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Review
. 2014 Feb 5;2014(2):CD004352.
doi: 10.1002/14651858.CD004352.pub3.

Betamimetics for inhibiting preterm labour

James P Neilson  1 , Helen M West, Therese Dowswell
Affiliations
Review

Betamimetics for inhibiting preterm labour

James P Neilson et al. Cochrane Database Syst Rev. .

Abstract

Background: Preterm birth is a major contributor to perinatal mortality and morbidity worldwide. Tocolytic agents are drugs used to inhibit uterine contractions. Betamimetics are tocolytic agents that have been widely used, especially in resource-poor countries.

Objectives: To assess the effects of betamimetics given to women with preterm labour.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2013) and reference lists of retrieved studies.

Selection criteria: Randomised controlled trials of betamimetics, administered by any route or any dose, in the treatment of women in preterm labour where betamimetics were compared with other betamimetics, placebo or no treatment.

Data collection and analysis: Two review authors assessed risk of bias and extracted the data independently.

Main results: Twenty-eight trials were assessed as eligible for inclusion in the review, but eight did not report any outcome data relevant to the review. Results are based on the 20 trials that contributed data.Twelve trials, involving 1367 women, compared betamimetics with placebo. Betamimetics decreased the number of women in preterm labour giving birth within 48 hours (average risk ratio (RR) 0.68, 95% confidence interval (CI) 0.53 to 0.88, 10 trials, 1209 women). There was a decrease in the number of births within seven days (average RR 0.80; 95% CI 0.65 to 0.98, five trials, 911 women) but there was no evidence of a reduction in preterm birth (before 37 weeks' gestation) (RR 0.95; 95% CI 0.88 to 1.03, 10 trials, 1212 women). No benefit was demonstrated for betamimetics for perinatal death (RR 0.84; 95% CI 0.46 to 1.55, 11 trials, 1332 infants), or neonatal death (RR 0.90; 95% CI 0.27 to 3.00, six trials, 1174 infants). No significant effect was demonstrated for respiratory distress syndrome (RR 0.87; 95% CI 0.71 to 1.08, eight trials, 1239 infants). A few trials reported on cerebral palsy, infant death and necrotising enterocolitis; no significant differences between groups were identified for any of these outcomes. Betamimetics were significantly associated with the following outcomes: withdrawal from treatment due to adverse effects; maternal chest pain; dyspnoea; palpitation; tremor; headaches; hypokalaemia; hyperglycaemia; nausea or vomiting; nasal stuffiness; and fetal tachycardia.Nine trials compared different types of betamimetics. Other betamimetics were compared with ritodrine in five trials (n = 948). Other comparisons were examined in single trials: hexoprenaline compared with salbutamol (n = 140), slow versus moderate release salbutamol (n = 52) and salbutamol compared with terbutaline (n = 200). Trials were small, varied, and of insufficient quality to delineate any consistent patterns of effect.

Authors' conclusions: Betamimetics help to delay birth, which may give time to allow women to be transferred to tertiary care or to complete a course of antenatal corticosteroids. However, multiple adverse effects must be considered. The data are too few to support the use of any particular betamimetic.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1
1
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Funnel plot of comparison: 1 All betamimetics versus placebo, outcome: 1.1 Birth within 48 hours of treatment.
4
4
Funnel plot of comparison: 1 All betamimetics versus placebo, outcome: 1.2 Perinatal death (7 days).
1.1
1.1. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 1 Birth within 48 hours of treatment.
1.2
1.2. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 2 Perinatal death (7 days).
1.3
1.3. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 3 Respiratory distress syndrome.
1.4
1.4. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 4 Cerebral palsy.
1.5
1.5. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 5 Birth within 7 days.
1.6
1.6. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 6 Birth less than 37 weeks' gestation.
1.7
1.7. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 7 Maternal death.
1.8
1.8. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 8 Pulmonary oedema.
1.9
1.9. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 9 Cardiac arrhythmias.
1.10
1.10. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 10 Myocardial ischemia.
1.11
1.11. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 11 Hypotension.
1.12
1.12. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 12 Cessation of treatment due to adverse drug reaction.
1.13
1.13. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 13 Palpitation.
1.14
1.14. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 14 Tachycardia.
1.15
1.15. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 15 Chest pain.
1.16
1.16. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 16 Dyspnoea.
1.17
1.17. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 17 Tremor.
1.18
1.18. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 18 Hyperglycaemia.
1.19
1.19. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 19 Hypokalaemia.
1.20
1.20. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 20 Nausea or vomiting.
1.21
1.21. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 21 Nasal stuffiness.
1.22
1.22. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 22 Headaches.
1.23
1.23. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 23 Neonatal death.
1.24
1.24. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 24 Infant death.
1.25
1.25. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 25 Necrotising enterocolitis.
1.26
1.26. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 26 Sepsis or infection.
1.27
1.27. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 27 Fetal hypoglycaemia.
1.28
1.28. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 28 Fetal tachycardia.
1.29
1.29. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 29 Infant long‐term neurological development (Bayley score: Psychomotor development).
1.30
1.30. Analysis
Comparison 1 All betamimetics versus placebo, Outcome 30 Infant long‐term neurological development (Bayley score: Mental development).
2.1
2.1. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 1 Birth within 48 hours.
2.2
2.2. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 2 Perinatal death.
2.3
2.3. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 3 Respiratory distress syndrome.
2.4
2.4. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 4 Birth within 7 days.
2.5
2.5. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 5 Birth less than 28 weeks' gestation.
2.6
2.6. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 6 Cessation of treatment due to adverse drug reactions.
2.7
2.7. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 7 Any maternal adverse effects.
2.8
2.8. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 8 Chest pain.
2.9
2.9. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 9 Shortness of breath or dyspnea.
2.10
2.10. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 10 Hyperglycaemia or abnormal glucose tolerance test.
2.11
2.11. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 11 Palpitations.
2.12
2.12. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 12 Tachycardia.
2.13
2.13. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 13 Arrhythmia.
2.14
2.14. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 14 Hypotension.
2.15
2.15. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 15 Nausea or vomiting.
2.16
2.16. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 16 Headache.
2.17
2.17. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 17 Anxiety.
2.18
2.18. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 18 Necrotising enterocolitis.
2.19
2.19. Analysis
Comparison 2 Terbutaline versus ritodrine, Outcome 19 Neonatal death.
3.1
3.1. Analysis
Comparison 3 Fenoterol versus ritodrine, Outcome 1 Perinatal death.
3.2
3.2. Analysis
Comparison 3 Fenoterol versus ritodrine, Outcome 2 Respiratory distress syndrome.
3.3
3.3. Analysis
Comparison 3 Fenoterol versus ritodrine, Outcome 3 Tachycardia.
3.4
3.4. Analysis
Comparison 3 Fenoterol versus ritodrine, Outcome 4 Hypoglycaemia.
3.5
3.5. Analysis
Comparison 3 Fenoterol versus ritodrine, Outcome 5 Fetal bradycardia.
3.6
3.6. Analysis
Comparison 3 Fenoterol versus ritodrine, Outcome 6 Neonatal death.
4.1
4.1. Analysis
Comparison 4 Ritodrine loading dose versus incremental dose, Outcome 1 Birth within 48 hours.
4.2
4.2. Analysis
Comparison 4 Ritodrine loading dose versus incremental dose, Outcome 2 Respiratory distress syndrome.
4.3
4.3. Analysis
Comparison 4 Ritodrine loading dose versus incremental dose, Outcome 3 Periventricular haemorrhage grade 3‐4.
4.4
4.4. Analysis
Comparison 4 Ritodrine loading dose versus incremental dose, Outcome 4 Birth less than 34 weeks.
4.5
4.5. Analysis
Comparison 4 Ritodrine loading dose versus incremental dose, Outcome 5 Birth less than 37 weeks.
4.6
4.6. Analysis
Comparison 4 Ritodrine loading dose versus incremental dose, Outcome 6 Any maternal adverse effects.
4.7
4.7. Analysis
Comparison 4 Ritodrine loading dose versus incremental dose, Outcome 7 Palpitations.
4.8
4.8. Analysis
Comparison 4 Ritodrine loading dose versus incremental dose, Outcome 8 Tachycardia.
4.9
4.9. Analysis
Comparison 4 Ritodrine loading dose versus incremental dose, Outcome 9 Nausea or vomiting.
4.10
4.10. Analysis
Comparison 4 Ritodrine loading dose versus incremental dose, Outcome 10 Headache.
4.11
4.11. Analysis
Comparison 4 Ritodrine loading dose versus incremental dose, Outcome 11 Sepsis.
4.12
4.12. Analysis
Comparison 4 Ritodrine loading dose versus incremental dose, Outcome 12 Neonatal death.
5.1
5.1. Analysis
Comparison 5 Hexoprenaline versus ritodrine, Outcome 1 Cessation of treatment due to adverse drug reactions.
5.2
5.2. Analysis
Comparison 5 Hexoprenaline versus ritodrine, Outcome 2 Any maternal adverse effects.
5.3
5.3. Analysis
Comparison 5 Hexoprenaline versus ritodrine, Outcome 3 Palpitations.
5.4
5.4. Analysis
Comparison 5 Hexoprenaline versus ritodrine, Outcome 4 Hypotension.
5.5
5.5. Analysis
Comparison 5 Hexoprenaline versus ritodrine, Outcome 5 Nausea or vomiting.
5.6
5.6. Analysis
Comparison 5 Hexoprenaline versus ritodrine, Outcome 6 Increase in fetal heart rate.
6.1
6.1. Analysis
Comparison 6 Hexoprenaline versus salbutamol, Outcome 1 Respiratory distress syndrome.
6.2
6.2. Analysis
Comparison 6 Hexoprenaline versus salbutamol, Outcome 2 Cessation of treatment due to adverse drug reactions.
6.3
6.3. Analysis
Comparison 6 Hexoprenaline versus salbutamol, Outcome 3 Any maternal adverse effects.
6.4
6.4. Analysis
Comparison 6 Hexoprenaline versus salbutamol, Outcome 4 Tachycardia.
6.5
6.5. Analysis
Comparison 6 Hexoprenaline versus salbutamol, Outcome 5 Nausea or vomiting.
6.6
6.6. Analysis
Comparison 6 Hexoprenaline versus salbutamol, Outcome 6 Headache.
6.7
6.7. Analysis
Comparison 6 Hexoprenaline versus salbutamol, Outcome 7 Tremor.
7.1
7.1. Analysis
Comparison 7 Terbutaline versus salbutamol, Outcome 1 BIrth within 48 hours.
7.2
7.2. Analysis
Comparison 7 Terbutaline versus salbutamol, Outcome 2 Side effects (overall).
7.3
7.3. Analysis
Comparison 7 Terbutaline versus salbutamol, Outcome 3 Tachycardia.
7.4
7.4. Analysis
Comparison 7 Terbutaline versus salbutamol, Outcome 4 Dyspnea.
7.5
7.5. Analysis
Comparison 7 Terbutaline versus salbutamol, Outcome 5 Nausea.
7.6
7.6. Analysis
Comparison 7 Terbutaline versus salbutamol, Outcome 6 Anxiety.
7.7
7.7. Analysis
Comparison 7 Terbutaline versus salbutamol, Outcome 7 Chills.
7.8
7.8. Analysis
Comparison 7 Terbutaline versus salbutamol, Outcome 8 Oedema.
7.9
7.9. Analysis
Comparison 7 Terbutaline versus salbutamol, Outcome 9 Duration of hospital admission (days).
8.1
8.1. Analysis
Comparison 8 Slow release versus normal release salbutamol, Outcome 1 Preterm birth (before 37 weeks).
8.2
8.2. Analysis
Comparison 8 Slow release versus normal release salbutamol, Outcome 2 Caesarean section.
8.3
8.3. Analysis
Comparison 8 Slow release versus normal release salbutamol, Outcome 3 Side effects leading to discontinuation of treatment.
8.4
8.4. Analysis
Comparison 8 Slow release versus normal release salbutamol, Outcome 4 Nausea.
8.5
8.5. Analysis
Comparison 8 Slow release versus normal release salbutamol, Outcome 5 Apgar score less than 7 at 5 minutes.
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References

References to studies included in this review

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Gamissans 1978 {published data only}
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Gamissans 1982 {published data only}
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Garite 1987 {published data only}
    1. Garite TJ, Keegan KA, Freeman RK, Nageotte MP. A randomized trial of ritodrine tocolysis vs expectant management in patients with premature rupture of membranes at 25 to 30 weeks of gestation. American Journal of Obstetrics and Gynecology 1987;157:388‐93. - PubMed
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Gonik 1988 {published data only}
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Guinn 1997 {published data only}
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Gummerus 1981 {published data only}
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Hallak 1992 {published data only}
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Hallak 1993 {published data only}
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Hatjis 1987 {published data only}
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Herzog 1995 {published data only}
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Howard 1982 {published data only}
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Ieda 1991 {published data only}
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Kanayama 1996 {published data only}
    1. Kanayama N, Maradny E, Yamamoto N, Tokunaga N, Maehara K, Terao T. Urinary trypsin inhibitor: a new drug to treat preterm labor: a comparative study with ritodrine. European Journal of Obstetrics & Gynecology and Reproductive Biology 1996;67(2):133‐8. - PubMed
Karlsson 1980 {published data only}
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Katz 1983 {published data only}
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Kim 1983 {published data only}
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Kosasa 1985 {published data only}
    1. Kosasa TS, Nakayama RT, Hale RW, Rinzler GS, Freitas CA. Ritodrine and terbutaline compared for the treatment of preterm labor. Acta Obstetricia et Gynecologica Scandinavica 1985;64:421‐6. - PubMed
Larsen 1986 {published data only}
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Lenz 1985 {published data only}
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Levy 1985 {published data only}
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Neri 2009 {published data only}
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Ritcher 1975 {published data only}
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Sciscione 1993 {published data only}
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Sirohiwal 2001 {published data only}
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Sivasamboo 1972 {published data only}
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Spatling 1989 {published data only}
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References to studies awaiting assessment

Roy 2006 {published data only}
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References to other published versions of this review

Anotayanonth 2004
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MeSH terms