Prophylactic oral betamimetics for reducing preterm birth in women with a twin pregnancy

Waralak Yamasmit; Surasith Chaithongwongwatthana; Jorge E Tolosa; Sompop Limpongsanurak; Leonardo Pereira; Pisake Lumbiganon

doi:10.1002/14651858.CD004733.pub4

双胎妊娠女性の早産を減らすための経口β刺激薬による予防投与

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Referencias

References to studies included in this review

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estudios excluidos
otras referencias
otras versiones publicadas

Ashworth MF, Spooner SF, Verkuyl DAA, Waterman R, Ashurst HM. Failure to prevent preterm labour and delivery in twin pregnancy using prophylactic oral salbutamol. British Journal of Obstetrics and Gynaecology 1990;97:878‐82.

Cetrulo CL, Freeman RK. Ritodrine HCL for the prevention of premature labor in twin pregnancies. Acta Geneticae Medicae et Gemellologiae 1976;25:321‐4.

Marivate M, de Villiers KQ, Fairbrother P. Effect of prophylactic outpatient administration of fenoterol on the time of onset of spontaneous labor and fetal growth rate in twin pregnancy. American Journal of Obstetrics and Gynecology 1977;128(7):707‐8.

Mathews DD, Friend JB, Michael CA. A double‐blind trial of oral isoxuprine in the prevention of premature labour. Journal of Obstetrics and Gynaecology of the British Commonwealth 1967;74:68‐70.

O'Connor MC, Murphy H, Dalrymple IJ. Double blind trial of ritodrine and placebo in twin pregnancy. British Journal of Obstetrics and Gynaecology 1979;86:706‐9.

Prescott P. Sensitivity of a double‐blind trial of ritodrine and placebo in twin pregnancy. British Journal of Obstetrics and Gynaecology 1980;87(5):393‐5.

Skjaerris J, Aberg A. Prevention of prematurity in twin pregnancy by orally administered terbutaline. Acta Obstetricia et Gynecologica Scandinavica 1982;61(Suppl 108):39‐40.

References to studies excluded from this review

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estudios incluidos
otras referencias
otras versiones publicadas

Endl J, Baumgarten K. Results of prophylactic oral long term tocolysis and cerclage for the prolongation of twin pregnancies (a multi‐center study) [Uber die ergebnisse der prophylaktischen oralen langzeittokolyse und cerclage zur verlangerung der zwillingsschwangerschaften (eine multicenterstudie)]. Zeitschrift fur Geburtshilfe und Perinatologie 1982;186:319‐25.

Gummerus M, Halonen O. The merits of betamimetic treatment and bed rest in multiple pregnancies [Vuodelevon ja beetasympatomimeettihoidon vaikutus monisikioisessa raskaudessa]. Duodecim 1985;101:1966‐71.

Gummerus M, Halonen O. Prophylactic long‐term oral tocolysis of multiple pregnancies. British Journal of Obstetrics and Gynaecology 1987;94:249‐51.

Keirse MJNC. A double‐blind trial of oral ritodrine in the prevention of preterm labour. Personal Communication1990.

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Melrose E. Effect of oral ritodrine administration in twin pregnancies. Personal Communication1988.

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Additional references

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estudios incluidos
estudios excluidos
otras versiones publicadas

Conde‐Agudelo A, Romero R. Prediction of preterm birth in twin gestations using biophysical and biochemical tests. American Journal of Obstetrics and Gynecology 2014;211(6):583‐95. [DOI: 10.1016/j.ajog.2014.07.047]

Crowther CA, Han S. Hospitalisation and bed rest for multiple pregnancy. Cochrane Database of Systematic Reviews 2010, Issue 7. [DOI: 10.1002/14651858.CD000110.pub2]

Dodd JM, Jones L, Flenady V, Cincotta R, Crowther CA. Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth. Cochrane Database of Systematic Reviews 2013, Issue 7. [DOI: 10.1002/14651858.CD004947.pub3]

Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Martin JA, Hamilton BE, Osterman MJK, Curtin SC, Mathews TJ. Births: final data for 2012. National Vital Statistics Reports 2013;62(9):11‐2.

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Mathews TJ, MacDorman MF. Infant mortality statistics from the 2010 period linked birth/infant death data set. National Vital Statistics Reports 2013;62(8):1‐26.

Neilson JP, West HM, Dowswell T. Betamimetics for inhibiting preterm labour. Cochrane Database of Systematic Reviews 2014, Issue 2. [DOI: 10.1002/14651858.CD004352.pub3]

Newman R, Unal ER. Multiple gestations. In: Gabbe SG, Niebyl JR, Simpson JL, Landon MB, Galan HL, Jauniaux ERM, et al. editor(s). Obstetrics: Normal and Problem Pregnancies. 6th Edition. Philadelphia: Saunders, 2012:678.

Rafael TJ, Berghella V, Alfirevic Z. Cervical stitch (cerclage) for preventing preterm birth in multiple pregnancy. Cochrane Database of Systematic Reviews 2014, Issue 9. [DOI: 10.1002/14651858.CD009166.pub2]

Reichmann JP. Home uterine activity monitoring: an evidence review of its utility in multiple gestations. Journal of Reproductive Medicine 2009;54(9):559‐62. [PUBMED: 19947033]

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The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Roberts D, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2006, Issue 3. [DOI: 10.1002/14651858.CD004454.pub2]

Sciscione AC, Ivester T, Largoza M, Manley J, Shlossman P, Colmogen GHC. Acute pulmonary edema in pregnancy. Obstetrics & Gynecology 2003;101(3):511‐5.

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Simhan HN, Caritis SN. Prevention of preterm delivery. New England Journal of Medicine 2007;357(5):477‐87. [PUBMED: 1767125]

Thorngren‐Jerneck K, Herbst A. Perinatal factors associated with cerebral palsy in children born in Sweden. Obstetrics & Gynecology 2006;108(6):1499‐505. [PUBMED: 17138786]

Topp M, Huusom LD, Langhoff‐Roos J, Delhumeau C, Hutton JL, Dolk H, SCPE Collaborative Group. Multiple birth and cerebral palsy in Europe: a multicenter study. Acta Obstetricia et Gynecologica Scandinavica 2004;383(6):548‐53. [PUBMED: 15144336]

Whitworth M, Quenby S. Prophylactic oral betamimetics for preventing preterm labour in singleton pregnancies. Cochrane Database of Systematic Reviews 2008, Issue 1. [DOI: 10.1002/14651858.CD006395.pub2]

References to other published versions of this review

Ir a:

estudios incluidos
estudios excluidos
otras referencias

Yamasmit W, Chaithongwongwatthana S, Tolosa JE, Limpongsanurak S, Pereira L, Lumbiganon P. Prophylactic oral betamimetics for reducing preterm birth in women with a twin pregnancy. Cochrane Database of Systematic Reviews 2012, Issue 9. [DOI: 10.1002/14651858.CD004733.pub3]

Yamasmit W, Chaithongwongwatthana S, Tolosa JE, Limpongsanurak S, Pereira L, Lumbiganon P. Prophylactic oral betamimetics for reducing preterm birth in women with a twin pregnancy. Cochrane Database of Systematic Reviews 2005, Issue 3. [DOI: 10.1002/14651858.CD004733.pub2]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

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estudios excluidos

Ashworth 1990

Methods	Blinding of intervention: yes. Blinding of outcome assessment: yes. Completeness of follow‐up: no.
Participants	Country: Zimbabwe. Number: 80 women in the intervention group and 80 women in the control group. Gestational age at trial entry: 24‐32 weeks.
Interventions	Salbutamol 4 mg 4 times a day vs placebo.
Outcomes	Incidence of ‐ birth less than 37 weeks; ‐ birth less than 32 weeks; ‐ neonatal mortality; ‐ birthweight less than 2500 g; ‐ respiratory distress syndrome; ‐ maternal death. Mean birthweight.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Coding for salbutamol or placebo was computer‐randomised.
Allocation concealment (selection bias)	Low risk	The code was placed in a sealed envelope.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Neither patients nor researchers knew the code.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Neither patients nor researchers knew the code.
Incomplete outcome data (attrition bias) All outcomes	Low risk	6 from the salbutamol group and 10 from the control group were lost to follow‐up.
Selective reporting (reporting bias)	Low risk	All outcomes were predefined and reported.
Other bias	Low risk	Salbutamol was supplied by industry sponsorship, but none of the authors affiliated with the company. Negative results were reported.

Cetrulo 1976

Methods	Blinding of intervention: yes. Blinding of outcome assessment: yes. Completeness of follow‐up: no.
Participants	Country: USA. Number: 100 women in the both groups. Gestational age at trial entry: after 20 weeks.
Interventions	Ritodrine vs placebo.
Outcomes	Incidence of ‐ preterm labour; ‐ perinatal mortality; ‐ birthweight less than 10th centile.
Notes	No outcome data were shown in this preliminary report of 30 participants.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Details were not reported.
Allocation concealment (selection bias)	Unclear risk	Details were not reported.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: “double blind”.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: “double blind”.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No report on complete follow‐up.
Selective reporting (reporting bias)	Unclear risk	The preliminary results were not significant, but no report on complete follow‐up.
Other bias	Low risk	The trial appears to be free of industry sponsorship.

Marivate 1977

Methods	Blinding of intervention: yes. Blinding of outcome assessment: yes. Completeness of follow‐up: no.
Participants	Country: South Africa. Number: 23 women in the intervention group and 23 women in the control group. Gestational age at trial entry: less than 33 weeks.
Interventions	Fenoterol 5 mg once a day vs placebo.
Outcomes	Incidence of ‐ birth less than 38 weeks; ‐ birthweight less than 10th centile. Mean birthweight.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Details were not reported.
Allocation concealment (selection bias)	Unclear risk	Details were not reported.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Administration of the drug was "double blind".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: “double blind” and two independent observers assessed each infant.
Incomplete outcome data (attrition bias) All outcomes	Low risk	46 women completed the trial.
Selective reporting (reporting bias)	Low risk	All outcomes were predefined and reported.
Other bias	Low risk	The trial appears to be free of industry sponsorship.

Mathews 1967

Methods	Blinding of intervention: yes. Blinding of outcome assessment: yes. Completeness of follow‐up: yes.
Participants	Country: England. Number: 20 women in the intervention group and 19 women in the control group. Gestational age at trial entry: 28‐34 weeks.
Interventions	Isoxuprine 30 mg 4 times a day vs placebo.
Outcomes	Incidence of ‐ birth less than 36 weeks; ‐ neonatal mortality; ‐ birthweight less than 2500 g. Mean gestational age. Mean birthweight.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Details were not reported.
Allocation concealment (selection bias)	Low risk	Full treatments were made up in advance and dispensed when prescribed according to a random schedule so that neither patient nor doctor knew whether Isoxuprine or the placebo had been given.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: “double blind”.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: “double blind”.
Incomplete outcome data (attrition bias) All outcomes	Low risk	The primary outcome was reported for all participants.
Selective reporting (reporting bias)	Unclear risk	The outcome measurement was not predefined.
Other bias	Low risk	Isoxuprine was supplied by industry sponsorship, but none of the authors affiliated with the company. Negative results were reported.

O'Connor 1979

Methods	Blinding of intervention: yes. Blinding of outcome assessment: yes. Completeness of follow‐up: yes.
Participants	Country: Ireland. Number: 25 women in the intervention group and 24 women in the control group. Gestational age at trial entry: 20‐34 weeks.
Interventions	Ritodrine 10 mg every 6 hours vs placebo.
Outcomes	Incidence of ‐ birth less than 37 weeks; ‐ birth less than 32 weeks; ‐ perinatal mortality; ‐ birthweight less than 10th centile.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Details were not reported.
Allocation concealment (selection bias)	Low risk	Patients were given a coded bottle of 100 tablets. The tablets contained either 10 mg of ritodrine hydrochloride or an inert placebo of identical appearance.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: “double blind”.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: “double blind”.
Incomplete outcome data (attrition bias) All outcomes	Low risk	There were 50 children in the intervention group and 48 children in the control group.
Selective reporting (reporting bias)	Low risk	All outcomes were predefined and reported.
Other bias	Low risk	The trial appears to be free of industry sponsorship.

Skjaerris 1982

Methods	Blinding of intervention: yes. Blinding of outcome assessment: yes. Completeness of follow‐up: yes.
Participants	Country: Sweden. Number: 25 women in the intervention group and 25 women in the control group. Gestational age at trial entry: 24‐30 weeks.
Interventions	Terbutaline 5 mg 3 times a day vs placebo.
Outcomes	Incidence of ‐ preterm labour; ‐ birth less than 37 weeks; ‐ birth less than 35 weeks; ‐ respiratory distress syndrome.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Details were not reported.
Allocation concealment (selection bias)	Unclear risk	Details were not reported.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: “double blind”.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: “double blind”.
Incomplete outcome data (attrition bias) All outcomes	Low risk	The study included 50 twin pregnancies. Two interrupted the treatment, one in the terbutaline group and one in the placebo group, both of them because of tachycardia and tremor. They were delivered in the 38th and 40th week, respectively.
Selective reporting (reporting bias)	Unclear risk	The outcome measurement was not predefined.
Other bias	Unclear risk	The conflict of interest was not declared.

vs: versus

Characteristics of excluded studies [ordered by study ID]

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estudios incluidos

Study	Reason for exclusion
Endl 1982	Trial tested the addition of a betamimetic agent to cervical cerclage.
Gummerus 1985	Trial of maintenance tocolytic therapy.
Gummerus 1987	Women eligible for trial entry included triplet pregnancies.
Keirse 1990	Trial of maintenance tocolytic therapy.
Melrose 1988	Trial tested the effects of routine hospitalisation compared with selective hospitalisation in women receiving ritodrine.

Data and analyses

Open in table viewer

Comparison 1. Oral betamimetic versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Preterm labour Show forest plot	2	194	Risk Ratio (M‐H, Fixed, 95% CI)	0.37 [0.17, 0.78]
Open in figure viewer Analysis 1.1 Comparison 1 Oral betamimetic versus placebo, Outcome 1 Preterm labour.
2 Prelabour rupture of membranes Show forest plot	1	144	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [0.42, 4.82]
Open in figure viewer Analysis 1.2 Comparison 1 Oral betamimetic versus placebo, Outcome 2 Prelabour rupture of membranes.
3 Preterm birth (less than 37 weeks' gestation) Show forest plot	4	276	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.65, 1.10]
Open in figure viewer Analysis 1.3 Comparison 1 Oral betamimetic versus placebo, Outcome 3 Preterm birth (less than 37 weeks' gestation).
4 Preterm birth (less than 34 weeks' gestation) Show forest plot	1	144	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.15, 1.50]
Open in figure viewer Analysis 1.4 Comparison 1 Oral betamimetic versus placebo, Outcome 4 Preterm birth (less than 34 weeks' gestation).
5 Neonatal mortality Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.5 Comparison 1 Oral betamimetic versus placebo, Outcome 5 Neonatal mortality.
5.1 Assuming independence between twins	3	452	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.15, 5.37]
5.2 Assuming complete correlation between twins	3	226	Risk Ratio (M‐H, Random, 95% CI)	0.74 [0.23, 2.38]
6 Low birthweight (less than 2500 g) Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.6 Comparison 1 Oral betamimetic versus placebo, Outcome 6 Low birthweight (less than 2500 g).
6.1 Assuming independence between twins	2	366	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.77, 1.85]
6.2 Assuming complete correlation between twins	2	183	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.81, 1.47]
7 Small‐for‐gestational age (birthweight less than 10th centile) Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.7 Comparison 1 Oral betamimetic versus placebo, Outcome 7 Small‐for‐gestational age (birthweight less than 10th centile).
7.1 Assuming independence between twins	2	178	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.41, 1.99]
7.2 Assuming complete correlation between twins	2	89	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.42, 2.13]
8 Birthweight (not prespecified) Show forest plot	3	478	Mean Difference (IV, Fixed, 95% CI)	111.22 [22.21, 200.24]
Open in figure viewer Analysis 1.8 Comparison 1 Oral betamimetic versus placebo, Outcome 8 Birthweight (not prespecified).
9 Respiratory distress syndrome Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.9 Comparison 1 Oral betamimetic versus placebo, Outcome 9 Respiratory distress syndrome.
9.1 Assuming independence between twins	2	388	Risk Ratio (M‐H, Fixed, 95% CI)	0.30 [0.12, 0.77]
9.2 Assuming complete correlation between twins	2	194	Risk Ratio (M‐H, Fixed, 95% CI)	0.35 [0.11, 1.16]
10 Maternal death Show forest plot	1	144	Risk Ratio (M‐H, Fixed, 95% CI)	2.84 [0.12, 68.57]
Open in figure viewer Analysis 1.10 Comparison 1 Oral betamimetic versus placebo, Outcome 10 Maternal death.

Figure 1

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

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Figure 2

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Analysis 1.1

Comparison 1 Oral betamimetic versus placebo, Outcome 1 Preterm labour.

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Analysis 1.2

Comparison 1 Oral betamimetic versus placebo, Outcome 2 Prelabour rupture of membranes.

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Analysis 1.3

Comparison 1 Oral betamimetic versus placebo, Outcome 3 Preterm birth (less than 37 weeks' gestation).

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Analysis 1.4

Comparison 1 Oral betamimetic versus placebo, Outcome 4 Preterm birth (less than 34 weeks' gestation).

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Analysis 1.5

Comparison 1 Oral betamimetic versus placebo, Outcome 5 Neonatal mortality.

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Analysis 1.6

Comparison 1 Oral betamimetic versus placebo, Outcome 6 Low birthweight (less than 2500 g).

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Analysis 1.7

Comparison 1 Oral betamimetic versus placebo, Outcome 7 Small‐for‐gestational age (birthweight less than 10th centile).

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Analysis 1.8

Comparison 1 Oral betamimetic versus placebo, Outcome 8 Birthweight (not prespecified).

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Analysis 1.9

Comparison 1 Oral betamimetic versus placebo, Outcome 9 Respiratory distress syndrome.

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Analysis 1.10

Comparison 1 Oral betamimetic versus placebo, Outcome 10 Maternal death.

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Summary of findings for the main comparison. Oral betamimetic versus placebo for pregnant women with a twin pregnancy to prevent preterm birth

Oral betamimetic versus placebo for pregnant women with a twin pregnancy to prevent preterm birth
Patient or population: pregnant women with a twin pregnancy Settings: studies were located in England, Ireland, Sount Africa, Sweden and Zimbabwe Intervention: oral betamimetic Comparison: placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Oral betamimetic versus placebo
Preterm labour Follow‐up: 10‐16 weeks	Study population		RR 0.37 (0.17 to 0.78)	194 (2 studies)	⊕⊕⊝⊝ low^1,2
	179 per 1000	66 per 1000 (30 to 140)
	Moderate
	314 per 1000	116 per 1000 (53 to 245)
Prelabour rupture of membranes Follow‐up: 8‐16 months	Study population		RR 1.42 (0.42 to 4.82)	144 (1 study)	⊕⊕⊝⊝ low³
	57 per 1000	81 per 1000 (24 to 275)
Preterm birth (less than 37 weeks' gestation) Follow‐up: 6‐20 weeks	Study population		RR 0.85 (0.65 to 1.10)	276 (4 studies)	⊕⊕⊝⊝ low³
	478 per 1000	406 per 1000 (311 to 526)
	Moderate
	427 per 1000	363 per 1000 (278 to 470)
Very preterm birth (less than 34 weeks' gestation) Follow‐up: 8‐16 months	Study population		RR 0.47 (0.15 to 1.50)	144 (1 study)	⊕⊕⊝⊝ low³
	114 per 1000	54 per 1000 (17 to 171)
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Unclear risk of selection bias (‐1). ² Few events and small sample size (‐1). ³ Wide confidence interval crossing the line of no effect, few events and small sample size (‐2).

Summary of findings for the main comparison. Oral betamimetic versus placebo for pregnant women with a twin pregnancy to prevent preterm birth

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Comparison 1. Oral betamimetic versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Preterm labour Show forest plot	2	194	Risk Ratio (M‐H, Fixed, 95% CI)	0.37 [0.17, 0.78]

2 Prelabour rupture of membranes Show forest plot	1	144	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [0.42, 4.82]

3 Preterm birth (less than 37 weeks' gestation) Show forest plot	4	276	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.65, 1.10]

4 Preterm birth (less than 34 weeks' gestation) Show forest plot	1	144	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.15, 1.50]

5 Neonatal mortality Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

5.1 Assuming independence between twins	3	452	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.15, 5.37]
5.2 Assuming complete correlation between twins	3	226	Risk Ratio (M‐H, Random, 95% CI)	0.74 [0.23, 2.38]
6 Low birthweight (less than 2500 g) Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

6.1 Assuming independence between twins	2	366	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.77, 1.85]
6.2 Assuming complete correlation between twins	2	183	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.81, 1.47]
7 Small‐for‐gestational age (birthweight less than 10th centile) Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

7.1 Assuming independence between twins	2	178	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.41, 1.99]
7.2 Assuming complete correlation between twins	2	89	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.42, 2.13]
8 Birthweight (not prespecified) Show forest plot	3	478	Mean Difference (IV, Fixed, 95% CI)	111.22 [22.21, 200.24]

9 Respiratory distress syndrome Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

9.1 Assuming independence between twins	2	388	Risk Ratio (M‐H, Fixed, 95% CI)	0.30 [0.12, 0.77]
9.2 Assuming complete correlation between twins	2	194	Risk Ratio (M‐H, Fixed, 95% CI)	0.35 [0.11, 1.16]
10 Maternal death Show forest plot	1	144	Risk Ratio (M‐H, Fixed, 95% CI)	2.84 [0.12, 68.57]

Comparison 1. Oral betamimetic versus placebo

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Referencias

References to studies included in this review

Ashworth 1990 {published data only}

Cetrulo 1976 {published data only}

Marivate 1977 {published data only}

Mathews 1967 {published data only}

O'Connor 1979 {published data only}

Skjaerris 1982 {published data only}

References to studies excluded from this review

Endl 1982 {published data only}

Gummerus 1985 {published data only}

Gummerus 1987 {published data only}

Keirse 1990 {unpublished data only}

Melrose 1988 {unpublished data only}

Additional references

Conde‐Agudelo 2014

Crowther 2010

Dodd 2013

Higgins 2011

Martin 2013

Mathews 2013

Neilson 2014

Newman 2012

Rafael 2014

Reichmann 2009

RevMan 2014 [Computer program]

Roberts 2006

Sciscione 2003

Simhan 2007

Thorngren‐Jerneck 2006

Topp 2004

Whitworth 2008

References to other published versions of this review

Yamasmit 2012

Yamasmit 2005

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Data and analyses

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