Combined ultrasound and biochemical screening for Down's Syndrome in the first trimester: a Scottish multicentre study

Abstract

Objective To evaluate the use of ultrasound measurements of fetal nuchal translucency (NT) obtained in a routine antenatal clinic setting in combination with appropriate biochemical markers as a first trimester screening test for Down's Syndrome. Design Multicentre observational study.Setting Fifteen Scottish maternity units.Population Pregnant women (n ¼ 17,229) attending routine antenatal clinics at 10 -14 weeks of gestation.Methods NT measurements were attempted in all women along with the measurement of maternal serum free beta human chorionic gonadotrophin (FhhCG) and pregnancy-associated plasma protein-A (PAPP-A). All results were converted to multiples of the appropriate gestational median (MoM) and using a statistical model the risk of an affected pregnancy was derived. No results were given to participating women but all were offered routine second trimester biochemical screening. All cases of Down's Syndrome within the study group were ascertained and the detection rate for each marker was estimated. Main outcome measures Success rate of obtaining NT measurements and overall effectiveness of ultrasound and biochemical markers individually and in combination for the detection of Down's Syndrome pregnancies. Results NT measurements were obtained in 72.9% of women and blood samples in 98.4%. Forty-five cases of Down's Syndrome were ascertained (2.6/1000). NT measurements were obtained in 37 cases (median NT 1.65 MoM), blood samples in 42 cases and both NT and blood in 34 cases. In combination with the a priori maternal age risk, observed detection rates at a 5% false positive rate were 20/37 (54%) for NT, 23/42 (55%) for FhhCG and PAPP-A and 28/34 (82%) for a combination of NT, FhhCG and PAPP-A using a cutoff risk of 1:250. The effect of failing to obtain NT measurements in all cases reduces the overall detection rate to 62% (i.e. 28/45) if the entire series of affected pregnancies within the study group is considered. Conclusions NT in combination with appropriate serum markers has the potential to detect over 80% of Down's Syndrome fetuses in early pregnancy. However, NT measurement is highly operator-dependent. It requires training, external quality control and adequate time to allow accurate measurement, otherwise suboptimal performance will result.

First‐trimester Down syndrome screening in women younger than 35 years old and cost‐effectiveness analysis in Taiwan population

“…For strategy two, AFTDSS, the detection rate and false‐positive rate of FTDSS for all ages ranged from 82% to 93% and from 2.1% to 5.9%, respectively. These ranges reference previous studies that include women ≥35 years of age, and they did not exceed 25% of the studied population [4,10–13,16]. Studies that the number of Down syndrome less than 10 cases were excluded [14,15].…”

Quality of nuchal translucency measurements in The Netherlands: a quantitative analysis

“…Two types of quality assurance can be distinguished, both of which have been applied to the measurement of NT7–9. With qualitative assurance, aspects which contribute to adequate NT measurement, for example a correct sectional plane view of the fetus or caliper placement, are evaluated through the submission of ultrasound prints by the operator to an examining body; based on scores given by experts the quality of NT measurements can be determined10.…”

Screening for Down's syndrome in the first trimester: Combined risk calculation, methodology, and validation of a web‐based system

“…In order to run an effective screening program, risk calculation software is required which can generate a combined risk utilizing the information from individual marker measurements, maternal age, and various maternal and pregnancy factors. Following completion of a prospective multicenter trial of first trimester combined ultrasound and biochemical screening (CUBS) (11) in Scotland, a lab‐based screening algorithm utilizing the study parameters was developed. This system underpinned the introduction of routine CUB screening in Scotland.…”