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Outcome of the first-trimester Down syndrome screening in younger population was less reported before. We present the outcome of this screening in Taiwanese women younger than 35 years old. We also test whether or not the first-trimester Down syndrome screening of women <35 years of age and women >35 years old routinely receiving amniocentesis is cost-effective compared with all pregnant women screened with this test in the setting of increased maternal age.From 1999 to 2007, the first-trimester Down syndrome screening including nuchal thickness, pregnancy-associated plasma protein A and free β-hCG are provided to 10 811 singleton women <35 years of age with the cut-off of 1/270. A cost-effectiveness analysis of young women receiving this screening and older women undergo amniocentesis versus all women undergo this screening was performed in Taiwan population from 1987 to 2006, in which advanced age pregnancies increased from 2.8% to 11.6% of total pregnancies.Detection rates of trisomy 21, trisomy 18, Turner syndrome and other chromosome anormalies in women <35 years of age are 87.5% (14/16), 50% (2/4), 80% (8/10) and 63% (12/19), respectively, with a false-positive rate of 5.5% (590/10 811). As advanced age pregnancies reached 11.6%, the average cost per one case averted for all women screened ranged from $77 204 to $98 421, while the cost ranged from $99 647 to $116 433 for only women <35 years of age receiving this screening.In an aging population, the first-trimester Down syndrome screening should be implemented for all pregnant women when it is available.