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Objectives: To describe the impact of maternal serum screening on the birth prevalence of Down's syndrome and on the use of amniocentesis and chorionic villus sampling in South Australia., Design: A descriptive population-based study., Setting: South Australia (population 1.48 million persons; approximately 20,000 births per year)., Participants: Women who had births or terminations of pregnancy with Down's syndrome in 1982-1996, women who had maternal serum screening in 1991-1996, amniocentesis or chorionic villus sampling in 1986-1996., Methods: Analysis of data from multiple sources on maternal serum screening, amniocentesis and chorionic villus sampling, births and terminations of pregnancy., Main Outcome Measures: Total prevalence and birth prevalence of Down's syndrome each year in 1982-1996; proportion of pregnant women using maternal serum screening in 1991-1996, and proportion using amniocentesis and chorionic villus sampling by indication in 1986-1996, by age group., Results: Use of maternal serum screening for Down's syndrome increased from 17% when introduced in 1991 to 76% of women who gave birth in 1996. Between 1982 and 1986 and 1996, terminations of pregnancy for fetal Down's syndrome increased from 7.1 % to 75% and the birth prevalence of Down's syndrome fell by 60% from 1.05 to 0.42 per 1,000 births, against the background of an increase in total prevalence due to increasing maternal age. The use of amniocentesis increased from 5.8% in 1991 to 10.1% in 1996 mainly due to the increase among women younger than 35 years with maternal serum screening as the main reason. The increasing chorionic villus sampling rate among younger women stabilised at 0.4%, while the rate among older women decreased from 11.0% to 7.4%., Conclusions: The introduction of maternal serum screening in South Australia has resulted in increased use of any prenatal testing for Down's syndrome from about 7% (mainly older women having amniocentesis or chorionic villus sampling) to 84% of women (about 8% having direct amniocentesis or chorionic villus sampling and 76% having maternal serum screening first). This has resulted in a significant fall in the birth prevalence of Down's syndrome. maternal serum screening was the first indication of Down's syndrome for about half the terminations of pregnancy for Down's syndrome in 1993-1996, including three quarters of those in younger women.