Interpretation
The FMF algorithm has been externally validated by several studies in various populations, showing comparable performance to that of the original study. Nevertheless, one study showed that some algorithms could underperform when applied to populations that were different to the population where they were developed22. In this study, we show that performance of the FMF algorithm in a Spanish population was similar to the performance obtained in the original study, further supporting the external validity of the FMF algorithm. By contrast, the predictive ability of the Gaussian algorithm has not been evaluated in other studies, aside from the original study where it was first validated. It must be noted that the Gaussian algorithm was not developed in our population, but just validated, since this algorithm was constructed using previously published data from a large meta-analysis. This might make this algorithm less likely to be overfitted to our population and therefore, less likely to underperform when applied to a different population. Since the first-trimester PE screening and aspirin prescription has been implemented in most countries across Europe, prospective external validation of the Gaussian algorithm in untreated populations seems unlikely. Therefore, a reasonable indirect approach to assess the predictive performance of the Gaussian algorithm is to compare it with the FMF algorithm, which has been extensively validated in various large populations. Although our results cannot be considered an external validation of the Gaussian algorithm, the similar accuracies of both algorithms suggest that the FMF algorithm is unlikely to outperform the Gaussian algorithm in our population where it is being routinely used in most maternities since 2018. For this reason, we believe that the Gaussian algorithm might be a reasonable alternative to the FMF algorithm for those settings where the latter cannot be applied dur to ultrasonographers performing UtAPI both transabdominally and transvaginally of for settings measuring biomarkers for the aneuploidy and PE screenings before 11 weeks.
Additionally, as seen in previous studies23, we confirm that PAPP-A does not increase the predictive accuracy of any of the algorithms when PlGF was being used; however, when PlGF is not available, PAPP-A could increase DR by 5% with some marker combinations.
Finally, we observed that a single measurement of MAP could decrease the predictive accuracy of the FMF algorithm; therefore, the appropriate methodology should be performed when using this algorithm.