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Antibiotics for preterm premature rupture of membranes
S Kenyon1, M Boulvain, J Neilson
1ORACLE Clinical Co-ordinating Centre, Leicester Royal Infirmary, Department of Obstetrics, Clinical Sciences Building, PO Box 65, Leicester, UK, LE2 7ZR. oracle@le.ac.uk
Insights
Administering antibiotics to mothers with preterm prelabour rupture of membranes significantly reduces maternal and neonatal infections. Macrolide antibiotics are recommended, while beta-lactam antibiotics increase the risk of necrotising enterocolitis in newborns.
Area of Science:
- Obstetrics and Gynecology
- Neonatal Medicine
- Infectious Diseases
Background:
- Preterm birth complications contribute significantly to neonatal morbidity and mortality.
- Subclinical infection is implicated as a cause of preterm prelabour rupture of membranes (pPROM).
- Antibiotic administration in pPROM aims to mitigate infectious complications.
Purpose of the Study:
- To evaluate the effectiveness of antibiotics for women with pPROM.
- To assess the immediate and long-term safety of antibiotic use in this population.
- To analyze effects on maternal, fetal, and neonatal outcomes, including childhood development.
Main Methods:
- Systematic review of randomized controlled trials (RCTs) identified by the Cochrane Pregnancy and Childbirth Group.
- Inclusion criteria focused on trials reporting clinically relevant outcomes.
- Data extraction from 13 trials involving over 6,000 women and neonates.
Main Results:
- Antibiotics significantly reduced maternal infection and morbidity post-delivery.
- Neonatal infection, positive blood cultures, and need for oxygen therapy were significantly reduced.
- Macrolide antibiotics (erythromycin) showed benefits, while beta-lactam antibiotics (augmentin) increased necrotising enterocolitis risk.
Conclusions:
- Routine prescription of macrolide antibiotics is recommended for preterm prelabour rupture of membranes.
- Beta-lactam antibiotics, specifically augmentin, are associated with increased neonatal necrotising enterocolitis.
- Antibiotic therapy in pPROM demonstrates a favorable risk-benefit profile with macrolides.
Background:
The consequences of prematurity continue to result in neonatal morbidity and mortality. One of the causes of prematurity is preterm prelabour rupture of membranes in which there is evidence that subclinical infection plays a role.
Objectives:
The aim of the review was to evaluate the effectiveness and the immediate and long-term safety of the effects of administering antibiotics to women with preterm prelabour rupture of membranes on maternal infectious morbidity, fetal and neonatal morbidity and mortality, and longer term childhood development.
Search Strategy:
All randomized trials identified using the search strategy described by the Cochrane Pregnancy and Childbirth Group. Date of last search: 31 May 2001.
Selection Criteria:
All trials which reported clinically relevant outcomes (as opposed to laboratory data) were included.
Data Collection And Analysis:
Data were extracted from each report without any blinding of either the results or the treatments which women received. Unpublished data were sought from a number of authors.
Main Results:
There were 13 trials included in the review which randomised over 6,000 women and their babies. The use of antibiotics following preterm prelabour rupture of membranes (pPROM) is associated with a statistically significant reduction in maternal infection after delivery prior to discharge (relative risk (RR) 0.85, 95% confidence interval (CI) 0.76,0.96) and morbidity (including chlorination) (RR 0.62, 95% CI 0.51,0.75) There was a statistically significant reduction in the numbers of babies born within 48 hours (RR 0.77, 95% CI 0.72,0.83) and seven days RR 0.88, 95% CI 0.84,0.92) of randomisation. Neonatal infection (including pneumonia) (RR 0.67, 95% CI 0.52,0.85) and positive blood culture (RR 0.75, 95% CI 0.60,0.93) were statistically significantly reduced in the babies whose mothers received antibiotics as was the numbers of babies requiring oxygen therapy overall (RR 0.88, 95% CI 0.81,0.96) and at 28 days of age or older (RR 0.81, 95% CI 0.68,0.97). One trial (ORACLE) found a statistically significant reduction in the use of surfactant (RR 0.83, 95% CI 0.72,0.96). There was also a statistically significant reduction in the number of babies diagnosed with abnormal cerebral ultrasound (RR 0.82, 95% CI 0.68,0.99) scans prior to discharge from hospital. Overall, there was no evidence of adverse effect. Intrinsically there are fewer data relating to specific antibiotics. When looking at the effect of beta lactum antibiotics (augmentin) where two trials were included, there was a statistically significant reduction in the number of babies born within 48 hours (RR 0.75, 95% CI 0.67,0.84) and seven days (RR 0.91, 95% CI 0.85,0.97) of randomisation. However, there was a highly significant increase in the numbers of babies with necrotising enterocolitis (RR 4.60, 95% CI 1.98,10.72) in the augmentin treatment group. The effect of macrolide antibiotics (erythromycin), included four trials and found statistically significant reductions in the number of babes born within 48 hours (RR 0.84, 95% CI 0.76,0.93) of randomisation but delivery < 7 days did not exclude unity. There was statistically significant reductions in those requiring oxygen therapy (RR 0.87, 95% CI 0.78,0.98) and those with a positive blood culture (RR 0.70, 95% CI 0.52,0.94).
Reviewer'S Conclusions:
There are sufficient data to recommend routine prescription of macrolide antibiotics in this clinical situation. The routine prescription of macrolide antibiotic (erythromycin) is recommended as beta lactum antibiotics (augmentin) is associated with a statistically significant increase in neonatal necrotising enterocolitis.