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Profilaxis con betamiméticos orales para la prevención del parto prematuro en mujeres con embarazo gemelar

Appendices

Appendix 1. Search strategy

Authors wrote and ran:

MEDLINE (OvidSP) (January 1966 to 31 July 2015)

1. randomized controlled trial.pt.

2. controlled clinical trial.pt.

3. randomized.ab.

4. placebo.ab.

5. drug therapy.fs.

6. randomly.ab.

7. trial.ab.

8. groups.ab.

9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8

10. exp Pregnancy, Twin/

11. (twin adj6 pregnanc$).mp.

12. (twin$).mp.

13. 10 or 11 or 12

14. exp Adrenergic beta‐Agonists/

15. (adrenergic adj6 beta$).mp.

16. betamimetics.mp.

17. 14 or 15 or 16

18. 9 and 13 and 17

EMBASE (OvidSP) (EMBASE (January 1985 to 31 July 2015)

1. randomized controlled trial/

2. controlled clinical trial/

3. random*.tw.

4. placebo*.tw.

5. assign*.tw.

6. allocat*.tw.

7. (doubl* near/6 blind*).tw.

8. (singl* near/6 blind*).tw.

9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8

10. exp Pregnancy, Twin/

11. (twin near/6 pregnanc*).tw.

12. (twin*).tw.

13. 10 or 11 or 12

14. exp Adrenergic beta‐Agonists/

15. (adrenergic near/6 beta*).tw.

16. betamimetics.tw.

17. 14 or 15 or 16

18. 9 and 13 and 17

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 1

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

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

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

Comparison 1 Oral betamimetic versus placebo, Outcome 1 Preterm labour.
Figuras y tablas -
Analysis 1.1

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

Comparison 1 Oral betamimetic versus placebo, Outcome 2 Prelabour rupture of membranes.
Figuras y tablas -
Analysis 1.2

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

Comparison 1 Oral betamimetic versus placebo, Outcome 3 Preterm birth (less than 37 weeks' gestation).
Figuras y tablas -
Analysis 1.3

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

Comparison 1 Oral betamimetic versus placebo, Outcome 4 Preterm birth (less than 34 weeks' gestation).
Figuras y tablas -
Analysis 1.4

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

Comparison 1 Oral betamimetic versus placebo, Outcome 5 Neonatal mortality.
Figuras y tablas -
Analysis 1.5

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

Comparison 1 Oral betamimetic versus placebo, Outcome 6 Low birthweight (less than 2500 g).
Figuras y tablas -
Analysis 1.6

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

Comparison 1 Oral betamimetic versus placebo, Outcome 7 Small‐for‐gestational age (birthweight less than 10th centile).
Figuras y tablas -
Analysis 1.7

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

Comparison 1 Oral betamimetic versus placebo, Outcome 8 Birthweight (not prespecified).
Figuras y tablas -
Analysis 1.8

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

Comparison 1 Oral betamimetic versus placebo, Outcome 9 Respiratory distress syndrome.
Figuras y tablas -
Analysis 1.9

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

Comparison 1 Oral betamimetic versus placebo, Outcome 10 Maternal death.
Figuras y tablas -
Analysis 1.10

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

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)

⊕⊕⊝⊝
low1,2

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).

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

Figuras y tablas -
Comparison 1. Oral betamimetic versus placebo