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Late-Onset Preeclampsia Markers Proposed From Proteomic Study

NEW YORK (GenomeWeb) – Researchers from the US and Israel have identified two maternal blood protein markers that shows promise for predicting late-onset preeclampsia.

The team, led by the National Institutes of Health and Wayne State University, tracked levels for more than 1,100 blood proteins in longitudinal samples from 90 women with normal pregnancies and 76 women who experienced late-onset preeclampsia, occurring at or beyond 34 weeks of gestation, for the retrospective study. The search led to roughly three dozen proteins with potential ties to the condition over one or more stages of pregnancy.

In particular, the researchers' analyses pointed to matrix metalloproteinase 7 (MMP-7) and placental growth factor (PIGF) — proteins found at altered levels in the blood of women who went on to have late-onset preeclampsia. As they reported in PLOS One yesterday, their models suggest heightened MMP-7 levels at eight to 22 weeks of pregnancy can predict late-onset preeclampsia cases with up to 70 percent sensitivity, while lower-than-usual blood levels of PIGF appeared more predictive later in pregnancy.

"Elevated MMP-7 early in gestation (eight to 22 weeks) and low PIGF later in gestation (after 22 weeks) are the strongest predictors for the subsequent development of late-onset preeclampsia," senior author Adi Tarca, an obstetrics and gynecology researcher affiliated with Wayne State University and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and co-authors wrote, "suggesting that the optimal identification of patients at risk may involve a two-step diagnostic process."

Though preeclampsia in general has been linked to maternal and perinatal mortality and morbidity, the team explained, mounting evidence suggests early and late forms of the condition may stem from different processes and produce somewhat different symptoms.

"Because the etiologies of early- and late-onset preeclampsia are different, biomarkers predicting their development are expected to diverge," the authors wrote, noting that they set out to find candidate biomarkers specific to the latter condition for the current study.

To that end, the researchers sent the blood samples — collected over time in 28 severe late-onset preeclampsia cases, 48 mild late-onset preeclampsia cases, and 90 unaffected pregnancies — for testing at Somalogic, where blood plasma levels of 1,125 proteins were assessed using the Colorado company's aptamer-based SOMAmer proteomic method. They then used linear mixed effects models to pull out the proteins most strongly associated with late-onset preeclampsia over five stages of pregnancy.

Higher MMP-7 protein levels in the blood predicted the pregnancy complication with 69 percent sensitivity and a false-positive rate of 20 percent during the eight to 16 week gestational window, for example. The same marker appeared to be the best predictor over 16.1 to 22 weeks of gestation as well, with 70 percent sensitivity for late-onset preeclampsia.

On the other hand, declining PIGF levels appeared to be more informative after 22 weeks of gestation, the team reported, predicting between one-third and half of late-onset preeclampsia with a 20 percent false-positive rate.

The researchers saw other potential protein markers for late-onset preeclampsia as well. Levels for at least 36 proteins coincided with the condition during at least one of the gestational periods considered, they noted, and proteins from a few pathways — including vascular endothelial growth factor receptor signaling and cell adhesion pathways — were overrepresented in the preeclampsia-associated sets.

Finally, the team saw hints that altered blood plasma protein levels differed between women with mild and severe forms of late-onset preeclampsia, particularly in blood samples taken after 22 weeks of gestation.