Serum soluble-fms-like tyrosine kinase 1-to-placental growth factor ratio on Elecsys immunoassay platform predicts preeclampsia with severe features in hospitalized women with hypertensive disorders of pregnancy.

BACKGROUND

Previous single-center studies conducted in the United States in women with suspected preeclampsia indicated that serum soluble fms-like tyrosine kinase 1-to-placental growth factor ratio values of >38 measured on a widely available Elecsys immunoassay platform during the third trimester of pregnancy predicted the development of preeclampsia with severe features and adverse outcomes within 2 weeks of testing.

OBJECTIVE

This study aimed to validate the Elecsys soluble fms-like tyrosine kinase 1-to-placental growth factor ratio test for the prediction of preeclampsia with severe features in a United States population using the prospective Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification cohort that recruited women with a hypertensive disorder of pregnancy (gestational hypertension, chronic hypertension, de novo and superimposed preeclampsia) across 18 tertiary and community hospitals throughout the United States.

STUDY

DESIGN

We measured soluble fms-like tyrosine kinase 1-to-placental growth factor ratios using the Elecsys platform in archived serum samples from the Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification study that recruited hospitalized women with a hypertensive disorder of pregnancy between 23 0/7 and 34 6/7 weeks of gestation. The primary study outcome was prediction of preeclampsia with severe features within 2 weeks after testing. The secondary outcomes included a composite of adverse maternal and fetal/neonatal outcomes and prediction of delivery within 2 weeks.

RESULTS

In the validation cohort of the Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification study (556 enrollments), the serum soluble fms-like tyrosine kinase 1-to-placental growth factor ratio at a cutoff value of >38 demonstrated a 67% positive predictive value (95% confidence interval, 61-73) and a 95% negative predictive value (95% confidence interval, 92-97) for the progression to preeclampsia with severe features within 2 weeks. Among women at <30 weeks of gestation (n=188), serum soluble fms-like tyrosine kinase 1-to-placental growth factor ratio at a cutoff value of >38 demonstrated a 78% positive predictive value (95% confidence interval, 68-86) and a 100% negative predictive value (95% confidence interval, 96-100) for the progression to preeclampsia with severe features within 2 weeks. The Elecsys soluble fms-like tyrosine kinase 1-to-placental growth factor ratio test performed better than standard-of-care clinical measures, with an area under the receiver operating characteristic curve of 0.92 (95% confidence interval, 0.89-0.90) for soluble fms-like tyrosine kinase 1-to-placental growth factor ratio vs <0.70 for standard-of-care tests, such as liver enzymes, platelet count, and serum creatinine (P<.001). Compared with women with a ratio of ≤38, those with a ratio of >38 had a higher risk of developing adverse maternal (relative risk, 4.9 [95% confidence interval, 2.6-9.9]; P<.001) and fetal/neonatal (relative risk, 3.2 [95% confidence interval, 2.6-4.0]; P<.001) outcomes and were more likely to deliver within 2 weeks (adjusted hazard ratio, 3.3 [95% confidence interval, 2.7-4.0]; P<.001).

CONCLUSION

The soluble fms-like tyrosine kinase 1-to-placental growth factor ratio of >38 measured on the Elecsys platform predicted the development of preeclampsia with severe features, delivery, and adverse maternal and fetal/neonatal outcomes within 2 weeks of testing among preterm pregnant women hospitalized with a hypertensive disorder of pregnancy.