A blueprint for the prevention of preterm birth: Vaginal progesterone in women with a short cervix

Journal of Perinatal Medicine

Volumn 41, Issue 1, 2013, Pages 27-44

  Romero, Roberto ^a,b   Yeo, Lami ^a,b,c   Miranda, Jezid ^a,b   Hassan, Sonia S ^a,b,c   Conde Agudelo, Agustin ^a,b   Chaiworapongsa, Tinnakorn ^a,b,c  

^a HUTZEL HOSPITAL   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

^c WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

17 hydroxyprogesterone caproate (17OHP C or 17P); Cervical cerclage; Cost effective analysis; Infant mortality; Pessary; Pregnancy; Prematurity; Respiratory distress syndrome

Indexed keywords

AZITHROMYCIN; GESTAGEN; GESTONORONE CAPROATE; INDOMETACIN; PLACEBO; PROGESTERONE; HYDROXYPROGESTERONE;

AMNIOCENTESIS; ARTIFICIAL VENTILATION; CERVICAL LENGTH MEASUREMENT; CLINICAL TRIAL; CONCEPTUAL FRAMEWORK; HOSPITAL ADMISSION; HUMAN; INTENSIVE CARE UNIT; NEWBORN INTENSIVE CARE; NEWBORN MORBIDITY; NEWBORN MORTALITY; PREMATURE LABOR; PRIORITY JOURNAL; RESPIRATORY DISTRESS SYNDROME; REVIEW; TRANSVAGINAL ECHOGRAPHY; UTERINE CERVIX; UTERINE CERVIX CERCLAGE; UTERINE CERVIX DISEASE; UTERINE CERVIX INCOMPETENCE; UTERINE CERVIX RIPENING; VAGINA PESSARY; CONGENITAL MALFORMATION; ECHOGRAPHY; FEMALE; HIGH RISK PREGNANCY; INTRAVAGINAL DRUG ADMINISTRATION; PREGNANCY; PREMATURITY; RISK;

17-ALPHA-HYDROXYPROGESTERONE; ADMINISTRATION, INTRAVAGINAL; CERVIX UTERI; FEMALE; HUMANS; PREGNANCY; PREGNANCY, HIGH-RISK; PREMATURE BIRTH; RISK;

EID: 84878396008     PISSN: 03005577     EISSN: 16193997     Source Type: Journal    
DOI: 10.1515/jpm-2012-0272     Document Type: Review

References (179)

1. ACOG Practice Bulletin. Cervical insufficiency. Obstet Gynecol. 2003;102:1091-9.
2. Althuisius SM, Dekker GA, Hummel P, Bekedam DJ, van Geijn HP. Final results of the Cervical Incompetence Prevention Randomized Cerclage Trial (CIPRACT): therapeutic cerclage with bed rest versus bed rest alone. Am J Obstet Gynecol. 2001;185:1106-12.
3. Althuisius S, Dekker G, Hummel P, Bekedam D, Kuik D, van Geijn H. Cervical Incompetence Prevention Randomized Cerclage Trial (CIPRACT): effect of therapeutic cerclage with bed rest vs. bed rest only on cervical length. Ultrasound Obstet Gynecol. 2002;20:163-7.
4. Althuisius SM, Dekker GA, Hummel P, van Geijn HP. Cervical incompetence prevention randomized cerclage trial: emergency cerclage with bed rest versus bed rest alone. Am J Obstet Gynecol. 2003;189:907-10.
5. Althuisius SM, Dekker GA, van Geijn HP. Cervical incompetence: a reappraisal of an obstetric controversy. Obstet Gynecol Surv. 2002;57:377-87.
6. Andersen HF. Transvaginal and transabdominal ultrasounography of the uterine cervix during pregnancy. J Clin Ultrasound. 1991;19:77-83.
7. Andersen HF, Nugent CE, Wanty SD, Hayashi RH. Prediction of risk for preterm delivery by ultrasonographic measurement of cervical length. Am J Obstet Gynecol. 1990;163:859-67.
8. Anum EA, Hill LD, Pandya A, Strauss JF 3rd. Connective tissue and related disorders and preterm birth: clues to genes contributing to prematurity. Placenta. 2009;30:207-15.
9. Arabin B, Halbesma JR, Vork F, Hubener M, van Eyck J. Is treatment with vaginal pessaries an option in patients with a sonographically detected short cervix? J Perinat Med. 2003;31: 122-33.
10. Ayers JW, DeGrood RM, Compton AA, Barclay M, Ansbacher R. Sonographic evaluation of cervical length in pregnancy: diagnosis and management of preterm cervical effacement in patients at risk for premature delivery. Obstet Gynecol. 1988;71(6 Pt 1):939-44.
11. Berghella V. Cerclage decreases preterm birth: finally the level I evidence is here. Am J Obstet Gynecol. 2011;205:89-90.
12. Berghella V, Kuhlman K, Weiner S, Texeira L, Wapner RJ. Cervical funneling: sonographic criteria predictive of preterm delivery. Ultrasound Obstet Gynecol. 1997;10:161-6.
13. Berghella V, Mackeen AD. Cervical length screening with ultrasound-indicated cerclage compared with history-indicated cerclage for prevention of preterm birth: a meta-analysis. Obstet Gynecol. 2011;118:148-55.
14. Berghella V, Odibo AO, Tolosa JE. Cerclage for prevention of preterm birth in women with a short cervix found on transvaginal ultrasound examination: a randomized trial. Am J Obstet Gynecol. 2004;191:1311-7.
15. Berghella V, Pereira L, Gariepy A, Simonazzi G. Prior cone biopsy: prediction of preterm birth by cervical ultrasound. Am J Obstet Gynecol. 2004;191:1393-7.
16. Berghella V, Rafael TJ, Szychowski JM, Rust OA, Owen J. Cerclage for short cervix on ultrasonography in women with singleton gestations and previous preterm birth: a meta-analysis. Obstet Gynecol. 2011;117:663-71.
17. Botsis D, Papagianni V, Vitoratos N, Makrakis E, Aravantinos L, Creatsas G. Prediction of preterm delivery by sonographic estimation of cervical length. Biol Neonate. 2005;88: 42-5.
18. Bowie JD, Andreotti RF, Rosenberg ER. Sonographic appearance of the uterine cervix in pregnancy: the vertical cervix. Am J Roentgenol. 1983;140:737-40.
19. Braithwaite JM, Economides DL. Acceptability by patients of transvaginal sonography in the elective assessment of the first-trimester fetus. Ultrasound Obstet Gynecol. 1997;9:91-3.
20. Brik M, Hernandez AI, Pedraz CC, Perales A. Phosphorylated insulin-like growth factor binding protein-1 and cervical measurement in women with threatening preterm birth. Acta Obstet Gynecol Scand. 2010;89:268-74.
21. Brook I, Feingold M, Schwartz A, Zakut H. Ultrasonography in the diagnosis of cervical incompetence in pregnancy-a new diagnostic approach. Br J obstet Gynaecol. 1981;88:640-3.
22. Bruinsma FJ, Quinn MA. The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and meta-analysis. Br J Obstet Gynaecol. 2011;118:1031-41.
23. Campbell S. Universal cervical-length screening and vaginal progesterone prevents early preterm births, reduces neonatal morbidity and is cost saving: doing nothing is no longer an option. Ultrasound Obstet Gynecol. 2011;38:1-9.
24. Carlomagno G, Di Blasi A, Monica MD. Congenital scoliosis associated with agenesis of the uterine cervix. Case report. BMC Womens Health. 2004;4:4.
25. Cetingoz E, Cam C, Sakalli M, Karateke A, Celik C, Sancak A. Progesterone effects on preterm birth in high-risk pregnancies: a randomized placebo-controlled trial. Arch Gynecol Obstet. 2011;283:423-9.
26. Chwalisz K. The use of progesterone antagonists for cervical ripening and as an adjunct to labour and delivery. Hum Reprod. 1994;9(Suppl 1):131-61.
27. Chwalisz K, Shi Shao O, Neff G, Elger J. The effect of antigestagen ZK 98,199 on the uterine cervix. Acta Endocrinol. 1987;283:113.
28. Combs CA, Garite T, Maurel K, Das A, Porto M. Failure of 17-hydroxyprogesterone to reduce neonatal morbidity or prolong triplet pregnancy: a double-blind, randomized clinical trial. Am J Obstet Gynecol. 2010;203:248 e1-9.
29. Conde-Agudelo A, Papageorghiou AT, Kennedy SH, Villar J. Novel biomarkers for the prediction of the spontaneous preterm birth phenotype: a systematic review and meta-analysis. Br J Obstet Gynaecol. 2011;118:1042-54.
30. Conde-Agudelo A, Romero R, Hassan SS, Yeo L. Transvaginal sonographic cervical length for the prediction of spontaneous preterm birth in twin pregnancies: a systematic review and metaanalysis. Am J Obstet Gynecol. 2010;203:128 e1-12.
31. Conde-Agudelo A, Romero R, Kusanovic JP. Nifedipine in the management of preterm labor: a systematic review and metaanalysis. Am J Obstet Gynecol. 2011;204:134 e1-20.
32. Conde-Agudelo A, Romero R, Nicolaides KH, Chaiworapongsa T, O'Brien J, Cetingoz E, et al. Vaginal progesterone vs cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis. Am J Obstet Gynecol. 2012 [in press].
33. Confino E, Mayden KL, Giglia RV, Vermesh M, Gleicher N. Pitfalls in sonographic imaging of the incompetent uterine cervix. Acta Obstet Gynecol Scand. 1986;65:593-7.
34. Craig CJ. Congenital abnormalities of the uterus and foetal wastage. S Afr Med J. 1973;47:2000-5.
35. Cukier J, Batzofin JH, Conner JS, Franklin RR. Genital tract reconstruction in a patient with congenital absence of the vagina and hypoplasia of the cervix. Obstet Gynecol. 1986;68:32S-6S.
36. Danti L, Prefumo F, Lojacono A, Corini S, Testori A, Frusca T. The combination of short cervical length and phIGFBP-1 in the prediction of preterm delivery in symptomatic women. J Matern Fetal Neonatal Med. 2011;24:1262-6.
37. de Carvalho MH, Bittar RE, Brizot ML, Bicudo C, Zugaib M. Prediction of preterm delivery in the second trimester. Obstet Gynecol. 2005;105:532-6.
38. Di Renzo GC, Al Saleh E, Mattei A, Koutras I, Clerici G. Use of tocolytics: what is the benefit of gaining 48 hours for the fetus? Br J Obstet Gynaecol. 2006;113(Suppl 3):72-7.
39. Di Renzo GC, Roura LC. Guidelines for the management of spontaneous preterm labor. J Perinat Med. 2006;34:359-66.
40. Elliott CL, Brennand JE, Calder AA. The effects of mifepristone on cervical ripening and labor induction in primigravidae. Obstet Gynecol. 1998;92:804-9.
41. Espinoza J, Erez O, Romero R. Preconceptional antibiotic treatment to prevent preterm birth in women with a previous preterm delivery. Am J Obstet Gynecol. 2006;194:630-7.
42. Final report of the Medical Research Council/Royal College of Obstetricians and Gynaecologists multicentre randomised trial of cervical cerclage. MRC/RCOG Working Party on Cervical Cerclage. Br J Obstet Gynaecol. 1993;100:516-23.
43. Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med. 2007;357:462-9.
44. Garfield RE, Chwalisz K, Shi L, Olson G, Saade GR. Instrumentation for the diagnosis of term and preterm labour. J Perinat Med. 1998;26:413-36.
45. Germain AM, Valenzuela GJ, Ivankovic M, Ducsay CA, Gabella C, Seron-Ferre M. Relationship of circadian rhythms of uterine activity with term and preterm delivery. Am J Obstet Gynecol. 1993;168:1271-7.
46. Gervasi M-T, Romero R, Maymon E, Pacora P, Jeanty P. Ultrasound examination of the uterine cervix during pregnancy. In: Fleischer AC, Manning FA, Jeanty P, Romero R, editors. Sonography in obstetrics and gynecology: principles and practice. 6th ed. New York: McGraw-Hill; 2001:821-41.
47. Giacalone PL, Daures JP, Faure JM, Boulot P, Hedon B, Laffargue F. The effects of mifepristone on uterine sensitivity to oxytocin and on fetal heart rate patterns. Eur J Obstet Gynecol Reprod Biol. 2001;97:30-4.
48. Gibbs RS, Romero R, Hillier SL, Eschenbach DA, Sweet RL. A review of premature birth and subclinical infection. Am J Obstet Gynecol. 1992;166:1515-28.
49. Goldberg JM, Falcone T. Effect of diethylstilbestrol on reproductive function. Fertil Steril. 1999;72:1-7.
50. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008;371:75-84.
51. Goldenberg RL, Iams JD, Mercer BM, Meis PJ, Moawad AH, Copper RL, et al. The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. NICHD MFMU Network. Am J Public Health. 1998;88:233-8.
52. Goldstein DP. Incompetent cervix in offspring exposed to diethylstilbestrol in utero. Obstet Gynecol. 1978;52:73S-5S.
53. Gomez R, Romero R, Nien JK, Medina L, Carstens M, Kim YM, et al. Antibiotic administration to patients with preterm premature rupture of membranes does not eradicate intra-amniotic infection. J Matern Fetal Neonatal Med. 2007;20:167-73.
54. Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev. 2002;8:3-13.
55. Goya M, Pratcorona L, Merced C, Rodo C, Valle L, Romero A, et al. Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial. Lancet. 2012;379:1800-6.
56. Grant A. Cervical cerclage to prolong pregnancy. In: Chalmers I, Enkin M, Keirse MJNC, editors. Effective care in pregnancy and children. Oxford: Oxford University Press; 1989:633-46.
57. Gray DJ, Robinson HB, Malone J, Thomson RB Jr. Adverse outcome in pregnancy following amniotic fluid isolation of Ureaplasma urealyticum. Prenat Diagn. 1992;12:111-7.
58. Grobman W. Randomized controlled trial of progesterone treatment for preterm birth prevention in nulliparous women with cervical length less than 30 mm. Am J Obstet Gynecol. 2012; S367.
59. Guzman ER, Mellon R, Vintzileos AM, Ananth CV, Walters C, Gipson K. Relationship between endocervical canal length between 15-24 weeks gestation and obstetric history. J Matern Fetal Med. 1998;7:269-72.
60. Guzman ER, Mellon C, Vintzileos AM, Ananth CV, Walters C, Gipson K. Longitudinal assessment of endocervical canal length between 15 and 24 weeks' gestation in women at risk for pregnancy loss or preterm birth. Obstet Gynecol. 1998;92:31-7.
61. Haran G, Elbaz M, Fejgin MD, Biron-Shental T. A comparison of surface acquired uterine electromyography and intrauterine pressure catheter to assess uterine activity. Am J Obstet Gynecol. 2012;206:412 e1-5.
62. Hasegawa I, Tanaka K, Takahashi K, Tanaka T, Aoki K, Torii Y, et al. Transvaginal ultrasonographic cervical assessment for the prediction of preterm delivery. J Matern Fetal Med. 1996;5:305-9.
63. Hassan SS, Romero R, Berry SM, Dang K, Blackwell SC, Treadwell MC, et al. Patients with an ultrasonographic cervical length < or = 15 mm have nearly a 50% risk of early spontaneous preterm delivery. Am J Obstet Gynecol. 2000;182:1458-67.
64. Hassan S, Romero R, Hendler I, Gomez R, Khalek N, Espinoza J, et al. A sonographic short cervix as the only clinical manifestation of intra-amniotic infection. J Perinat Med. 2006;34:13-9.
65. Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011;38:18-31.
66. Heath VC, Souka AP, Erasmus I, Gibb DM, Nicolaides KH. Cervical length at 23 weeks of gestation: the value of Shirodkar suture for the short cervix. Ultrasound Obstet Gynecol. 1998;12:318-22.
67. Heath VC, Southall TR, Souka AP, Elisseou A, Nicolaides KH. Cervical length at 23 weeks of gestation: prediction of spontaneous preterm delivery. Ultrasound Obstet Gynecol. 1998;12:312-7.
68. Heath VC, Southall TR, Souka AP, Novakov A, Nicolaides KH. Cervical length at 23 weeks of gestation: relation to demographic characteristics and previous obstetric history. Ultrasound Obstet Gynecol. 1998;12:304-11.
69. Hegele-Hartung C, Chwalisz K, Beier HM, Elger W. Ripening of the uterine cervix of the guinea-pig after treatment with the progesterone antagonist onapristone (ZK 98.299): an electron microscopic study. Hum Reprod. 1989;4:369-77.
70. Hernandez-Andrade E, Romero R, Ahn H, Hussein Y, Yeo L, Korzeniewski SJ, et al. Transabdominal evaluation of uterine cervical length during pregnancy fails to identify a substantial number of women with a short cervix. J Matern Fetal Neonatal Med. 2012;25:1682-9.
71. Hertzberg BS, Livingston E, DeLong DM, McNally PJ, Fazekas CK, Kliewer MA. Ultrasonographic evaluation of the cervix: transperineal versus endovaginal imaging. J Ultrasound Med. 2001;20:1071-8.
72. Hibbard JU, Tart M, Moawad AH. Cervical length at 16-22 weeks of gestation and risk for preterm delivery. Obstet Gynecol. 2000;96:972-8.
73. Higgins JPT, Altman DG, Sterne JAC. Assessing risk of bias in included studies. In: Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions, version 5.1.0. (updated March 2011). The Cochrane Collaboration 2011.
74. Husslein P, Cabero Roura L, Dudenhausen JW, Helmer H, Frydman R, Rizzo N, et al. Atosiban versus usual care for the management of preterm labor. J Perinat Med. 2007;35: 305-13.
75. Iams JD, Goldenberg RL, Meis PJ, Mercer BM, Moawad A, Das A, 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. N Engl J Med. 1996;334:567-72.
76. Iams JD, Johnson FF, Sonek J, Sachs L, Gebauer C, Samuels P. Cervical competence as a continuum: a study of ultrasonographic cervical length and obstetric performance. Am J Obstet Gynecol. 1995;172:1097-103.
77. Iams JD, Newman RB, Thom EA, Goldenberg RL, Mueller-Heubach E, Moawad A, et al. Frequency of uterine contractions and the risk of spontaneous preterm delivery. N Engl J Med. 2002;346:250-5.
78. Jacod BC, Graatsma EM, Van Hagen E, Visser GH. A validation of electrohysterography for uterine activity monitoring during labour. J Matern Fetal Neonatal Med. 2010;23:17-22.
79. Jeanty P, d'Alton M, Romero R, Hobbins JC. Perineal scanning. Am J Perinatol. 1986;3:289-95.
80. Kawarabayashi T, Kuriyama K, Kishikawa T, Sugimori H. Clinical features of small contraction wave recorded by an external tocodynamometer. Am J Obstet Gynecol. 1988;158: 474-8.
81. Keeler SM, Kiefer DG, Rust OA, Vintzileos A, Atlas RO, Bornstein E, et al. Comprehensive amniotic fluid cytokine profile evaluation in women with a short cervix: which cytokine(s) correlates best with outcome? Am J Obstet Gynecol. 2009;201:276 e1-6.
82. Keirse MJ. Progesterone and preterm: seventy years of "déjàvu" or "still to be seen"? Birth. 2004;31:230-5.
83. Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev. 2010: (8):CD001058.
84. Kenyon SL, Taylor DJ, Tarnow-Mordi W. Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group. Lancet. 2001;357:979-88.
85. Kiefer DG, Keeler SM, Rust OA, Wayock CP, Vintzileos AM, Hanna N. Is midtrimester short cervix a sign of intraamniotic inflammation? Am J Obstet Gynecol. 2009;200:374 e1-5.
86. Kim CJ, Romero R, Kusanovic JP, Yoo W, Dong Z, Topping V, et al. The frequency, clinical significance, and pathological features of chronic chorioamnionitis: a lesion associated with spontaneous preterm birth. Mod Pathol. 2010;23:1000-11.
87. Kriplani A, Kachhawa G, Awasthi D, Kulshrestha V. Laparoscopic-assisted uterovaginal anastomosis in congenital atresia of uterine cervix: follow-up study. J Minim Invasive Gynecol. 2012;19:477-84.
88. Kristensen J, Langhoff-Roos J, Wittrup M, Bock JE. Cervical conization and preterm delivery/low birth weight. A systematic review of the literature. Acta Obstet Gynecol Scand. 1993;72:640-4.
89. Kushnir O, Vigil DA, Izquierdo L, Schiff M, Curet LB. Vaginal ultrasonographic assessment of cervical length changes during normal pregnancy. Am J Obstet Gynecol. 1990;162:991-3.
90. Lee SM, Lee J, Seong HS, Lee SE, Park JS, Romero R, et al. The clinical significance of a positive Amnisure test in women with term labor with intact membranes. J Matern Fetal Neonatal Med. 2009;22:305-10.
91. Lee J, Romero R, Dong Z, Xu Y, Qureshi F, Jacques S, et al. Unexplained fetal death has a biological signature of maternal anti-fetal rejection: chronic chorioamnionitis and alloimmune anti-human leucocyte antigen antibodies. Histopathology. 2011;59:928-38.
92. Lee SE, Romero R, Park CW, Jun JK, Yoon BH. The frequency and significance of intraamniotic inflammation in patients with cervical insufficiency. Am J Obstet Gynecol. 2008;198:633 e1-8.
93. Lee SM, Romero R, Park JW, Kim SM, Park CW, Korzeniewski SJ, et al. The clinical significance of a positive Amnisure test in women with preterm labor and intact membranes. J Matern Fetal Neonatal Med. 2012;25:1690-8.
94. Lee J, Romero R, Xu Y, Kim JS, Park JY, Kusanovic JP, et al. Maternal HLA panel-reactive antibodies in early gestation positively correlate with chronic chorioamnionitis: evidence in support of the chronic nature of maternal anti-fetal rejection. Am J Reprod Immunol. 2011;66:510-26.
95. Lee J, Romero R, Xu Y, Kim JS, Topping V, Yoo W, et al. A signature of maternal anti-fetal rejection in spontaneous preterm birth: chronic chorioamnionitis, anti-human leukocyte antigen antibodies, and C4d. PloS One. 2011;6:e16806.
96. Lee CL, Wang CJ, Swei LD, Yen CF, Soong YK. Laparoscopic hemi-hysterectomy in treatment of a didelphic uterus with a hypoplastic cervix and obstructed hemivagina. Hum Reprod. 1999;14:1741-3.
97. Leung TN, Pang MW, Leung TY, Poon CF, Wong SM, Lau TK. Cervical length at 18-22 weeks of gestation for prediction of spontaneous preterm delivery in Hong Kong Chinese women. Ultrasound Obstet Gynecol. 2005;26:713-7.
98. Levine RU, Berkowitz KM. Conservative management and pregnancy outcome in diethylstilbestrol-exposed women with and without gross genital tract abnormalities. Am J Obstet Gynecol. 1993;169:1125-9.
99. Lockwood CJ, Dudenhausen JW. New approaches to the prediction of preterm delivery. J Perinat Med. 1993;21:441-52.
100. Lucovnik M, Kuon RJ, Chambliss LR, Maner WL, Shi SQ, Shi L, et al. Use of uterine electromyography to diagnose term and preterm labor. Acta Obstet Gynecol Scand. 2011;90:150-7.
101. Lucovnik M, Maner WL, Chambliss LR, Blumrick R, Balducci J, Novak-Antolic Z, et al. Noninvasive uterine electromyography for prediction of preterm delivery. Am J Obstet Gynecol. 2011;204:228 e1-10.
102. Ludmir J, Landon MB, Gabbe SG, Samuels P, Mennuti MT. Management of the diethylstilbestrol-exposed pregnant patient: a prospective study. Am J Obstet Gynecol. 1987;157: 665-9.
103. Mahendroo M. Cervical remodeling in term and preterm birth: insights from an animal model. Reproduction. 2012;143:429-38.
104. Main DM, Grisso JA, Wold T, Snyder ES, Holmes J, Chiu G. Extended longitudinal study of uterine activity among low-risk women. Am J Obstet Gynecol. 1991;165:1317-22.
105. Mangan CE, Borow L, Burtnett-Rubin MM, Egan V, Giuntoli RL, Mikuta JJ. Pregnancy outcome in 98 women exposed to diethylstilbestrol in utero, their mothers, and unexposed siblings. Obstet Gynecol. 1982;59:315-9.
106. Mason GC, Maresh MJ. Alterations in bladder volume and the ultrasound appearance of the cervix. Br J Obstet Gynaecol. 1990;97:457-8.
107. Matijevic R, Grgic O, Vasilj O. Is sonographic assessment of cervical length better than digital examination in screening for preterm delivery in a low-risk population? Acta Obstet Gynecol Scand. 2006;85:1342-7.
108. Maul H, Maner WL, Olson G, Saade GR, Garfield RE. Non-invasive transabdominal uterine electromyography correlates with the strength of intrauterine pressure and is predictive of labor and delivery. J Matern Fetal Neonatal Med. 2004;15:297-301.
109. Mays JK, Figueroa R, Shah J, Khakoo H, Kaminsky S, Tejani N. Amniocentesis for selection before rescue cerclage. Obstet Gynecol. 2000;95:652-5.
110. Mazor M, Chaim W, Maymon E, Hershkowitz R, Romero R. The role of antibiotic therapy in the prevention of prematurity. Clin Perinatol. 1998;25:659-85, x.
111. Mazor M, Hershkovitz R, Chaim W, Levy J, Sharony Y, Leiberman JR, et al. Human preterm birth is associated with systemic and local changes in progesterone/17 beta-estradiol ratios. Am J Obstet Gynecol. 1994;171:231-6.
112. Mazor M, Hershkowitz R, Ghezzi F, Cohen J, Silber A, Levy J, et al. Maternal plasma and amniotic fluid 17 beta-estradiol, progesterone and cortisol concentrations in women with successfully and unsuccessfully treated preterm labor. Arch Gynecol Obstet. 1996;258:89-96.
113. McDonald IA. Suture of the cervix for inevitable miscarriage. J Obstet Gynaecol Br Emp. 1957;64:346-50.
114. Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348:2379-85.
115. Mercer B. Antibiotics in the management of PROM and preterm labor. Obstet Gynecol Clin North Am. 2012;39:65-76.
116. Mercer BM, Miodovnik M, Thurnau GR, Goldenberg RL, Das AF, Ramsey RD, et al. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. J Am Med Assoc. 1997;278:989-95.
117. Millar LK, DeBuque L, Wing DA. Uterine contraction frequency during treatment of pyelonephritis in pregnancy and subsequent risk of preterm birth. J Perinat Med. 2003;31:41-6.
118. Moinian M, Andersch B. Does cervix conization increase the risk of complications in subsequent pregnancies? Acta Obstet Gynecol Scand. 1982;61:101-3.
119. Norman J. Antiprogesterones. Br J Hosp Med. 1991;45:372-5.
120. Norman JE, Mackenzie F, Owen P, Mactier H, Hanretty K, Cooper S, et al. Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, doubleblind, placebo-controlled study and meta-analysis. Lancet. 2009;373:2034-40.
121. O'Brien JM, Adair CD, Lewis DF, Hall DR, Defranco EA, Fusey S, et al. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007;30:687-96.
122. Ogge G, Romero R, Lee DC, Gotsch F, Than NG, Lee J, et al. Chronic chorioamnionitis displays distinct alterations of the amniotic fluid proteome. J Pathol. 2011;223:553-65.
123. Okitsu O, Mimura T, Nakayama T, Aono T. Early prediction of preterm delivery by transvaginal ultrasonography. Ultrasound Obstet Gynecol. 1992;2:402-9.
124. Owen J, Hankins G, Iams JD, Berghella V, Sheffield JS, Perez-Delboy A, 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.e1-8.
125. Podobnik M, Bulic M, Smiljanic N, Bistricki J. Ultrasonography in the detection of cervical incompetency. J Clin Ultrasound. 1988;16:383-91.
126. Raio L, Ghezzi F, Di NE, Gomez R, Luscher KP. Duration of pregnancy after carbon dioxide laser conization of the cervix: influence of cone height. Obstet Gynecol. 1997;90:978-82.
127. Raynal P, Le Meaux JP, Epelboin S, Tournaire M. [Early prophylactic cervical cerclage for hypoplastic cervix following exposure to DES in utero]. J Gynecol Obstet Biol Reprod (Paris). 2005;34:572-80.
128. Riley L, Frigoletto FD Jr, Benacerraf BR. The implications of sonographically identified cervical changes in patients not necessarily at risk for preterm birth. J Ultrasound Med. 1992;11:75-9.
129. Riley RD, Lambert PC, Abo-Zaid G. Meta-analysis of individual participant data: rationale, conduct, and reporting. Br Med J. 2010;340:c221.
130. Rode L, Klein K, Nicolaides K, Krampl-Bettelheim E, Tabor A. Prevention of preterm delivery in twin gestations (PREDICT): a multicentre randomised placebo-controlled trial on the effect of vaginal micronised progesterone. Ultrasound Obstet Gynecol. 2011;38:272-80.
131. Romero R. Prevention of spontaneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment. Ultrasound Obstet Gynecol. 2007;30:675-86.
132. Romero R. Progesterone to prevent preterm birth in twin gestations: what is the next step forward? Br J Obstet Gynaecol. 2012 [in press].
133. Romero R. Vaginal progesterone to reduce the rate of preterm birth and neonatal morbidity: a solution at last. Womens Health (Lond Engl). 2011;7:501-4.
134. Romero R, Chaiworapongsa T, Gotsch F, Yeo L, Madan I, Hassan SS. The diagnosis and management of preterm labor with intact membranes. In: Winn HN, Chervenak FA, Romero R, editors. Clinical maternal-fetal medicine online. 2nd ed. London: Informa Healthcare; 2011.
135. Romero R, Espinoza J, Erez O, Hassan S. The role of cervical cerclage in obstetric practice: can the patient who could benefit from this procedure be identified? Am J Obstet Gynecol. 2006;194:1-9.
136. Romero R, Espinoza J, Kusanovic JP, Gotsch F, Hassan S, Erez O, et al. The preterm parturition syndrome. Br J Obstet Gynaecol. 2006;113(Suppl 3):17-42.
137. Romero R, Ghidini A, Mazor M, Behnke E. Microbial invasion of the amniotic cavity in premature rupture of membranes. Clin Obstet Gynecol. 1991;34:769-78.
138. Romero R, Gomez R, Mazor M, Ghezzi F, Yoon BH. The preterm labor syndrome. In: Elder MG, Romero R, Lamont RF, editors. Preterm labor. New York, NY: Churchill Livingstone; 1997:29-49.
139. Romero R, Gonzalez R, Sepulveda W, Brandt F, Ramirez M, Sorokin Y, et al. Infection and labor. VIII. Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance. Am J Obstet Gynecol. 1992;167:1086-91.
140. Romero R, Hagay Z, Nores J, Sepulveda W, Mazor M. Eradication of Ureaplasma urealyticum from the amniotic fluid with transplacental antibiotic treatment. Am J Obstet Gynecol. 1992;166:618-20.
141. Romero R, Mazor M, Munoz H, Gomez R, Galasso M, Sherer DM. The preterm labor syndrome. Ann NY Acad Sci. 1994;734:414-29.
142. Romero R, Nicolaides K, Conde-Agudelo A, Tabor A, O'Brien JM, Cetingoz E, et al. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol. 2012;206:124 e1-19.
143. Romero R, Quintero R, Oyarzun E, Wu YK, Sabo V, Mazor M, et al. Intraamniotic infection and the onset of labor in preterm premature rupture of the membranes. Am J Obstet Gynecol. 1988;159:661-6.
144. Romero R, Scioscia AL, Edberg SC, Hobbins JC. Use of parenteral antibiotic therapy to eradicate bacterial colonization of amniotic fluid in premature rupture of membranes. Obstet Gynecol. 1986;67:15S-7S.
145. Romero R, Scoccia B, Mazor M, Wu YK, Benveniste R. Evidence for a local change in the progesterone/estrogen ratio in human parturition at term. Am J Obstet Gynecol. 1988;159:657-60.
146. Romero R, Sibai B, Caritis S, Paul R, Depp R, Rosen M, et al. Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial. Am J Obstet Gynecol. 1993;169:764-74.
147. Romero R, Sibai BM, Sanchez-Ramos L, Valenzuela GJ, Veille JC, Tabor B, et al. An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue. Am J Obstet Gynecol. 2000;182:1173-83.
148. Romero R, Espinoza J, Mazor M, Chaiworapongsa T. The preterm parturition syndrome. In: Critchely H, Bennett P, Thornton S, editors. Preterm birth. London: RCOG Press; 2004:28-60.
149. Rust OA, Atlas RO, Reed J, van Gaalen J, Balducci J. Revisiting the short cervix detected by transvaginal ultrasound in the second trimester: why cerclage therapy may not help. Am J Obstet Gynecol. 2001;185:1098-105.
150. Saling E. Prevention of prematurity-a complex undertaking reply. J Perinat Med. 2012;40:103.
151. Salle B, Sergeant P, Awada A, Bied-Damon V, Gaucherand P, Boisson C, et al. Transvaginal ultrasound studies of vascular and morphological changes in uteri exposed to diethylstilbestrol in utero. Hum Reprod. 1996;11:2531-6.
152. Schlembach D, Maner WL, Garfield RE, Maul H. Monitoring the progress of pregnancy and labor using electromyography. Eur J Obstet Gynecol Reprod Biol. 2009;144(Suppl 1): S33-9.
153. Serra V, Perales A, Meseguer J, Parrilla J, Lara C, Bellver J, et al. Increased doses of vaginal progesterone for the prevention of preterm birth in twin pregnancies: a randomised controlled double-blind multicentre trial. Br J Obstet Gynaecol. 2012. DOI: 10.1111/j.1471-0528.2012.03448.x [Epub ahead of print].
154. Shirodkar VN. A new method of operative treatment for habitual abortions in the second trimester of pregnancy. Antiseptic. 1955;52:299-300.
155. Stenlund PM, Ekman G, Aedo AR, Bygdeman M. Induction of labor with mifepristone-a randomized, double-blind study versus placebo. Acta Obstet Gynecol Scand. 1999;78:793-8.
156. Stewart LA, Parmar MK. Meta-analysis of the literature or of individual patient data: is there a difference? Lancet. 1993;341:418-22.
157. Stys SJ, Clewell WH, Meschia G. Changes in cervical compliance at parturition independent of uterine activity. Am J Obstet Gynecol. 1978;130:414-8.
158. Sutton AJ, Kendrick D, Coupland CA. Meta-analysis of individual- and aggregate-level data. Stat Med. 2008;27:651-69.
159. Taipale P, Hiilesmaa V. Sonographic measurement of uterine cervix at. 18-22 weeks of gestation and the risk of preterm delivery. Obstet Gynecol. 1998;92:902-7.
160. Theron G, Schabort C, Norman K, Thompson M, Geerts L. Centile charts of cervical length between 18 and 32 weeks of gestation. Int J Gynaecol Obstet. 2008;103:144-8.
161. Thompson SG, Higgins JP. Treating individuals 4: can metaanalysis help target interventions at individuals most likely to benefit? Lancet. 2005;365:341-6.
162. Timmons B, Akins M, Mahendroo M. Cervical remodeling during pregnancy and parturition. Trends Endocrinol Metab. 2010;21:353-61.
163. To MS, Alfirevic Z, Heath VC, Cicero S, Cacho AM, Williamson PR, et al. Cervical cerclage for prevention of preterm delivery in women with short cervix: randomised controlled trial. Lancet. 2004;363:1849-53.
164. To MS, Skentou C, Cicero S, Nicolaides KH. Cervical assessment at the routine 23-weeks'scan: problems with transabdominal sonography. Ultrasound Obstet Gynecol. 2000;15:292-6.
165. To MS, Skentou C, Liao AW, Cacho A, Nicolaides KH. Cervical length and funneling at 23 weeks of gestation in the prediction of spontaneous early preterm delivery. Ultrasound Obstet Gynecol. 2001;18:200-3.
166. Tongsong T, Kamprapanth P, Srisomboon J, Wanapirak C, Piyamongkol W, Sirichotiyakul S. Single transvaginal sonographic measurement of cervical length early in the third trimester as a predictor of preterm delivery. Obstet Gynecol. 1995;86:184-7.
167. Vaalamo P, Kivikoski A. The incompetent cervix during pregnancy diagnosed by ultrasound. Acta Obstet Gynecol Scand. 1983;62:19-21.
168. Vaisbuch E, Hassan SS, Mazaki-Tovi S, Nhan-Chang CL, Kusanovic JP, Chaiworapongsa T, et al. Patients with an asymptomatic short cervix (< or = 15 mm) have a high rate of subclinical intraamniotic inflammation: implications for patient counseling. Am J Obstet Gynecol. 2010;202:433 e1-8.
169. Valenzuela GJ, Sanchez-Ramos L, Romero R, Silver HM, Koltun WD, Millar L, et al. Maintenance treatment of preterm labor with the oxytocin antagonist atosiban. The Atosiban PTL-098 Study Group. Am J Obstet Gynecol. 2000;182: 1184-90.
170. Varma TR, Patel RH, Pillai U. Ultrasonic assessment of cervix in 'at risk' patients. Acta Obstet Gynecol Scand. 1986;65:147-52.
171. Varma TR, Patel RH, Pillai U. Ultrasonic assessment of cervix in normal pregnancy. Acta Obstet Gynecol Scand. 1986;65:229-33.
172. Warren JE, Silver RM, Dalton J, Nelson LT, Branch DW, Porter TF. Collagen 1Alpha1 and transforming growth factorbeta polymorphisms in women with cervical insufficiency. Obstet Gynecol. 2007;110:619-24.
173. Watson WJ, Stevens D, Welter S, Day D. Observations on the sonographic measurement of cervical length and the risk of premature birth. J Matern Fetal Med. 1999;8:17-9.
174. Werner EF, Han CS, Pettker CM, Buhimschi CS, Copel JA, Funai EF, et al. Universal cervical-length screening to prevent preterm birth: a cost-effectiveness analysis. Ultrasound Obstet Gynecol. 2011;38:32-7.
175. Wolf JP, Sinosich M, Anderson TL, Ulmann A, Baulieu EE, Hodgen GD. Progesterone antagonist (RU 486) for cervical dilation, labor induction, and delivery in monkeys: effectiveness in combination with oxytocin. Am J Obstet Gynecol. 1989;160:45-7.
176. Wood S, Ross S, Tang S, Miller L, Sauve R, Brant R. Vaginal progesterone to prevent preterm birth in multiple pregnancy: a randomized controlled trial. J Perinat Med. 2012.
177. Word RA, Li XH, Hnat M, Carrick K. Dynamics of cervical remodeling during pregnancy and parturition: mechanisms and current concepts. Semin Reprod Med. 2007;25:69-79.
178. Xu Y, Tarquini F, Romero R, Kim CJ, Tarca AL, Bhatti G, et al. Peripheral CD300a+CD8+ T lymphocytes with a distinct cytotoxic molecular signature increase in pregnant women with chronic chorioamnionitis. Am J Reprod Immunol. 2012;67:184-97.
179. Zemlyn S. The length of the uterine cervix and its significance. J Clin Ultrasound. 1981;9:267-9.