Using Sigma Quality Control to Verify and Monitor Performance in a Multi-Instrument, Multisite Integrated Health Care Network.

The authors developed a system-wide integrated network of instrumentation and Sigma-based quality control for fundamental chemistry, coagulation, and hematology analysis. The authors have based selection of Westgard rules for run management on a straightforward, Sigma-driven selection process. The network includes multiple hospitals and large regional clinic laboratories. Most hospitals have multiple instruments; overall there are at least four distinct instrument models active from each manufacturer. The authors have measured and monitored Sigma values in this network for more than five years, to verify and validate performance and to provide ongoing justification for rules selection and rules changes when necessary.

Impact of folic acid fortification in the United States: markedly diminished high maternal serum alpha-fetoprotein values.

OBJECTIVE: Folic acid fortification of breads and grains was implemented in the United States in 1998 in an attempt to reduce the incidence of neural tube defects. Outcome data from birth registries have shown a 20% drop-less than originally predicted. In this study, we ascertain if the impact of folic acid fortification is better seen at the time of midtrimester prenatal diagnosis by looking at incidence of high maternal serum alpha-fetoprotein (MSAFP) values. METHODS: Data regarding MSAFP levels in 61,119 patients undergoing maternal serum screening at a large commercial laboratory were categorized by multiples of the median (MoM). The data were compared between 2 groups: before mandatory supplementation in the United States in 1997 and after mandatory supplementation in 2000. High MSAFP values were further categorized as high (2.75-4.00 MoM) or very high (more than 4.00 MoM). Data were analyzed by chi(2) analysis. RESULTS: Comparative data showed a 32% decrease of patients with MoM greater than 2.75 + (2.5% -1.7%). Further categorizations revealed similar decreases. CONCLUSION: The introduction of folic acid fortification has produced a profound decrease in the number of high MSAFP values, reflective of a decreased incidence of neural tube defects. Our results help to validate the decision to fortify food with folic acid, which represents a highly successful public health policy for primary prevention of birth defects. LEVEL OF EVIDENCE: II-2

Standardization of methods reduces variability: explanation for historical discrepancies in biochemical screening.

Over the past decade, many studies have argued the relative merits of different chromosome abnormality biochemical screening protocols in different labs. Results and interpretations have varied markedly (e.g., double vs. triple screening). In this study we sought to compare coefficients of variation (CV) among 12 laboratories in one system, using identical and different methodologies for the three parameters. Ten identical specimens were processed as part of the 1999 College of American Pathologists (CAP) (FP-A, FP-B) proficiency tests. Results were compared among 12 laboratories using the Abbott ELISA for alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), and two methods for estriol [Diagnostic Services Laboratory (DSL) and an "in house" assay]. The range on the 10 specimens of means for AFP varied from 12.56 to 117.87; hCG 14.05-68.08; and estriol 0.61-2.73. CV for AFP specimens averaged 10%, hCG 8%, and estriol 35% (F = 22.4). However, when only DSL was used for estriol, the CV was reduced to 8.7%. Standardization of AFP and hCG across 12 labs has reduced CV to <10%, which is similar to accepted between run results. Wide variation of uE3 among different methods may explain the widely divergent results in the literature. With national standardization of all parameters, the widely divergent results seen in the literature should narrow, and regional medians will no longer be necessary.

Correction for insulin-dependent diabetes in maternal serum alpha-fetoprotein testing has outlived its usefulness.

OBJECTIVE: Historically, alpha-fetoprotein (AFP) levels in insulin-dependent diabetes (IDDM) have shown an approximately 20% decrement, and a correction factor is used to standardize multiples of the median (MOMs). With new laboratory methods and improved precision, we sought to re-evaluate the correctness of this approach. STUDY DESIGN: Consecutive biochemical screens were conducted among 60,287 nondiabetic patients and 307 patients with IDDM. Analyses were conducted in one laboratory, and comparisons were made with use of standard formula weight adjustments including a 20% correction factor for IDDM. Patients were then stratified according to maternal weight. RESULTS: Nondiabetic patients averaged 1.00 MOM, IDDM patients 0.91 MOM with no adjustments, 0.96 MOM adjusting for weight only, and 1.20 MOM adjusting for weight and diabetes status. To explain the "overcorrection," analysis by maternal weight showed significant overrepresentation of IDDM patients at 175 pounds or above. In fact, the mean weight in pounds for nondiabetic subjects was 151 +/- 35 and for those with IDDM 174 +/- 52 (P <.001). With use of an upper limit weight cutoff of 200 pounds, results are within 4% of normal. CONCLUSIONS: With current methodologies, the 20% correction factor for IDDM erroneously overcorrects. Two hundred pounds is sufficient, the weight correction for diabetic status should be abandoned.

High-resolution two-dimensional electrophoretic survey of serum protein genetic types in Schmiedeleut Hutterites.

High-resolution, two-dimensional electrophoresis (2DE) was used to examine allele frequencies in eight serum protein marker systems and to screen for rare or previously undescribed alleles in 152 members of the Schmiedeleut branch of the Hutterite Brethren. The results include the first report of α2 -HS glycoprotein, apolipoprotein E, and SPPM-158 frequencies and haptoglobin 1F and 2S subtype frequencies in the Hutterites. Designed as part of ongoing genetic studies in this reproductively isolated population, this study was done to determine which markers might correlate with medical features or could be useful in population studies. Prior studies of erythrocyte surface and enzymatic markers, lymphocyte surface and enzymatic markers, and serum proteins by other investigators have identified common, rare, and private markers in approximately 40 polymorphic systems. This study included five serum protein markers that were not examined in previous studies. The study identified a 2DE marker, SPPM-158, that was later confirmed in other populations to be a ubiquitous serum protein polymorphism. Allele frequencies for α2 -HS glycoprotein, apolipoprotein E, group-specific globulin, haptoglobin, SPPM-158, α1 -antitrypsin, apolipoprotein A-IV, and transferrin are presented. The first five of these had allele frequencies useful for population studies. We did not find any rare or private variants with 2DE in these systems. Overall, the 2DE data were in good agreement with prior studies in the Hutterites and relevant European populations.