Antibiotics for preterm rupture of membranes

Sara Kenyon; Michel Boulvain; James P Neilson

doi:10.1002/14651858.CD001058.pub3

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Figure 1

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Figure 2

Funnel plot of comparison: 1 Any antibiotic versus placebo, outcome: 1.3 Perinatal death/death before discharge.

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Figure 3

Funnel plot of comparison: 1 Any antibiotic versus placebo, outcome: 1.4 Neonatal infection including pneumonia.

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Figure 4

Funnel plot of comparison: 1 Any antibiotic versus placebo, outcome: 1.5 Neonatal necrotising enterocolitis.

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Figure 5

Funnel plot of comparison: 1 Any antibiotic versus placebo, outcome: 1.7 Major cerebral abnormality on ultrasound before discharge.

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Analysis 1.1

Comparison 1 Any antibiotic versus placebo, Outcome 1 Maternal death.

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Analysis 1.3

Comparison 1 Any antibiotic versus placebo, Outcome 3 Perinatal death/death before discharge.

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Analysis 1.4

Comparison 1 Any antibiotic versus placebo, Outcome 4 Neonatal infection including pneumonia.

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Analysis 1.5

Comparison 1 Any antibiotic versus placebo, Outcome 5 Neonatal necrotising enterocolitis.

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Analysis 1.6

Comparison 1 Any antibiotic versus placebo, Outcome 6 Oxygen treatment > 36 weeks' postconceptual age.

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Analysis 1.7

Comparison 1 Any antibiotic versus placebo, Outcome 7 Major cerebral abnormality on ultrasound before discharge.

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Analysis 1.8

Comparison 1 Any antibiotic versus placebo, Outcome 8 Birth before 37 weeks' gestation.

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Analysis 1.9

Comparison 1 Any antibiotic versus placebo, Outcome 9 Major adverse drug reaction.

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Analysis 1.10

Comparison 1 Any antibiotic versus placebo, Outcome 10 Maternal infection after delivery prior to discharge.

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Analysis 1.11

Comparison 1 Any antibiotic versus placebo, Outcome 11 Chorioamnionitis.

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Analysis 1.12

Comparison 1 Any antibiotic versus placebo, Outcome 12 Caesarean section.

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Analysis 1.15

Comparison 1 Any antibiotic versus placebo, Outcome 15 Birth within 48 hours of randomisation.

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Analysis 1.16

Comparison 1 Any antibiotic versus placebo, Outcome 16 Birth within 7 days of randomisation.

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Analysis 1.17

Comparison 1 Any antibiotic versus placebo, Outcome 17 Birthweight.

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Analysis 1.18

Comparison 1 Any antibiotic versus placebo, Outcome 18 Birthweight < 2500 g.

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Analysis 1.19

Comparison 1 Any antibiotic versus placebo, Outcome 19 Neonatal intensive care.

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Analysis 1.20

Comparison 1 Any antibiotic versus placebo, Outcome 20 Days in neonatal intensive care unit.

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Analysis 1.21

Comparison 1 Any antibiotic versus placebo, Outcome 21 Positive neonatal blood culture.

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Analysis 1.22

Comparison 1 Any antibiotic versus placebo, Outcome 22 Neonatal respiratory distress syndrome.

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Analysis 1.23

Comparison 1 Any antibiotic versus placebo, Outcome 23 Treatment with surfactant.

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Analysis 1.24

Comparison 1 Any antibiotic versus placebo, Outcome 24 Number of babies requiring ventilation.

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Analysis 1.25

Comparison 1 Any antibiotic versus placebo, Outcome 25 Number of babies requiring oxygen therapy.

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Analysis 1.26

Comparison 1 Any antibiotic versus placebo, Outcome 26 Neonatal oxygenation > 28 days.

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Analysis 1.27

Comparison 1 Any antibiotic versus placebo, Outcome 27 Neonatal encephalopathy.

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Analysis 1.28

Comparison 1 Any antibiotic versus placebo, Outcome 28 Serious childhood disability at 7 years.

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Analysis 2.3

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 3 Major adverse drug reaction.

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Analysis 2.4

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 4 Maternal infection after delivery prior to discharge.

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Analysis 2.6

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 6 Caesarean section.

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Analysis 2.9

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 9 Birth within 48 hours of randomisation.

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Analysis 2.10

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 10 Birth within 7 days of randomisation.

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Analysis 2.11

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 11 Birth before 37 weeks' gestation.

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Analysis 2.12

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 12 Birthweight.

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Analysis 2.13

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 13 Birthweight < 2500 g.

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Analysis 2.14

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 14 Neonatal intensive care.

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Analysis 2.17

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 17 Positive neonatal blood culture.

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Analysis 2.18

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 18 Neonatal necrotising enterocolitis.

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Analysis 2.19

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 19 Neonatal respiratory distress syndrome.

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Analysis 2.20

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 20 Treatment with surfactant.

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Analysis 2.21

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 21 Number of babies requiring ventilation.

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Analysis 2.22

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 22 Number of babies requiring oxygen therapy.

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Analysis 2.23

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 23 Neonatal oxygenation > 28 days.

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Analysis 2.24

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 24 Oxygen treatment > 36 weeks' postconceptual age.

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Analysis 2.26

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 26 Major cerebral abnormality on ultrasound before discharge.

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Analysis 2.27

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 27 Perinatal death/death before discharge.

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Analysis 2.28

Comparison 2 Erythromycin versus co‐amoxiclav, Outcome 28 Serious childhood disability at 7 years.

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Analysis 4.1

Comparison 4 Antibiotics versus no antibiotic, Outcome 1 Perinatal death/death before discharge.

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Analysis 5.4

Comparison 5 3 versus 7 day ampicillin regimens, Outcome 4 Maternal infection after delivery prior to discharge.

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Analysis 5.5

Comparison 5 3 versus 7 day ampicillin regimens, Outcome 5 Chorioamnionitis.

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Analysis 5.6

Comparison 5 3 versus 7 day ampicillin regimens, Outcome 6 Caesarean section.

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Analysis 5.9

Comparison 5 3 versus 7 day ampicillin regimens, Outcome 9 Birth within 48 hours of randomisation.

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Analysis 5.10

Comparison 5 3 versus 7 day ampicillin regimens, Outcome 10 Birth within 7 days of randomisation.

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Analysis 5.14

Comparison 5 3 versus 7 day ampicillin regimens, Outcome 14 Neonatal intensive care.

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Analysis 5.18

Comparison 5 3 versus 7 day ampicillin regimens, Outcome 18 Neonatal necrotising enterocolitis.

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Analysis 5.19

Comparison 5 3 versus 7 day ampicillin regimens, Outcome 19 Neonatal respiratory distress syndrome.

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Analysis 5.26

Comparison 5 3 versus 7 day ampicillin regimens, Outcome 26 Neonatal intraventricular haemorrhage.

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Analysis 5.27

Comparison 5 3 versus 7 day ampicillin regimens, Outcome 27 Perinatal death/death before discharge.

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Comparison 1. Any antibiotic versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Maternal death Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Any antibiotic versus placebo	3	763	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.2 All penicillin (excluding co‐amoxiclav) versus placebo	1	85	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.3 Beta lactum (including co‐amoxiclav) versus placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.4 Macrolide (including erythromycin) versus placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.5 Other antibiotic versus placebo	2	678	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 Serious maternal morbidity	0		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
2.1 Any antibiotic versus placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.2 All penicillin (excluding co‐amoxiclav) versus placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.3 Beta lactum (including co‐amoxiclav) versus placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.4 Macrolide (including erythromycin) versus placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.5 Other antibiotic versus placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3 Perinatal death/death before discharge Show forest plot	12		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 Any antibiotic versus placebo	12	6301	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.76, 1.14]
3.2 All penicillin (excluding co‐amoxiclav) versus placebo	4	332	Risk Ratio (M‐H, Random, 95% CI)	0.78 [0.31, 1.97]
3.3 Beta lactum (including co‐amoxiclav) versus placebo	2	1880	Risk Ratio (M‐H, Random, 95% CI)	0.62 [0.15, 2.56]
3.4 Macrolide (including erythromycin) versus placebo	4	2138	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.43, 1.60]
3.5 Other antibiotic versus placebo	3	762	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.68, 1.88]
4 Neonatal infection including pneumonia Show forest plot	12		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

4.1 Any antibiotic versus placebo	12	1680	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.52, 0.85]
4.2 All penicillin (excluding co‐amoxiclav) versus placebo	5	521	Risk Ratio (M‐H, Random, 95% CI)	0.30 [0.13, 0.68]
4.3 Beta lactum (including co‐amoxiclav) versus placebo	1	62	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.01, 7.88]
4.4 Macrolide (including erythromycin) versus placebo	3	334	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.45, 1.37]
4.5 Other antibiotic versus placebo	3	763	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.53, 0.95]
5 Neonatal necrotising enterocolitis Show forest plot	11		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

5.1 Any antibiotic versus placebo	11	6229	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.65, 1.83]
5.2 All penicillin (excluding co‐amoxiclav) versus placebo	3	262	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.25, 2.97]
5.3 Beta lactum (including co‐amoxiclav) versus placebo	2	1880	Risk Ratio (M‐H, Random, 95% CI)	4.72 [1.57, 14.23]
5.4 Macrolide (including erythromycin) versus placebo	3	2076	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.45, 1.69]
5.5 Other antibiotic versus placebo	4	823	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.54, 1.47]
6 Oxygen treatment > 36 weeks' postconceptual age Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

6.1 Any antibiotic versus placebo	1	4809	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.70, 1.17]
6.2 All penicillin (excluding co‐amoxiclav) versus placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6.3 Beta lactum (including co‐amoxiclav) versus placebo	1	1818	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.63, 1.36]
6.4 Macrolide (including erythromycin) versus placebo	1	1803	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.61, 1.32]
6.5 Other antibiotic versus placebo	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7 Major cerebral abnormality on ultrasound before discharge Show forest plot	12		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

7.1 Any antibiotic versus placebo	12	6289	Risk Ratio (M‐H, Random, 95% CI)	0.81 [0.68, 0.98]
7.2 All penicillin (excluding co‐amoxiclav) versus placebo	3	262	Risk Ratio (M‐H, Random, 95% CI)	0.49 [0.25, 0.96]
7.3 Beta lactum (including co‐amoxiclav) versus placebo	2	1880	Risk Ratio (M‐H, Random, 95% CI)	0.78 [0.52, 1.16]
7.4 Macrolide (including erythromycin) versus placebo	4	2136	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.60, 1.44]
7.5 Other antibiotic versus placebo	4	823	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.45, 1.64]
8 Birth before 37 weeks' gestation Show forest plot	3	4931	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.98, 1.03]

9 Major adverse drug reaction Show forest plot	3	5487	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

10 Maternal infection after delivery prior to discharge Show forest plot	4	5547	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.80, 1.02]

11 Chorioamnionitis Show forest plot	11	1559	Risk Ratio (M‐H, Random, 95% CI)	0.66 [0.46, 0.96]

12 Caesarean section Show forest plot	11	6317	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.88, 1.05]

13 Days from birth till discharge of mother	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
14 Days from randomisation to birth	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
15 Birth within 48 hours of randomisation Show forest plot	7	5927	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.58, 0.87]

16 Birth within 7 days of randomisation Show forest plot	7	5965	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.71, 0.89]

17 Birthweight Show forest plot	12	6374	Mean Difference (IV, Random, 95% CI)	53.83 [7.06, 100.60]

18 Birthweight < 2500 g Show forest plot	2	4876	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.96, 1.04]

19 Neonatal intensive care Show forest plot	4	5023	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.84, 1.13]

20 Days in neonatal intensive care unit Show forest plot	3	225	Mean Difference (IV, Random, 95% CI)	‐5.05 [‐9.77, ‐0.33]

21 Positive neonatal blood culture Show forest plot	3	4961	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.63, 0.99]

22 Neonatal respiratory distress syndrome Show forest plot	12	6287	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.83, 1.09]

23 Treatment with surfactant Show forest plot	1	4809	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.72, 0.96]

24 Number of babies requiring ventilation Show forest plot	2	4924	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.80, 1.02]

25 Number of babies requiring oxygen therapy Show forest plot	1	4809	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.81, 0.96]

26 Neonatal oxygenation > 28 days Show forest plot	3	5487	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.61, 1.03]

27 Neonatal encephalopathy Show forest plot	1	60	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

28 Serious childhood disability at 7 years Show forest plot	1	3171	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.91, 1.12]

Comparison 1. Any antibiotic versus placebo

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Comparison 2. Erythromycin versus co‐amoxiclav

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Maternal death	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 Serious maternal morbidity	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3 Major adverse drug reaction Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

4 Maternal infection after delivery prior to discharge Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.87, 1.20]

5 Chorioamnionitis	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
6 Caesarean section Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.90, 1.16]

7 Days from randomisation to birth	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8 Days from birth till discharge of mother	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Birth within 48 hours of randomisation Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	1.14 [1.02, 1.28]

10 Birth within 7 days of randomisation Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.99, 1.13]

11 Birth before 37 weeks' gestation Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.96, 1.03]

12 Birthweight Show forest plot	1	2395	Mean Difference (IV, Random, 95% CI)	19.0 [‐41.92, 79.92]

13 Birthweight < 2500 g Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.95, 1.05]

14 Neonatal intensive care Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.95, 1.05]

15 Days in neonatal intensive care unit	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
16 Neonatal infection including pneumonia	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
17 Positive neonatal blood culture Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	0.84 [0.62, 1.15]

18 Neonatal necrotising enterocolitis Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	0.46 [0.23, 0.94]

19 Neonatal respiratory distress syndrome Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.84, 1.16]

20 Treatment with surfactant Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.81, 1.19]

21 Number of babies requiring ventilation Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.86, 1.17]

22 Number of babies requiring oxygen therapy Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.87, 1.10]

23 Neonatal oxygenation > 28 days Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	0.86 [0.66, 1.12]

24 Oxygen treatment > 36 weeks' postconceptual age Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.70, 1.34]

25 Neonatal encephalopathy	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
26 Major cerebral abnormality on ultrasound before discharge Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	1.10 [0.74, 1.63]

27 Perinatal death/death before discharge Show forest plot	1	2395	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.66, 1.23]

28 Serious childhood disability at 7 years Show forest plot	1	1612	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.79, 1.01]

Comparison 2. Erythromycin versus co‐amoxiclav

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Comparison 4. Antibiotics versus no antibiotic

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Perinatal death/death before discharge Show forest plot	18		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Antibiotics versus no antibiotics (all studies)	18	6872	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.74, 1.08]
1.2 Antibiotics versus no treatment (no placebo)	6	571	Risk Ratio (M‐H, Random, 95% CI)	0.69 [0.41, 1.14]

Comparison 4. Antibiotics versus no antibiotic

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Comparison 5. 3 versus 7 day ampicillin regimens

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Maternal death	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 Serious maternal morbidity	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3 Major adverse drug reaction	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4 Maternal infection after delivery prior to discharge Show forest plot	1	84	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.36, 4.33]

5 Chorioamnionitis Show forest plot	1	84	Risk Ratio (M‐H, Random, 95% CI)	0.73 [0.33, 1.63]

6 Caesarean section Show forest plot	1	84	Risk Ratio (M‐H, Random, 95% CI)	1.18 [0.72, 1.91]

7 Days from randomisation to birth	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
8 Days from birth till discharge of mother	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
9 Birth within 48 hours of randomisation Show forest plot	1	84	Risk Ratio (M‐H, Random, 95% CI)	1.14 [0.46, 2.87]

10 Birth within 7 days of randomisation Show forest plot	1	84	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.70, 1.42]

11 Birth before 37 weeks' gestation	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
12 Birthweight	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
13 Birthweight < 2500 g	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
14 Neonatal intensive care Show forest plot	1	84	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.84, 1.19]

15 Days in neonatal intensive care unit	0	0	Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
16 Neonatal infection including pneumonia	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
17 Positive neonatal blood culture	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
18 Neonatal necrotising enterocolitis Show forest plot	2	130	Risk Ratio (M‐H, Random, 95% CI)	0.43 [0.07, 2.86]

19 Neonatal respiratory distress syndrome Show forest plot	2	130	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.62, 1.49]

20 Treatment with surfactant	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
21 Number of babies requiring ventilation	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
22 Number of babies requiring oxygen therapy	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
23 Neonatal oxygenation > 28 days	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
24 Oxygen treatment > 36 weeks' postconceptual age	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
25 Neonatal encephalopathy	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
26 Neonatal intraventricular haemorrhage Show forest plot	2	130	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.04, 3.12]

27 Perinatal death/death before discharge Show forest plot	2	130	Risk Ratio (M‐H, Random, 95% CI)	0.40 [0.05, 2.94]

28 Serious childhood disability at 7 years	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 5. 3 versus 7 day ampicillin regimens

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