Maternal serum placental growth factor and α-fetoprotein testing in first trimester screening for Down syndrome.

OBJECTIVE: The aim of this research was to evaluate the addition of first trimester maternal serum placental growth factor (PlGF) and α-fetoprotein (AFP) to the combined test for Down syndrome and a serum only protocol of PlGF, AFP, free ß-human chorionic gonadotropin and pregnancy-associated plasma protein-A. METHODS: Samples were from 92 Down syndrome cases with 552 matched controls. All women had a combined test at 11-14 weeks gestation. PlGF and AFP were measured and expressed in multiples of the gestation-specific median (MoM), adjusting for maternal weight and smoking status. Multivariate Gaussian modeling was used to predict detection and false-positive rates. RESULTS: The median PlGF level in the cases was 0.694 MoM and controls 1.000 MoM (p = <0.0001). The corresponding values for AFP were 0.764 MoM and 0.990 MoM (p < 0.0001). Statistical modeling predicted that for a given false-positive rate, the addition of PlGF to the combined test increases the detection rate by 4-7%. For a given detection rate, the false-positive rate could be almost halved. When both PlGF and AFP are used, the detection rate increase is 5-8%. A serum only protocol had a predicted a detection rate of 71% for a false-positive rate of 5%. CONCLUSIONS: Results suggest a substantial benefit of adding PlGF to the combined test.

Second trimester maternal serum ADAM12 levels in Down's syndrome pregnancies.

OBJECTIVE: To estimate the utility of maternal serum ADAM12 as a Down's syndrome marker. METHODS: Samples from 71 Down's syndrome affected pregnancies were retrieved from - 20 degrees C storage together with 710 controls matched for gestation and storage time. ADAM12 was measured prior to identification of the affected pregnancies, and expressed in multiples of the gestation-specific median (MoM). RESULTS: The median ADAM12 level in the affected pregnancies was 1.36 MoM with a 10th-90th centile range of 0.90-1.94 MoM compared with 1.01 and 0.65-1.52 MoM in the unaffected control pregnancies (P = < 0.0001, two-side Wilcoxon Rank Sum Test). The Mahalanobis distance between the medians was 0.96 compared with 0.92, 1.18, 1.07 and 1.24 for alpha-fetoprotein, intact human chorionic gonadotrophin (hCG), unconjugated estriol and inhibin-A respectively in the same samples. In unaffected pregnancies there were highly statistically significant correlations between ADAM12 and each of the other markers; in the affected pregnancies the only significant correlations were with hCG (P< or =0.0001) and inhibin-A (P< or =0.05). Statistical modelling predicted that ADAM12 as a fifth marker could increase the detection rate by 2-3% or reduce the false-positive rate by 0.9-1.7%. CONCLUSIONS: ADAM12 is a second trimester marker of Down's syndrome, with discriminatory power similar to existing markers. It could be considered in multi-marker combinations.