Infant Outcome After Maternal Antibiotic Therapy for Premature Rupture of the Me
Infant Outcome After Maternal Antibiotic Therapy for Premature Rupture of the Membranes
ABSTRACT & COMMENTARY
Synopsis: Maternal antibiotic treatment (ampicillin/amoxicillin and erythromycin) for seven days at the time of preterm premature rupture of the membranes (PPROM) prior to the onset of labor significantly improved the overall infant outcome.
Source: Mercer BM, et al. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. JAMA 1997;278:989-995.
A multicenter, randomized, double-blind, placebo-controlled trial of 614 out of 804 eligible pregnancies with preterm premature rupture of the membranes (PPROM) from 24 to 32 weeks’ gestation evaluated the effect of maternal antibiotic treatment or a matching placebo regimen on fetal outcome. The antibiotic regimen was intravenous ampicillin (2 g every 6 hours) and erythromycin (250 mg every 6 hours) for 48 hours, followed by oral amoxicillin (250 mg every 6 hours) and erythromycin base (333 mg every 8 hours) for five days. Mothers had not received corticosteroids for fetal lung maturation or antibiotic treatment within one week of randomization. In the total study population, overall complications for the fetus-infant (fetal or infant death, respiratory distress, early-onset sepsis, or severe intracranial hemorrhage or necrotizing enterocolitis) were less frequent with antibiotics (44.1% vs 52.9%; P = 0.04). Individually, respiratory distress (40.5% vs 48.7%; P = 0.04) and necrotizing enterocolitis (2.3% vs 5.8%; P = 0.03) were less frequent with antibiotics. In women negative for group B Streptococcus colonization, antibiotic treatment resulted in a significant pregnancy prolongation (P < 0.001) as well as decreased overall complications (44.5% vs 54.5%; P = 0.03), respiratory distress (40.8% vs 50.6%; P = 0.03), overall sepsis (8.4% vs 15.6%; P = 0.01), and pneumonia (2.9% vs 7.0%; P = 0.04).
COMMENT BY HAL B. JENSON, MD, FAAP
Intrauterine infection is thought to be a major cause of PPROM and results in significant neonatal mortality and morbidity. Previous studies of maternal antibiotic therapy have demonstrated prolongation of pregnancy but an inconsistent effect on infant morbidity. The results of this study support the use of expectant antibiotic treatment of mothers with pregnancies complicated with PPROM prior to the onset of labor to reduce infant morbidity. This study focused on women who were not colonized with group B Streptococcus and would not be candidates to receive peripartum antibiotic prophylaxis for prevention of group B Streptococcus infections.1,2 Since the current guidelines for group B Streptococcus recommend screening beginning at 35 weeks’ gestation, the carrier status of mothers with PPROM remote from term will not likely be known.
This study will have an immediate effect on obstetricians responsible for the management of pregnancies complicated by PPROM. Expectant antibiotic treatment of PPROM prior to the onset of labor will probably become common and will likely be offered to women beyond the 32 weeks’ gestation parameter of this study. In some situations, expectant maternal antibiotic treatment will also constitute treatment of early or incipient infection of the fetus. Some of these women will deliver before completing this antibiotic regimen. The dilemma for pediatricians is to determine if maternal antibiotic treatment provided sufficient protection to the fetus-infant. A single dose of intrapartum antibiotics administered less than four hours before delivery is not considered to provide adequate group B Streptococcus prophylaxis and similarly may be inadequate under these circumstances. Another important component of management of asymptomatic newborns who are not treated with antibiotics is the recommendation for observation in the hospital for a minimum of 48 hours after delivery.
Symptomatic newborns of mothers with PPROM should be completely evaluated and treated for sepsis. Symptomatic newborns should be treated with the usual broad-spectrum antibiotics (e.g., ampicillin + gentamicin or ampicillin + cefotaxime) for a full-course of 7-10 days regardless of whether the mother received a partial or complete course of antibiotics.
Asymptomatic full-term newborns (> 35 weeks’ gestation) of mothers who received one dose of antibiotics more than four hours prior to delivery should be clinically evaluated for signs of sepsis and should have further laboratory testing or receive empiric treatment if sepsis is suspected.
I recommend that asymptomatic premature newborns (< 35 weeks’ gestation) or full-term newborns of mothers who received a single dose of antibiotics within four hours of delivery have a limited evaluation. Premature newborns, who have a much greater risk of sepsis, should be evaluated regardless of the number of doses of maternal antibiotics administered. Empiric therapy is not mandatory for these newborns if they remain asymptomatic and are observed in the hospital for at least 48 hours. In practice, many premature newborns have some signs consistent with sepsis (e.g., rapid breathing) and are treated empirically.
References
1. American Academy of Pediatrics. Committee on Infectious Diseases and Committee on Fetus and Newborn. Revised guidelines for prevention of early-onset group B streptococcal (GBS) infection. Pediatrics 1997;99: 489-496.
2. Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease: A public health perspective. MMWR Morb Mortal Wkly Rep 1996;45(RR-7):1-24.
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