Screening for trisomy 21 in twin pregnancies in the first trimester using free ?-hCG and PAPP-A, combined with fetal nuchal translucency thickness

The risk of an individual woman having a pregnancy associated with Down's syndrome was estimated from her age and her serum alpha-fetoprotein (AFP) level at 14-20 weeks gestation. The estimates were made using published data on the risk of Down's syndrome in relation to maternal age from 4528 affected and over 5 million unaffected pregnancies, and on the risk in relation to serum AFP from 68 affected and 36,645 unaffected pregnancies. Separate estimates were derived for AFP levels using gestational age based on the time since the first day of the last menstrual period and on an ultrasound biparietal diameter measurement. In each case this was done with and without adjusting AFP levels to take account of maternal weight. The same sources of data were also used to construct six Down's syndrome screening policies, each combining information on maternal age and serum AFP. For example with one policy the detection rate would be 28% and would involve selecting 2.8% of unaffected pregnancies for amniocentesis; using age alone the same detection rate could only be achieved by selecting 4.3% of unaffected pregnancies for amniocentesis--an increase of 50%. In general, screening for Down's syndrome using both maternal age and serum AFP is more efficient than either alone.

To examine the potential impact of combining maternal age with fetal nuchal translucency thickness and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in screening for trisomy 21 at 10-14 weeks of gestation. Maternal serum free beta-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 beta-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. 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 beta-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. 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.

To determine the prevalence of increased fetal nuchal translucency thickness in twin pregnancies and to evaluate screening for trisomy 21 by a combination of translucency thickness and maternal age.