The review concluded that antibiotics administered to women with pre-term pre-labour rupture of membrane reduced complications due to pre-term delivery and post-natal infection in high-income countries; there was limited evidence from low-income countries. Despite unclear reporting of the review process, the conclusion appears reliable given the evidence presented.

To estimate the effect of antibiotics administered to women with pre-term, pre-labour rupture of membrane (pPROM) in reducing neonatal mortality due to pre-term birth complications or infection in low- and middle-income countries.

This was an update of a previous Cochrane review (see Other Publications of Related Interest),

Searches were conducted without language restrictions of trials from a previous Cochrane review (published 2003), PubMed, The Cochrane Library and all World Health Organisation Regional Databases. Search terms were reported, but date restrictions were not.

Eligible studies were of women with pre-term pre-labour rupture of membrane (pPROM). The intervention had to be antibiotics given alone or in combination with antenatal steroids and surfactants. Eligible studies had to use a randomised design for trials from any setting, but could use observational data if the setting was a low- or middle-income country. Studies had to assess neonatal mortality or morbidity, defined as either necrotising enterocolitis, intra-ventricular haemorrhage, respiratory distress syndrome (RDS) or confirmed sepsis. Studies in the Cochrane review were excluded if all women were treated with antibiotics for only three or seven days or co-amoxiclav was compared with either placebo or no antibiotic treatment; the co-amoxiclav arm of another trial was excluded. Randomised and clinical controlled trials only were sought through PubMed.

All studies except one were RCTs; one study was observational. Most studies were conducted in high-income countries such as USA, UK, Denmark and Finland; some were conducted in low- and middle-income countries such as Mozambique, Turkey, Chile and Pakistan. Where reported, participants ranged from 20 to 37 weeks gestation. Year of publication ranged from 1988 to 2006. Where reported, antibiotics commonly used included ampicillin and erythromycin; other treatments used included mezlocillin, benzylpenicillin, clindamycin, gentamycin, metronidazole, pivampicillin and potassium phenoxymethyl penicillin.

It appeared that more than one author performed the study selection.

The reviewers stated that they used a Child Health Epidemiology Reference Group (CHERG) checklist based on an adaptation of the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

It appeared that more than one author performed validity assessment.

It appeared that at least two authors extracted data required to calculate risk ratios (RRs) with 95% confidence intervals (CIs) for neonatal mortality and a range of severe morbidity outcomes.

Pooled risk ratios with 95% CIs were calculated using either a fixed-effect or random-effects model for the outcome of mortality and a range of severe morbidity outcomes. It appeared that the Χ² test was performed to assess heterogeneity; if evidence for heterogeneity was weak (threshold p>0.10) a fixed-effect rather than random-effects model was used to pool data.

It appeared that more than one author performed the synthesis.

Nineteen studies (n=4,810 live births, range 31 to 2,415 live births) were included in the review: 18 RCTs (n=4,585) and one observational study (n=225). For most of the included RCTs, methods of randomisation, allocation concealment, assessor blinding and use of intention-to-treat analysis were assessed as adequate.

No statistically significant effect of antibiotics was identified for mortality outcomes, although the trend favoured antibiotics over controls (RR 0.90, 95% CI 0.72 to 1.12; 15 studies, n=4,265 live births).

For morbidity outcomes, statistically significant effects in favour of the intervention were identified for the outcomes of respiratory distress syndrome (RR 0.88, 95% CI 0.80 to 0.97; 13 studies, n=4,104 live births), intra-ventricular haemorrhage (RR 0.67, 95% CI 0.49 to 0.92; 12 studies, n=1,702 live births) and confirmed sepsis (RR 0.61, 95% CI 0.48 to 0.77; 13 studies, n=3,693 live births). There was a statistically non significant favourable effect for necrotizing enterocolitis.

Statistical heterogeneity was non significant for all outcomes listed (I²=0%) and so a fixed-effect model was used throughout.

The authors stated that very few data were available from low- and middle-income countries.

Antibiotics for pPROM reduced complications due to pre-term delivery and post-natal infection in high-income countries. There was moderate quality evidence that in low-income countries with limited access to other interventions, antibiotics for pPROM could prevent 4% of neonatal deaths due to complications of prematurity and 8% of deaths due to infection.

This study addressed a clear review question with generally clear and appropriate inclusion and exclusion criteria. The search generally appeared appropriate, although the search restriction within one of the databases to clinical trials may have meant that relevant observational studies were missed, which potentially reduced the external validity of the findings (given that most of the non-observational studies included were performed in high-income countries). It was unclear how closely the search strategy and selection criteria of this review matched those of the Cochrane review on which it was based; if the selection criteria were significantly different then a more comprehensive search of other sources may have been appropriate. Few details about review process were presented, but consistent use of the term "we" implied that all stages were conducted by more than one reviewer and so the risk of reviewer error and bias was reduced. Comprehensive details of primary study characteristics and validity assessment were presented in a supplementary appendix online. The method of synthesis appeared appropriate, although use of a standard test for assessment of heterogeneity (such as Χ²) was implied rather than stated explicitly. The results were clearly reported and appeared consistent across outcomes. Although the reporting of the review process could have been more transparent and a restrictive search may have affected the external validity of the findings, the conclusions regarding high-income countries appeared reliable and reflected the evidence presented; conclusions for low- and middle-income countries were based on more limited evidence and so may not be reliable.

Practice: The reviewers did not state any implications for practice.

Research: The reviewers stated that studies to assess translational feasibility of the intervention in low- and middle-income countries were needed urgently.

Bell & Melinda Gates Foundation (grants 43 386 and 50 124); UNICEF; Save The Children USA.

Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database of Systematic Reviews 2010, Issue 8. Art. No.: CD001058. DOI: 10.1002/14651858.CD001058.pub2

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.