Technical standards and guidelines: prenatal screening for Down syndrome that includes first-trimester biochemistry and/or ultrasound measurements.

This statement is intended to augment the current general ACMG Standards and Guidelines for Clinical Genetics Laboratories and to address guidelines specific to first-trimester screening for Down syndrome. The aim is to provide the laboratory the necessary information to ensure accurate and reliable Down syndrome screening results given a screening protocol (e.g., combined first trimester and integrated testing). Information about various test combinations and their expected performance are provided, but other issues such as availability of reagents, patient interest in early test results, access to open neural tube defect screening, and availability of chorionic villus sampling are all contextual factors in deciding which screening protocol(s) will be selected by individual health care providers. Individual laboratories are responsible for meeting the quality assurance standards described by the Clinical Laboratory Improvement Act, the College of American Pathologists, and other regulatory agencies, with respect to appropriate sample documentation, assay validation, general proficiency, and quality control measures. These guidelines address first-trimester screening that includes ultrasound measurement and interpretation of nuchal translucency thickness and protocols that combine markers from both the first and second trimesters. Laboratories can use their professional judgment to make modification or additions.

Comparison of fresh frozen serum to proficiency testing material in College of American Pathologists surveys: alpha-fetoprotein, carcinoembryonic antigen, human chorionic gonadotropin, and prostate-specific antigen.

CONTEXT: Most proficiency testing materials (PTM) contain an artificial matrix that may cause immunoassays to perform differently with this material than with clinical samples. We hypothesized that matrix effects would be reduced by using fresh frozen serum (FFS). OBJECTIVE: To compare the performance of an FFS pool to standard PTM for measurement of alpha-fetoprotein, carcinoembryonic antigen, human chorionic gonadotropin (hCG), and prostate-specific antigen (PSA). DESIGN: One FFS specimen and 4 different admixtures of PTM were distributed in the 2003 College of American Pathologists K/KN-A (for alpha-fetoprotein, carcinoembryonic antigen, hCG, and total and free PSA) and C-C (hCG only) Surveys. PARTICIPANTS: The number of laboratories that participated in the surveys varied from a low of 288 (free PSA, K/KN-A Survey) to a high of 2659 (hCG, C-C Survey). MAIN OUTCOME MEASURES: Method imprecision and method bias were compared between the FFS specimen and the standard PTM specimen with the closest value. Method imprecision was determined by calculating the coefficients of variation for each method and for all methods combined. Bias was defined as the proportional difference between peer-group mean and the median of all method means. RESULTS: The FFS specimen gave significantly higher imprecision than PTM for the analytes alpha-fetoprotein, carcinoembryonic antigen, total PSA, and free PSA. For hCG, no substantial imprecision differences were observed in both surveys. Bias was significantly greater for the alpha-fetoprotein, carcinoembryonic antigen, and total PSA assays and significantly lower for the hCG and free PSA assays when comparing the FFS with the PTM. CONCLUSIONS: Fresh frozen serum did not provide consistently lower imprecision or bias than standard PTM in a survey of commonly ordered tumor markers.

Revised sections F7.5 (quantitative amino acid analysis) and F7.6 (qualitative amino acid analysis): American College of Medical Genetics Standards and Guidelines for Clinical Genetics Laboratories, 2003.

Determination of plasma amino acid levels has become a key piece of information in the diagnosis and clinical management of a group of metabolic genetic disorders. Appropriate laboratory methodologies have been published for amino acid analysis, yet there is a need for direction for the laboratory in performing this testing. The following guidelines were generated by a working group of the American College of Medical Genetics Laboratory Quality Assurance Committee. Based upon a body of knowledge and professional experience, these guidelines and standards are to be the benchmark for performance of amino acid analysis for clinical interpretation.