Antibiotics for preterm premature rupture of membranes.
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.


OBJECTIVE
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.


METHODS
All randomized trials identified using the search strategy described by the Cochrane Pregnancy and Childbirth Group. Date of last search: 31 May 2001.


METHODS
All trials which reported clinically relevant outcomes (as opposed to laboratory data) were included.


METHODS
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 Unpublished data were sought from a number of authors.


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).


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.
Kenyon
S
S
ORACLE Clinical Co-ordinating Centre, Leicester Royal Infirmary, Department of Obstetrics, Clinical Sciences Building, PO Box 65, Leicester, UK, LE2 7ZR. oracle@le.ac.uk
Boulvain
M
M
Neilson
J
J
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000188:drug therapy*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000517:prevention & control; D018942:Macrolides; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic
D000900:Anti-Bacterial Agents; D018942:Macrolides