Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2013 Dec 5;2013(12):CD000246.
doi: 10.1002/14651858.CD000246.pub2.

Prophylactic antibiotics for inhibiting preterm labour with intact membranes

Vicki Flenady  1 , Glenda Hawley, Owen M Stock, Sara Kenyon, Nadia Badawi
Affiliations
Meta-Analysis

Prophylactic antibiotics for inhibiting preterm labour with intact membranes

Vicki Flenady et al. Cochrane Database Syst Rev. .

Abstract

Background: The aetiology of preterm birth is complex and there is evidence that subclinical genital tract infection influences preterm labour in some women but the role of prophylactic antibiotic treatment in the management of preterm labour is controversial. Since rupture of the membranes is an important factor in the progression of preterm labour, it is important to see if the routine administration of antibiotics confers any benefit or causes harm, prior to membrane rupture.

Objectives: To assess the effects of prophylactic antibiotics administered to women in preterm labour with intact membranes, on maternal and neonatal outcomes.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2013).

Selection criteria: Randomised trials that compared antibiotic treatment with placebo or no treatment for women in preterm labour (between 20 and 36 weeks' gestation) with intact membranes.

Data collection and analysis: Two review authors independently assessed trial eligibility, and undertook quality assessment and data extraction. We contacted study authors for additional information. Results are presented using risk ratio (RR) for categorical data and mean difference (MD) for data measured on a continuous scale with their respective 95% confidence intervals (CI). The number needed to treat to benefit (NNTB) and the number needed to treat to harm (NNTH) was calculated where appropriate.

Main results: In this update (2013), with the addition of three trials (305 women), the large ORACLE II 2001 trial continues to dominate the results of this review. This review now includes a total of 14 studies randomising 7837 women. No significant difference was shown in perinatal or infant mortality for infants of women allocated to any prophylactic antibiotics compared with no antibiotics. However, an increase in neonatal deaths was shown for infants of women receiving any prophylactic antibiotics when compared with placebo (RR 1.57, 95% CI 1.03 to 2.40; NNTH 149, 95% CI 2500 to 61). No reduction in preterm birth or other clinically important short-term outcomes for the infant were shown.Long-term child outcomes to seven years of age were available for infants in the UK enrolled in the ORACLE II trial. Comparing any antibiotics with placebo, a marginally non-statistically significant increase was shown in any functional impairment (RR 1.10, 95% CI 0.99 to 1.23) and cerebral palsy (CP) (RR 1.82, 95% CI 0.99 to 3.34). In subgroup analysis, CP was statistically significantly increased for infants of women allocated to macrolide and beta-lactam antibiotics combined compared with placebo (RR 2.83, 95% CI 1.02 to 7.88; NNTH 35, 95% CI 333 to 9).Further, exposure to any macrolide antibiotics (including erythromycin alone or erythromycin plus co-amoxiclav) versus no macrolide antibiotics (including placebo and co-amoxiclav alone) was shown to increase neonatal death (RR 1.52, 95% CI 1.05 to 2.19; NNTH 139, 95% CI 1429 to 61), any functional impairment (RR 1.11, 95% CI 1.01 to 1.20; NNTH 24, 95% CI 263 to 13) and CP (RR 1.90, 95% CI 1.20 to 3.01; NNTH 64, 95% CI 286 to 29). Exposure to any beta-lactam (beta-lactam alone or in combination with macrolide antibiotics) versus no beta-lactam antibiotics resulted in more neonatal deaths (RR 1.51, 95% CI 1.06 to 2.15; NNTH 143, 95% CI 1250 to 63) and CP (RR 1.67, 95% CI 1.06 to 2.61; NNTH 79, 95% CI 909 to 33), however no difference was shown in functional impairment.Maternal infection was reduced with the use of any prophylactic antibiotics compared with placebo (RR 0.74, 95% CI 0.63 to 0.86; NNTB 34, 95% CI 24 to 63) and any beta-lactam compared with no beta-lactam antibiotics (RR 0.80, 95% CI 0.69 to 0.92; NNTB 47, 95% CI 31 to 119). However, caution should be exercised with this finding due to the possibility of bias shown by funnel plot asymmetry. Any beta-lactam compared with no beta-lactam antibiotics was associated with an increase in maternal adverse drug reaction (RR 1.61, 95% CI 1.02 to 2.54; NNTH 17, 95% CI 526 to 7).

Authors' conclusions: This review did not demonstrate any benefit in important neonatal outcomes with the use of prophylactic antibiotics for women in preterm labour with intact membranes, although maternal infection may be reduced. Of concern, is the finding of short- and longer-term harm for children of mothers exposed to antibiotics. The evidence supports not giving antibiotics routinely to women in preterm labour with intact membranes in the absence of overt signs of infection.Further research is required to develop sensitive markers of subclinical infection for women in preterm labour with intact membranes, as this is a group that might benefit from future novel interventions, including new modalities of antibiotic therapy. The results of this review demonstrate the need for future trials in the area of preterm birth to include assessment of long-term neurodevelopmental outcome.

PubMed Disclaimer

Conflict of interest statement

Sara Kenyon led the ORACLE trial and was the CI for the ORACLE Children's Study.

Figures

1
1
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
3
3
Funnel plot of comparison: 1 Any antibiotics versus no antibiotics, outcome: 1.1 Perinatal mortality.
4
4
Funnel plot of comparison: 1 Any antibiotics versus no antibiotics, outcome: 1.12 Preterm birth (< 36 or < 37 weeks).
5
5
Funnel plot of comparison: 1 Any antibiotics versus no antibiotics, outcome: 1.20 Neonatal sepsis.
6
6
Funnel plot of comparison: 1 Any antibiotics versus no antibiotics, outcome: 1.9 Maternal infection.
1.1
1.1. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 1 Perinatal mortality.
1.2
1.2. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 2 Stillbirth.
1.3
1.3. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 3 Neonatal death.
1.4
1.4. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 4 Infant death.
1.5
1.5. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 5 Any functional impairment at 7 years of age..
1.6
1.6. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 6 Moderate/severe functional impairment at 7 years of age..
1.7
1.7. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 7 Cerebral palsy at 7 years.
1.8
1.8. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 8 Maternal adverse drug reaction requiring cessation of treatment.
1.9
1.9. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 9 Maternal infection.
1.10
1.10. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 10 Delay in birth (subgrouped by interval).
1.11
1.11. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 11 Interval between randomisation and birth (days).
1.12
1.12. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 12 Preterm birth (< 36 or < 37 weeks).
1.13
1.13. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 13 Gestational age at birth.
1.14
1.14. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 14 Birthweight.
1.15
1.15. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 15 Birthweight < 2500 g.
1.16
1.16. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 16 Admission to neonatal intensive or special care nursery.
1.17
1.17. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 17 Neonatal mechanical ventilation.
1.18
1.18. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 18 Respiratory distress syndrome.
1.19
1.19. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 19 Neonatal positive blood culture.
1.20
1.20. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 20 Neonatal sepsis.
1.21
1.21. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 21 Intraventricular haemorrhage.
1.22
1.22. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 22 Necrotising enterocolitis.
1.23
1.23. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 23 Major cerebral abnormality.
1.24
1.24. Analysis
Comparison 1 Any antibiotics versus no antibiotics, Outcome 24 Chronic neonatal lung disease.
2.1
2.1. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 1 Perinatal mortality.
2.2
2.2. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 2 Stillbirth.
2.3
2.3. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 3 Neonatal death.
2.4
2.4. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 4 Infant death.
2.5
2.5. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 5 Any functional impairment at 7 years of age..
2.6
2.6. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 6 Moderate/severe functional impairment at 7 years of age..
2.7
2.7. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 7 Cerebral palsy at 7 years of age.
2.8
2.8. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 8 Maternal adverse drug reaction requiring cessation of treatment.
2.9
2.9. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 9 Maternal infection.
2.10
2.10. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 10 Birth within 48 hours of randomisation.
2.11
2.11. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 11 Interval between randomisation and birth (days).
2.12
2.12. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 12 Preterm birth (< 36 or < 37 weeks' gestation).
2.13
2.13. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 13 Respiratory distress syndrome.
2.14
2.14. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 14 Necrotising enterocolitis.
2.15
2.15. Analysis
Comparison 2 Antibiotics versus no antibiotics (subgrouped by type of antibiotic), Outcome 15 Intraventricular haemorrhage.
3.1
3.1. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 1 Perinatal mortality.
3.2
3.2. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 2 Stillbirth.
3.3
3.3. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 3 Neonatal death.
3.4
3.4. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 4 Infant death.
3.5
3.5. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 5 Any functional impairment at 7 years of age..
3.6
3.6. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 6 Moderate/severe functional impairment at 7 years of age..
3.7
3.7. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 7 Cerebral palsy at 7 years.
3.8
3.8. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 8 Maternal adverse drug reaction requiring cessation of treatment.
3.9
3.9. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 9 Maternal infection.
3.10
3.10. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 10 Birth within 48 hours of randomisation.
3.11
3.11. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 11 Interval between randomisation and birth (days).
3.12
3.12. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 12 Preterm birth (< 36 or < 37 weeks).
3.13
3.13. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 13 Respiratory distress syndrome.
3.14
3.14. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 14 Intraventricular haemorrhage.
3.15
3.15. Analysis
Comparison 3 Any macrolide versus no macrolide, Outcome 15 Necrotising enterocolitis.
4.1
4.1. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 1 Perinatal mortality.
4.2
4.2. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 2 Stillbirth.
4.3
4.3. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 3 Neonatal death.
4.4
4.4. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 4 Infant death.
4.5
4.5. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 5 Any functional impairment at 7 years of age..
4.6
4.6. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 6 Moderate/severe functional impairment at 7 years of age..
4.7
4.7. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 7 Cerebral palsy at 7 years.
4.8
4.8. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 8 Maternal adverse drug reaction requiring cessation of treatment.
4.9
4.9. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 9 Maternal infection.
4.10
4.10. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 10 Birth within 48 hours of randomisation.
4.11
4.11. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 11 Interval between randomisation and birth (days).
4.12
4.12. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 12 Preterm birth (< 36 or < 37 weeks).
4.13
4.13. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 13 Respiratory distress syndrome.
4.14
4.14. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 14 Intraventricular haemorrhage.
4.15
4.15. Analysis
Comparison 4 Any beta‐lactam versus no beta‐lactam, Outcome 15 Necrotising enterocolitis.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Cox 1996 {published data only (unpublished sought but not used)}
    1. Cox SM, Boham V, Sherman ML, Leveno KJ. Single‐center randomized placebo controlled trial of antimicrobials for prevention of preterm birth [abstract]. American Journal of Obstetrics and Gynecology 1994;170:388.
    1. Cox SM, Bohman VR, Sherman L, Leveno KJ. Randomized investigation of antimicrobials for the prevention of preterm birth. American Journal of Obstetrics and Gynecology 1996;174(1):206‐10. - PubMed
Gordon 1995 {published data only}
    1. Gordon M, Samuels P, Shubert P, Johnson F, Gebauer C, Iams J. A randomized, prospective study of adjunctive ceftizoxime in preterm labor. American Journal of Obstetrics and Gynecology 1995;172(5):1546‐52. - PubMed
    1. Gordon M, Shubert PJ, Samuels P, Johnson F, Gebauer C, Iams JD. A randomized prospective study of adjunctive ceftizoxime in preterm labor. American Journal of Obstetrics and Gynecology 1994;170:389. - PubMed
Kenyon 2001a {published and unpublished data}
    1. Jones DR, Pike K, Kenyon S, Pike L, Henderson B, Brocklehurst P, et al. Routine educational outcome measures in health studies: Key Stage 1 in the ORACLE Children Study follow‐up of randomised trial cohorts. Archives of Disease in Childhood 2011;96(1):25‐9. - PubMed
    1. Kenyon S, Brocklehurst P, Jones D, Marlow N, Salt A, Taylor D. MRC ORACLE children study. Long term outcomes following prescription of antibiotics to pregnant women with either spontaneous preterm labour or preterm rupture of the membranes. BMC Pregnancy and Childbirth 2008;8:14. - PMC - PubMed
    1. Kenyon S, Pike K, Jones DR, Brocklehurst P, Marlow N, Salt A, et al. Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7‐year follow‐up of the ORACLE II trial. Lancet 2008;372:1319‐27. - PubMed
    1. Kenyon SL, Taylor DJ, Tarnow‐Mordi W, ORACLE Collaborative Group. Broad‐spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group. Lancet 2001;357(9261):989‐94. - PubMed
Keuchkerian 2005 {published data only}
    1. Keuchkerian SE, Sosa CG, Fernandez A, Alonso JG, Laborde A, Cuadro JC. Effect of amoxicillin sulbactam in threatened preterm labour with intact membranes: a randomised controlled trial. European Journal of Obstetrics & Gynecology and Reproductive Biology 2005;119:21‐6. - PubMed
McGregor 1991 {published and unpublished data}
    1. McGregor JA, French JI, Seo K. Adjunctive clindamycin therapy for preterm labor: results of a double‐blind, placebo‐controlled trial. American Journal of Obstetrics and Gynecology 1991;165(4):867‐75. - PubMed
    1. McGregor JA, French JI, Seo K. Adjunctive clindamycin therapy for preterm labor: results of a double‐blinded randomized, placebo‐controlled trial. American Journal of Obstetrics and Gynecology 1991;164(1 Pt 2):259. - PubMed
Newton 1989 {published data only (unpublished sought but not used)}
    1. Newton ER, Dinsmoor MJ, Gibbs RS. A randomized, blinded, placebo‐controlled trial of antibiotics in idiopathic preterm labor. Obstetrics and Gynecology 1989;74(4):562‐6. - PubMed
Newton 1991 {published data only (unpublished sought but not used)}
    1. Newton ER, Shields L, Ridgway LE, Berkus MD, Elliott BD. Combination antibiotics and indomethacin in idiopathic preterm labor: a randomized double‐blind clinical trial. American Journal of Obstetrics and Gynecology 1991;165(6):1753‐9. - PubMed
Norman 1994 {published and unpublished data}
    1. Norman K, Pattinson R, de Sousa, Jong P. PRAM: a preterm labour management randomised controlled trial investigating antibiotic intervention on a multicentre basis. Proceedings of 26th British Congress of Obstetrics and Gynaecology; 1992; Manchester, UK. 1992:3.
    1. Norman K, Pattinson RC, Kirsten G, Sousa J, Jong P, Moller G. PRAM: a preliminary report. Proceedings of 10th Conference on Priorities in Perinatal Care in South Africa; Eastern Transvaal, South Africa. 1991:33‐8.
    1. Norman K, Pattinson RC, Souza J, Jong P, Moller G, Kirsten G. Ampicillin and metronidazole treatment in preterm labour: a multicentre, randomised controlled trial. British Journal of Obstetrics and Gynaecology 1994;101:404‐8. - PubMed
Oyarzun 1998 {published data only}
    1. Oyarzun E, Gomez R, Rioseco A, Gonzalez P, Gutierrez P, Donoso E, et al. Antibiotic treatment in preterm labor and intact membranes: a randomized, double‐blinded, placebo‐controlled trial. Journal of Maternal Fetal Medicine 1998;7:105‐10. - PubMed
Rajaei 2006 {published data only}
    1. Rajaei M, Sultani M, Zare S. A randomized controlled trial of adjunctive erythromycin in women with idiopathic preterm labor. Journal of Maternal‐Fetal & Neonatal Medicine 2006;19(1):17‐20. - PubMed
Reimer 1999 {published data only}
    1. Reimer T, Ulfig N, Friese K. Antibiotics: treatment of preterm labor. Journal of Perinatal Medicine 1999;27(1):35‐40. - PubMed
Romero 1993 {published data only (unpublished sought but not used)}
    1. Guinn DA, Goldenberg RL, Hauth JC, Andrews WW, Thom E, Romero R. Risk factors for the development of preterm premature rupture of the membranes after arrest of preterm labor. American Journal of Obstetrics and Gynecology 1995;173:1310‐5. - PubMed
    1. Guinn DA, Goldenberg RL, Hauth JC, Thom E, Romero R, McNellis D. Risk factors for the development of preterm rupture of membranes following arrest of preterm labor. American Journal of Obstetrics and Gynecology 1995;172 (1 Pt 2):412. - PubMed
    1. Ovalle A, Romero R, Gomez R, Martinez MA, Nien JK, Ferrand P, et al. Antibiotic administration to patients with preterm labor and intact membranes: is there a beneficial effect in patients with endocervical inflammation?. Journal of Maternal‐Fetal & Neonatal Medicine 2006;19(8):453‐64. - PubMed
    1. Romero R, Sibai B, Caritis S, Paul R, Depp R, Klebanoff M, et al. Antibiotic treatment of preterm labour with intact membranes: a multicenter, randomized, double blind, placebo‐controlled trial. American Journal of Obstetrics and Gynecology 1993;168(1 Pt 2):288. - PubMed
    1. 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. American Journal of Obstetrics and Gynecology 1993;169(4):764‐74. - PubMed
Svare 1997 {published and unpublished data}
    1. Svare J, Langhoff ‐Roos J, Andersen LF, Kryger‐Baggesen N, Borch‐Christensen H, Heisterberg L, et al. Ampicillin‐metronidazole treatment in idiopathic preterm labour: a randomised controlled multicentre trial. British Journal of Obstetrics and Gynaecology 1997;104:892‐7. - PubMed
    1. Svare J, Langhoff‐Roos J, Andersen L, Kryger‐Baggesen N, Borch‐Christensen H, Heisterberg L, et al. Ampicillin‐metronidazole treatment in threatening preterm delivery. Acta Obstetricia et Gynecologica Scandinavica 1997;76(167:1):86.
    1. Svare J, Langhoff‐Ross J, Anderson LF, Baggesen NK, Borch‐Christensen H, Heisterberg L, et al. Antibiotic treatment in preterm labor or preterm premature rupture of the membranes ‐ a randomised controlled double‐blind trial. Acta Obstetrica et Gynecologica Scandinavica Supplement 1996;75(Suppl 162):36.
Watts 1994 {published and unpublished data}
    1. Watts DH, Krohn MA, Hillier SL, Eschenbach DA. Randomized trial of antibiotics in addition to tocolytic therapy to treat preterm labor. Infectious Diseases in Obstetrics and Gynecology 1994;1:220‐7. - PMC - PubMed

References to studies excluded from this review

Gurbuz 2004 {published data only}
    1. Gurbuz A, Karateke A, Kabaca C. Erythromycin treatment in idiopathic preterm labor. International Journal of Gynecology and Obstetrics 2004;86:27‐8. - PubMed
Hensen 1987 {published and unpublished data}
    1. Hensen B. A randomised prospective study of antibiotic therapy for the treatment and prevention of premature labor. Personal communication 1987.
Lauterbach 2012 {published data only}
    1. Lauterbach R, Rytlewski K, Pawlik D, Hurkala J, Wojtowicz A, Breborowicz G, et al. Effect of Pentoxifylline, administered in preterm labour, on the foetal‐placental circulation and neonatal outcome: a randomized, prospective pilot study. Basic and Clinical Pharmacology and Toxicology 2012;110(4):342‐6. - PubMed
McCaul 1992 {published data only}
    1. McCaul JF, Perry KG, Martin RW, Morrison C. Treatment of idiopathic preterm rupture of membranes or labor with adjunctive ampicillin. American Journal of Obstetrics and Gynecology 1991;164:376.
    1. McCaul JF, Perry KG, Moore JL, Martin RW, Bucovaz ET, Morrison JC. Adjunctive antibiotic treatment of women with preterm rupture of membranes or preterm labor. International Journal of Gynecology and Obstetrics 1992;38:19‐24. - PubMed
    1. Morrison JC. Antibiotic treatment for patients in preterm labor 20‐34 weeks with intact membranes. Personal communication December 14 1993.
McGregor 1986 {published data only}
    1. McGregor JA, French JI, Reller LB, Todd JK, Makowski EL. Adjunctive erythromycin treatment for idiopathic preterm labour: results of a randomized, double‐blind, placebo‐controlled trial. American Journal of Obstetrics and Gynecology 1986;154:98‐103. - PubMed
McGregor 1988 {unpublished data only}
    1. McGregor JA, French JI, Richter R, Vuchetich M, Bachus V, Franco‐Buff A, et al. Prospective, double‐blinded, randomized, controlled trial of short‐course erythromycin (E) base in women at high risk of preterm birth. Proceedings of the Society for Gynecologic Investigation 1988.
Morales 1988 {published data only}
    1. Morales W, Angel JL, O'Brien WF, Knuppel RA, Finazzo M. A randomized study of antibiotic therapy in idiopathic preterm labor. Obstetrics and Gynecology 1988;72(6):829‐33. - PubMed
Nadisauskiene 1996 {published data only}
    1. Nadisauskiene R, Bergstrom S. Impact of intrapartum intravenous ampicillin on pregnancy outcome in women with preterm labor: a randomised placebo‐controlled study. Gynecologic and Obstetric Investigation 1996;41:85‐8. - PubMed
    1. Nadisauskiene R, Bergstrom S, Kilda A. Ampicillin in the treatment of preterm labor: a randomised, placebo‐controlled study. Gynecologic and Obstetric Investigation 1996;41:89‐92. - PubMed
    1. Nadisauskiene R, Kilda A. Ampicillin in the treatment of preterm labour. International Journal of Gynecology and Obstetrics 1994;46:232.
    1. Nadisauskiene R, Vaitkiene D. The impact of ampicillin in the treatment of preterm labour [abstract]. Proceedings of 14th European Congress of Perinatal Medicine; 1994 June 5‐8; Helsinki, Finland. 1994:416.
Naef 1994 {published data only}
    1. Naef RW, Magann EF, Allbert JR, Roberts WE, Martin RW, Morrison JC. Prospective comparison of empiric antibiotic therapy in patients with idiopathic preterm labor. American Journal of Obstetrics and Gynecology 1994;170:376.
Ogasawara 1996 {published data only}
    1. Ogasawara KK, Goodwin TM. Efficacy of azithromycin in reducing lower genital ureaplasma colonization in women at risk for preterm delivery. American Journal of Obstetrics and Gynecology 1997;176(1 Pt 2):S57. - PubMed
    1. Ogasawara KK, Goodwin TM. Efficacy of azithromycin in reducing lower genital ureaplasma urealyticum colonization in women at risk for preterm delivery. Journal of Maternal Fetal Medicine 1999;8:12‐6. - PubMed
    1. Ogasawara KK, Goodwin TM. The efficacy of treating ureaplasma urealyticum in patients with preterm labor or preterm rupture of membranes. American Journal of Obstetrics and Gynecology 1996;174(1 Pt 2):401.
Oszukowski 2000 {published and unpublished data}
    1. Oszukowski P, Pieta A, Nowak M. The influence of antibiotics in preterm labor on the inherited infection rate in newborns. XVI FIGO World Congress of Obstetrics & Gynecology (Book 3); 2000 Sept 3‐8; Washington DC, USA. 2000:70.
Ovalle 2006 {published data only}
    1. Ovalle A, Romero R, Gomez R, Martinez MA, Nien JK, Ferrand P, et al. Antibiotic administration to patients with preterm labor and intact membranes: is there a beneficial effect in patients with endocervical inflammation?. Journal of Maternal Fetal & Neonatal Medicine 2006;12(2):45‐8. - PubMed
Ozden 2000 {published data only}
    1. Ozden S, Akcaoglu F, Dayicioglu V. Oral administration of ampicilline‐sulbactam adjuvant to tocolytic therapy in cases of chorioamniotic membranes intact preterm labour: A placebo controlled and double‐blinded study. Italian Journal of Gynaecology & Obstetrics 2000;12(2):45‐8.
Purwar 1997 {published data only}
    1. Purwar MB, Sarodey C, Karale S. Ampicillin and metronidazole in preterm labor management: an RCT. Journal of Clinical Epidemiology 1997;50 Suppl 1:22S.
Saez‐Llorens 1995 {published data only}
    1. Saez‐Llorens X, Ah‐Chu M, Castano E, Cortes L, Torres A, Suarez M, et al. Intrapartum prophylaxis with ceftriaxone decreases rates of bacterial colonization and early‐onset infection in newborns. Clinical Infectious Diseases 1995;21:876‐80. - PubMed
Winkler 1988 {published data only}
    1. Winkler M, Baumann L, Ruckhaberle K, Schiller E. Erythromicin therapy for subclinical uterine infections in threatened preterm delivery ‐ a preliminary report. Journal of Perinatal Medicine 1988;16:253‐6. - PubMed

Additional references

Bejar 1981
    1. Bejar R, Curbelo V, Davis C, Gluck L. Premature labor. II. Bacterial sources of phospholipase. Obstetrics and Gynecology 1981;57(4):479‐82. - PubMed
Clarke 2001
    1. Clarke M, Oxman AD, editors. Cochrane Reviewers’ Handbook 4.1.4 [updated October 2001]. In: Review Manager (RevMan) [Computer program]. Version 4.1. Oxford, England: The Cochrane Collaboration, 2001.
Cobo 2009
    1. Cobo T, Palacio M, Navarro‐Sastre A, Ribes A, Bosch J, Filella X, et al. Predictive value of combined amniotic fluid proteomic biomarkers and interleukin‐6 in preterm labor with intact membranes.. American Journal of Obstetrics and Gynecology 2009;200(5):e1‐e6. - PubMed
Gates 2004
    1. Gates S, Brocklehurst P. How should randomised trials including multiple pregnancies be analysed?. British Journal of Obstetrics and Gynaecolgy 2004;111:213‐9. - PubMed
Goldenberg 2000
    1. Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. New England Journal of Medicine 2000;342:1500‐7. - PubMed
Hamilton 2006
    1. Hamilton BE, Martin JA, Ventura SJ. Births: preliminary data for 2005. Health E‐Stats. Hyattsville, MD, 2006. http://www.cdc.gov/nchs/products/pubs/pubd/hestats/prelimbirths05/prelim.... - PubMed
Hauth 1995
    1. Hauth JC, Goldenberg RL, Andrews WW, DuBard MB, Copper RL. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. New England Journal of Medicine 1995;333:1732‐6. - PubMed
Heikkinen 2000
    1. Heikkinen T, Laine K, Neuvonen PJ, Ekblad U. The transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycin. BJOG: an international journal of obstetrics and gynaecology 2000;107(6):770‐5. - PubMed
Henderson 2012
    1. Henderson JJ, McWilliam OA, Newnham JP, Pennell CE. Preterm birth aetiology 2004‐2008. Maternal factors associated with three phenotypes: spontaneous preterm labour, preterm pre‐labour rupture of membranes and medically indicated preterm birth. Journal of Maternal Fetal and Neonatal Medicine 2012;25(6):642‐7. - PubMed
Higgins 2011
    1. Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated September 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Kallen 2005
    1. Kallen BA, Otterblad Olausson P, Danielsson BR. Is erythromycin therapy teratogenic in humans?. Reproductive Toxicology 2005;20:209‐14. - PubMed
Kayem 2009
    1. Kayem G, Maillard F, Schmitz T, Jarreau PH, Cabrol D, Breart G, et al. Prediction of clinical infection in women with preterm labour with intact membranes: a score based on ultrasonographic, clinical and biological markers. European Journal of Obstetrics & Gynecology, and Reproductive Biology 2009;145(1):36‐40. - PubMed
Keelan 2011
    1. Keelan JA, Nitsos I, Saito M, Musk GC, Kemp MW, Timmins M, Li S, et al. Maternal‐amniotic‐fetal distribution of macrolide antibiotics following intravenous, intramuscular, and intraamniotic administration in late pregnant sheep. American Journal of Obstetrics and Gynecology 2011;204(6):546.e10‐546.e17. - PubMed
Kenyon 2008a
    1. Kenyon S, Pike K, Jones DR, Brocklehurst P, Marlow N, Salt A, et al. Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7‐year follow‐up of the ORACLE II trial. Lancet 2008;372:1319‐27. - PubMed
Kenyon 2008b
    1. Kenyon S, Brocklehurst P, Jones D, Marlow N, Salt A, Taylor D. MRC ORACLE children study. Long term outcomes following prescription of antibiotics to pregnant women with either spontaneous preterm labour or preterm rupture of the membranes. BMC Pregnancy and Childbirth 2008;8:14. - PMC - PubMed
Kenyon 2010
    1. Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database of Systematic Reviews 2010, Issue 8. [DOI: 10.1002/14651858.CD001058.pub2] - DOI - PubMed
Lawn 2010
    1. Lawn JE, Gravett MG, Nunes TM, Rubens CE, Stanton C, for the GAPPS Review Group. Global report on preterm birth and stillbirth (1 of 7): definitions, description of the burden and opportunities to improve data. BMC Pregnancy Childbirth 2010;10 Suppl 1:S1. - PMC - PubMed
Marlow 2012
    1. Marlow N, Pike K, Bowers E, Brocklehurst P, Jones D, Kenyon S, et al. Characteristics of children with cerebral palsy in the ORACLE children study. Developmental Medicine and Child Neurology 2012;54:640–6. - PubMed
McGregor 1997
    1. McGregor JA, French JI. Evidence‐based prevention of preterm birth and rupture of membranes: infection and inflammation. Journal of the Society of Obstetricians and Gynaecologists of Canada 1997;19:835‐52.
Moutquin 1996
    1. Moutquin JM, Milot‐Roy V, Irion O. Preterm birth prevention: effectiveness of current strategies. Journal of the Society of Obstetricians and Gynaecologists of Canada 1996;18:571‐88.
Muglia 2010
    1. Muglia LJ, Katz M. The enigma of spontaneous preterm birth. New England Journal of Medicine 2010;362(6):529‐35. - PubMed
Norman 2009
    1. Norman JE, Morris C, Chalmers J. The effect of changing patterns of obstetric care in Scotland (1980‐2004) on rates of preterm birth and its neonatal consequences: perinatal database study. PLoS Medicine 2009;6(9):e1000153. - PMC - PubMed
RevMan 2012 [Computer program]
    1. The Cochrane Collaboration. Review Manager (RevMan). Version 5.2. Copenhagen, The Nordic Cochrane Centre: The Cochrane Collaboration, 2012.
Romero 2006
    1. Romero R, Espinoza J, Kusanovic JP, Gotsch F, Hassan S, Erez O, et al. The preterm parturition syndrome. BJOG: an international journal of obstetrics and gynaecology 2006;113(Suppl 3):17‐42. - PMC - PubMed
Romero 2010
    1. Romero R, Kusanovic JP, Gotsch F, Erez O, Vaisbuch E, Mazaki‐Tovi S, et al. Isobaric labeling and tandem mass spectrometry: a novel approach for profiling and quantifying proteins differentially expressed in amniotic fluid in preterm labor with and without intra‐amniotic infection/inflammation. Journal of Maternal‐Fetal Medicine 2010;23(4):261‐80. [PUBMED: 19670042] - PMC - PubMed
Saigal 1994
    1. Saigal S, Rosenbaum P, Stoskopf B, Hoult L, Furlong W, Feeny D, et al. Comprehensive assessment of the health status of extremely low birthweight children at eight years of age: comparisons with a reference group. Journal of Pediatrics 1994;125:411‐7. - PubMed
Smith 2007
    1. Smith R. Parturition. New England Journal of Medicine 2007;356(3):271‐83. - PubMed
Sweet 1987
    1. Sweet RL, Landers DV, Walker C, Schachter J. Chlamydia trachomatis infection and pregnancy outcome. American Journal of Obstetrics and Gynecology 1987;156:824‐33. - PubMed
Tracy 2007
    1. Tracy SK, Tracy MB, Dean J, Laws P, Sullivan E. Spontaneous preterm birth of liveborn infants in women at low risk in Australia over 10 years: a population‐based study. BJOG: an international journal of obstetrics and gynaecology 2007;114(6):731‐5. - PubMed
Yoon 2000
    1. Yoon BH, Romero R, Park JS, Kim CJ, Kim SH, Choi JH, et al. Fetal exposure to intra‐amniotic inflammation and the development of cerebral palsy at the age of three years. American Journal of Obstetrics and Gynecology 2000;182:675‐81. - PubMed
Yoon 2003
    1. Yoon BH, Romero R, Lim JH, Shim SS, Hong JS, Shim JY, et al. The clinical significance of detecting Ureaplasma urealyticum by the polymerase chain reaction in the amniotic fluid of patients with preterm labor. American Journal of Obstetrics and Gynecology 2003;189:919‐24. - PubMed

References to other published versions of this review

Crowley 1995
    1. Crowley P. Antibiotics in preterm labour with intact membranes. [revised 05 May 1994] In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP, Crowther C (eds.) Pregnancy and Childbirth Module. In: The Cochrane Database of Systematic Reviews [database on disk and CDROM]. The Cochrane Collaboration; Issue 2, Oxford: Update Software; 1995.
King 2002a
    1. King J, Flenady V, Murray L. Prophylactic antibiotics for inhibiting preterm labour with intact membranes. Cochrane Database of Systematic Reviews 2002, Issue 4. [DOI: 10.1002/14651858.CD000246] - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources