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

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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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