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Large-Scale Proteomics and Hypertensive Disorders of Pregnancy
Quick Takes
- Protein analysis did not improve risk prediction of hypertensive disorders of pregnancy.
- Other models are needed in order to predict pregnancies complicated by hypertensive disorders of pregnancy.
Study Questions:
Can proteome assessment of first-trimester blood samples be used to predict the development of hypertensive disorders of pregnancy (HDP)?
Methods:
This was an ancillary study of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), a multicenter observational study at eight academic US medical centers. Clinical data and first trimester plasma samples (collected from 2010–2013) were analyzed. HDP included gestational hypertension and pre-eclampsia. Controls were selected from participants who delivered at 37 weeks or later without any HDP, preterm birth, or small-for-gestational age infant. The aptamer-based proteomics panel included 6,481 unique human proteins.
Results:
Of 1,850 participants with analyzable proteomic assay results, 753 had HDP and 1,097 were controls. Overall, the mean age was 26.9 years. Analysis was performed with the elastic net model, allowing for forced inclusion of prespecified covariates. No proteins were selected to augment the clinical and demographic covariates. Predictive models showed only modest discriminative results: The area under the receiver operating characteristic curve (AUC) was 0.64 (95% confidence interval [CI], 0.61-0.67) in a training set, and 0.62 (95% CI, 0.56-0.68) in a test set.
Conclusions:
The authors conclude that an aptamer-based proteomics panel did not improve prediction of HDP over and above routine clinical and demographic factors.
Perspective:
HDP complicate 10-15% of first pregnancies and, in addition to immediate high-risk consequences, are associated with long-term increased risk of future cardiovascular disease. The ability to predict which patients are at highest risk for HDP would potentially help prevent the associated complications. Several prior studies have explored various biomarkers but have been unable to provide predictive ability. This study explored a large-scale proteomics panel; however, no protein out of >6,000 unique human proteins was found to be effective in predicting HDP, nor was any predictive model that included clinical and demographic variables. This well-designed large study suggests that other approaches may be needed in order to better predict HDP, and investigators should continue to seek ways to improve care for these patients.
Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Prevention, Vascular Medicine, Hypertension
Keywords: Cardio-Obstetrics, Hypertension, Pregnancy-Induced, Proteomics
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