In these studies, we will focus on the early detection of placental dysfunction using the hypertensive disorder of pregnancy, preeclampsia (PE), as proof-of-principle. This serious condition in pregnant women affects 5-7% of all pregnancies in the U.S., manifests after 20 weeks gestation, and is caused by placental dysfunction. Although environmental factors, such as obesity, are associated with the development of PE, there is a paucity of information as to how environmental factors affect placental function. Furthermore, there is currently no approved method of early detection to determine the clinical trajectory of a patient toward the development of placental disorders like PE, which would allow physicians to intervene early and possibly effect/limit the severity of these diseases. To address these critical needs, Raman spectroscopy methods will be employed to quantitatively detect lipid-based biomarkers of placental function (i.e., PE development) from the plasma and urine of pregnant women in the 1st and 2nd trimesters. Indeed, lipid-based biomarkers are the diagnostic focus of these studies as the pathophysiologic role of bioactive lipids in PE is undeniable. For just one example, women with a medical history of early-onset PE are now administered daily low-dose aspirin beginning in the late first trimester to reduce the production of pro-inflammatory arachidonic acid-derived eicosanoids (e.g., thromboxane). Other favorable effects of aspirin, such as increased production of anti-inflammatory lipids (e.g., lipoxins), are also occurring. Hence, the effectiveness of aspirin in preventing recurrent PE strongly suggests an imbalance favoring pro-inflammatory eicosanoids as causative agents. Furthermore, isoprostanes, triglycerides, free fatty acids, and 2- methoxyestradiol have all been reported as early lipid-based biomarkers for PE development. Based on these reports, we undertook an additional study using advanced lipidomic technology to examine the levels of multiple classes of bioactive lipids in the plasma of pregnant women. Importantly, the fingerprint of patients who developed PE strongly correlated with early changes in the levels of the reported lipid markers as well as new classes were identified. We have already obtained specific Raman spectrum for a number these bioactive lipids to allow for the rapid development of early detection technologies to assess placental function throughout pregnancy. Indeed, lipid microparticles (exosomes) originating from the placenta are now recognized to transmit to the mother's circulation, so simple non-invasive blood or urine tests using Raman technology are now feasible to determine early placental dysfunction. Therefore, we hypothesize that Raman spectroscopy can be utilized and rapidly implemented for real-time assessment of lipid-based fingerprints of placental function/dysfunction in early trimesters to allow for early intervention by physicians. Our studies are designed to validate this hypothesis as well as develop and test a prototype device with the flexibility to offer real-time assessment and monitoring of patients for placental function in al OB/GYN offices and even at home.

Public Health Relevance

In this study, we will focus on the early detection of placental dysfunction in the hypertensive disorder of pregnancy, preeclampsia (PE), a serious condition in pregnant women, which affects 5-7% of all pregnancies in the U.S. Our studies are designed to develop and test a prototype device with the flexibility to offer 'real-time' assessment and monitoring of patients for placental function (i.e., PE risk) in OB/GYN offices and even at home.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01HD087198-01
Application #
9076360
Study Section
Special Emphasis Panel ()
Program Officer
Weinberg, David H
Project Start
2015-09-17
Project End
2019-08-31
Budget Start
2015-09-17
Budget End
2019-08-31
Support Year
1
Fiscal Year
2015
Total Cost
$4,228,935
Indirect Cost
$1,420,239
Name
Virginia Commonwealth University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
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