Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes

A randomized controlled trial

Brian M. Mercer, Menachem Miodovnik, Gary R. Thurnau, Robert L. Goldenberg, Anita F. Das, Risa Ramsey, Yolanda A. Rabello, Paul J. Meis, Atef H. Moawad, Jay D. Iams, J. Peter Van Dorsten, Richard H. Paul, Sidney F. Bottoms, Gerald Merenstein, Elizabeth A. Thom, James M. Roberts, Donald McNellis

Research output: Contribution to journalArticle

362 Citations (Scopus)

Abstract

Context.-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. Design.- Randomized, double-blind, placebo-controlled trial. Setting.-University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units NetWork. Patients.-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. Interventions.-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. Main Outcome Measures.-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.

Original languageEnglish (US)
Pages (from-to)989-995
Number of pages7
JournalJournal of the American Medical Association
Volume278
Issue number12
StatePublished - Sep 24 1997

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Randomized Controlled Trials
Anti-Bacterial Agents
Morbidity
Streptococcus agalactiae
Pregnancy
Necrotizing Enterocolitis
Erythromycin
Random Allocation
Therapeutics
Sepsis
Adrenal Cortex Hormones
Placebos
National Institute of Child Health and Human Development (U.S.)
Tocolysis
Fetal Death
Amoxicillin
Ampicillin
Pregnancy Outcome
Preterm Premature Rupture of the Membranes
Pneumonia

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes : A randomized controlled trial. / Mercer, Brian M.; Miodovnik, Menachem; Thurnau, Gary R.; Goldenberg, Robert L.; Das, Anita F.; Ramsey, Risa; Rabello, Yolanda A.; Meis, Paul J.; Moawad, Atef H.; Iams, Jay D.; Van Dorsten, J. Peter; Paul, Richard H.; Bottoms, Sidney F.; Merenstein, Gerald; Thom, Elizabeth A.; Roberts, James M.; McNellis, Donald.

In: Journal of the American Medical Association, Vol. 278, No. 12, 24.09.1997, p. 989-995.

Research output: Contribution to journalArticle

Mercer, BM, Miodovnik, M, Thurnau, GR, Goldenberg, RL, Das, AF, Ramsey, R, Rabello, YA, Meis, PJ, Moawad, AH, Iams, JD, Van Dorsten, JP, Paul, RH, Bottoms, SF, Merenstein, G, Thom, EA, Roberts, JM & McNellis, D 1997, 'Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes: A randomized controlled trial', Journal of the American Medical Association, vol. 278, no. 12, pp. 989-995.
Mercer, Brian M. ; Miodovnik, Menachem ; Thurnau, Gary R. ; Goldenberg, Robert L. ; Das, Anita F. ; Ramsey, Risa ; Rabello, Yolanda A. ; Meis, Paul J. ; Moawad, Atef H. ; Iams, Jay D. ; Van Dorsten, J. Peter ; Paul, Richard H. ; Bottoms, Sidney F. ; Merenstein, Gerald ; Thom, Elizabeth A. ; Roberts, James M. ; McNellis, Donald. / Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes : A randomized controlled trial. In: Journal of the American Medical Association. 1997 ; Vol. 278, No. 12. pp. 989-995.
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abstract = "Context.-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. Design.- Randomized, double-blind, placebo-controlled trial. Setting.-University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units NetWork. Patients.-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. Interventions.-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. Main Outcome Measures.-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.",
author = "Mercer, {Brian M.} and Menachem Miodovnik and Thurnau, {Gary R.} and Goldenberg, {Robert L.} and Das, {Anita F.} and Risa Ramsey and Rabello, {Yolanda A.} and Meis, {Paul J.} and Moawad, {Atef H.} and Iams, {Jay D.} and {Van Dorsten}, {J. Peter} and Paul, {Richard H.} and Bottoms, {Sidney F.} and Gerald Merenstein and Thom, {Elizabeth A.} and Roberts, {James M.} and Donald McNellis",
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T1 - Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes

T2 - A randomized controlled trial

AU - Mercer, Brian M.

AU - Miodovnik, Menachem

AU - Thurnau, Gary R.

AU - Goldenberg, Robert L.

AU - Das, Anita F.

AU - Ramsey, Risa

AU - Rabello, Yolanda A.

AU - Meis, Paul J.

AU - Moawad, Atef H.

AU - Iams, Jay D.

AU - Van Dorsten, J. Peter

AU - Paul, Richard H.

AU - Bottoms, Sidney F.

AU - Merenstein, Gerald

AU - Thom, Elizabeth A.

AU - Roberts, James M.

AU - McNellis, Donald

PY - 1997/9/24

Y1 - 1997/9/24

N2 - Context.-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. Design.- Randomized, double-blind, placebo-controlled trial. Setting.-University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units NetWork. Patients.-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. Interventions.-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. Main Outcome Measures.-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.

AB - Context.-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. Design.- Randomized, double-blind, placebo-controlled trial. Setting.-University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units NetWork. Patients.-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. Interventions.-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. Main Outcome Measures.-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.

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