First trimester screening for Down syndrome using nuchal translucency, maternal serum pregnancy-associated plasma protein A, free-β human chorionic gonadotrophin, placental growth factor, and α-fetoprotein.

Objective: The aim of this study was to assess the screening performance for Down syndrome using first trimester combined screening (FTS) and two additional markers, serum placental growth factor (PlGF) and α-fetoprotein (AFP).

Methods: This is a retrospective case-control study of 137 pregnancies affected by Down syndrome and 684 individually matched unaffected pregnancies. Stored serum samples were tested for all four markers, and results were expressed as multiples of the gestation-specific median (MoM). Multivariate Gaussian modeling was used to calculate risks for different combinations of markers and to predict the detection rate (DR) and false positive rate (FPR). The predicted performance of enhanced FTS (FTS plus PlGF and AFP) was compared with FTS; the performance without nuchal translucency (first trimester quad) was assessed.

Results: For affected pregnancies, the median PlGF level was 0.622 MoM and median AFP 0.764 MoM. Adding PlGF and AFP improved the screening performance. At 3% FPR, DR increased by 4.4% from 83.8% to 88.2% using enhanced FTS; at 95% DR, FPR decreased by 8.3%, from 19.3% to 11.0%. At 3% FPR, DR using first trimester quad test was 76.4%.

Conclusions: The performance of FTS can be enhanced by adding PlGF and AFP. Even without nuchal translucency, the test would perform well.