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Objective: To determine the incidence of cystic fibrosis (CF) and its time trends over a 16-year period (1990 to 2005) in 2 European regions with a long history of newborn screening (NBS) for CF, and to investigate the impact of some external factors., Study Design: This study focused on data from NBS and prenatal diagnosis (PD) in Brittany (western France) and Veneto/Trentino Alto-Adige (northeastern Italy)., Results: Similar birth incidences of CF were observed in the 2 regions (1/3153 vs 1/3540; P = .245). Time trend analysis using Poisson regression revealed that the birth incidence decreased significantly in the Italian area only (average annual percent change [AAPC] = -4.7%; 95% confidence interval [CI] = -7.3 to -2; P = .0008). The use of PD appeared more common in Brittany, and considering the terminations of CF-affected fetuses, the adjusted incidence was 1/2191 in Brittany and 1/3116 in Veneto/Trentino, corresponding to variations of 30.5% (highly significant; P = .0002) and 12% (not significant; P = .16), respectively. Recording the reason for each PD allowed ready assessment of the affect of various public health policies on incidence. The affect of population mixing also appeared to be relevant in the Italian area., Conclusions: This study highlights how the incidence of CF has evolved in 2 European regions that have different attitudes toward PD and immigration policy.