Randomized Interventional Study on Prediction of Preeclampsia/Eclampsia in Women With Suspected Preeclampsia: INSPIRE.

The ratio of maternal serum sFlt-1 (soluble fms-like tyrosine kinase 1) to PlGF (placental growth factor) has been used retrospectively to rule out the occurrence of preeclampsia, a pregnancy hypertensive disorder, within 7 days in women presenting with clinical suspicion of preeclampsia. A prospective, interventional, parallel-group, randomized clinical trial evaluated the use of sFlt-1/PlGF ratio in women presenting with suspected preeclampsia. Women were assigned to reveal (sFlt-1/PlGF result known to clinicians) or nonreveal (result unknown) arms. A ratio cutoff of 38 was used to define low (≤38) and elevated risk (>38) of developing the condition in the subsequent week. The primary end point was hospitalization within 24 hours of the test. Secondary end points were development of preeclampsia and other adverse maternal-fetal outcomes. We recruited 370 women (186 reveal versus 184 nonreveal). Preeclampsia occurred in 85 women (23%). The number of admissions was not significantly different between groups (n=48 nonreveal versus n=60 reveal; P=0.192). The reveal trial arm admitted 100% of the cases that developed preeclampsia within 7 days, whereas the nonreveal admitted 83% (P=0.038). Use of the test yielded a sensitivity of 100% (95% CI, 85.8-100) and a negative predictive value of 100% (95% CI, 97.1-100) compared with a sensitivity of 83.3 (95% CI, 58.6-96.4) and negative predictive value of 97.8 (95% CI, 93.7-99.5) with clinical practice alone. Use of the sFlt-1/PlGF ratio significantly improved clinical precision without changing the admission rate. Clinical Trial Registration- URL: http://www.isrctn.com. Unique identifier: ISRCTN87470468.

Extending the scope of pooled analyses of individual patient biomarker data from heterogeneous laboratory platforms and cohorts using merging algorithms.

BACKGROUND: A common challenge in medicine, exemplified in the analysis of biomarker data, is that large studies are needed for sufficient statistical power. Often, this may only be achievable by aggregating multiple cohorts. However, different studies may use disparate platforms for laboratory analysis, which can hinder merging. METHODS: Using circulating placental growth factor (PlGF), a potential biomarker for hypertensive disorders of pregnancy (HDP) such as preeclampsia, as an example, we investigated how such issues can be overcome by inter-platform standardization and merging algorithms. We studied 16,462 pregnancies from 22 study cohorts. PlGF measurements (gestational age ⩾20 weeks) analyzed on one of four platforms: R&D Systems, AlereTriage, RocheElecsys or AbbottArchitect, were available for 13,429 women. Two merging algorithms, using Z-Score and Multiple of Median transformations, were applied. RESULTS: Best reference curves (BRC), based on merged, transformed PlGF measurements in uncomplicated pregnancy across six gestational age groups, were estimated. Identification of HDP by these PlGF-BRCs was compared to that of platform-specific curves. CONCLUSIONS: We demonstrate the feasibility of merging PlGF concentrations from different analytical platforms. Overall BRC identification of HDP performed at least as well as platform-specific curves. Our method can be extended to any set of biomarkers obtained from different laboratory platforms in any field. Merged biomarker data from multiple studies will improve statistical power and enlarge our understanding of the pathophysiology and management of medical syndromes.