Objectives: To evaluate trends of nasal bone length (NBL), prenasal thickness (PT), nuchal fold (NF), prenasal thickness to nasal bone length (PT-NBL) ratio, and prefrontal space ratio (PFSR), measured serially in second- and third-trimester Down syndrome (DS) fetuses. Methods: Prenatal databases were searched for cases of continuing DS pregnancies with serial measurements, taken at least two weeks apart. Trends were plotted on previously reported normal ranges. Results: Serial measurements were available in 25 Down syndrome fetuses. Median gestational age (GA) was 25 weeks; average number of visits per case was 2.44, with a median interval of 39 days between investigations. In DS fetuses, NBL and PT showed fairly stable trends with gestation. PFSR, but especially NF, had a more unpredictable trend. The PT-NBL ratio was the most stable marker, remaining unchanged in 95% of cases. NBL, PT, and NF showed more deviance from the normal range with advancing gestation, but MoM values remained stable. All but two fetuses had ultrasound markers or structural anomalies, especially heart defects. Conclusions: The PT-NBL ratio is the most constant DS marker throughout gestation, following a predictable trend.