Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.
BACKGROUND
Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has been shown to prolong pregnancy, but the effect on infant morbidity has been inconsistent.


OBJECTIVE
To determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity.


METHODS
Randomized, double-blind, placebo-controlled trial.


METHODS
University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.


METHODS
A total of 614 of 804 eligible gravidas with PPROM between 24 weeks' and 0 days' and 32 weeks' and 0 days' gestation who were considered candidates for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of randomization.


METHODS
Intravenous ampicillin (2-g dose every 6 hours) and erythromycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxicillin (250-mg dose every 8 hours) and erythromycin base (333-mg dose every 8 hours) for 5 days vs a matching placebo regimen. Group B streptococcus (GBS) carriers were identified and treated. Tocolysis and corticosteroids were prohibited after randomization.


METHODS
The composite primary outcome included pregnancies complicated by at least one of the following: fetal or infant death, respiratory distress, severe intraventricular hemorrhage, stage 2 or 3 necrotizing enterocolitis, or sepsis within 72 hours of birth. These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed.


RESULTS
In the total study population, the primary outcome (44.1 % vs 52.9%; P=.04), respiratory distress (40.5% vs 48.7%; P=.04), and necrotizing enterocolitis (2.3% vs 5.8%; P=.03) were less frequent with antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%; P=.03), respiratory distress (40.8% vs 50.6%; P=.03), overall sepsis (8.4% vs 15.6%; P=.01), pneumonia (2.9% vs 7.0%; P=.04), and other morbidities. Among GBS-negative women, significant pregnancy prolongation was seen with antibiotics (P<.001).


CONCLUSIONS
We recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity.
Mercer
B M
BM
University of Tennessee, Memphis 38103, USA. bmercer@utmem1.utmem.edu
Miodovnik
M
M
Thurnau
G R
GR
Goldenberg
R L
RL
Das
A F
AF
Ramsey
R D
RD
Rabello
Y A
YA
Meis
P J
PJ
Moawad
A H
AH
Iams
J D
JD
Van Dorsten
J P
JP
Paul
R H
RH
Bottoms
S F
SF
Merenstein
G
G
Thom
E A
EA
Roberts
J M
JM
McNellis
D
D
D000328:Adult; D000658:Amoxicillin / Q000008:administration & dosage / Q000627:therapeutic use; D000667:Ampicillin / Q000008:administration & dosage / Q000627:therapeutic use; D002353:Carrier State / Q000188:drug therapy / Q000503:physiopathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D004917:Erythromycin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000453:epidemiology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000503:physiopathology; D011256:Pregnancy Outcome; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D016016:Proportional Hazards Models; D018709:Statistics, Nonparametric; D013290:Streptococcal Infections / Q000188:drug therapy / Q000503:physiopathology; D013292:Streptococcus agalactiae
D004917:Erythromycin; D000667:Ampicillin; D000658:Amoxicillin