Up to 3.5 percent of all pregnancies and 30 to 40 percent of preterm deliveries are complicated by preterm rupture of the fetal membranes (PROM). The etiology of PROM is multifactorial. Bacterial infection may weaken the fetal membranes leading to rupture, and colonization after rupture can cause chorioamnionitis, deciduitis, or fetal infection. Although antibiotic therapy could be expected to reduce infectious complications of PROM, concerns have been raised that delaying delivery after rupture could be associated with neurodevelopmental delay in the infant. Kenyon and colleagues conducted a systematic review of the outcomes of antibiotic use in PROM, including a comparison of the different agents commonly used to prevent complications.

The authors identified relevant randomized placebo-controlled trials by searching electronic databases of publications, clinical trials, and conference abstracts. Maternal outcomes were death, serious morbidity, adverse reaction to medication, chorioamnionitis, and infection after delivery or before discharge. Neonatal outcomes included perinatal death, neonatal morbidity, and developmental delay in childhood.

Of the 33 studies identified during the search, 19 trials involving 6,951 mothers met criteria for inclusion in the analysis. The use of antibiotics after PROM was associated with a significant reduction in chorioamnionitis (relative risk [RR] = 0.57), and in the number of infants born within 48 hours (RR = 0.71) and seven days (RR = 0.80) of randomization. No adverse drug reactions were noted from antibiotic therapy.

The use of antibiotics after PROM also significantly reduced the number of neonatal infections (RR = 0.67); the number of infants requiring oxygen therapy (RR = 0.88); the number of days infants spent in neonatal intensive care (by approximately five days); and the number of neonates with an abnormal cerebral ultrasound scan before hospital discharge. It also increased the birth weight (average: 51.53 g) of the infants. The number of women who needed to be treated with antibiotics to avoid one additional unfavorable outcome in the infant ranged from seven to 69 (see accompanying table).Overall, use of antibiotics was not associated with a statistically significant reduction in perinatal mortality.

Benefit was demonstrated in trials involving penicillins and erythromycin, but data were insufficient to compare different antibiotic regimens. Because erythromycin was used in larger trials, the evidence supporting its use was more robust. The incidence of necrotizing enterocolitis rose significantly when amoxicillin-clavulanate (Augmentin) was used.

The authors conclude that the use of antibiotics after PROM reduces maternal and neonatal morbidity. The data support the routine use of erythromycin or other penicillins to improve outcomes for mothers and infants. The authors also advise against the use of amoxicillin-clavulanate because of its increased risk of necrotizing enterocolitis. Further long-term follow-up will need to be completed to assess the health and development of the children involved in this trial.