Placental health is essential for the well-being of pregnancy, with implications for mother and offspring's lifelong health. Recognition exists that aberrations in placental implantation, cellular development and/or maturation adversely affect the materno-fetal supply of nutrients with detrimental effects on the developing newborn. Currently the clinical tools available for assessing placental well-being consist of ultrasound (U/S), and secondary analysis of maternal tests performed for other indications, such as fetal aneuploidies; these include serum biomarkers, non-invasive prenatal testing (NIPT), and invasive procedures accessing chorionic villi, amniotic fluid or umbilical venous blood. However many if not all of these diagnostic modalities are plagued with limitations either related to suboptimal sensitivity, specificity and accuracy in predictability, or related to the invasive nature of testing with possible complications. Hence, there is a dire need for non-invasive and easy to deploy diagnostic tools that portray high sensitivity and specificity in predicting placental health. At a minimum, the ability to deploy a screening test early in 1st trimester towards recommending a more elaborate imaging to assess placental health is necessary. To this end, our preliminary data on a prospectively established cohort demonstrated that maternal plasma and urine collected longitudinally through pregnancy can be analyzed for a combination of cfDNA, cfRNA, exosome RNA/miRNA, and proteins, arising from placenta. To overcome the cumbersome analysis of cfDNA, cfRNA and exosome RNA/micro(mi)RNA/proteins by traditional methods, we have most recently developed an electromagnetic and electrochemical biosensor based technology named ?electrochemical liquid biopsy? (eLB), for separation and identification of RNAs and proteins from bodily fluid (e.g. urine, saliva) samples. This novel technology provides us the ability in non-invasively investigating key transcripts/proteins that display high sensitivity, specificity and predictability of subsequent clinical placental disorders. Based on this collection of preliminary data, we hypothesize that a non-invasive biosensor capable of rapidly detecting RNAs/miRNAs and proteins in urine will allow longitudinal detection of placental health in a reliable manner. Such a tool if made ultimately available for point-of-care testing can revolutionize monitoring of placental health in real-time during pregnancy with accuracy, allowing timely introduction of novel interventions (e.g. statins) to prevent and thereby terminate placenta-associated clinical disorders. To test this hypothesis we propose two specific aims: 1) To develop and test an eLB device in separation and simultaneous measurement of multiple transcripts/proteins in urine collected longitudinally during normal pregnancies. 2) To determine the ability and validity in deploying the electrochemical biosensor tool in detecting transcript/protein differences between normal and high-risk pregnancies in preparation for future point-of-care testing in achieving real-time non-invasive and rapid monitoring of placental health. Validation by comparing urinary results to paired blood samples with predictability assessed by the archived collection of placental MR imaging, clinical features and placental histopathology.

Public Health Relevance

Development of the Electrochemical Liquid Biopsy Technology for urine samples reflecting placental health will be powerful in monitoring normal and high-risk pregnancies. This will lend to enhancing the ability of rapidly and effectively diagnosing aberrations in placental health before setting in of clinical symptoms. Further, it will increase the sensitivity and specificity of diagnosing problems during pregnancy that will have a negative effect on mother and child.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Ilekis, John V
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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