A screening program for trisomy 21 at 10–14 weeks using fetal nuchal translucency, maternal serum free β‐human chorionic gonadotropin and pregnancy‐associated plasma protein‐A

TLDR

The study aimed to evaluate whether adding maternal age, fetal nuchal translucency, and maternal serum free β‑hCG and PAPP‑A improves trisomy 21 screening at 10–14 weeks. Researchers measured free β‑hCG and PAPP‑A by Kryptor in 210 trisomy 21 and 946 matched controls, combined these with ultrasound‑measured nuchal translucency and crown‑rump length, calculated MoM distributions and likelihood ratios, and integrated them with age‑related risk to estimate detection rates at fixed false‑positive rates for the UK population. The combined marker approach achieved an estimated 89 % detection at a 5 % false‑positive rate (or 70 % detection at 1 % false‑positive), adding 16 % to detection over nuchal translucency and age alone, and the rapid Kryptor assay supports one‑stop clinics that improve sensitivity and reduce patient anxiety. © 1999 International Society of Ultrasound in Obstetrics and Gynecology.

Abstract

Abstract Objective To examine the potential impact of combining maternal age with fetal nuchal translucency thickness and maternal serum free β‐human chorionic gonadotropin (β‐hCG) and pregnancy‐associated plasma protein‐A (PAPP‐A) in screening for trisomy 21 at 10–14 weeks of gestation. Methods Maternal serum free β‐hCG and PAPP‐A were measured by Kryptor, a random access immunoassay analyzer using time‐resolved amplified cryptate emission, in 210 singleton pregnancies with trisomy 21 and 946 chromosomally normal controls, matched for maternal age, gestation and sample storage time. In all cases the fetal crown–rump length and nuchal translucency thickness had been measured by ultrasonography at 10–14 weeks of gestation and maternal blood had been obtained at the time of the scan. The distributions (in multiples of the median; MoM) of free β‐hCG and PAPP‐A (corrected for maternal weight) and fetal nuchal translucency (NT) were determined in the trisomy 21 group and the controls. Likelihood ratios for the various marker combinations were calculated and these were used together with the age‐related risk for trisomy 21 in the first trimester to calculate the expected detection rate of affected pregnancies, at a fixed false‐positive rate, in a population with the maternal age distribution of pregnancies in England and Wales. Results In a population with the maternal age distribution of pregnancies in England and Wales, it was estimated that, using the combination of maternal age, fetal nuchal translucency thickness and maternal serum free ß‐hCG and PAPP‐A, the detection of trisomy 21 pregnancies would be 89% at a fixed false‐positive rate of 5%. Alternatively, at a fixed detection rate of 70%, the false‐positive rate would be 1%. The inclusion of biochemical parameters added an additional 16% to the detection rate obtained using NT and maternal age alone. Conclusions Rapid diagnostic technology like Kryptor, which can provide automated reproducible biochemical measurements within 30 min of obtaining a blood sample, will allow the development of interdisciplinary one‐stop clinics for early fetal assessment. Such clinics will be able to deliver improved screening sensitivity, rapidly and more efficiently, leading to reduced patient anxiety and stress. Copyright © 1999 International Society of Ultrasound in Obstetrics and Gynecology