Antibiotics for preterm rupture of membranes
Neonatal infection is one of the leading causes of neonatal mortality in developing countries. Administration of antibiotics following preterm, prelabour rupture of membranes not only significantly reduces chorioamnionitis, it also delays delivery and lowers the risk of serious neonatal morbidity.
RHL Commentary by Festin M
1. EVIDENCE SUMMARY
Preterm prelabour rupture of membranes (pPROM) is a common cause of infectious morbidity in the mother and the neonate. The recently updated review includes 19 trials (out of 33 identified articles) with more than 6000 women overall. Giving antibiotics to women with pPROM is associated with a statistically significant reduction in chorioamnionitis (Relative risk [RR]: 0.57, 95% confidence interval [CI] 0.37 0.86). There was also a statistically significant reduction in deliveries within 48 hours (RR 0.71, 95% CI 0.58 0.87) and 7 days of randomization (RR 0.80, 95% CI 0.71 0.90).
The following markers of neonatal morbidity were also reduced: neonatal infection (including pneumonia) (RR 0.68, 95% CI 0.53 0.87), use of surfactant (RR 0.83, 95% CI 0.72 0.96), the numbers of babies requiring oxygen therapy overall (RR 0.88, 95% CI 0.81 0.96) and the number of babies diagnosed with abnormal cerebral ultrasound (RR 0.82, 95% CI 0.68 0.98). There was a significant increase in cases of babies with necrotizing enterocolitis (two trials, RR 4.60, 95% CI 1.98 10.72) in babies who received co-amoxyclav or augmentin as antibiotics.
The conclusion of the review is that antibiotic administration following pPROM is associated with a delay in delivery and a reduction in markers of serious neonatal morbidity with the exception of necrotizing enterocolitis.
All adequately controlled trials, which could be identified, have been included and appropriately analysed. There were some articles which were excluded in the previous version of this review which were now included, despite being available at the previous time. This led to some changes in the values of the relative risks, although the conclusions remained practically the same.
2. RELEVANCE TO UNDER-RESOURCED SETTINGS
2.1. Magnitude of the problem
Preterm delivery is an acknowledged factor in neonatal morbidity and mortality. While many factors and diagnostic tests have been studied to predict preterm delivery, there has been little progress in reducing its incidence. One of the identified factors associated with preterm delivery is infection, which may also lead to infection in utero and in the fetus. This is also a common cause of low birth weight deliveries.
Neonatal infection is also a major problem in developing countries. It is one of the leading causes of neonatal mortality. Neonatal infection is more common in disadvantaged population groups, who usually do not have access to good nursery facilities and adequate antibiotic coverage. In the Philippines, as in many other developing countries, many hospitals are not able to handle very preterm newborns because of the lack of equipment and skilled personnel to assist these infants. Most deliveries also take place at home or in birthing centres that have only the basic equipment for normal low-risk pregnancies and are at some distance from the hospitals.
2.2. Applicability of the results
The studies that were included in the review were conducted in both developing as well as developed countries. The possible aetiologic agents in developed and developing countries may vary from site to site, and vigilance in trying to identify these would be needed. However, bacteriological culture facilities may be lacking or costly in many areas in developing countries and broad spectrum antibiotics may have to be used empirically. Because of the higher rates of neonatal infection and morbidity in developing countries, the routine administration of antibiotics in these cases would have a relatively higher impact in improvement of the clinical outcomes compared to industrialized countries. Many types of antibiotic and different routes of administration (oral and parenteral) were studied in the trials. The reviewers seemed to recommend one single antibiotic (erythromycin) over another drug (co-amoxyclav or augmentin) because of the latter’s side effects, particularly necrotizing enterocolitis. These antibiotics that have been used in the trials could be used in practice. The studies generally looked at the more common, but important, outcomes clinicians are concerned with in cases of pPROM, such as infectious and other complications, mortality and patterns of hospital care.
2.3. Implementation of the intervention
Since antibiotics are relatively easily available in developing countries this intervention could be feasible and effective provided women come to the health facility early enough after the appearance of signs of pPROM. The choice of antibiotics was apparently erythromycin, and there is the rather worrying finding of increased necrotizing enterocolitis with the use of co-amoxyclav or augmentin. Another important consideration in terms of feasibility is the inability of the woman or the health service to afford the antibiotics needed.
In areas where nursery facilities are indeed wanting, antibiotics have been proven by this review to prolong the pregnancy for at least 48 hours and as much as seven days. The choice of antibiotics would preferably be based on the common organisms found in cultures from the genital tract of pregnant women in the country. If such information is not available, a broad spectrum antibiotic which is safe for pregnant women should be used intravenously until the patient delivers; if the woman is not delivered within the next few days, the antibiotic should be continued for at least a week. In the presence of fetal distress or signs of infection in the mother or the fetus, the clinical situation must be evaluated for immediate delivery. While antibiotics may be relatively easy to administer, it may be advisable to administer these in the hospital setting, rather than in the community, as delivery timing could be difficult to predict in women with pPROM.
For many hospitals, obtaining a supply of antibiotics may be much easier than investing in intensive care equipment for women with preterm prelabour rupture of membranes. For example, this is true for hospitals in rural Philippines (and in many other developing countries). This prolongation of pregnancy through the use of antibiotics can allow the mother to be transferred to a facility with better equipment for management of such cases.
Aside from using antibiotics in the management of pPROM, the health providers should also give steroids to enhance lung maturity.
3. RESEARCH
More studies that can define the most cost-effective antibiotics for use in such cases would be useful. It is also important to confirm whether the oral route of administration is as effective as the parenteral route; if this proves to be the case, it will render patient management much simpler and less costly. The effect of such variables as level of activity of the mother diagnosed with preterm prelabour rupture of the membranes, level of nursery care capability and resources, and the chances of survival in the various levels of health delivery, may also be interesting for further study. The search for the ideal choice of antibiotics continues for this problem, although this review has attempted to describe both beneficial and potentially risky antibiotics.
Another important issue is whether the concurrent use of steroids along with antibiotics can lead to better outcomes for the newborn and the mother. However, the Cochrane Review corticosteroids prior to preterm delivery on the use of corticosteroids before preterm birth indicates that corticosteroids are beneficial regardless of whether the membranes are ruptured or not. Therefore, until further research indicates otherwise women with preterm prelabour rupture of membranes should also be given corticosteroids.
The long term effects of the interventions on the infant’s growth and development should be studied. It may also be interesting to note if there would be a reduction in the rates of preterm delivery in subsequent pregnancies.
Sources of support: National Institutes of Health, University of the Philippines, Manila, The Philippines.
Acknowledgement: None.
This document should be cited as: Festin M. Antibiotics for preterm rupture of membranes: RHL commentary (last revised: 14 June 2003). The WHO Reproductive Health Library; Geneva: World Health Organization.