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Detecting Preterm Labor with Raman Spectroscopy

preterm    Prematurity is the second leading cause of neonatal mortality, leading to a myriad of complications, including delayed development and cerebral palsy. Currently, there is no way to accurately predict when a woman will deliver prematurely, making the prevention and treatment of preterm birth virtually impossible. While there are some populations at risk for preterm labor (patients with a history of previous preterm birth or uterine/cervical abnormalities), over half of all preterm births do not fall into any high-risk category.
    This study seeks to understand, predict, and prevent preterm labor by using Raman spectroscopy to detect biochemical changes in the cervix during pregnancy. Previous results indicate that molecular and cellular changes that occur in precancerous as well as benign tissues yield distinct Raman features. As the cervix is known to undergo an extensive remodeling process in preparation for delivery, it follows that the Raman spectra will reflect these changes and provide insight into the onset of labor. We have acquired in vivo Raman spectra from 68 patients at various time points during their pregnancy, and the results demonstrate significant changes in spectral signatures associated with collagen, actin, lipids and blood. We also observed significant differences in the spectra of normal compared to high BMI patients, and those who have had a previous pregnancy compared to those who have not. Complimentary work in mouse models of pregnancy showed that Raman spectroscopy is sensitive to biochemical changes in the cervices of mice with abnormal delivery timing. A visually-guided Raman spectroscopy probe was recently developed and validated in order to improve the clinical translation of this approach by eliminating the need for a speculum exam.
    Future directions include acquiring in vivo measurement of patients with known risk factors for preterm labor, and evaluation of additional mouse models of preterm labor. Ultimately, the results obtained in mice and in humans will be used to develop an algorithm which predicts a patient's time to delivery based on their Raman spectra. This technology has the potential to improve outcomes for both mother and baby by providing an early indicator of labor onset.

Researchers

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      Post Doctoral Scholars and  Graduate Students

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Publications

Herington JL, O'Brien C, Robuck MF, Lei W, Brown N, Slaughter JC, Paria BC, Mahadevan-Jansen A, Reese J. Prostaglandin-Endoperoxide Synthase 1 Mediates the Timing of Parturition in Mice Despite Unhindered Uterine Contractility. Endocrinology. 2018;159(1):490-505. PMID: 29029054.

McCarthy R, Martin-Fairey C, Sojka DK, Herzog ED, Jungheim ES, Stout MJ, Fay JC, Mahendroo M, Reese J, Herington JL, Plosa EJ, Shelton EL, England SK. Mouse models of preterm birth: suggested assessment and reporting guidelines. Biol Reprod. 2018. PMID: 29733339.

O'Brien CM, Vargis E, Rudin A, Slaughter JC, Thomas G, Newton JM, Reese J, Bennett KA, Mahadevan-Jansen A. In vivo Raman spectroscopy for biochemical monitoring of the human cervix throughout pregnancy. Am J Obstet Gynecol. 2018;218(5):528 e1- e18. PMID: 29410109.

Robuck MF, O'Brien CM, Knapp KM, Shay SD, West JD, Newton JM, Slaughter JC, Paria BC, Reese J, Herington JL. Monitoring uterine contractility in mice using a transcervical intrauterine pressure catheter. Reproduction. 2018;155(5):447-56. PMID: 29500186.

O'Brien CM, Herington JL, Brown N, Pence IJ, Paria BC, Slaughter JC, Reese J, Mahadevan-Jansen A. In vivo Raman spectral analysis of impaired cervical remodeling in a mouse model of delayed parturition. Sci Rep. 2017;7(1):6835. PMID: 28754971.

Robuck M, O'Brien C, Reese J, Herington J. Measuring In Vivo Uterine Contractile Activity of Pregnant Mice via a Transcervical Intrauterine Pressure Catheter (IUPC). Reprod Sci. 2017; Volume: 25 issue: 1_suppl, page(s): 55A-324A. https://doi.org/10.1177/1933719118759999

O'Brien CM, Brown N, Rudin A, Slaughter C, Bennett KA, Reese J, Mahadevan-Jansen A. Detection of Biochemical Changes in the Cervix During Induction of Labor in Human Subjects and Mouse Models Using In Vivo Raman Spectroscopy. Reprod Sci. 2016; Volume: 23 issue: 1_suppl, page(s): 51A-344A https://doi.org/10.1177/1933719116641257

Pence I, Mahadevan-Jansen A. Clinical instrumentation and applications of Raman spectroscopy. Chem Soc Rev. 2016;45(7):1958-79. PMID: 26999370.

O'Brien CM, Vargis E, Slaughter C, Rudin AP, Herington JL, Bennett KA, Reese J, Mahadevan-Jansen A. Characterization of human cervical remodeling throughout pregnancy using in vivo Raman spectroscopy. Proc Spie. 2015; doi: Artn 93032f10.1117/12.2077775. https://www.spiedigitallibrary.org/conference-proceedings-of-spie/9303/93032F/Characterization-of-human-cervical-remodeling-throughout-pregnancy-using-in-vivo/10.1117/12.2077775.short?SSO=1

O'Brien CM, Vargis E, Paria BC, Bennett KA, Mahadevan-Jansen A, Reese J. Raman spectroscopy provides a noninvasive approach for determining biochemical composition of the pregnant cervix in vivo. Acta Paediatrica. 2014;103(7):715-21. PMID: 24628401.

Vargis E, Byrd TT, O'Brien CM, Logan Q, Khabele D, Mahadevan-Jansen A. In Vivo Raman Spectroscopy Detects Cervical Intraepithelial Neoplasia with High Accuracy in Diverse Population. Reprod Sci. 2014 Volume: 21 issue: 3_suppl, page(s): 71A-418A. https://doi.org/10.1177/1933719114528275

O'Brien C, Vargis E, Borwn N, Reese J, Paria BC, Mahadevan-Jansen A. In Vivo Detection of Biochemical Change in the Pregnant Cervix in Humans and Mouse Models. Reprod Sci. 2013; Volume: 20 issue: 3_suppl, page(s): 61A-341A. https://doi.org/10.1177/1933719113482088