OBJECTIVE: To provide the necessary mathematical formulae to construct a risk calculation package for Down's syndrome using maternal serum free beta human chorionic gonadotrophin, pregnancy associated plasma protein A, and ultrasound nuchal translucency(NT) measurements in the first trimester for use in a web-based system. SETTING: Swedish antenatal screening program. POPULATION: Swedish women choosing to have first trimester screening for Down's syndrome. METHODS: A standard Gaussian approach to calculation of likelihood ratios for each marker value was used following conversion of analyte concentrations and NT measurements to multiples of the normal gestational median (MoM). Validation of the algorithm was carried out on a study group of 3,900 pregnancies (including 29 cases of Down's syndrome). Predicted detection and screen positive rates were compared with an alternative calculation package. MAIN OUTCOME MEASURES: Sensitivity and specificity of screening delivered by risk calculation package. RESULTS: A cut-off risk of 1 in 200 produced a detection rate of 90% at a 4.7% false-positive rate. In addition, use of the calculation package in a web-based system proved efficient in routine practice, providing rapid access by individual centers to results and easy central monitoring and auditing of the program. CONCLUSIONS: The system described here fulfills the requirement for an appropriately validated risk calculation package, is fully user configurable with easy access through a web-based system allowing extension of the screening program to multiple centers.
OBJECTIVE: To provide the necessary mathematical formulae to construct a risk calculation package for Down's syndrome using maternal serum free beta human chorionic gonadotrophin, pregnancy associated plasma protein A, and ultrasound nuchal translucency(NT) measurements in the first trimester for use in a web-based system. SETTING: Swedish antenatal screening program. POPULATION: Swedish women choosing to have first trimester screening for Down's syndrome. METHODS: A standard Gaussian approach to calculation of likelihood ratios for each marker value was used following conversion of analyte concentrations and NT measurements to multiples of the normal gestational median (MoM). Validation of the algorithm was carried out on a study group of 3,900 pregnancies (including 29 cases of Down's syndrome). Predicted detection and screen positive rates were compared with an alternative calculation package. MAIN OUTCOME MEASURES: Sensitivity and specificity of screening delivered by risk calculation package. RESULTS: A cut-off risk of 1 in 200 produced a detection rate of 90% at a 4.7% false-positive rate. In addition, use of the calculation package in a web-based system proved efficient in routine practice, providing rapid access by individual centers to results and easy central monitoring and auditing of the program. CONCLUSIONS: The system described here fulfills the requirement for an appropriately validated risk calculation package, is fully user configurable with easy access through a web-based system allowing extension of the screening program to multiple centers.
Authors: S Kate Alldred; Yemisi Takwoingi; Boliang Guo; Mary Pennant; Jonathan J Deeks; James P Neilson; Zarko Alfirevic Journal: Cochrane Database Syst Rev Date: 2017-03-15