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Pathogenesis of spontaneous preterm birth

Charles J Lockwood, MD, MHCM
Section Editor
Vincenzo Berghella, MD
Deputy Editor
Vanessa A Barss, MD, FACOG


Preterm birth (PTB) is the leading cause of infant morbidity and mortality in the industrialized world (table 1). For this reason, the pathogenic processes leading to PTB and development of preventive interventions are major targets of obstetric research.

This topic will discuss the major pathogenic mechanisms that lead to PTB. Risk factors for PTB and risk reduction interventions are reviewed separately. (See "Preterm birth: Risk factors and interventions for risk reduction".)


Compelling clinical and research evidence suggest that a number of pathogenic processes can lead to a final common pathway that results in spontaneous PTB. The four primary processes are:

Premature activation of the maternal or fetal hypothalamic-pituitary-adrenal axis

Exaggerated inflammatory response/infection

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Literature review current through: Dec 2017. | This topic last updated: Oct 24, 2017.
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  1. Moroz LA, Simhan HN. Rate of sonographic cervical shortening and biologic pathways of spontaneous preterm birth. Am J Obstet Gynecol 2014; 210:555.e1.
  2. Berkowitz GS, Kasl SV. The role of psychosocial factors in spontaneous preterm delivery. J Psychosom Res 1983; 27:283.
  3. Lobel M, Dunkel-Schetter C, Scrimshaw SC. Prenatal maternal stress and prematurity: a prospective study of socioeconomically disadvantaged women. Health Psychol 1992; 11:32.
  4. Copper RL, Goldenberg RL, Das A, et al. The preterm prediction study: maternal stress is associated with spontaneous preterm birth at less than thirty-five weeks' gestation. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 1996; 175:1286.
  5. Wadhwa PD, Sandman CA, Porto M, et al. The association between prenatal stress and infant birth weight and gestational age at birth: a prospective investigation. Am J Obstet Gynecol 1993; 169:858.
  6. Kogan MD, Alexander GR. Social and behavioral factors in preterm birth. Prenat Neonat Med 1998; 3:29.
  7. Murphy CC, Schei B, Myhr TL, Du Mont J. Abuse: a risk factor for low birth weight? A systematic review and meta-analysis. CMAJ 2001; 164:1567.
  8. Dole N, Savitz DA, Hertz-Picciotto I, et al. Maternal stress and preterm birth. Am J Epidemiol 2003; 157:14.
  9. Ding XX, Wu YL, Xu SJ, et al. Maternal anxiety during pregnancy and adverse birth outcomes: a systematic review and meta-analysis of prospective cohort studies. J Affect Disord 2014; 159:103.
  10. Li D, Liu L, Odouli R. Presence of depressive symptoms during early pregnancy and the risk of preterm delivery: a prospective cohort study. Hum Reprod 2009; 24:146.
  11. Lipkind HS, Curry AE, Huynh M, et al. Birth outcomes among offspring of women exposed to the September 11, 2001, terrorist attacks. Obstet Gynecol 2010; 116:917.
  12. Arias F, Rodriquez L, Rayne SC, Kraus FT. Maternal placental vasculopathy and infection: two distinct subgroups among patients with preterm labor and preterm ruptured membranes. Am J Obstet Gynecol 1993; 168:585.
  13. Ott WJ. Intrauterine growth retardation and preterm delivery. Am J Obstet Gynecol 1993; 168:1710.
  14. Salafia CM, Ghidini A, Lopèz-Zeno JA, Pezzullo JC. Uteroplacental pathology and maternal arterial mean blood pressure in spontaneous prematurity. J Soc Gynecol Investig 1998; 5:68.
  15. Kelly R, Holzman C, Senagore P, et al. Placental vascular pathology findings and pathways to preterm delivery. Am J Epidemiol 2009; 170:148.
  16. Kramer MS, McLean FH, Eason EL, Usher RH. Maternal nutrition and spontaneous preterm birth. Am J Epidemiol 1992; 136:574.
  17. Lykke JA, Paidas MJ, Langhoff-Roos J. Recurring complications in second pregnancy. Obstet Gynecol 2009; 113:1217.
  18. McLean M, Bisits A, Davies J, et al. A placental clock controlling the length of human pregnancy. Nat Med 1995; 1:460.
  19. Korebrits C, Ramirez MM, Watson L, et al. Maternal corticotropin-releasing hormone is increased with impending preterm birth. J Clin Endocrinol Metab 1998; 83:1585.
  20. Challis JR, Hooper S. Birth: outcome of a positive cascade. Baillieres Clin Endocrinol Metab 1989; 3:781.
  21. Zoumakis E, Makrigiannakis A, Margioris AN, et al. Endometrial corticotropin-releasing hormone. Its potential autocrine and paracrine actions. Ann N Y Acad Sci 1997; 828:84.
  22. Petraglia F, Potter E, Cameron VA, et al. Corticotropin-releasing factor-binding protein is produced by human placenta and intrauterine tissues. J Clin Endocrinol Metab 1993; 77:919.
  23. Jones SA, Brooks AN, Challis JR. Steroids modulate corticotropin-releasing hormone production in human fetal membranes and placenta. J Clin Endocrinol Metab 1989; 68:825.
  24. Petraglia F, Coukos G, Volpe A, et al. Involvement of placental neurohormones in human parturition. Ann N Y Acad Sci 1991; 622:331.
  25. Jones SA, Challis JR. Effects of corticotropin-releasing hormone and adrenocorticotropin on prostaglandin output by human placenta and fetal membranes. Gynecol Obstet Invest 1990; 29:165.
  26. Lockwood CJ, Radunovic N, Nastic D, et al. Corticotropin-releasing hormone and related pituitary-adrenal axis hormones in fetal and maternal blood during the second half of pregnancy. J Perinat Med 1996; 24:243.
  27. Perkins AV, Eben F, Wolfe CD, et al. Plasma measurements of corticotrophin-releasing hormone-binding protein in normal and abnormal human pregnancy. J Endocrinol 1993; 138:149.
  28. Majzoub JA, McGregor JA, Lockwood CJ, et al. A central theory of preterm and term labor: putative role for corticotropin-releasing hormone. Am J Obstet Gynecol 1999; 180:S232.
  29. Grammatopoulos DK, Hillhouse EW. Role of corticotropin-releasing hormone in onset of labour. Lancet 1999; 354:1546.
  30. Gibb W. The role of prostaglandins in human parturition. Ann Med 1998; 30:235.
  31. Madsen G, Zakar T, Ku CY, et al. Prostaglandins differentially modulate progesterone receptor-A and -B expression in human myometrial cells: evidence for prostaglandin-induced functional progesterone withdrawal. J Clin Endocrinol Metab 2004; 89:1010.
  32. Guzeloglu-Kayisli O, Kayisli UA, Semerci N, et al. Mechanisms of chorioamnionitis-associated preterm birth: interleukin-1β inhibits progesterone receptor expression in decidual cells. J Pathol 2015; 237:423.
  33. McLean M, Bisits A, Davies J, et al. Predicting risk of preterm delivery by second-trimester measurement of maternal plasma corticotropin-releasing hormone and alpha-fetoprotein concentrations. Am J Obstet Gynecol 1999; 181:207.
  34. Buhimschi CS, Turan OM, Funai EF, et al. Fetal adrenal gland volume and cortisol/dehydroepiandrosterone sulfate ratio in inflammation-associated preterm birth. Obstet Gynecol 2008; 111:715.
  35. Schatz F, Guzeloglu-Kayisli O, Basar M, et al. Enhanced Human Decidual Cell-Expressed FKBP51 May Promote Labor-Related Functional Progesterone Withdrawal. Am J Pathol 2015; 185:2402.
  36. Smith R, Mesiano S, Chan EC, et al. Corticotropin-releasing hormone directly and preferentially stimulates dehydroepiandrosterone sulfate secretion by human fetal adrenal cortical cells. J Clin Endocrinol Metab 1998; 83:2916.
  37. Chakravorty A, Mesiano S, Jaffe RB. Corticotropin-releasing hormone stimulates P450 17alpha-hydroxylase/17,20-lyase in human fetal adrenal cells via protein kinase C. J Clin Endocrinol Metab 1999; 84:3732.
  38. Lye SJ, Nicholson BJ, Mascarenhas M, et al. Increased expression of connexin-43 in the rat myometrium during labor is associated with an increase in the plasma estrogen:progesterone ratio. Endocrinology 1993; 132:2380.
  39. Bale TL, Dorsa DM. Cloning, novel promoter sequence, and estrogen regulation of a rat oxytocin receptor gene. Endocrinology 1997; 138:1151.
  40. Windmoller R, Lye SJ, Challis JR. Estradiol modulation of ovine uterine activity. Can J Physiol Pharmacol 1983; 61:722.
  41. Matsui K, Higashi K, Fukunaga K, et al. Hormone treatments and pregnancy alter myosin light chain kinase and calmodulin levels in rabbit myometrium. J Endocrinol 1983; 97:11.
  42. McGregor JA, Jackson GM, Lachelin GC, et al. Salivary estriol as risk assessment for preterm labor: a prospective trial. Am J Obstet Gynecol 1995; 173:1337.
  43. Rainey WE, Rehman KS, Carr BR. Fetal and maternal adrenals in human pregnancy. Obstet Gynecol Clin North Am 2004; 31:817.
  44. Turan OM, Turan S, Funai EF, et al. Ultrasound measurement of fetal adrenal gland enlargement: an accurate predictor of preterm birth. Am J Obstet Gynecol 2011; 204:311.e1.
  45. Ramos GC. Inflammation as an animal development phenomenon. Clin Dev Immunol 2012; 2012:983203.
  46. Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell 2010; 140:771.
  47. Sheiner E, Mazor-Drey E, Levy A. Asymptomatic bacteriuria during pregnancy. J Matern Fetal Neonatal Med 2009; 22:423.
  48. Smaill F. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2001; :CD000490.
  49. Donders GG, Van Calsteren K, Bellen G, et al. Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy. BJOG 2009; 116:1315.
  50. Offenbacher S, Lieff S, Boggess KA, et al. Maternal periodontitis and prematurity. Part I: Obstetric outcome of prematurity and growth restriction. Ann Periodontol 2001; 6:164.
  51. Khader YS, Ta'ani Q. Periodontal diseases and the risk of preterm birth and low birth weight: a meta-analysis. J Periodontol 2005; 76:161.
  52. Lockwood CJ, Kuczynski E. Markers of risk for preterm delivery. J Perinat Med 1999; 27:5.
  53. Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med 2000; 342:1500.
  54. DiGiulio DB, Callahan BJ, McMurdie PJ, et al. Temporal and spatial variation of the human microbiota during pregnancy. Proc Natl Acad Sci U S A 2015; 112:11060.
  55. Nygren P, Fu R, Freeman M, et al. Evidence on the benefits and harms of screening and treating pregnant women who are asymptomatic for bacterial vaginosis: an update review for the U.S. Preventive Services Task Force. Ann Intern Med 2008; 148:220.
  56. Han YW. Can oral bacteria cause pregnancy complications? Womens Health (Lond) 2011; 7:401.
  57. Polyzos NP, Polyzos IP, Mauri D, et al. Effect of periodontal disease treatment during pregnancy on preterm birth incidence: a metaanalysis of randomized trials. Am J Obstet Gynecol 2009; 200:225.
  58. Jeffcoat M, Parry S, Sammel M, et al. Periodontal infection and preterm birth: successful periodontal therapy reduces the risk of preterm birth. BJOG 2011; 118:250.
  59. Gravett MG, Novy MJ, Rosenfeld RG, et al. Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers. JAMA 2004; 292:462.
  60. Hitti J, Nugent R, Boutain D, et al. Racial disparity in risk of preterm birth associated with lower genital tract infection. Paediatr Perinat Epidemiol 2007; 21:330.
  61. Anum EA, Springel EH, Shriver MD, Strauss JF 3rd. Genetic contributions to disparities in preterm birth. Pediatr Res 2009; 65:1.
  62. Menon R, Pearce B, Velez DR, et al. Racial disparity in pathophysiologic pathways of preterm birth based on genetic variants. Reprod Biol Endocrinol 2009; 7:62.
  63. Macones GA, Parry S, Elkousy M, et al. A polymorphism in the promoter region of TNF and bacterial vaginosis: preliminary evidence of gene-environment interaction in the etiology of spontaneous preterm birth. Am J Obstet Gynecol 2004; 190:1504.
  64. Miyake K. Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin Immunol 2007; 19:3.
  65. Menon R, Velez DR, Morgan N, et al. Genetic regulation of amniotic fluid TNF-alpha and soluble TNF receptor concentrations affected by race and preterm birth. Hum Genet 2008; 124:243.
  66. Dulay AT, Buhimschi CS, Zhao G, et al. Soluble TLR2 is present in human amniotic fluid and modulates the intraamniotic inflammatory response to infection. J Immunol 2009; 182:7244.
  67. Baumann P, Romero R, Berry S, et al. Evidence of participation of the soluble tumor necrosis factor receptor I in the host response to intrauterine infection in preterm labor. Am J Reprod Immunol 1993; 30:184.
  68. Buhimschi IA, Zhao G, Pettker CM, et al. The receptor for advanced glycation end products (RAGE) system in women with intraamniotic infection and inflammation. Am J Obstet Gynecol 2007; 196:181.e1.
  69. Van Meir CA, Sangha RK, Walton JC, et al. Immunoreactive 15-hydroxyprostaglandin dehydrogenase (PGDH) is reduced in fetal membranes from patients at preterm delivery in the presence of infection. Placenta 1996; 17:291.
  70. Challis JR, Lye SJ, Gibb W, et al. Understanding preterm labor. Ann N Y Acad Sci 2001; 943:225.
  71. So T, Ito A, Sato T, et al. Tumor necrosis factor-alpha stimulates the biosynthesis of matrix metalloproteinases and plasminogen activator in cultured human chorionic cells. Biol Reprod 1992; 46:772.
  72. Fortunato SJ, Menon R, Lombardi SJ. Role of tumor necrosis factor-alpha in the premature rupture of membranes and preterm labor pathways. Am J Obstet Gynecol 2002; 187:1159.
  73. Oner C, Schatz F, Kizilay G, et al. Progestin-inflammatory cytokine interactions affect matrix metalloproteinase-1 and -3 expression in term decidual cells: implications for treatment of chorioamnionitis-induced preterm delivery. J Clin Endocrinol Metab 2008; 93:252.
  74. Lockwood CJ, Arcuri F, Toti P, et al. Tumor necrosis factor-alpha and interleukin-1beta regulate interleukin-8 expression in third trimester decidual cells: implications for the genesis of chorioamnionitis. Am J Pathol 2006; 169:1294.
  75. Arcuri F, Toti P, Buchwalder L, et al. Mechanisms of leukocyte accumulation and activation in chorioamnionitis: interleukin 1 beta and tumor necrosis factor alpha enhance colony stimulating factor 2 expression in term decidua. Reprod Sci 2009; 16:453.
  76. Lei H, Furth EE, Kalluri R, et al. A program of cell death and extracellular matrix degradation is activated in the amnion before the onset of labor. J Clin Invest 1996; 98:1971.
  77. Lockwood CJ, Murk WK, Kayisli UA, et al. Regulation of interleukin-6 expression in human decidual cells and its potential role in chorioamnionitis. Am J Pathol 2010; 177:1755.
  78. Lee SY, Buhimschi IA, Dulay AT, et al. IL-6 trans-signaling system in intra-amniotic inflammation, preterm birth, and preterm premature rupture of the membranes. J Immunol 2011; 186:3226.
  79. Dudley DJ, Trautman MS, Araneo BA, et al. Decidual cell biosynthesis of interleukin-6: regulation by inflammatory cytokines. J Clin Endocrinol Metab 1992; 74:884.
  80. Fortunato SJ, Menon RP, Swan KF, Menon R. Inflammatory cytokine (interleukins 1, 6 and 8 and tumor necrosis factor-alpha) release from cultured human fetal membranes in response to endotoxic lipopolysaccharide mirrors amniotic fluid concentrations. Am J Obstet Gynecol 1996; 174:1855.
  81. Lynch AM, Gibbs RS, Murphy JR, et al. Complement activation fragment Bb in early pregnancy and spontaneous preterm birth. Am J Obstet Gynecol 2008; 199:354.e1.
  82. Sbarra AJ, Thomas GB, Cetrulo CL, et al. Effect of bacterial growth on the bursting pressure of fetal membranes in vitro. Obstet Gynecol 1987; 70:107.
  83. Andrews WW, Hauth JC, Goldenberg RL, et al. Amniotic fluid interleukin-6: correlation with upper genital tract microbial colonization and gestational age in women delivered after spontaneous labor versus indicated delivery. Am J Obstet Gynecol 1995; 173:606.
  84. Wei SQ, Fraser W, Luo ZC. Inflammatory cytokines and spontaneous preterm birth in asymptomatic women: a systematic review. Obstet Gynecol 2010; 116:393.
  85. Buhimschi IA, Christner R, Buhimschi CS. Proteomic biomarker analysis of amniotic fluid for identification of intra-amniotic inflammation. BJOG 2005; 112:173.
  86. Romero R, Espinoza J, Rogers WT, et al. Proteomic analysis of amniotic fluid to identify women with preterm labor and intra-amniotic inflammation/infection: the use of a novel computational method to analyze mass spectrometric profiling. J Matern Fetal Neonatal Med 2008; 21:367.
  87. Esplin MS, Merrell K, Goldenberg R, et al. Proteomic identification of serum peptides predicting subsequent spontaneous preterm birth. Am J Obstet Gynecol 2011; 204:391.e1.
  88. Pereira L, Reddy AP, Jacob T, et al. Identification of novel protein biomarkers of preterm birth in human cervical-vaginal fluid. J Proteome Res 2007; 6:1269.
  89. Lee DC, Hassan SS, Romero R, et al. Protein profiling underscores immunological functions of uterine cervical mucus plug in human pregnancy. J Proteomics 2011; 74:817.
  90. Sbarra AJ, Selvaraj RJ, Cetrulo CL, et al. Infection and phagocytosis as possible mechanisms of rupture in premature rupture of the membranes. Am J Obstet Gynecol 1985; 153:38.
  91. McGregor JA, Lawellin D, Franco-Buff A, et al. Protease production by microorganisms associated with reproductive tract infection. Am J Obstet Gynecol 1986; 154:109.
  92. Gibbs RS, Romero R, Hillier SL, et al. A review of premature birth and subclinical infection. Am J Obstet Gynecol 1992; 166:1515.
  93. Turnbaugh PJ, Ley RE, Hamady M, et al. The human microbiome project. Nature 2007; 449:804.
  94. Han YW, Shen T, Chung P, et al. Uncultivated bacteria as etiologic agents of intra-amniotic inflammation leading to preterm birth. J Clin Microbiol 2009; 47:38.
  95. DiGiulio DB, Romero R, Amogan HP, et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS One 2008; 3:e3056.
  96. Pierce BT, Pierce LM, Wagner RK, et al. Hypoperfusion causes increased production of interleukin 6 and tumor necrosis factor alpha in the isolated, dually perfused placental cotyledon. Am J Obstet Gynecol 2000; 183:863.
  97. Zeitlin J, Ancel PY, Saurel-Cubizolles MJ, Papiernik E. The relationship between intrauterine growth restriction and preterm delivery: an empirical approach using data from a European case-control study. BJOG 2000; 107:750.
  98. Christian LM. Effects of stress and depression on inflammatory immune parameters in pregnancy. Am J Obstet Gynecol 2014; 211:275.
  99. Harger JH, Hsing AW, Tuomala RE, et al. Risk factors for preterm premature rupture of fetal membranes: a multicenter case-control study. Am J Obstet Gynecol 1990; 163:130.
  100. Williams MA, Mittendorf R, Lieberman E, Monson RR. Adverse infant outcomes associated with first-trimester vaginal bleeding. Obstet Gynecol 1991; 78:14.
  101. Salafia CM, López-Zeno JA, Sherer DM, et al. Histologic evidence of old intrauterine bleeding is more frequent in prematurity. Am J Obstet Gynecol 1995; 173:1065.
  102. Buhimschi CS, Schatz F, Krikun G, et al. Novel insights into molecular mechanisms of abruption-induced preterm birth. Expert Rev Mol Med 2010; 12:e35.
  103. Gargano JW, Holzman CB, Senagore PK, et al. Polymorphisms in thrombophilia and renin-angiotensin system pathways, preterm delivery, and evidence of placental hemorrhage. Am J Obstet Gynecol 2009; 201:317.e1.
  104. Strobino B, Pantel-Silverman J. Gestational vaginal bleeding and pregnancy outcome. Am J Epidemiol 1989; 129:806.
  105. Lam H, Hamar B, Rosen T, et al. Thrombin effects on endometrial stromal cell levels of matrix metalloproteinase-1 and metaloproteinase-3 may provide a link between bleeding and rupture of the membranes. Am J Obstet Gynecol 1999; 180:S3.
  106. Mackenzie AP, Schatz F, Krikun G, et al. Mechanisms of abruption-induced premature rupture of the fetal membranes: Thrombin enhanced decidual matrix metalloproteinase-3 (stromelysin-1) expression. Am J Obstet Gynecol 2004; 191:1996.
  107. Rosen T, Schatz F, Kuczynski E, et al. Thrombin-enhanced matrix metalloproteinase-1 expression: a mechanism linking placental abruption with premature rupture of the membranes. J Matern Fetal Neonatal Med 2002; 11:11.
  108. Buhimschi IA, Zhao G, Rosenberg VA, et al. Multidimensional proteomics analysis of amniotic fluid to provide insight into the mechanisms of idiopathic preterm birth. PLoS One 2008; 3:e2049.
  109. Lockwood CJ, Toti P, Arcuri F, et al. Mechanisms of abruption-induced premature rupture of the fetal membranes: thrombin-enhanced interleukin-8 expression in term decidua. Am J Pathol 2005; 167:1443.
  110. Lockwood CJ, Murk W, Kayisli UA, et al. Progestin and thrombin regulate tissue factor expression in human term decidual cells. J Clin Endocrinol Metab 2009; 94:2164.
  111. Norwitz ER, Snegovskikh V, Schatz F, et al. Progestin inhibits and thrombin stimulates the plasminogen activator/inhibitor system in term decidual stromal cells: implications for parturition. Am J Obstet Gynecol 2007; 196:382.e1.
  112. Elovitz MA, Saunders T, Ascher-Landsberg J, Phillippe M. Effects of thrombin on myometrial contractions in vitro and in vivo. Am J Obstet Gynecol 2000; 183:799.
  113. O'Sullivan CJ, Allen NM, O'Loughlin AJ, et al. Thrombin and PAR1-activating peptide: effects on human uterine contractility in vitro. Am J Obstet Gynecol 2004; 190:1098.
  114. Lockwood CJ, Kayisli UA, Stocco C, et al. Abruption-induced preterm delivery is associated with thrombin-mediated functional progesterone withdrawal in decidual cells. Am J Pathol 2012; 181:2138.
  115. Elovitz MA, Baron J, Phillippe M. The role of thrombin in preterm parturition. Am J Obstet Gynecol 2001; 185:1059.
  116. Vidaeff AC, Monga M, Ramin SM, et al. Is thrombin activation predictive of subsequent preterm delivery? Am J Obstet Gynecol 2013; 208:306.e1.
  117. Ou CW, Orsino A, Lye SJ. Expression of connexin-43 and connexin-26 in the rat myometrium during pregnancy and labor is differentially regulated by mechanical and hormonal signals. Endocrinology 1997; 138:5398.
  118. Word RA, Stull JT, Casey ML, Kamm KE. Contractile elements and myosin light chain phosphorylation in myometrial tissue from nonpregnant and pregnant women. J Clin Invest 1993; 92:29.
  119. Adams Waldorf KM, Singh N, Mohan AR, et al. Uterine overdistention induces preterm labor mediated by inflammation: observations in pregnant women and nonhuman primates. Am J Obstet Gynecol 2015; 213:830.e1.
  120. Sooranna SR, Engineer N, Loudon JA, et al. The mitogen-activated protein kinase dependent expression of prostaglandin H synthase-2 and interleukin-8 messenger ribonucleic acid by myometrial cells: the differential effect of stretch and interleukin-1{beta}. J Clin Endocrinol Metab 2005; 90:3517.
  121. Maradny EE, Kanayama N, Halim A, et al. Stretching of fetal membranes increases the concentration of interleukin-8 and collagenase activity. Am J Obstet Gynecol 1996; 174:843.
  122. Kanayama N, Fukamizu H. Mechanical stretching increases prostaglandin E2 in cultured human amnion cells. Gynecol Obstet Invest 1989; 28:123.
  123. Nemeth E, Tashima LS, Yu Z, Bryant-Greenwood GD. Fetal membrane distention: I. Differentially expressed genes regulated by acute distention in amniotic epithelial (WISH) cells. Am J Obstet Gynecol 2000; 182:50.
  124. Owen J, Hankins G, Iams JD, et al. Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length. Am J Obstet Gynecol 2009; 201:375.e1.
  125. Warren JE, Nelson LM, Stoddard GJ, et al. Polymorphisms in the promoter region of the interleukin-10 (IL-10) gene in women with cervical insufficiency. Am J Obstet Gynecol 2009; 201:372.e1.
  126. Jakobsson M, Gissler M, Paavonen J, Tapper AM. Loop electrosurgical excision procedure and the risk for preterm birth. Obstet Gynecol 2009; 114:504.
  127. Shanbhag S, Clark H, Timmaraju V, et al. Pregnancy outcome after treatment for cervical intraepithelial neoplasia. Obstet Gynecol 2009; 114:727.
  128. Sheikh IA, Ahmad E, Jamal MS, et al. Spontaneous preterm birth and single nucleotide gene polymorphisms: a recent update. BMC Genomics 2016; 17:759.
  129. Zhang G, Feenstra B, Bacelis J, et al. Genetic Associations with Gestational Duration and Spontaneous Preterm Birth. N Engl J Med 2017; 377:1156.