Predictive value of the triple screening test for the phenotype of Down syndrome

Abstract

Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) are routinely measured in the second trimester ("triple" test) and combined with maternal age to evaluate risk for fetal Down syndrome. Triple test results and clinical findings were retrospectively reviewed for 30 newborns with Down syndrome to determine whether analyte values or second trimester risks for Down syndrome were more extreme in affected pregnancies where cardiac or other severe congenital malformations were present compared to those cases where major anatomical abnormalities were absent. Mean MS-AFP, uE3, maternal age, and second trimester Down syndrome risk were all similar in the two groups of pregnancies. However, hCG concentrations did appear to be higher in the group of Down syndrome pregnancies with anatomical anomalies (mean 1.74 MoM versus 1.19 MoM) (P<0.05). Overall, there was no significant difference in the incidence of major anomalies in patients with screen-positive test results versus those cases that were not identified by the triple test. Prenatal counseling should therefore reflect the general expectations of the Down syndrome phenotype that have been established from live-born infants with this disorder.

Down Syndrome Screening: Evidence that Test Results Differ According to Phenotype

“…Nevertheless, the observed median NT MoM in DS pregnancies with cardiac defects is 1.13 times of that in those without a cardiac defect with 95 % confidence interval 0.90-1.41. This is consistent with the confidence interval on the median value in euploid pregnancies with cardiac defects in one published study, which is 1.07-2.16 MoM [3] and in our series, it is 1.29-1.46 MoM. The observed increase in median maternal serum AFP in DS pregnancies with cardiac defects of 1.14 times, was not statistically significant.…”

“…No statistically significant difference between those with and without a severe phenotype but the numbers studied was small. A second study included 30 births with DS in women who had second trimester screening with AFP, uE 3 , and hCG; 50 % (15/30) had cardiac defects, and 67 % (20/30) had an anatomical abnormality [3]. The only statistically significant difference was an increased mean hCG level in those with anatomical abnormalities.…”