Drug Therapy During Labor and Delivery, Part 1

Gerald G. Briggs; Stephanie R. Wan


Am J Health Syst Pharm. 2006;63(11):1038-1047. 

In This Article


PROM occurs in 2-3.5% of pregnancies, and it is the precursor of delivery in 30-40% of preterm births.[44] It is defined as the rupture of membranes before the onset of labor; preterm PROM is rupture occurring before 37 weeks' gestation. Perinatal morbidities associated with PROM include maternal infection, umbilical cord compression due to oligohydramnios, abruptio placentae, and neonatal infection and morbidities related to premature birth, including respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, and sepsis.[45]

The gestational age at which membrane rupture occurs is an important predictor of the consequences of PROM and the way care is managed. Evidence of overt intrauterine infection, advanced cervical dilation, or fetal distress following membrane rupture is an indication for immediate delivery. In addition, labor induction may be considered if pulmonary maturity has been documented after PROM at 32-36 weeks' gestation, since serious neonatal morbidity is uncommon in this setting.[46] When such indications are not present, significant neonatal benefits may be attained by prolonging the latency period between rupture and delivery. Prolonging the latency period can significantly improve perinatal morbidity and mortality, particularly in cases of PROM remote from term (i.e., between 23-31 weeks' gestation). Moreover, such prolongation will allow sufficient time for antenatal corticosteroids to be administered for fetal lung immaturity or for appropriate transfer of the mother to a tertiary care center for the treatment of a potentially premature infant.

The pathological mechanisms that cause PROM are multifactorial. Infection may be a key player in the pathophysiology of PROM, with ascending infection from the vagina causing rupture of membranes due to deciduitis, chorioamnionitis, or fetal infection.[47] Collagenases, mucinases, and proteases produced by vaginal microorganisms may also weaken the amnion and chorion, leading to PROM.[47] Prophylactic antibiotics are widely used in PROM to reduce maternal and fetal infectious morbidity and extend the latency period between time of rupture and delivery. Most antibiotic regimens are capable of prolonging the latency period when compared to no treatment, with significant reductions in the numbers of infants born within 48 hours and within seven days of rupture of membranes.[47,48]

A meta-analysis of 19 trials examined the use of antibiotics after PROM.[47] In 14 trials, antibiotics were associated with statistically significant reductions in chorioamnionitis, postpartum endometritis, neonatal infection and early-onset neonatal sepsis, and infants requiring oxygen therapy and surfactant, as well as infants with an abnormal cerebral ultrasound before discharge from the hospital. The authors concluded, however, that the use of antibiotics after PROM was not associated with a statistically significant reduction in overall perinatal mortality. The results of a multicenter trial conducted by the Maternal-Fetal Medicine Units Network indicated that among women receiving prophylactic antibiotics after PROM, only the neonates whose mothers were GBS negative had reductions in neonatal morbidity and mortality.[48] Comprehensive comparisons and conclusions drawn from studies of the use of antibiotics after PROM are difficult, since differences exist among the trials in the selection of antibiotic regimen, the use of corticosteroids and tocolysis, and the gestational age at membrane rupture.

A number of antibiotic regimens appear to be effective in prolonging the latency period. Regimens using initial parenteral treatment, followed by oral antibiotic therapy, are preferred secondary to their apparent ability to prolong pregnancy and improve perinatal outcomes. The Maternal-Fetal Medicine Units Network trial studied the combination of ampicillin (2 g i.v. every 6 hours for 48 hours, followed by amoxicillin, 250 mg p.o. every 8 hours for 5 days) and erythromycin (250 mg [as the lactobionate] i.v. every 6 hours for 48 hours, followed by one 333-mg [as the base] enteric-coated tablet p.o. every 8 hours for 5 days).[48] The study demonstrated significant perinatal benefit in reducing neonatal morbidity and maternal and neonatal infectious morbidity. The ORACLE I study evaluated the use of oral antibiotics only.[49] This large, multicenter, placebo-controlled trial compared the perinatal outcomes of using either or both erythromycin and amoxicillin-clavulonate or placebo for up to 10 days (or until delivery occurred) in women (single and multiple gestations included) with preterm PROM at less than 37 weeks. Data were presented comparatively by antibiotic group and not by gestational age subgroup, which was a limitation to the study. Only the use of erythromycin alone resulted in reduced neonatal morbidity, whereas the use of either antibiotic or both antibiotics prolonged the latency period. However, oral amoxicillin-clavulonate was also associated with an increased risk of necrotizing enterocolitis, without reducing other neonatal or composite morbidities.[49]

At our institution, local susceptibility patterns and the potential for selection of resistant organisms responsible for early-onset neonatal sepsis are considered in the antibiotics selected. This regimen, while not shown to reduce morbidity and mortality in a published study, is cefazolin (2 g i.v. every 8 hours) plus erythromycin (250 mg i.v. every 6 hours) for 48 hours, followed by cephalexin (500 mg p.o. every 6 hours) plus erythromycin (250 mg p.o. every 6 hours) for 5 days unless delivery occurs. This regimen has been evaluated in our institution, and we have demonstrated a doubling of the latency interval-9 days increased to 17 days (data on file).


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