Screening for Down's syndrome: changes in marker levels and detection rates between first and second trimesters

To monitor changes with gestation in levels of alpha-fetoprotein (AFP), free beta human chorionic gonadotrophin (F beta hCG) and pregnancy associated plasma protein-A (PAPP-A) in Down's syndrome pregnancies and to compare risks estimated in the first trimester with those obtained by routine screening in the second trimester for the same pregnancies.

In each of 47 Down's syndrome pregnancies two maternal serum samples were obtained, one in the first trimester and one in the second trimester. Comparison of marker levels with 10,600 first trimester controls and a smaller sample of second trimester controls allowed case identification criteria based on optimum marker combinations to be developed and compared directly between trimesters.

Biochemical genetics laboratory.

F beta hCG was an effective marker of Down's syndrome in both the first and second trimesters. PAPP-A levels were significantly reduced in trisomy 21 pregnancies in the first trimester only. Using a population model, these two markers in combination with maternal age gave an overall detection rate of 55% for a 5% false positive rate in the first trimester. For the paired first and second trimester samples, three of six cases classified as low risk by routine second trimester screening were classified as high risk by the first trimester screening protocol of F beta hCG/PAPP-A/maternal age. However, fifteen cases identified as high risk by routine second trimester screening were classified as low risk in the first trimester, a net loss in detection of 12 cases by first trimester screening.

The data suggest that first trimester detection rates for Down's syndrome using a combination of F beta hCG and PAPP-A may vary with gestation and will be lower than those currently obtained by routine second trimester screening with AFP/hCG.