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Review

Landscape of Preterm Birth Therapeutics and a Path Forward

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Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USA
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Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USA
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Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada
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Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON M5G 1E2, Canada
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Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2R7, Canada
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Departments of Pediatrics, Université de Montréal, Montréal, QC H3T 1J4, Canada
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Departments of Pediatrics and Physiology, University of Alberta, Edmonton, AB T6G 2S2, Canada
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Department of Biological Sciencies, Columbia University, New York, NY 10027, USA
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Mothers and Babies Research Centre, School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia
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Hunter Medical Research Institute, 1 Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia
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John Hunter Hospital, New Lambton Heights, NSW 2305, Australia
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Department of Global Health, University of Washington, Seattle, WA 98195, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Alexander Heazell and Sylvie Girard
J. Clin. Med. 2021, 10(13), 2912; https://doi.org/10.3390/jcm10132912
Received: 15 May 2021 / Revised: 24 June 2021 / Accepted: 28 June 2021 / Published: 29 June 2021
(This article belongs to the Special Issue Diagnostic or Therapeutic Strategies for Pregnancy Complications)
Preterm birth (PTB) remains the leading cause of infant morbidity and mortality. Despite 50 years of research, therapeutic options are limited and many lack clear efficacy. Tocolytic agents are drugs that briefly delay PTB, typically to allow antenatal corticosteroid administration for accelerating fetal lung maturity or to transfer patients to high-level care facilities. Globally, there is an unmet need for better tocolytic agents, particularly in low- and middle-income countries. Although most tocolytics, such as betamimetics and indomethacin, suppress downstream mediators of the parturition pathway, newer therapeutics are being designed to selectively target inflammatory checkpoints with the goal of providing broader and more effective tocolysis. However, the relatively small market for new PTB therapeutics and formidable regulatory hurdles have led to minimal pharmaceutical interest and a stagnant drug pipeline. In this review, we present the current landscape of PTB therapeutics, assessing the history of drug development, mechanisms of action, adverse effects, and the updated literature on drug efficacy. We also review the regulatory hurdles and other obstacles impairing novel tocolytic development. Ultimately, we present possible steps to expedite drug development and meet the growing need for effective preterm birth therapeutics. View Full-Text
Keywords: tocolytic; preterm birth; preterm labor; neonate; prematurity; pregnancy; therapeutic; progesterone; fetus tocolytic; preterm birth; preterm labor; neonate; prematurity; pregnancy; therapeutic; progesterone; fetus
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MDPI and ACS Style

Coler, B.S.; Shynlova, O.; Boros-Rausch, A.; Lye, S.; McCartney, S.; Leimert, K.B.; Xu, W.; Chemtob, S.; Olson, D.; Li, M.; Huebner, E.; Curtin, A.; Kachikis, A.; Savitsky, L.; Paul, J.W.; Smith, R.; Adams Waldorf, K.M. Landscape of Preterm Birth Therapeutics and a Path Forward. J. Clin. Med. 2021, 10, 2912. https://doi.org/10.3390/jcm10132912

AMA Style

Coler BS, Shynlova O, Boros-Rausch A, Lye S, McCartney S, Leimert KB, Xu W, Chemtob S, Olson D, Li M, Huebner E, Curtin A, Kachikis A, Savitsky L, Paul JW, Smith R, Adams Waldorf KM. Landscape of Preterm Birth Therapeutics and a Path Forward. Journal of Clinical Medicine. 2021; 10(13):2912. https://doi.org/10.3390/jcm10132912

Chicago/Turabian Style

Coler, Brahm S., Oksana Shynlova, Adam Boros-Rausch, Stephen Lye, Stephen McCartney, Kelycia B. Leimert, Wendy Xu, Sylvain Chemtob, David Olson, Miranda Li, Emily Huebner, Anna Curtin, Alisa Kachikis, Leah Savitsky, Jonathan W. Paul, Roger Smith, and Kristina M. Adams Waldorf 2021. "Landscape of Preterm Birth Therapeutics and a Path Forward" Journal of Clinical Medicine 10, no. 13: 2912. https://doi.org/10.3390/jcm10132912

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