Down syndrome (DS), also known as Trisomy 21, is a genetic disorder caused by the presence of an additional copy of chromosome 21 in each cell. Traditional second-trimester serum screening (STSS has been widely used in China, but is limited in diagnostic accuracy. In contrast, the use of cell-free fetal DNA in maternal blood through non-invasive prenatal testing (NIPT) shows excellent diagnostic accuracy, though at a higher cost. This study was conducted in China using actual data from 140,472 pregnant women who underwent both NIPT and STSS to assess the clinical and economic effectiveness of several DS screening techniques.
The study historically examined data from 140,265 eligible individuals who participated between March 2018 and December 2020. Researchers combined STSS, NIPT, and classic age-based screening to examine eight unique screening methods. NIPT significantly outperformed STSS in terms of sensitivity (97.02% vs. 49.4%), specificity (99.98% vs. 91.99%), and positive predictive value (82.32% vs. 0.73%).
NIPT continuously reduced the number of false positives and unnecessary invasive diagnostic procedures. The most DS cases were discovered by Universal NIPT (Strategy 1), which had the best safety index (0.0036), the highest accuracy (99.97%), and the highest detection rate. Strategy 7 also maintained high accuracy and safety while providing the lowest incremental cost-effectiveness ratio (ICER) compared to Strategy 5, which detected a slightly higher number of DS cases (142 vs. 134). Strategy 8 (Traditional screening) resulted in the largest number of disruptive or unnecessary invasive procedures (43,573), the lowest cost-efficacy, and the poorest safety profile.
Strategy 1 (Universal NIPT) was considered the most cost-effective option when the NIPT price dropped to RMB 295.28. The majority of the 140,265 pregnant women in the analysis were aged between 25 and 34 years, with an average age of 30.15 ± 4.02 years. The average gestational age was 16.64 weeks, with 96.27% of participants in their second trimester of pregnancy (14-27 weeks). NIPT consistently demonstrated superior performance across all age groups, with no significant differences in sensitivity or specificity.
In the Public Welfare Program in Changsha City of China, the cost per NIPT test was RMB 600 compared to RMB 160 for STSS. The analysis did not include discounting as the expenditure of the public health project was fixed and predicted.
Strategy 5 demonstrated strong health economic benefits by offering a low cost-effectiveness ratio as well as high accuracy and safety. While NIPT has excellent diagnostic performance, its high cost has limited its use as a primary screening method. Previous research has suggested that if the cost per unit falls below USD 453, then NIPT could be economically viable for universal use among pregnant women.
This study also highlighted the ineffectiveness and potential risks of standard age-based screening (Strategy 8), which is associated with a high number of unnecessary invasive procedures and related complications. The findings support universal NIPT as the safest and most accurate method of screening for DS, especially as costs decline. A combined or stepwise approach involving STSS and NIPT may offer a more cost-effective and high-performing alternative.
Reference: Liu J, Wang S, Zhou S, et al. Cost-effectiveness of different screening strategies for Down syndrome: a real-world analysis in 140,472 women. Front Public Health. 2025;13:1535381. doi:10.3389/fpubh.2025.1535381
