A-361 Long-term analytical variation of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) for preeclampsia risk assessment: a 5-year review
Bibliographic record
Abstract
Abstract Background Preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality. Dysregulation of pro-angiogenic [placental growth factor (PlGF)] and anti-angiogenic [soluble fms-like tyrosine kinase-1 (sFlt-1)] mediators represents contributing factors to multi-system disease pathogenesis. An increased ratio of sFlt-1 to PlGF is associated with preeclampsia risk. Within the laboratory, long-term analytical variation of both assays has not been formally assessed. The objective of this study was to evaluate analytical variations in PlGF and sFlt-1 assays and their impact on the clinical interpretation of test results. Methods Five years of retrospective patient results for sFlt-1, PlGF and sFlt-1:PlGF ratio were extracted since clinical implementation at a tertiary hospital with a high-risk obstetrical unit (N=1958, Roche cobas 8000 e602 and cobas Pro e802). Descriptive statistics were determined across unique reagent lots. sFlt-1:PlGF results were classified according to preeclampsia risk based on the landmark PROGNOSIS study as low (<39), moderate (39 to 85), or high (>85). The percentage of results in each risk category were compared across unique sFlt-1 and PlGF reagent lot combinations. In addition to retrospective patient data, aggregate results from two external quality assurance (EQA) programs for sFlt-1 and PlGF were reviewed. The first EQA program (Weqas) included four years of monthly EQA survey data on one instrumentation (Roche cobas, N=15-22 participant laboratories). The second EQA program (RIQAS) consisted of a one-time pilot survey and included four different assays (Roche cobas, Brahms KRYPTOR, DELFIA Xpress, SNIBE Maglumi, N=89 participant laboratories). Results In retrospective patient data, the percentage of sFlt-1:PlGF results classified as high risk varied between 12% to 30% across 11 unique PlGF and sFLt-1 lot combinations (N=59 to 587 per lot). PlGF results varied with reagent lot with medians ranging from 183 ng/L (IQR: 83-299 ng/L) to 231.5 ng/L (96-330 ng/L). sFlt-1 also demonstrated variation in lot-specific patient result medians ranging from 176 ng/L (IQR: 89-325 ng/L) to 212 ng/L (103-293 ng/L). Shifts in sFlt-1 and PlGF distribution across lots were not statistically significant and did not correlate to any change observed in sFlt-1:PlGf ratio classification. Based on review of four years of EQA data (Weqas), coefficient of variation (CV) across participating laboratories was higher for PlGF (median: 8.4%, IQR: 6.3-10.6%) relative to sFlt-1 (median: 4.7%, IQR: 4.0-5.4%). Pilot EQA survey (RIQAS) that included different instrumentation demonstrated assay-specific differences in observed CV and was dependent on the target concentration. Conclusion This study evaluates a comprehensive dataset of sFlt-1:PlGF results from patients assessed for preeclampsia risk. These data were linked with laboratory information, including reagent lot and EQA results, to assess long-term variations in analytical performance. Our findings suggest that observed variations in sFlt-1:PlGF risk classifications with reagent lot are likely due to patient-specific factors as opposed to changes in analytical performance. EQA data also support robust long-term performance; however, higher CVs were observed for PlGF relative to sFlt-1 and demonstrated dependence on assay platforms. These findings contribute to our understanding of analytical considerations for preeclampsia testing and may serve as a resource of laboratories considering implementation.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".