Multicenter clinical experience with non-invasive cell-free DNA screening for monosomy X and related X-chromosome variants

Objective

We aimed to investigate how the presence of fetal anomalies and different X chromosome variants influences Cell-free DNA (cfDNA) screening results for monosomy X.

Methods

From a multicenter retrospective survey on 673 pregnancies with prenatally suspected or confirmed Turner syndrome, we analyzed the subgroup for which prenatal cfDNA screening and karyotype results were available. A cfDNA screening result was defined as true positive (TP) when confirmatory testing showed 45,X or an X-chromosome variant.

Results

We had cfDNA results, karyotype, and phenotype data for 55 pregnancies. cfDNA results were high risk for monosomy X in 48/55, of which 23 were TP and 25 were false positive (FP). 32/48 high-risk cfDNA cases did not show fetal anomalies. Of these, 7 were TP. All were X-chromosome variants. All 16 fetuses with high-risk cfDNA result and ultrasound anomalies were TP. Of fetuses with abnormalities, those with 45,X more often had fetal hydrops/cystic hygroma, whereas those with “variant” karyotypes had different anomalies.

Conclusion

Both, 45,X or X-chromosome variants can be detected after a high-risk cfDNA result for monosomy X. When there are fetal anomalies, the result is more likely a TP. In the absence of fetal anomalies, it is most often an FP or X-chromosome variant.     

Historical development and future outlook of the flood damage potential of residential areas in the Alpine Lech Valley (Austria) between 1971 and 2030

In the recent past, the Alpine Lech valley (Austria) experienced three damaging flood events within 6 years despite the various structural flood protection measures in place. For an improved flood risk management, the analysis of flood damage potentials is a crucial component. Since the expansion of built-up areas and their associated values is seen as one of the main drivers of rising flood losses, the goal of this study is to analyze the spatial development of the assets at risk, particularly of residential areas, due to land use changes over a historic period (since 1971) and up to possible shifts in future (until 2030). The analysis revealed that the alpine study area was faced to remarkable land use changes like urbanization and the decline of agriculturally used grassland areas. Although the major agglomeration of residential areas inside the flood plains took place before 1971, a steady growth of values at risk can still be observed until now. Even for the future, the trend is ongoing, but depends very much on the assumed land use scenario and the underlying land use policy. Between 1971 and 2006, the annual growth rate of the damage potential of residential areas amounted to 1.1 % (‘constant values,’ i.e., asset values at constant prices of reference year 2006) or 3.0 % (‘adjusted values,’ i.e., asset values adjusted by GDP increase at constant prices of reference year 2006) for three flood scenarios. For the projected time span between 2006 and 2030, a further annual increase by 1.0 % (‘constant values’) or even 4.2 % (‘adjusted values’) may be possible when the most extreme urbanization scenario ‘Overall Growth’ is considered. Although socio-economic development is regarded as the main driver for increasing flood losses, our analysis shows that settlement development does not preferably take place within flood prone areas.