Cervical etiology of spontaneous preterm birth.

The cervix functions as a barrier between the uterus and vagina and keeps the uterus closed until term so that the fetus can develop. For delivery the cervix must soften and dilate, and finally reconstitute to close the uterus. This complex process involves precisely timed activation of molecular and microstructural events. Spontaneous preterm birth (sPTB) can result from aberrant timing of these events in the cervix. Unfortunately, the pathophysiology of sPTB due to cervical causes remains unclear and thus our treatment options remain limited - even if all appropriate candidates were identified and correctly treated with currently available interventions, the rate of sPTB would only be reduced by 5%. Very recent molecular and microstructural investigation is challenging prevailing concepts about cervical remodeling in pregnancy. We believe that progress toward novel, targeted solutions for the diverse pathways to sPTB entails a paradigm shift in which the overlapping and complex interactions between the cervix, uterus, membranes, fetus, placenta, and surrounding (structural and molecular) environment are suitably honored.

[1]  E. Thom,et al.  The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network. , 1996, The New England journal of medicine.

[2]  D. Danforth,et al.  The morphology of the human cervix. , 1983, Clinical obstetrics and gynecology.

[3]  D. Wing,et al.  Cervical funneling: effect on gestational length and ultrasound-indicated cerclage in high-risk women. , 2009, American journal of obstetrics and gynecology.

[4]  S. Chung,et al.  Sonographically accessed funneling of the uterine cervix as a predictor of successful labor induction , 2015, Obstetrics & gynecology science.

[5]  Michael House,et al.  Changes in the biochemical constituents and morphologic appearance of the human cervical stroma during pregnancy. , 2009, European journal of obstetrics, gynecology, and reproductive biology.

[6]  S. Socrate,et al.  Mechanical and biochemical properties of human cervical tissue. , 2008, Acta biomaterialia.

[7]  Katherine Luby-Phelps,et al.  Cervical Softening During Pregnancy: Regulated Changes in Collagen Cross-Linking and Composition of Matricellular Proteins in the Mouse1 , 2011, Biology of reproduction.

[8]  V. Berghella,et al.  Cerclage for Short Cervix on Ultrasonography in Women With Singleton Gestations and Previous Preterm Birth: A Meta-Analysis , 2011, Obstetrics and gynecology.

[9]  H. Wolfe,et al.  Patients with an ultrasonographic cervical length < or =15 mm have nearly a 50% risk of early spontaneous preterm delivery. , 2000, American journal of obstetrics and gynecology.

[10]  T. Porter,et al.  Collagen 1&Agr;1 and Transforming Growth Factor-&bgr; Polymorphisms in Women With Cervical Insufficiency , 2007 .

[11]  S Jambawalikar,et al.  Investigating the mechanical function of the cervix during pregnancy using finite element models derived from high-resolution 3D MRI , 2016, Computer methods in biomechanics and biomedical engineering.

[12]  Meredith Akins,et al.  Cervical remodeling during pregnancy and parturition , 2010, Trends in Endocrinology & Metabolism.

[13]  Gynecologists.  Practice bulletin no. 130: prediction and prevention of preterm birth. , 2012, Obstetrics and gynecology.

[14]  Jim Larson,et al.  Preventing preterm births: analysis of trends and potential reductions with interventions in 39 countries with very high human development index , 2013, The Lancet.

[15]  V. Berghella.  Progesterone and preterm birth prevention: translating clinical trials data into clinical practice. , 2012, American journal of obstetrics and gynecology.

[16]  R. Romero,et al.  Progesterone to prevent spontaneous preterm birth. , 2014, Seminars in fetal & neonatal medicine.

[17]  L. Keith,et al.  Precocious cervical ripening as a screening target to predict spontaneous preterm delivery among asymptomatic singleton pregnancies: a systematic review. , 2015, American journal of obstetrics and gynecology.

[18]  G. Stoddard,et al.  Polymorphisms in the promoter region of the interleukin-10 (IL-10) gene in women with cervical insufficiency. , 2009, American journal of obstetrics and gynecology.

[19]  Michael Bajka,et al.  The mechanical role of the cervix in pregnancy. , 2015, Journal of biomechanics.

[20]  D. Altman,et al.  The distribution of clinical phenotypes of preterm birth syndrome: implications for prevention. , 2015, JAMA pediatrics.

[21]  P. Gallop,et al.  Cross-linking in collagen and elastin. , 1984, Annual review of biochemistry.

[22]  J. Iams,et al.  The rate of cervical change and the phenotype of spontaneous preterm birth. , 2011, American journal of obstetrics and gynecology.

[23]  S. Srinivas,et al.  Second-trimester loss and subsequent pregnancy outcomes: What is the real risk? , 2006, American journal of obstetrics and gynecology.

[24]  Lene Hee.  Overview of the methods available for biomechanical testing of the uterine cervix in vivo , 2014, Acta obstetricia et gynecologica Scandinavica.

[25]  M. Elovitz,et al.  Inflammation promotes a cytokine response and disrupts the cervical epithelial barrier: a possible mechanism of premature cervical remodeling and preterm birth. , 2012, American journal of obstetrics and gynecology.

[26]  T. Hall,et al.  Changes in shear wave speed pre‐ and post‐induction of labor: a feasibility study , 2015, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[27]  D. Danforth,et al.  COLLAGEN-MUSCLE RATIO IN CLINICALLY NORMAL AND CLINICALLY INCOMPETENT CERVICES. , 1965, American journal of obstetrics and gynecology.

[28]  J. Lydon,et al.  Hyaluronan in cervical epithelia protects against infection-mediated preterm birth. , 2014, The Journal of clinical investigation.

[29]  L. Muglia,et al.  Prevention of preterm birth: Harnessing science to address the global epidemic , 2014, Science Translational Medicine.

[30]  E. Carreras,et al.  Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial , 2012, The Lancet.

[31]  Laura M. Heiser,et al.  Distinct cervical microRNA profiles are present in women destined to have a preterm birth. , 2014, American journal of obstetrics and gynecology.

[32]  Cande V Ananth,et al.  A systematic evaluation of collagen cross-links in the human cervix. , 2015, American journal of obstetrics and gynecology.

[33]  V Dubrauszky,et al.  [The fibre system of connective tissue in the childbearing age, menopause, and pregnancy]. , 1971, Archiv fur Gynakologie.

[34]  T. Hall,et al.  Estimation of shear wave speed in the human uterine cervix , 2014, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[35]  R. Word,et al.  Cervical remodeling during pregnancy and parturition: molecular characterization of the softening phase in mice. , 2007, Reproduction.

[36]  J. Hauth,et al.  Vaginal sonography and cervical incompetence. , 2003, American journal of obstetrics and gynecology.

[37]  T. Leung,et al.  Cerclage Pessary for Preventing Preterm Birth in Women with a Singleton Pregnancy and a Short Cervix at 20 to 24 Weeks: A Randomized Controlled Trial , 2012, American Journal of Perinatology.

[38]  V. Berghella,et al.  Cerclage for Short Cervix on Ultrasonography: Meta-Analysis of Trials Using Individual Patient-Level Data , 2005, Obstetrics and gynecology.

[39]  Lynette Mackay,et al.  Cervical ripening and insufficiency: from biochemical and molecular studies to in vivo clinical examination. , 2009, European journal of obstetrics, gynecology, and reproductive biology.

[40]  N. Uldbjerg,et al.  Cervical collagen in non-pregnant women with previous cervical incompetence. , 1996, European journal of obstetrics, gynecology, and reproductive biology.

[41]  Kevin W Eliceiri,et al.  Nonlinear optical microscopy and ultrasound imaging of human cervical structure , 2013, Journal of biomedical optics.

[42]  P. Leppert,et al.  Decreased elastic fibers and desmosine content in incompetent cervix. , 1987, American journal of obstetrics and gynecology.

[43]  V. Berghella,et al.  534: Cerclage for short cervix on ultrasound in singleton gestations with prior preterm birth: meta-analysis of trials using individual patient-level data , 2011 .

[44]  Michael House,et al.  Relationships between mechanical properties and extracellular matrix constituents of the cervical stroma during pregnancy. , 2009, Seminars in perinatology.

[45]  R M Aspden,et al.  Collagen organisation in the cervix and its relation to mechanical function. , 1988, Collagen and related research.

[46]  David Paik,et al.  Quantitative Evaluation of Collagen Crosslinks and Corresponding Tensile Mechanical Properties in Mouse Cervical Tissue during Normal Pregnancy , 2014, PloS one.

[47]  Mala Mahendroo,et al.  Cervical remodeling in term and preterm birth: insights from an animal model. , 2012, Reproduction.

[48]  D. Danforth,et al.  The Muscular Cervix—A Cause of Incompetency in Pregnancy , 1961, Obstetrics and gynecology.