Enhanced First Trimester Aneuploidy Screening with Placental Growth Factor and Alpha Feto-Protein: Detection of Trisomies 18 and 13

Abstract

Objectives: To assess the performance of first trimester combined screening (FTS) when enhanced with placental growth factor and alpha feto-protein in the detection of trisomies 18 and 13.

Methods: A retrospective case-control study. Marker parameters were derived using frozen serum samples. Multivariate Gaussian modelling predicted the detection rate (DR) and false-positive rate (FPR) for trisomies 18 and 13 with FTS and enhanced first trimester screening (eFTS) using the risk of trisomy 21 alone and an additional risk cut-off for trisomy 18, or trisomies 18 or 13.

Results: There were 83 trisomy 18, 22 trisomy 13, and 588 controls. The median placental growth factor levels in trisomies 18 and 13 were 0.75 and 0.65 multiple of the median of controls, respectively (both P < 0.0001). There were no statistically significant differences in alpha feto-protein levels. Modelling predicts that using a trisomy 21 risk cut-off alone, at FPR of 3%, eFTS increases the DR for trisomies 18 and 13 by 0.6-0.8% compared with FTS. Additionally using a trisomy 18 risk cut-off, at an extra FPR of 0.2%, eFTS increased the DR by 0.6-0.9% over FTS; using a trisomy 18 or 13 risk cut-off did not further increase detection for FTS or eFTS. The increase in DR was greater at higher FPR.

Conclusion: eFTS increases the detection of trisomies 18 and 13 to a small extent.

Keywords: First trimester; alpha feto-protein; placental growth factor; screening; trisomy 13; trisomy 18.