title: Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth.
abstract: BACKGROUND
  Preterm birth is a major complication of pregnancy associated with perinatal mortality and morbidity. Progesterone for the prevention of preterm labour has been advocated.
  
  
  OBJECTIVE
  To assess the benefits and harms of progesterone for the prevention of preterm birth for women considered to be at increased risk of preterm birth and their infants.
  
  
  METHODS
  We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 January 2013) and reviewed the reference list of all articles.
  
  
  METHODS
  Randomised controlled trials, in which progesterone was given for preventing preterm birth.
  
  
  METHODS
  Two review authors independently evaluated trials for methodological quality and extracted data.
  
  
  RESULTS
  Thirty-six randomised controlled trials (8523 women and 12,515 infants) were included. Progesterone versus placebo for women with a past history of spontaneous preterm birth Progesterone was associated with a statistically significant reduction in the risk of perinatal mortality (six studies; 1453 women; risk ratio (RR) 0.50, 95% confidence interval (CI) 0.33 to 0.75), preterm birth less than 34 weeks (five studies; 602 women; average RR 0.31, 95% CI 0.14 to 0.69), infant birthweight less than 2500 g (four studies; 692 infants; RR 0.58, 95% CI 0.42 to 0.79), use of assisted ventilation (three studies; 633 women; RR 0.40, 95% CI 0.18 to 0.90), necrotising enterocolitis (three studies; 1170 women; RR 0.30, 95% CI 0.10 to 0.89), neonatal death (six studies; 1453 women; RR 0.45, 95% CI 0.27 to 0.76), admission to neonatal intensive care unit (three studies; 389 women; RR 0.24, 95% CI 0.14 to 0.40), preterm birth less than 37 weeks (10 studies; 1750 women; average RR 0.55, 95% CI 0.42 to 0.74) and a statistically significant increase in pregnancy prolongation in weeks (one study; 148 women; mean difference (MD) 4.47, 95% CI 2.15 to 6.79). No differential effects in terms of route of administration, time of commencing therapy and dose of progesterone were observed for the majority of outcomes examined. Progesterone versus placebo for women with a short cervix identified on ultrasound Progesterone was associated with a statistically significant reduction in the risk of preterm birth less than 34 weeks (two studies; 438 women; RR 0.64, 95% CI 0.45 to 0.90), preterm birth at less than 28 weeks' gestation (two studies; 1115 women; RR 0.59, 95% CI 0.37 to 0.93) and increased risk of urticaria in women when compared with placebo (one study; 654 women; RR 5.03, 95% CI 1.11 to 22.78). It was not possible to assess the effect of route of progesterone administration, gestational age at commencing therapy, or total cumulative dose of medication. Progesterone versus placebo for women with a multiple pregnancy Progesterone was associated with no statistically significant differences for the reported outcomes. Progesterone versus no treatment/placebo for women following presentation with threatened preterm labour Progesterone, was associated with a statistically significant reduction in the risk of infant birthweight less than 2500 g (one study; 70 infants; RR 0.52, 95% CI 0.28 to 0.98). Progesterone versus placebo for women with 'other' risk factors for preterm birth Progesterone, was associated with a statistically significant reduction in the risk of infant birthweight less than 2500 g (three studies; 482 infants; RR 0.48, 95% CI 0.25 to 0.91).
  
  
  CONCLUSIONS
  The use of progesterone is associated with benefits in infant health following administration in women considered to be at increased risk of preterm birth due either to a prior preterm birth or where a short cervix has been identified on ultrasound examination. However, there is limited information available relating to longer-term infant and childhood outcomes, the assessment of which remains a priority.Further trials are required to assess the optimal timing, mode of administration and dose of administration of progesterone therapy when given to women considered to be at increased risk of early birth.
authors.affiliation: School of Paediatrics and Reproductive Health, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Adelaide,Australia. jodie.dodd@adelaide.edu.au.
authors.forename: Jodie M
authors.initials: JM
authors.lastname: Dodd
authors.forename: Leanne
authors.initials: L
authors.lastname: Jones
authors.forename: Vicki
authors.initials: V
authors.lastname: Flenady
authors.forename: Robert
authors.initials: R
authors.lastname: Cincotta
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Crowther
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D011247:Pregnancy; D018566:Pregnancy, High-Risk; D047928:Premature Birth / Q000517:prevention & control*; D011295:Prenatal Care / Q000379:methods; D011374:Progesterone / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic
chemical_list: D011374:Progesterone; D019326:17-alpha-Hydroxyprogesterone
references.citation: Am J Obstet Gynecol. 2007 Feb;196(2):131.e1-6
references.pmid: 17306652
references.citation: N Engl J Med. 2003 Jun 12;348(24):2379-85
references.pmid: 12802023
references.citation: Gynecol Obstet Invest. 1984;18(5):252-63
references.pmid: 6526341
references.citation: Am J Obstet Gynecol. 1999 Nov;181(5 Pt 1):1216-21
references.pmid: 10561648
references.citation: Nature. 1998 Apr 2;392(6675):509-12
references.pmid: 9548257
references.citation: Am J Obstet Gynecol. 1983 May 15;146(2):187-90
references.pmid: 6682631
references.citation: Am J Obstet Gynecol. 2012 Nov;207(5):396.e1-8
references.pmid: 22959763
references.citation: N Engl J Med. 1975 Oct 2;293(14):675-80
references.pmid: 1099445
references.citation: Am J Obstet Gynecol. 2011 Mar;204(3):221.e1-8
references.pmid: 21376161
references.citation: Stat Med. 2002 Jun 15;21(11):1539-58
references.pmid: 12111919
references.citation: Am J Perinatol. 2010 Aug;27(7):537-42
references.pmid: 20175042
references.citation: Obstet Gynecol. 2005 Feb;105(2):267-72
references.pmid: 15684150
references.citation: Int J Gynaecol Obstet. 1979 Mar-Apr;16(5):381-4
references.pmid: 86468
references.citation: South Med J. 2009 Sep;102(9):900-4
references.pmid: 19668021
references.citation: Cochrane Database Syst Rev. 2012 Apr 18;(4):CD008991
references.pmid: 22513970
references.citation: Obstet Gynecol. 2007 Oct;110(4):865-72
references.pmid: 17906021
references.citation: Eur J Obstet Gynecol Reprod Biol. 2003 Jun 10;108(2):177-81
references.pmid: 12781407
references.citation: Ultrasound Obstet Gynecol. 2007 Oct;30(5):687-96
references.pmid: 17899572
references.citation: BMC Pregnancy Childbirth. 2012 Aug 06;12:79
references.pmid: 22866909
references.citation: Health Technol Assess. 2016 May;20(41):1-92
references.pmid: 27225013
references.citation: Am J Obstet Gynecol. 2005 Sep;193(3 Pt 2):1127-31
references.pmid: 16157124
references.citation: Natl Vital Stat Rep. 2003 Dec 17;52(10):1-113
references.pmid: 14717305
references.citation: Am J Obstet Gynecol. 2012 Feb;206(2):124.e1-19
references.pmid: 22284156
references.citation: Am J Obstet Gynecol. 2011 Jan;204(1):54.e1-5
references.pmid: 20869038
references.citation: J Matern Fetal Neonatal Med. 2010 Dec;23(12):1360-4
references.pmid: 20441408
references.citation: Ultrasound Obstet Gynecol. 2007 Oct;30(5):697-705
references.pmid: 17899571
references.citation: J Paediatr Child Health. 1999 Apr;35(2):145-50
references.pmid: 10365350
references.citation: BJOG. 2013 Jan;120(1):50-7
references.pmid: 22882759
references.citation: Am J Obstet Gynecol. 1997 Mar;176(3):682-91
references.pmid: 9077629
references.citation: Ultrasound Obstet Gynecol. 2011 Jul;38(1):18-31
references.pmid: 21472815
references.citation: Lancet. 2009 Jun 13;373(9680):2034-40
references.pmid: 19523680
references.citation: Ultrasound Obstet Gynecol. 2011 Sep;38(3):272-80
references.pmid: 21739497
references.citation: Lancet. 2012 Jun 9;379(9832):2162-72
references.pmid: 22682464
references.citation: Eur J Obstet Gynecol Reprod Biol. 2002 Jan 10;100(2):196-8
references.pmid: 11750964
references.citation: Am J Obstet Gynecol. 1984 Nov 15;150(6):716-22
references.pmid: 6496593
references.citation: Ultrasound Obstet Gynecol. 2011 Sep;38(3):281-7
references.pmid: 21739499
references.citation: BMC Pregnancy Childbirth. 2011 Oct 24;11:77
references.pmid: 22023876
references.citation: Obstet Gynecol. 2011 Sep;118(3):513-520
references.pmid: 21860279
references.citation: Am J Obstet Gynecol. 1966 May 15;95(2):222-7
references.pmid: 5935707
references.citation: Am J Obstet Gynecol. 1962 Apr 15;83:1094-8
references.pmid: 13872839
references.citation: J Obstet Gynaecol Res. 2011 Oct;37(10):1342-5
references.pmid: 21564406
references.citation: Obstet Gynecol. 1980 Dec;56(6):692-5
references.pmid: 7443111
references.citation: Int J Epidemiol. 1973 Summer;2(2):195-204
references.pmid: 4777775
references.citation: Int J Gynaecol Obstet. 2009 Jan;104(1):40-3
references.pmid: 18929360
references.citation: Am J Perinatol. 2011 May;28(5):377-81
references.pmid: 21380990
references.citation: Am J Obstet Gynecol. 2003 Feb;188(2):303
references.pmid: 12592229
references.citation: JAMA. 2000 Mar 22-29;283(12):1591-6
references.pmid: 10735396
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9518-23
references.pmid: 12886011
references.citation: BMC Res Notes. 2011 Dec 29;4:568
references.pmid: 22206581
references.citation: J Matern Fetal Neonatal Med. 2005 Oct;18(4):265-9
references.pmid: 16318978
references.citation: Cochrane Database Syst Rev. 2014 Sep 10;(9):CD009166
references.pmid: 25208049
references.citation: Obstet Gynecol. 2005 Sep;106(3):557-61
references.pmid: 16135587
references.citation: N Engl J Med. 1998 Jul 30;339(5):313-20
references.pmid: 9682045
references.citation: N Engl J Med. 2007 Aug 2;357(5):454-61
references.pmid: 17671253
references.citation: Obstet Gynecol. 2003 Nov;102(5 Pt 1):1115-6
references.pmid: 14672496
references.citation: Am J Obstet Gynecol. 1994 Jan;170(1 Pt 1):54-62
references.pmid: 8296845
references.citation: Am J Perinatol. 2008 Sep;25(8):503-6
references.pmid: 18756431
references.citation: Paediatr Perinat Epidemiol. 2001 Jul;15 Suppl 2:7-16
references.pmid: 11520396
references.citation: BJOG. 2004 Mar;111(3):213-9
references.pmid: 14961881
references.citation: Med J Aust. 1988 Sep 5;149(5):234, 236, 238 passim
references.pmid: 3412212
references.citation: Br J Obstet Gynaecol. 1985 Sep;92(9):921-8
references.pmid: 4041398
references.citation: BMC Pregnancy Childbirth. 2007 Jun 19;7:7
references.pmid: 17578562
references.citation: BMC Pregnancy Childbirth. 2009 Feb 24;9:6
references.pmid: 19239712
references.citation: Reprod Biomed Online. 2012 Aug;25(2):133-8
references.pmid: 22695310
references.citation: Reprod Sci. 2011 May;18(5):435-46
references.pmid: 21558462
references.citation: Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004947
references.pmid: 16437505
references.citation: Aust N Z J Obstet Gynaecol. 2002 Oct;42(4):353-7
references.pmid: 12403279
references.citation: Am J Obstet Gynecol. 2012 Mar;206(3):206.e1-9
references.pmid: 22381603
references.citation: Am J Obstet Gynecol. 2011 Aug;205(2):135.e1-9
references.pmid: 21600550
references.citation: Am J Obstet Gynecol. 2012 Nov;207(5):390.e1-8
references.pmid: 23010094
references.citation: Epidemiol Rev. 1993;15(2):414-43
references.pmid: 8174665
references.citation: Am J Obstet Gynecol. 2010 Sep;203(3):248.e1-9
references.pmid: 20816146
references.citation: BJOG. 2003 Apr;110 Suppl 20:39-45
references.pmid: 12763110
references.citation: Aust N Z J Obstet Gynaecol. 2008 Feb;48(1):58-63
references.pmid: 18275573
references.citation: Endocr Rev. 1995 Oct;16(5):608-48
references.pmid: 8529574
references.citation: Obstet Gynecol. 2001 Sep;98(3):379-85
references.pmid: 11530116
references.citation: Am J Obstet Gynecol. 2009 Oct;201(4):392.e1-5
references.pmid: 19716543
references.citation: Am J Obstet Gynecol. 2013 Jan;208(1):42.e1-42.e18
references.pmid: 23157855
references.citation: J Med Assoc Thai. 1986 Oct;69(10):538-42
references.pmid: 3819611
references.citation: Cochrane Database Syst Rev. 2008 Apr 16;(2):CD003511
references.pmid: 18425891
references.citation: Am J Obstet Gynecol. 2003 Feb;188(2):419-24
references.pmid: 12592250
references.citation: Pediatrics. 1999 Jan;103(1 Suppl E):319-28
references.pmid: 9917474
references.citation: Am J Obstet Gynecol. 1979 Dec 15;135(8):1086-103
references.pmid: 517593
references.citation: N Engl J Med. 2003 Jun 12;348(24):2453-5
references.pmid: 12802032
references.citation: Semin Perinatol. 2001 Aug;25(4):204-14
references.pmid: 11561908
references.citation: BMC Pregnancy Childbirth. 2012 Mar 15;12:13
references.pmid: 22420582
references.citation: Gynecol Obstet Invest. 2011;72(4):269-73
references.pmid: 22086108
references.citation: Am J Obstet Gynecol. 2008 Nov;199(5):506.e1-7
references.pmid: 18456237
references.citation: West J Surg Obstet Gynecol. 1964 Jan-Feb;72:30-6
references.pmid: 14107505
references.citation: J Perinat Med. 1974;2(1):30-6
references.pmid: 4468289
references.citation: Ultrasound Obstet Gynecol. 2009 Dec;34(6):653-9
references.pmid: 19918965
references.citation: Arch Gynecol Obstet. 2011 Mar;283(3):423-9
references.pmid: 20091317
references.citation: Am J Obstet Gynecol. 2010 Apr;202(4):351.e1-6
references.pmid: 20350641
references.citation: J Perinat Med. 2009;37(5):473-9
references.pmid: 19492920
references.citation: Am J Obstet Gynecol. 2007 May;196(5):453.e1-4; discussion 421
references.pmid: 17466698
references.citation: J Obstet Gynaecol. 2009 Aug;29(6):493-8
references.pmid: 19697195
references.citation: Eur J Obstet Gynecol Reprod Biol. 2007 Aug;133(2):134-42
references.pmid: 17452071
references.citation: J Soc Gynecol Investig. 2002 May-Jun;9(3):125-36
references.pmid: 12009386
references.citation: Paediatr Perinat Epidemiol. 1992 Apr;6(2):298-310
references.pmid: 1584730
references.citation: Obstet Gynecol. 2009 Feb;113(2 Pt 1):285-92
references.pmid: 19155896
references.citation: Mol Hum Reprod. 2001 Sep;7(9):875-9
references.pmid: 11517295
references.citation: N Engl J Med. 2007 Aug 2;357(5):462-9
references.pmid: 17671254
references.citation: Am J Obstet Gynecol. 1985 Mar 1;151(5):574-7
references.pmid: 3976757
references.citation: Am J Obstet Gynecol. 2005 Sep;193(3 Pt 2):1181-6
references.pmid: 16157134
references.citation: JAMA. 2000 Aug 16;284(7):843-9
references.pmid: 10938173
references.citation: Int J Technol Assess Health Care. 2010 Apr;26(2):141-8
references.pmid: 20392316