0841 7-year follow up of antibiotics for PROM and preterm labour

Preterm delivery has long been recognised as a major cause of morbidity and mortality, and while substantial human and financial resources have been deployed in developing technology and skills directed towards treatment of the preterm infant, prevention of preterm delivery and protection of the exposed foetus and infant have also been foci of attention. Infection i.e. chorioamnionitis and risk factors for such infection (e.g. zinc deficiency) have been under the spotlight in this context and administration of antibiotics to the mother emerged as an apparently worthwhile strategy. In the case of spontaneous preterm labour (SPL) with intact membranes, randomised controlled trials have failed to provide clear evidence of the value of antibiotic therapy (and in fact some data suggest higher neonatal mortality with such treatment). In the case of preterm rupture of membranes (PROM), erythromycin administration prolonged pregnancy and decreased morbidity and mortality in singleton offspring. Co-amoxyclav also prolonged pregnancy but appeared to be associated with a higher incidence of neonatal NEC. Researchers involved in these studies have recently published 7-year follow up data on the products of these pregnancies. In the follow up of the PROM study (which involved 4148 women and their infants) there were no differences in functional impairment in recipients of erythromycin ± co-amoxyclav vs controls. However, the 7-year follow up of the SPL group (originally involving 4221 subjects) showed that erythromycin ± co-amoxyclav was associated with ± 20% more in the way of functional impairment (using the Multi-Attribute Health Status classification system) than was seen in controls. A sub-analysis showed further that exposure to antibiotics was associated with more reported cerebral palsy (~3.3% vs ~1,8%). An accompanying editorial comment suggests that the prenatal exposure to antibiotics might have suppressed rather than eradicated infection from the amniotic fluid and that the treated foetus might therefore have been exposed to a damaging environment for longer. Such an explanation is difficult to accept given that antibiotics prolonged pregnancy in the PROM group (with no sequelae on follow up) whereas sequelae were seen in the SPL group. The cerebral palsy data are also difficult to understand, particularly since no functional sequelae were observed i.e. CP without the condition affecting function would be unusual.

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Lancet 2008; 372: 1276-8 1310-8 1319-27
Br J Obstet Gynaecol 2006; 113: 758-65
Lancet 2001; 357: 981-90 and 991-6