had negative consequences that persisted to the next beetle generation. Ultimately, to establish an effective management strategy for crop pests such as leafhoppers, it is essential to consider the positive indirect effects of induced resistance along with the negative direct effects on crop yield.     

Post-Glacial Lead Dynamics in a Forest Soil

The use of alkyl-Pb additives in gasoline during the 20th century resulted in widespread Pb pollution. The objective of this study was to determine the relative importance of atmospherically deposited Pb and Pb released through weathering to soil Pb pools at the Hubbard Brook Experimental Forest, New Hampshire. We employed a selective extraction method to estimate the amount of Pb that was: water-soluble + exchangeable (EX); inorganically bound (IB); organically bound (ORG); bound to amorphous oxides (AMOX); and bound in crystalline minerals (RES). After normalizing crystalline-Pb concentrations to the immobile element Ti, we estimated that 14.1 kg ha^-1 of Pb has been weathered from Hubbard Brook soils in the 12,000–14,000 yr since deglaciation – a long-term average release of 1.0–1.2 g ha^-1 a^-1. Analysis of Ti-normalized total Pb concentrations indicated a net post-glacial decrease of 7.2 kg ha^-1 in the total Pb pool – consisting of a net accumulation of 4.9 kg ha^-1 in the O horizon, and a net loss of 12.1 kg ha^-1 from mineral soil. Atmospheric deposition of Pb between 1926 and 1989 (estimated as 8.7 kg ha^-1) was a major source of Pb in the post-glacial period. Together, long-term weathering release and 20th century atmospheric deposition could account for all of the Pb in the EX, IB, ORG, and AMOX fractions. Lead from gasoline appears to constitute a major fraction of the total Pb burden in Hubbard Brook soils. Periodic analysis of soil Pb fractions may be useful in monitoring the fate of Pb in forest soils.     

Seasonal variation in paediatric blood lead levels in Syracuse,NY, USA

Venous blood lead values for 2,633 children aged 0–4 years in Syracuse, New York, collected between 1 April 1992 and 31 March 1993 were summarised by census tract for study of geographic variability. A demographic exposure model is presented showing housing stock and SES (socioeconomic status) parameters as the most significant predictor variables. A seasonal trend in blood lead levels was observed with late summer values about 40% higher than late winter values for census tracts with the highest geometric mean PbB levels. Seasonal variation is compared with a biokinetic uptake model to examine hypotheses about temporal variations in soil and dust lead exposure patterns.     

Medaka (Oryzias latipes) for use in evaluating developmental effects of endocrine active chemicals with special reference to gonadal intersex (testis-ova).

Japanese medaka (Oryzias latipes) has been widely used for the evaluation of the toxicity of endocrine active chemicals (EACs) and other chemicals as well as for monitoring the adverse effects of effluent discharges in relation to sexual development and function. It is useful for these evaluations for many reasons including the following: 1) it has a short life cycle facilitating studies extending over long phases of development and over multigenerations, 2) it is easy to rear, 3) male and female phenotypes can easily be distinguished on the basis of secondary sex characteristics, and 4) a genetic marker (DMY) is available for identifying the true genotypic sex. Several biomarkers have been found to be useful for identifying the effects of exposure to estrogenic and androgenic chemicals in medaka and they include increased levels of hepatic vitellogenin (VTG) and testis-ova induction in males for exposure to estrogenic chemicals, and decreased levels of hepatic VTG in females and an altered morphology of dorsal and anal fins and formation of papillae for androgenic chemicals. In this paper, we present a critical analysis of the use of medaka as a test species for studies of endocrine disruption and report on the use of sex-related genetic markers and alterations in gonadal development, including the induction of testis-ova formation, for assessing the disruptive effects of EACs. In this paper, we focus on some of the more recent studies and findings.