First-Trimester Prediction of Preeclampsia in Low-Risk Nulliparous Women

Objective—To identify clinical characteristics and biochemical markers in first-trimester samples that would possibly predict the subsequent development of preeclampsia. Methods—We conducted a multicenter observational study in 2,434 low-risk nulliparous women to identify biomarkers that possibly predict preeclampsia. Clinical history, complete blood count, and biochemical markers were assessed in the first trimester. The trophoblast and angiogenesis markers ADAM-12 (a disintegrin and metalloprotease 12), pregnancy-associated plasma proteinA (PAPP-A), PP13, placental growth factor (PlGF), soluble fms-like tyrosine kinase-1, and endoglin were measured in a case-control subset of 174 women with preeclampsia and 509 controls. Results—Univariable analysis revealed maternal age, race, marital status, years of education, source of medical payment, prenatal caregiver, body mass index (BMI), and systolic blood pressure at enrollment were significantly associated with preeclampsia. Mean platelet volume was greater at enrollment in women who later developed preeclampsia (median 9.4 vs 9.0fl, p=0.02). First-trimester concentrations (multiples of the median) of ADAM-12 (1.14 vs 1.04, p=0.003), Corresponding Author: Leslie Myatt, PhD, University of Texas Health Science Center San Antonio, Mail Code 7836, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, Myattl@uthscsa.edu, tel 210 567 7044, fax 210 567 5033. Dr. Spong, Associate Editor of Obstetrics & Gynecology, was not involved in the review or decision to publish this article. Presented at the 57th Annual Meeting of the Society for Gynecologic Investigation, Orlando FL, March 24–27, 2010. Financial Disclosure: The authors did not report any potential conflicts of interest. NIH Public Access Author Manuscript Obstet Gynecol. Author manuscript; available in PMC 2013 June 01. Published in final edited form as: Obstet Gynecol. 2012 June ; 119(6): 1234–1242. doi:10.1097/AOG.0b013e3182571669. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript PAPP-A (0.94 vs 0.98, p=0.04), and PlGF (0.83 vs 1.04, p<0.001) were significantly different in women who developed preeclampsia compared with controls. The optimal multivariable model included African American race, systolic blood pressure, BMI, education level, ADAM-12, PAPP-A and PlGF, and yielded an area under the curve of 0.73 (95% CI 0.69–0.77) and a sensitivity of 46.1% (95% CI 38.3–54.0) for 80% specificity. Conclusion—A multivariable analysis of clinical data and biochemical markers in the first trimester did not identify a model that had clinical utility for predicting preeclampsia in a low-risk nulliparous population.