National Institute of Child Health and Human Development
Maternal Fetal Medicine Units Network

MFMU Network Randomized Clinical Trial of Adjunctive
Antibiotic Treatment with Preterm Premature
Rupture of Membranes

Related Publications & Presentations

Objective

To establish whether administration of adjunctive antibiotics to women with preterm premature rupture of membranes (pPROM) and a negative vaginal culture for group B streptococcus (GBS) on admission will decrease adverse perinatal outcome defined as composite mortality and morbidity.

Conclusion

The trial concluded that antimicrobial therapy of expectantly managed pPROM at 24⁰to 32⁰ weeks gestation significantly reduces infectious and non-infectious infant morbidity. For patients without group B strep who received antibiotics, neonatal morbidity/mortality, especially RDS, was reduced.

Clinical Centers

Tennessee, Southern California, Alabama, Wayne State, South Carolina, Cincinnati, Bowman Gray, Chicago, Oklahoma, Ohio Sate

Major Eligibility Criteria

• Diagnosis of pPROM with "controlled" labor:
• 24-32 completed weeks
• Absence of significant uterine activity
• Absence of progressive change in cervical dilatation/ effacement
• Membrane rupture < 36 hours
• Informed consent

Groups

• Experimental = Antibiotics & expectant management
• Placebo = Placebo & expectant management

Sample Size

• Goal = 700 (350/group)

Management Protocols

• Coded medication:
• IV ampicillin & erythromycin (w/in 4 hours of randomization for 2 days)
• Oral amoxicillin & erythromycin (5 additional days)
• Coded medication discontinued:
• Overt infection (chorio/pyelonephritis)
• Progressive labor/delivery
• Severe side effects
• Steroids/Tocolysis:
• No steroids. No tocolysis after randomization
• Admission vaginal culture + for GBS:
• Oral ampicillin (500 mg po q6h) for 7 days
• Retreat for + repeat vaginal cultures
• Intrapartum tx of IV ampicillin (2gm IVq6)

Outcome Measures

• Primary:
  Adverse perinatal outcome:
• Mortality (stillbirth, death prior to discharge home or to chronic care)
• Morbidity (RDS, documented sepsis, IVH>3, NEC>2)
• Secondary:
• Latency from randomization to deliver
• Maternal infectious morbidity/placental infection
• Long term infant morbidity (BPD/PIE/PDA/PVL.ROP)

Timetable

• Randomization (n=614): 2/92 - 1/95
• Follow-up: Thru - 7/95