First trimester Down syndrome screening: distribution of markers and comparison of assays for quantification of pregnancy-associated plasma protein-A.

OBJECTIVE: First trimester screening for fetal chromosomal disease is now possible using the maternal serological markers pregnancy-associated plasma protein-A (PAPP-A) and the free ss-form of human chorionic gonadotrophin (sshCG) in combination with the ultrasound marker nuchal translucency (NT) thickness. The availability of well-defined analytical methods and reference ranges for the involved parameters, and knowledge of the correlation between markers and clinical parameters, e.g. maternal weight, parity and age, are important for the design of efficient screening programs.
MATERIAL AND METHODS: Women (n = 2702), with singleton pregnancies, participating in the Copenhagen First Trimester Screening Study had PAPP-A and sshCG values determined and NT measured at a gestational age of 11 to 14 weeks, as determined from crown rump length (CRL). The distribution of gestational age-independent multiples of the median (MoM) of the parameters was defined and reference intervals established. Three methods for determination of PAPP-A, one manual in-house poly-monoclonal ELISA and two commercial semi-automatic double-monoclonal methods, i.e. PAPP-A for the AutoDelfia platform and PAPP-A for the Kryptor platform, were compared in 260 women.
RESULTS: All markers had log-normally distributed MoMs. Gestational age independent reference intervals were established. Maternal weight should be included in risk algorithms. The semi-automated PAPP-A assays (AutoDelfia and Kryptor) gave similar values, mean difference 10.5 %, whereas the manual assay gave higher values, mean differences 50.4 % and 41.0 %, respectively,
CONCLUSIONS: This calls for better standardization and a uniform quality control scheme that is focused on discriminatory ability rather than adherence to mean values from a large number of laboratories.