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Meta-Analysis
. 2014 Feb 27;2014(2):CD007062.
doi: 10.1002/14651858.CD007062.pub3.

Tocolytics for preterm premature rupture of membranes

A Dhanya Mackeen  1 , Jolene Seibel-Seamon, Jacqueline Muhammad, Jason K Baxter, Vincenzo Berghella
Affiliations
Meta-Analysis

Tocolytics for preterm premature rupture of membranes

A Dhanya Mackeen et al. Cochrane Database Syst Rev. .

Abstract

Background: In women with preterm labor, tocolysis has not been shown to improve perinatal mortality; however, it is often given for 48 hours to allow for the corticosteroid effect for fetal maturation. In women with preterm premature rupture of membranes (PPROM), the use of tocolysis is still controversial. In theory, tocolysis may prolong pregnancy in women with PPROM, thereby allowing for the corticosteroid benefit and reducing the morbidity and mortality associated with prematurity.

Objectives: To assess the potential benefits and harms of tocolysis in women with preterm premature rupture of membranes.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 January 2014).

Selection criteria: We included pregnant women with singleton pregnancies and PPROM (23 weeks to 36 weeks and six days). We included any tocolytic therapy compared to no tocolytic, placebo, or another tocolytic.

Data collection and analysis: All review authors assessed the studies for inclusion. We extracted and quality assessed data.

Main results: We included eight studies with a total of 408 women. Seven of the studies compared tocolysis to no tocolysis. One study compared nifedipine to terbutaline. Compared to no tocolysis, tocolysis was not associated with a significant effect on perinatal mortality in women with PPROM (risk ratio (RR) 1.67; 95% confidence interval (CI) 0.85 to 3.29). Tocolysis was associated with longer latency (mean difference (MD) 73.12 hours; 95% CI 20.21 to 126.03; three trials of 198 women) and fewer births within 48 hours (average RR 0.55; 95% CI 0.32 to 0.95; six trials of 354 women; random-effects, Tau² = 0.18, I² = 43%) compared to no tocolysis. However, tocolysis was associated with increased five-minute Apgar of less than seven (RR 6.05; 95% CI 1.65 to 22.23; two trials of 160 women) and increased need for ventilation of the neonate (RR 2.46; 95% CI 1.14 to 5.34; one trial of 81 women). In the subgroup analysis comparing betamimetic to no betamimetics, tocolysis was associated with increased latency and borderline significance for chorioamnionitis. Prophylactic tocolysis with PPROM was associated with increased overall latency, without additional benefits for maternal/neonatal outcomes. For women with PPROM before 34 weeks, there was a significantly increased risk of chorioamnionitis in women who received tocolysis. However, neonatal outcomes were not significantly different. There were no significant differences in maternal/neonatal outcomes in subgroup analyses comparing cox inhibitor versus no tocolysis, calcium channel blocker versus betamimetic, antibiotic, corticosteroid or combined antibiotic/corticosteroid.

Authors' conclusions: Our review suggests there is insufficient evidence to support tocolytic therapy for women with PPROM, as there was an increase in maternal chorioamnionitis without significant benefits to the infant. However, studies did not consistently administer latency antibiotics and corticosteroids, both of which are now considered standard of care.

PubMed Disclaimer

Conflict of interest statement

None known.

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.
1.1
1.1. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 1 Perinatal mortality.
1.2
1.2. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 2 Intrauterine fetal demise.
1.3
1.3. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 3 Neonatal death.
1.4
1.4. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 4 Gestational age.
1.5
1.5. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 5 Birthweight (grams).
1.6
1.6. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 6 Apgar < 7 at 5 minutes.
1.7
1.7. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 7 Neonatal Sepsis.
1.8
1.8. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 8 Necrotizing enterocolitis.
1.9
1.9. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 9 Intraventricular haemorrhage.
1.10
1.10. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 10 Respiratory distress syndrome.
1.11
1.11. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 11 Neonate required ventilation.
1.12
1.12. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 12 Latency (hours).
1.13
1.13. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 13 Latency (birth within 48 hours).
1.14
1.14. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 14 Latency (birth within 7 days).
1.15
1.15. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 15 Chorioamnionitis.
1.16
1.16. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 16 Endometritis.
1.17
1.17. Analysis
Comparison 1 Tocolytic versus no tocolytic, Outcome 17 Maternal hospital stay (days).
2.1
2.1. Analysis
Comparison 2 Cyclo‐oxygenase inhibitor versus no cyclo‐oxygenase inhibitor subgroup analysis, Outcome 1 Perinatal mortality.
2.2
2.2. Analysis
Comparison 2 Cyclo‐oxygenase inhibitor versus no cyclo‐oxygenase inhibitor subgroup analysis, Outcome 2 Intrauterine fetal demise.
2.3
2.3. Analysis
Comparison 2 Cyclo‐oxygenase inhibitor versus no cyclo‐oxygenase inhibitor subgroup analysis, Outcome 3 Neonatal death.
2.4
2.4. Analysis
Comparison 2 Cyclo‐oxygenase inhibitor versus no cyclo‐oxygenase inhibitor subgroup analysis, Outcome 4 Neonatal sepsis.
2.5
2.5. Analysis
Comparison 2 Cyclo‐oxygenase inhibitor versus no cyclo‐oxygenase inhibitor subgroup analysis, Outcome 5 Necrotizing enterocolitis.
2.6
2.6. Analysis
Comparison 2 Cyclo‐oxygenase inhibitor versus no cyclo‐oxygenase inhibitor subgroup analysis, Outcome 6 Intraventricular haemorrhage.
2.7
2.7. Analysis
Comparison 2 Cyclo‐oxygenase inhibitor versus no cyclo‐oxygenase inhibitor subgroup analysis, Outcome 7 Respiratory distress syndrome.
2.8
2.8. Analysis
Comparison 2 Cyclo‐oxygenase inhibitor versus no cyclo‐oxygenase inhibitor subgroup analysis, Outcome 8 Latency (birth within 48 hours).
2.9
2.9. Analysis
Comparison 2 Cyclo‐oxygenase inhibitor versus no cyclo‐oxygenase inhibitor subgroup analysis, Outcome 9 Latency (birth within 7 days).
2.10
2.10. Analysis
Comparison 2 Cyclo‐oxygenase inhibitor versus no cyclo‐oxygenase inhibitor subgroup analysis, Outcome 10 Chorioamnionitis.
3.1
3.1. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 1 Perinatal mortality.
3.2
3.2. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 2 Intrauterine fetal demise.
3.3
3.3. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 3 Neonatal death.
3.4
3.4. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 4 Gestational age.
3.5
3.5. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 5 Birthweight (grams).
3.6
3.6. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 6 Apgar < 7 at 5 minutes.
3.7
3.7. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 7 Neonatal sepsis.
3.8
3.8. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 8 Necrotizing enterocolitis.
3.9
3.9. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 9 Intraventricular haemorrhage.
3.10
3.10. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 10 Respiratory distress syndrome.
3.11
3.11. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 11 Latency (hours).
3.12
3.12. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 12 Latency (birth within 48 hours).
3.13
3.13. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 13 Latency (birth within 7 days).
3.14
3.14. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 14 Chorioamnionitis.
3.15
3.15. Analysis
Comparison 3 Betamimetic versus no betamimetic, Outcome 15 Maternal endometritis.
4.1
4.1. Analysis
Comparison 4 Nifedipine versus Terbutaline, Outcome 1 Respiratory distress syndrome.
4.2
4.2. Analysis
Comparison 4 Nifedipine versus Terbutaline, Outcome 2 Latency (birth within 48 hours).
5.1
5.1. Analysis
Comparison 5 Prophylactic tocolysis (PPROM without contractions), Outcome 1 Perinatal mortality.
5.2
5.2. Analysis
Comparison 5 Prophylactic tocolysis (PPROM without contractions), Outcome 2 Intrauterine fetal demise.
5.3
5.3. Analysis
Comparison 5 Prophylactic tocolysis (PPROM without contractions), Outcome 3 Neonatal death.
5.4
5.4. Analysis
Comparison 5 Prophylactic tocolysis (PPROM without contractions), Outcome 4 Gestational age.
5.5
5.5. Analysis
Comparison 5 Prophylactic tocolysis (PPROM without contractions), Outcome 5 Birthweight (grams).
5.6
5.6. Analysis
Comparison 5 Prophylactic tocolysis (PPROM without contractions), Outcome 6 Neonatal sepsis.
5.7
5.7. Analysis
Comparison 5 Prophylactic tocolysis (PPROM without contractions), Outcome 7 Necrotizing enterocolitis.
5.8
5.8. Analysis
Comparison 5 Prophylactic tocolysis (PPROM without contractions), Outcome 8 Intraventricular haemorrhage.
5.9
5.9. Analysis
Comparison 5 Prophylactic tocolysis (PPROM without contractions), Outcome 9 Respiratory distress syndrome.
5.10
5.10. Analysis
Comparison 5 Prophylactic tocolysis (PPROM without contractions), Outcome 10 Latency (hours).
5.11
5.11. Analysis
Comparison 5 Prophylactic tocolysis (PPROM without contractions), Outcome 11 Latency (birth within 48 hours).
5.12
5.12. Analysis
Comparison 5 Prophylactic tocolysis (PPROM without contractions), Outcome 12 Latency (birth within 7 days).
5.13
5.13. Analysis
Comparison 5 Prophylactic tocolysis (PPROM without contractions), Outcome 13 Chorioamnionitis.
6.1
6.1. Analysis
Comparison 6 Antibiotic subgroup analysis, Outcome 1 Perinatal mortality.
6.2
6.2. Analysis
Comparison 6 Antibiotic subgroup analysis, Outcome 2 Intrauterine fetal demise.
6.3
6.3. Analysis
Comparison 6 Antibiotic subgroup analysis, Outcome 3 Neonatal death.
6.4
6.4. Analysis
Comparison 6 Antibiotic subgroup analysis, Outcome 4 Neonatal sepsis.
6.5
6.5. Analysis
Comparison 6 Antibiotic subgroup analysis, Outcome 5 Necrotizing enterocolitis.
6.6
6.6. Analysis
Comparison 6 Antibiotic subgroup analysis, Outcome 6 Intraventricular haemorrhage.
6.7
6.7. Analysis
Comparison 6 Antibiotic subgroup analysis, Outcome 7 Respiratory distress syndrome.
6.8
6.8. Analysis
Comparison 6 Antibiotic subgroup analysis, Outcome 8 Latency (birth within 48 hours).
6.9
6.9. Analysis
Comparison 6 Antibiotic subgroup analysis, Outcome 9 Latency (birth within 7 days).
6.10
6.10. Analysis
Comparison 6 Antibiotic subgroup analysis, Outcome 10 Chorioamnionitis.
7.1
7.1. Analysis
Comparison 7 Steroid subgroup analysis, Outcome 1 Perinatal mortality.
7.2
7.2. Analysis
Comparison 7 Steroid subgroup analysis, Outcome 2 Intrauterine fetal demise.
7.3
7.3. Analysis
Comparison 7 Steroid subgroup analysis, Outcome 3 Neonatal death.
7.4
7.4. Analysis
Comparison 7 Steroid subgroup analysis, Outcome 4 Neonatal sepsis.
7.5
7.5. Analysis
Comparison 7 Steroid subgroup analysis, Outcome 5 Necrotizing enterocolitis.
7.6
7.6. Analysis
Comparison 7 Steroid subgroup analysis, Outcome 6 Intraventricular haemorrhage.
7.7
7.7. Analysis
Comparison 7 Steroid subgroup analysis, Outcome 7 Respiratory distress syndrome.
7.8
7.8. Analysis
Comparison 7 Steroid subgroup analysis, Outcome 8 Latency (birth within 48 hours).
7.9
7.9. Analysis
Comparison 7 Steroid subgroup analysis, Outcome 9 Latency (birth within 7 days).
7.10
7.10. Analysis
Comparison 7 Steroid subgroup analysis, Outcome 10 Chorioamnionitis.
8.1
8.1. Analysis
Comparison 8 Antibiotic and steroid subgroup analysis, Outcome 1 Perinatal mortality.
8.2
8.2. Analysis
Comparison 8 Antibiotic and steroid subgroup analysis, Outcome 2 Intrauterine fetal demise.
8.3
8.3. Analysis
Comparison 8 Antibiotic and steroid subgroup analysis, Outcome 3 Neonatal death.
8.4
8.4. Analysis
Comparison 8 Antibiotic and steroid subgroup analysis, Outcome 4 Neonatal sepsis.
8.5
8.5. Analysis
Comparison 8 Antibiotic and steroid subgroup analysis, Outcome 5 Necrotizing enterocolitis.
8.6
8.6. Analysis
Comparison 8 Antibiotic and steroid subgroup analysis, Outcome 6 Intraventricular haemorrhage.
8.7
8.7. Analysis
Comparison 8 Antibiotic and steroid subgroup analysis, Outcome 7 Respiratory distress syndrome.
8.8
8.8. Analysis
Comparison 8 Antibiotic and steroid subgroup analysis, Outcome 8 Latency (birth within 48 hours).
8.9
8.9. Analysis
Comparison 8 Antibiotic and steroid subgroup analysis, Outcome 9 Latency (birth within 7 days).
8.10
8.10. Analysis
Comparison 8 Antibiotic and steroid subgroup analysis, Outcome 10 Chorioamnionitis.
9.1
9.1. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 1 Perinatal mortality.
9.2
9.2. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 2 Intrauterine fetal demise.
9.3
9.3. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 3 Neonatal death.
9.4
9.4. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 4 Gestational age.
9.5
9.5. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 5 Birthweight (grams).
9.6
9.6. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 6 Apgar < 7 at 5 minutes.
9.7
9.7. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 7 Neonatal sepsis.
9.8
9.8. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 8 Necrotizing enterocolitis.
9.9
9.9. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 9 Intraventricular haemorrhage.
9.10
9.10. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 10 Respiratory distress syndrome.
9.11
9.11. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 11 Latency (hours).
9.12
9.12. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 12 Latency (birth within 48 hours).
9.13
9.13. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 13 Latency (birth within 7 days).
9.14
9.14. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 14 Chorioamnionitis.
9.15
9.15. Analysis
Comparison 9 Less than 34 week PPROM subgroup analysis, Outcome 15 Endometritis.
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Update of

References

References to studies included in this review

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References to ongoing studies

El‐Sayed 2010 {published data only}
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References to other published versions of this review

Mackeen 2011
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