Prenatal diagnosis of aneuploidy in the first trimester using ultrasound and maternal serum biochemistry

Screening for trisomy 21, often in conjunction with screening for neural tube defects, by the measurement of second trimester maternal serum biochemical markers has become an established part of obstetric practice in many countries.
Although trisomy 21 screening protocols vaiy from centre to centre the average detection rate in prospective studies has been 64% (range 48-75%) for a false positive rate of about 5%. For the other major chromosomal anomalies, only algorithms for trisomy 18 have been successfully implemented in routine practice.
During the last decade, extensive research has demonstrated that effective screening for chromosomal abnormalities can be achieved by maternal serum free b-hCG and pregnancy associated plasma protein-A (PAPP-A) and the ultrasonographic measurement of fetal nuchal translucency (NT) thickness. In a multicentre study involving about 100,000 pregnancies screening by fetal NT, with measurements performed in a standardised way (defined by the Fetal Medicine Foundation; www.fetalmedicine.com) by suitably trained sonographers, the detection rate for trisomy 21 was 73% for a 5% screen positive rate.
Subsequently, it was estimated that a combination of fetal NT with maternal serum free b-hCG and PAPP-A would increase the detection rate for trisomy 21 to about 90% and also allow the detection of 90%) of other chromosomal anomalies, including trisomy 13, trisomy 18, turner's syndrome and triploidy.
The advent of rapid immunoassays, suitable for point-of-care testing, has enabled the development of a nuilticlisciplinary one-stop clinic for assessment of risk for fetal anomalies (OSCAR). Within a one hour visit, the patient can receive pre-test counseling, blood collection and biochemical testing, ultrasound examination and post-test counseling of a combined risk estimate. The first year of prospective intervention screening using this approach has been reported.
In this paper I will summarise results from three years of screening for chromosomal anomalies in our routine NHS OSCAR clinic in which we have screen approximately 12,000 women. The uptake of first trimester screening was 97.5%) and the uptake of invasive testing in the increased risk group was 77%. The rate of detection of trisomy 21 was 92% (23 of 25), of trisomy 13 or 18 was 100% (all 15) and of all aneuploides was 96% (49 of 51). The false positive rate was 5.2%. I will also report on the Outcome of screening 15,030 pregnancies in a private Fetal Medicine Centre, in which 91.5%o (75 of 82) cases of trisomy 21 were identified along with 88.5%) (54 of 61) of pregnancies with other chromosomal anomalies. I will also outline results from 3 years of screening in our private self referral OSCAR centre. 
I will conclude with a discussion of new research initiatives which may enhance the OSCAR process and lead to even higher detection rates (95%) at a much lower false positive rate (2%) for trisomy 21.