Verifying Risk Calculations for Down Syndrome
The College of American Pathologists' (CAP) Chemistry and Toxicology Checklist contains a question (CHM.32200 Phase II) for laboratories performing prenatal screening to provide documentation that the accuracy of the risk calculation for Down syndrome has been verified.
One approach to verifying this calculation is to use data contained in the multiple marker evaluation report that is part of the CAP Maternal Screening Survey (FP). For each proficiency testing serum specimen, the laboratory's own reported maternal age and multiples of the medians (MoM) values (AFP/uE3/hCG or AFP/uE3/hCG/DIA) are used to calculate a Down syndrome risk. This computed risk can then be compared with the actual risk reported by the laboratory.
To compute reliable Down syndrome risks, it is important:
- to collect accurate estimates of maternal age and gestational age,
- to measure accurately and precisely the needed analytes,
- to convert those measurements using appropriate medians into multiples of the median, and
- to combine this information into a patient specific risk for Down syndrome.
The last step requires the use of published "parameter sets" that mathematically describe the multi-dimensional relationships between these markers in Down syndrome and unaffected pregnancies. Without suitable parameter sets, the Down syndrome risks will not be as reliable as they could be in screening programs.
All laboratories should understand the importance of selecting and maintaining the parameter sets used for computing clinical Down syndrome risk estimates.
Benefits of Updating Parameter Sets
Laboratories should update their parameter sets to use the most reliable data for interpretation and to allow for reported Down syndrome risks to become more harmonized both within and between laboratories. Using older parameter sets may not allow for quadruple testing or transformation of uE3 measurements to a logarithmic scale or may have other weaknesses.
Laboratories using Wald et al (1988), Wald et al (1992), or Wald et al (2000) parameter sets should consider updating to Knight et al (1998), or SURUSS (Serum, Urine, and Ultrasound Screening Study) 2013, or 2003 parameter sets.
Fetal Size and Dating Chart
- British Medical Ultrasound Society (BMUS) Recommended Fetal Size and Dating Chart (Ultrasound. 2009;17:161–167)
Second Trimester Risk Validation (Triple/Quadruple)
- SURUSS 2013 (PDF, 74 KB)
- SURUSS 2003 (updated 2004; PDF, 74 KB)
- Knight 1998 (updated 2004; PDF, 57 KB)
First Trimester Risk Validation (Combined)
- SURUSS 2003 with free beta (PDF, 69 KB)
- SURUSS 2003 with total hCG (PDF, 65 KB)
- Haddow/Nicolaides with free beta (PDF, 59 KB)