Background: Sonographic and biochemical methods for Down's syndrome screening have developed simultaneously, but independently. As a consequence, the rate of invasive procedures for fetal karyotyping has dramatically increased and become an important public health issue which needs to be controlled. One approach is to combine sonographic and biochemical results into a single risk assessment.
Methods: In a multicentre interventional study, nuchal translucency (NT) was measured between 12(+0) and 14(+0) weeks of gestation. Maternal serum markers (MSM) were measured between 14(+1) and 17(+0) weeks of gestation. Karyotyping was advised when: (i) NT was > or =3 mm; or (ii) the MSM-related risk was > or =1 in 250 at term. Karyotyping was delayed until after a maternal blood sample had been taken. NT and MSM were expressed as multiples of the medians (MoMs), and risks were calculated and tailored to the study population. A combined risk for NT and MSM was estimated retrospectively. Costs per case diagnosed, and the cost per case averted were calculated for the three screening strategies.
Results: A total of 9444 women was screened. Twenty-one fetuses (0.22%) had Down's syndrome, whilst 326 women (3.4%) were lost to follow-up. Among 9118 women followed up, 5506 had both NT and MSM, 821 had only NT, and 2791 had only MSM. Median maternal age was 30.5 years. False-positive rates for NT, MSM and NT combined with MSM were 3.0, 5.8 and 0.23% respectively. The false-positive rate generated by a sequential two-stage screening was 8.6%. Detection rates of Down's syndrome were 62 and 55% for NT and MSM respectively. Seven cases with Down's syndrome (35%) had raised NT and MSM, and 17 (81%) had either raised NT, MSM, or both. For a 5% false-positive rate, detection rates were 55 and 80% for NT alone and for combined NT and MSM respectively. Ultrasound alone appears to be more cost-effective ( pound50 per case diagnosed) than both tests ( pound61 per case diagnosed).
Conclusions: The study results suggest a 25% increase in the detection rate of Down's syndrome using a combination of NT measurement at 12(+0)-14(+0) weeks and MSM at 14(+1)-17(+0) weeks for a 5% false-positive rate, with modest increase in cost.