Professional Documents
Culture Documents
(Revisin)
Kenyon S, Boulvain M, Neilson JP
Reproduccin de una revisin Cochrane prepara y actualiza por la
Colaboracin Cochrane y publicada en La Biblioteca Cochrane Plus
2010, No. 8
http://www.thecochranelibrary.com
Antibiticos para la rotura prematura de membranas
(Revisin)
Copyright 2010, La Colaboracin Cochrane. Publicado por
John Wiley & Sons, Ltd.
NDICE
HEADER. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RESUMEN. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Resumen en trminos
sencillos. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antecedentes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
OBJETIVOS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
MTODOS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figura 1.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figura 2.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figura 3.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figura 4.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figura 5.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RESULTADOS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DISCUSIN. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusiones de los revisores. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
AGRADECIMIENTOS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
REFERENCIAS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Caractersticas de los estudios. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DATOS Y ANLISIS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
REACCIN. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
QU HAY DE NUEVO. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
HISTORIA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTRIBUCIONES DE LOS
AUTORES. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DECLARACIONES DE INTERS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
FUENTES DE FINANCIACIN. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
INDICE DE TRMINOS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Criterios de seleccin
Se incluyeron los ensayos controlados aleatorios que compararon la
administracin de antibiticos con placebo que informaron resultados
clnicamente relevantes como lo fueron ensayos de diferentes
antibiticos. Se incluyeron los ensayos en los que no se us placebo
para el resultado de muerte perinatal solo.
Recopilacin y anlisis de datos
Se extrajeron los datos de cada informe sin cegamiento de los
resultados ni de los tratamientos que recibieron las mujeres. Se
buscaron datos no publicados de una serie de autores.
Resultados principales
Se incluyeron 22 ensayos, con 6800 mujeres y bebs.
El uso de antibiticos despus de la RPM se asocia con reducciones
estadsticamente significativas en la corioamnionitis (cociente de
riesgo medio (RR) 0,66, intervalo de confianza del 95% (IC) 0,46 a
0,96, y una reduccin en el nmero de bebs nacidos en las 48 horas
(RR promedio 0,71, IC del 95%: 0,58 a 0,87) y de siete das de la
aleatorizacin (RR promedio 0,79, IC del 95%: 0,71 a 0,89). Los
siguientes marcadores de morbilidad neonatal se redujeron: infeccin
neonatal (RR 0,67, IC del 95%: 0,52 a 0,85), uso de surfactante (RR
0,83, IC del 95%: 0,72 a 0,96), la terapia de oxgeno (RR 0,88, IC del
95%: 0,81 a 0,96), y la ecografa cerebral anormal escanean antes del
alta hospitalaria (RR0,81, IC del 95%: 0,68 a 0,98). La amoxicilinaclavulnico se asoci con un mayor riesgo de enterocolitis
necrotizante neonatal (RR 4,72, 95% IC 1,57-14,23).
Un estudio evalu la salud de los nios a los siete aos de edad
(ORACLE Children Study) y encontr antibiticos pareca tener poco
efecto sobre la salud de los nios.
Conclusiones de los autores
La decisin de prescribir antibiticos para las mujeres con RPM no es
tajante. Los beneficios en algunos resultados a corto plazo
(prolongacin del el embarazo, la infeccin, la ecografa cerebral
anormal menos antes del alta del hospital) deben equilibrarse con la
falta de evidencia de beneficiar a los dems, incluida la mortalidad
perinatal, y los resultados a largo plazo. Si se recetan antibiticos no
est claro qu hara ser el antibitico de eleccin.
La amoxicilina-clavulnico debe evitarse en mujeres con riesgo de
parto prematuro debido al aumento del riesgo de enterocolitis
necrotizante neonatal.
Resumen en trminos sencillos
Antibiticos para la rotura prematura de membranas
Ciertos antibiticos administrados a las mujeres con ruptura
temprana de aguas van a mejorar la salud de los bebs. Los bebs
Enterocolitis necrotizante;
Tratamiento con oxgeno mayor que 36 semanas edad
postconceptual;
Anormalidad importante en la ecografa cerebral antes de la
descargarse.
Los resultados secundarios
Reaccin adversa materna mayor de drogas.
La infeccin materna despus del parto antes de la descarga.
La corioamnionitis (infeccin del tero).
Cesrea.
Das desde la aleatorizacin hasta el nacimiento.
Das, desde el nacimiento hasta el alta hospitalaria.
Nacimiento en 48 horas.
Nacimiento dentro de los siete das.
A luz antes de las 37 semanas.
El peso al nacer.
El peso al nacer menor de 2500 gramos.
Necesidad de cuidados intensivos.
Das en la unidad de cuidados intensivos neonatales.
Positivo hemocultivo neonatal.
Sndrome de dificultad respiratoria.
El tratamiento con agente tensioactivo.
Das de ventilacin.
Das de la terapia de oxgeno.
El tratamiento con oxgeno mayor de 28 das.
Encefalopata neonatal.
Los resultados de salud a largo plazo (tal como se definen los autores
del ensayo) despus de al menos dos aos.
Mtodos de bsqueda para la identificacin de los estudios
Bsquedas electrnicas
Se realizaron bsquedas en la Cochrane de Embarazo y Parto Grupo
Trials Registrarse ponindose en contacto con los Juicios de
Coordinador de Bsqueda (29 de abril 2010).
El Cochrane de Embarazo y Parto Registro del Grupo es mantenida
por los Juicios de Coordinador de Bsqueda y contiene ensayos
identificados a partir de:
1. Bsquedas trimestrales en el Registro Cochrane Central de
Ensayos Controlados (CENTRAL);. 2 bsquedas mensuales en
MEDLINE;3. Manuales en 30 revistas y en los resmenes de
conferencias; 4. Alertas semanales de actualizacin ermanente en
otras 44 revistas ms alertas mensuales por correo electrnico en
ioMed Central.
Los detalles de las estrategias de bsqueda en CENTRAL y MEDLINE,
la lista de revistas consultadas manualmente y los resmenes de
congresos, y la lista de revistas revisadas por medio del servicio de
informacin actualizada se pueden encontrar en la seccin "Registro
Especializado" dentro de la editorial informacin material acerca de
la Cochrane de Embarazo y Parto Grupo .
REFERENCIAS
References to studies included in this review
CHARACTERISTICSOFSTUD IES
Characteristics of included studies
[ordered by study ID]
Amon 1988a
Mtodos
Randomised trial. No mention of method of randomisation. Not
placebo controlled or
cegado
Los participantes
82 women treatment 43 control 39. Inclusions: 20-34 weeks'
pregnant. PPROM confirmed by sterile speculum. Singleton pregnancy only
Interventions
Los participantes
148womenat2137weekswithprematureruptureofthemembranespretermconfirmed
with positive nitrazine test and 'ferning' of amniotic fluid or by seeing
vaginal pool of
amniotic fluid from os. No tocolytics or steroids given. Multiple
pregnancies included.
Exclusions are not clearly stated.
Intervenciones
4 hourly IV 1 million units benzylpenicillin for 12-24 hours - oral 250
mg penicillin
twice daily before delivery or a matched placebo
Outcomes
Latency period, infection complications and neonatal
outcomes studies. Data on death not included.
Notas
Study conducted from March 2 1989 to May 29 1991, in a single site
(North Carolina,
EE.UU.). 148 women.
71 placebo.
77 treatment.
4 women were excluded because of protocol violation in placebo arm
(antibiotics given)
Information on neonatal death not given.
Risk of bias
Artculo
Authors' judgement
Descripcin
Adequate sequence generation?
S
Table of random numbers.
Allocation concealment?
S
Stated that nurses were not involved in the
preparation or release of eitherantibiotic or
placebo
Blinding?
All outcomes
S
Patients and staff blinded.
Incomplete outcome data addressed?
All outcomes
S
Data excluded for 4 women who were
treated with antibiotics outside the protocol
Free of selective reporting?
Incierta
Protocol not available.
Free of other bias?
Incierta
No information given.
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Fuhr 2006
Mtodos
Randomised double blind placebo controlled trial - multicentre
Los participantes
105 pregnant women with PROM between 24+0 and 32+6 weeks.
Exclusion criteria not clearly stated nor whether multiple pregnancy
included
Interventions
Metzlocillin 2 gm given 3 x day for 7 days or placebo.
All women given corticosteroids and tocolytics IV.
Outcomes
Prolongation of pregnancy and neonatal mortality and morbidity
Notas
5 centres in Germany - dates not given.
47 women in treatment arm and 58 in control.
Risk of bias
Artculo
Authors' judgement
Descripcin
Adequate sequence generation?
Incierta
No information given.
Allocation concealment?
Incierta
No information given.
Blinding?
All outcomes
S
Stated as double blind trial.
Incomplete outcome data addressed?
All outcomes
S
Data appears complete.
Free of selective reporting?
Incierta
Protocol not available.
Free of other bias?
Incierta
No information given.
Garcia 1995
Mtodos
S
Data appear complete.
Free of selective reporting?
Incierta
Protocol not available.
Free of other bias?
Incierta
No information given.
Grable 1996
Mtodos
60 women randomised to double blind placebo controlledtrial.
Randomisation based on
random numbers tables with blocks providing 1:1 ratio and balancing
every 6 women.
Randomisation conducted in pharmacy
Los participantes
60 women randomised. Inclusions <= 35 weeks with documented
PPROM.
Exclusions: digital examination of cx, non-reassuring stress test,
presence of chorioamnionitis, abruptio placenta, pre-eclampsia, multiple pregnancy and
penicillin allergy
Interventions
IV ampicillin 2 gm every 6 hours for 24 hours followed by 500 mg oral
ampicillin until
delivery or discharge. Matched placebos
Outcomes
Maternal morbidity. Neonatal mortality and morbidity.
Notas
Study divided into GBS positive and negative patients. Unclear
whether clinician knew
of positive culture
Risk of bias
Artculo
Authors' judgement
Descripcin
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Grable 1996 ( Continued)
Adequate sequence generation?
S
Randomisation based on random numbers
tables with blocks providing 1:1 ratio and
balancing every 6 women
Allocation concealment?
S
Randomisation and preparation of drugs
conducted in pharmacy
Blinding?
All outcomes
S
Double blind trial.
Incomplete outcome data addressed?
All outcomes
S
Data appears complete.
Free of selective reporting?
Incierta
Protocol not available.
Free of other bias?
Incierta
No information given.
Johnston 1990
Mtodos
Randomised double-blind placebo controlled trial. Randomisation
table generated by
consecutive coin toss, the randomisation schedule kept in pharmacy
Los participantes
85 women randomised. Inclusions: mothers with singleton gestations
between 20-34
weeks with PPROM confirmed by sterile speculum for pooling, ferning
and nitrazine
paper testing.
Exclusions: penicillin allergy, taking antibiotics at the time of PPROM,
had fever> 100.4
degrees Fahrenheit, had signs of chorioamnionitis, were in active
labour (defined by 3 or
more contractions per 10 minute period for 1 hour or presented with
cervical dilatation
> 3 cm confirmed at the time of sterile speculum. Fetal indications for
exclusion were the
presence of fetal distress, defined as repetitive late deceleration or
sustained bradycardia,
or congenital abnormality on ultrasound
Intervenciones
IV mezlocillin for 48 hours followed by oral ampicillin until delivery or
matched (IV +
oral) placebo.
No doses noted. After randomisation no tocolytic steroids given.
Study drugs discontinued if infection diagnosed.
Outcomes
Not clearly defined other than maternal or perinatal morbidity and
mortality.
Outcomes looked at included length of pregnancy, maternal infectious
morbidity, mode
Descripcin
Adequate sequence generation?
S
By computer using randomly generated
blocks of 4.
Allocation concealment?
S
Sequentially numbered drug boxes of identical appearance.
Blinding?
All outcomes
S
Stated that clinicians remained blind to
treatment allocation in all but 9 cases and
that all staff and participants remained
blind to treatment allocation
For the follow up study all participants bar
1womenandallStudyStaffremainedblind
to treatment allocation
Incomplete outcome data addressed?
All outcomes
S
2 women lost to follow up and 15 protocol
violations.
In the follow up study outcome data were
determined for 75% of eligible children
Free of selective reporting?
S
No selective reporting.
Protocol published for follow up study.
Free of other bias?
S
The study appears to be free of other
sources of bias.
Kurki 1992
Mtodos
Randomised double blind placebo controlled trial.
Los participantes
101 women randomised between 23-36 weeks' pregnant with visible
leakage of amniotic
fluid who did not go into labour within 12 hours of admission. Sterile
speculum, digital
examination and infection screening was performed on admission.
Multiple pregnancies
incluido
Interventions
2 doses of IV penicillin (5 mu) or matched placebo.
Outcomes
Prolongation of pregnancy. Infection, neonatal morbidity and mortality.
Long-term de-
velopment at 2 years
Notas
Department of Obstetrics and Gynaecology, Helsinki, Finland.
No mention of where the study was conducted. Sealed envelope
randomisation.
Results in 76 women not randomised but admitted during the same
period are also
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Kurki 1992 ( Continued)
reportado
Risk of bias
Artculo
Authors' judgement
Descripcin
Adequate sequence generation?
Incierta
No information given.
Allocation concealment?
S
Stated as being by sealed envelope.
Blinding?
All outcomes
S
Stated as double blind trial.
Incomplete outcome data addressed?
All outcomes
S
Data appear complete.
Free of selective reporting?
Incierta
Protocol not available.
Free of other bias?
Incierta
No information given.
Lewis 2003
Mtodos
Randomised trial looking at 3 or 7 days antibiotic therapy.
Randomised using table of
arbitrary numbers in blocks of 10. Indicator cards placed in sealed
envelopes which were
sequentially numbered and stored on an area away from the
enrolment site
Los participantes
No information given.
Lockwood 1993a
Mtodos
Randomised double blind placebo controlled trial.
Los participantes
75 women randomised with a single fetus at 24-34 completedweeks
(accurate gestational
age), admitted with PROM. No digital examination unless active
labour. Women had
infection screening.
Exclusions: abruption, lethal fetal abnormalities clinical
chorioamnionitis, maternal illness, diabetes, PIH, lupus, severe maternal disease, fetal growth
retardation, fetal distress,
cervical cerclage, active herpes. Women having received antibiotics
for existing infection
were also excluded
Interventions
Piperacillin 3 gm IV 6 hourly 72 hours or placebo.
Outcomes
Prolongation of pregnancy.
Neonatal outcomes.
Notas
Recruitment in 3 centres (USA) from January 1987 to January 1992. 75
women were
randomised (treatment 38, placebo 37).
3 babies (1 in the experimental group and 2 in controls) were lost to
follow up
Risk of bias
Artculo
Authors' judgement
Descripcin
Adequate sequence generation?
S
Computer-generated randomisation secuencia.
Allocation concealment?
S
Same deposited in pharmacy.
Blinding?
All outcomes
S
Statedall healthcare providers were blinded
to allocation.
Incomplete outcome data addressed?
All outcomes
S
Data appear complete.
Free of selective reporting?
Incierta
Artculo
Authors' judgement
Descripcin
Adequate sequence generation?
S
Computer-generated random number list.
Allocation concealment?
S
Sequentially numbered bottles.
Blinding?
All outcomes
S
Stated as double blind trial.
Incomplete outcome data addressed?
All outcomes
S
Data appears complete after 10 exclusions.
Free of selective reporting?
Incierta
Protocol not available.
Free of other bias?
Incierta
No hay informacin disponible.
Mercer 1992
Mtodos
Randomised double blind placebo controlled trial.
Computerised random number tables. Administered by the pharmacy.
Stratified at 30 weeks. la edad gestacional.
Los participantes
Inclusions: 220 women 20-34/6 weeks pregnant with PPROM - sterile
speculum and
evaluation of cervix. Amniocentesis done for infection screen. Multiple
pregnancies
incluido.
Exclusions: PPROM > 72 hours duration, cervical dilatation > 4 cm,
progressive labour,
vaginal bleeding, temperature 99 degrees Fahrenheit or greater,
active infection requiring
antibiotic therapy, antibiotic therapy within 1 week prior to admission,
active hepatic
disease, erythromycin allergy, cervical cerclage or medical condition
requiring delivery.
IUGR (< 10 centile), congenital abnormalities, evidence of fetal
distress, unsuccessful
tocolysis on admission for preterm labour
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Mercer 1992 ( Continued)
Interventions
Oral 333 mg erythromycin. 8 hourly from randomisation to delivery
with matched
placebo
Outcomes
Not clearly stated.
Prolongation of pregnancy. Reduction of infectious morbidity
Notas
Single centre (Memphis, Tennessee, USA).
March 1989-August 1990.
Women had infection screen before randomisation.
220 randomised, (treatment 106, placebo 114) 3 lost to follow up
Risk of bias
Artculo
Authors' judgement
Descripcin
Adequate sequence generation?
S
Computerised random number tables.
Allocation concealment?
S
Administered by the pharmacy.
Blinding?
All outcomes
S
States that all involved remained blind to
treatment allocation
Incomplete outcome data addressed?
All outcomes
S
Data appear complete.
Free of selective reporting?
Incierta
Protocol not available.
Free of other bias?
Incierta
No information given.
Mercer 1997
Mtodos
Randomised double blind placebo controlled trial. Urn randomisation
scheme (a procedure to increase the likelihood of obtaining an equal number of
subjects in each arm)
, stratified by centre
Los participantes
614 women with PPROM at 24-32 weeks' gestation. Inclusion criteria:
membrane rup-
Artculo
Authors' judgement
Descripcin
Adequate sequence generation?
S
Urn randomisation scheme (a procedure
to increase the likelihood of obtaining an
equal number of subjects in each arm),
stratified by centre
Allocation concealment?
S
Treatment given by pharmacy.
Blinding?
All outcomes
S
States all involved remained blinded to
treatment allocation
Incomplete outcome data addressed?
All outcomes
S
Only 3 withdrawals (2 in placebo and 1 in
treatment arm).
Free of selective reporting?
Incierta
No protocol available.
Free of other bias?
Incierta
No information given.
Morales 1989
Mtodos
Randomised trial not placebo controlled. RCT of antenatal steroids +
ampicillin. 4
groups - GP1 - neither, GP2 steroids only, GP3 antibiotic only, GP4
both. Aleatorios
by using sealed envelopes into 1 of groups
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Morales 1989 ( Continued)
Los participantes
Randomised: 41 = GP1, 43 = GP2, 37 = GP3, 44 = GP4.
Inclusion criteria 26-34 weeks' pregnant singleton gestation. PROM
confirmed by sterile
speculum L/S ratio less than 2.0.
Exclusions: In labour within 12 hours of randomisation women with
uterine tenderness,
arriba.
Free of selective reporting?
Incierta
Protocol not available.
Free of other bias?
No
Trial stopped after intermediate evaluation
showed treatment group had better outvenir
Owen 1993a
Mtodos
Randomised not placebo controlled. Randomised using sealed opaque
envelopes determined by computer algorithm
Los participantes
118 randomised 1 lost to follow up. 59 treatment 58 controls.
Inclusions 24 to 34 weeks'
gestacin. PPROM confirmed by speculum. Exclusions in labour,
clinical evidence of
infection suspected fetal compromise, membrane rupture over 2
days, fetal abnormality,
antibiotics in last 7 days, multiple pregnancy, cervical cerclage,
prompt delivery required
Intervenciones
IV 1 gm ampicillin 6 hourly for 24 hours then 500 mg ampicillin orally
every 6 hours.
If allergic to penicillin 500 mg erythromycin used 6 hourly. Treatment
continued with
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Owen 1993a ( Continued)
delivery or diagnosis of chorioamnionitis
Outcomes
Death only included.
Notas
Risk of bias
Artculo
Authors' judgement
Descripcin
Adequate sequence generation?
S
By computer algorithm.
Allocation concealment?
S
Sealed opaque envelope.
Blinding?
All outcomes
No
Not blinded.
Incomplete outcome data addressed?
All outcomes
S
Data appear complete - 1 woman lost to
follow up in control group
Free of selective reporting?
Incierta
Protocol not available.
Free of other bias?
Incierta
No information given.
Segel 2003
Mtodos
Randomised double blind placebo controlled trial of 3 or 7 days
treatment. Farmacia
provided randomisation with a computer-generated random number
table in blocks of
4
Los participantes
48 women randomised: 24 in each arm-analysis on 23 in each arm.
Women 24-33 weeks
with clinically confirmed ruptured membranes. Exclusions included
penicillin allergy,
active labour, suspected infection, multiple pregnancy, known
medical maternal or fetal
problems and exposure to antibiotics within 1 week before admission
Intervenciones
For first 48 hours all women received parenteral ampicillin 2 g every 6
hours. Mujeres
werethenrandomlyselectedtoreceiveeither3or7daysoralampicillin.Wo
menallocated
the 3 day course received a matching placebo
Outcomes
Primary outcome of prolongation of pregnancy for at least 7 days.
Secondary outcomes
included rated of chorioamnionitis, postpartum endometritis and
neonatal morbidity
and mortality
Notas
Study took place between September 1999 - December 2001,
Pennsylvania USA
Risk of bias
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Segel 2003 ( Continued)
Artculo
Authors' judgement
Descripcin
Adequate sequence generation?
S
Computer-generated random number table in blocks of 4.
Allocation concealment?
S
Studymedicine givenbypharmacyinidentical packs.
Blinding?
All outcomes
S
Stated as double blind trial.
Incomplete outcome data addressed?
All outcomes
S
Data appear complete.
Free of selective reporting?
Incierta
Protocol not available.
Free of other bias?
Incierta
No information given.
Svare 1997a
Mtodos
Randomised double blind placebo controlled trial. Block randomisation
done using
computer-generated numbers
Los participantes
67 women randomised. 26 + 0 - 33 + 6 rupture of membranes,
leakage of amniotic fluid
at vaginal speculum examination. Preceding onset of uterine
contractions. Singleton
embarazos
Intervenciones
Ampicillin 2 gm IV 6 hourly. 24 hours - pivampicillin 500 g orally 8
hourly for 7 days
plus IV metronidazole 500 mg every 8 hours for 24 hours, followed by
metronidazole
400 mg orally every 8 hours for 7 days or identical placebo
Outcomes
Latency period from admission - delivery. Gestational age at delivery.
Preterm delivery
less than 37/40 maternal - neonatal infection birthweight
Notas
October 1991-April 1994. 6 centres around Copenhagen.
67 women randomised.
30 antibiotics.
37 placebo.
Data sent from Mr Svare and extracted from PhD thesis.
Risk of bias
Artculo
Authors' judgement
Descripcin
Adequate sequence generation?
S
Block randomisation done using computer-generated numbers.
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Svare 1997a ( Continued)
Allocation concealment?
Incierta
No hay informacin disponible.
Blinding?
All outcomes
S
Stated as double blind trial.
Incomplete outcome data addressed?
All outcomes
S
Data appear complete.
Free of selective reporting?
Incierta
Protocol not available.
Free of other bias?
Incierta
No information available
cx: cervix
EDD: expected date of delivery
GBS:
GP: group
IM: intramuscular
IUCD: intrauterine contraceptive device
IUGR: intrauterine growth retardation
IV: intravenous
IVH: intraventricular haemorrhage
L/S:
NEC: necrotising enterocolitis
Fortunato 1990
Study which investigated active versus passive management of
women with PPROM. 55 women were recruited
when admitted and given antibiotics. The control group were women
who presented with {PPROM. 19851987 before use of active protocol. Excluded as not double blinded,
randomised or controlled
Gordon 1974
Participants allocated to treatment or no treatment group on the
arbitrary basis of the last digit of the admission
number (unsatisfactory concealment of allocation). No mention of
blinding
Halis 2001
Abstract containing no usable data. GBS prophylaxis also given for
carriers
Julien 2002
Study compared antibiotic versus placebo only after 48 hour
intravenous antibiotic treatment to all
Kim 2008
Study was nether randomised or placebo controlled.
Lebherz 1963
Double blind randomised controlled trial of 1912 women but no
mention of gestation at recruitment
Lewis 1995
Study comparing treatment of women with PROM at 25 to 35 weeks'
gestation in a randomised blinded
trial comparing ampicillin-sulbactam with ampicillin: ie comparison of
similar antibiotics - so excluded as this
antibiotic comparison was not included in this review
Lewis 1996
This is a randomised trial of corticosteroids in women with PPROM
after a minimum of 12 hours ampicillin
sulbactam
77 women were enrolled. No statistically significant difference in
latency period was noted. Neonatal and
maternal infectious morbidity were similar. A significant reduction in
the incidence of RDS, 18.4% versus
43.6%, was observed in the steroid group
Lovett 1997
Double blind placebo controlled trial of 112 women with PPROM 23 to
25 weeks' gestation to receive
ampicillin/sulbactam or ampicillin or placebo
Excluded because of a high rate of exclusions (52/164: 32%). Further
information has been requested from the
autores
Matsuda 1993a
Comparative study; not placebo controlled.
Matsuda 1993b
Prospective study, not randomised, of conservative versus aggressive
management of women with PPROM.
2
678
Risk Ratio (MH, Random, 95% CI)
Not estimable
2 Serious maternal morbidity
0
Risk Ratio (MH, Random, 95% CI)
Subtotals only
2.1 Any antibiotic versus
placebo
0
0
Risk Ratio (MH, Random, 95% CI)
Not estimable
2.2 All penicillin (excluding
co-amoxiclav) versus placebo
0
0
Risk Ratio (MH, Random, 95% CI)
Not estimable
2.3 Beta lactum (including coamoxiclav) versus placebo
0
0
Risk Ratio (MH, Random, 95% CI)
Not estimable
2.4 Macrolide (including
erythromycin) versus placebo
0
0
Risk Ratio (MH, Random, 95% CI)
Not estimable
2.5 Other antibiotic versus
placebo
0
0
Risk Ratio (MH, Random, 95% CI)
Not estimable
3 Perinatal death/death before
descarga
12
Risk Ratio (MH, Random, 95% CI)
Subtotals only
3.1 Any antibiotic versus
placebo
12
6301
Risk Ratio (MH, Random, 95% CI)
0.93 [0.76, 1.14]
3.2 All penicillin (excluding
Pgina 44
4.4 Macrolide (including
erythromycin) versus placebo
3
334
Risk Ratio (MH, Random, 95% CI)
0.79 [0.45, 1.37]
4.5 Other antibiotic versus
placebo
3
763
Risk Ratio (MH, Random, 95% CI)
0.71 [0.53, 0.95]
5 Neonatal necrotising
enterocolitis
11
Risk Ratio (MH, Random, 95% CI)
Subtotals only
5.1 Any antibiotic versus
placebo
11
6229
Risk Ratio (MH, Random, 95% CI)
1.09 [0.65, 1.83]
5.2 All penicillin (excluding
co-amoxiclav) versus placebo
3
262
Risk Ratio (MH, Random, 95% CI)
0.85 [0.25, 2.97]
5.3 Beta lactum (including coamoxiclav) versus placebo
2
1880
Risk Ratio (MH, Random, 95% CI)
4.72 [1.57, 14.23]
5.4 Macrolide (including
erythromycin) versus placebo
3
2076
Risk Ratio (MH, Random, 95% CI)
0.88 [0.45, 1.69]
5.5 Other antibiotic versus
placebo
4
823
Risk Ratio (MH, Random, 95% CI)
0.89 [0.54, 1.47]
4961
Risk Ratio (MH, Random, 95% CI)
0.79 [0.63, 0.99]
22 Neonatal respiratory distress
sndrome
12
6287
Risk Ratio (MH, Random, 95% CI)
0.95 [0.83, 1.09]
23 Treatment with surfactant
1
4809
Risk Ratio (MH, Random, 95% CI)
0.83 [0.72, 0.96]
24 Number of babies requiring
ventilacin
2
4924
Risk Ratio (MH, Random, 95% CI)
0.90 [0.80, 1.02]
25 Number of babies requiring
oxygen therapy
1
4809
Risk Ratio (MH, Random, 95% CI)
0.88 [0.81, 0.96]
26 Neonatal oxygenation > 28
da
3
5487
Risk Ratio (MH, Random, 95% CI)
0.79 [0.61, 1.03]
27 Neonatal encephalopathy
1
60
Risk Ratio (MH, Random, 95% CI)
Not estimable
28 Serious childhood disability at
approximately 2 years
1
3171
Risk Ratio (MH, Random, 95% CI)
1.01 [0.91, 1.12]
Comparison 2. Erythromycin versus co-amoxiclav
Outcome or subgroup title
N de
estudios
N de
participantes
Mtodo estadstico
18 Neonatal necrotising
enterocolitis
1
2395
Risk Ratio (MH, Random, 95% CI)
0.46 [0.23, 0.94]
19 Neonatal respiratory distress
sndrome
1
2395
Risk Ratio (MH, Random, 95% CI)
0.99 [0.84, 1.16]
20 Treatment with surfactant
1
2395
Risk Ratio (MH, Random, 95% CI)
0.98 [0.81, 1.19]
21 Number of babies requiring
ventilacin
1
2395
Risk Ratio (MH, Random, 95% CI)
1.00 [0.86, 1.17]
22 Number of babies requiring
oxygen therapy
1
2395
Risk Ratio (MH, Random, 95% CI)
0.98 [0.87, 1.10]
23 Neonatal oxygenation > 28
da
1
2395
Risk Ratio (MH, Random, 95% CI)
0.86 [0.66, 1.12]
24 Oxygen treatment > 36 weeks'
postconceptual age
1
2395
Risk Ratio (MH, Random, 95% CI)
0.97 [0.70, 1.34]
25 Neonatal encephalopathy
0
0
Risk Ratio (MH, Random, 95% CI)
Not estimable
26 Major cerebral abnormality on
ultrasound before discharge
1
2395
Not estimable
2 Serious maternal morbidity
0
0
Risk Ratio (MH, Random, 95% CI)
Not estimable
3 Major adverse drug reaction
0
0
Risk Ratio (MH, Random, 95% CI)
Not estimable
4 Maternal infection after delivery
prior to discharge
1
84
Risk Ratio (MH, Random, 95% CI)
1.25 [0.36, 4.33]
5 Chorioamnionitis
1
84
Risk Ratio (MH, Random, 95% CI)
0.73 [0.33, 1.63]
44
Antibiotics for preterm rupture of membranes (Review)
Copyright 2010, La Colaboracin Cochrane. Published by
John Wiley & Sons, Ltd.
Pgina 47
6 Caesarean section
1
84
Risk Ratio (MH, Random, 95% CI)
1.18 [0.72, 1.91]
7 Days from randomisation to
nacimiento
0
0
Mean Difference (IV, Random, 95% CI)
Not estimable
8 Days from birth till discharge of
madre
0
0
Mean Difference (IV, Random, 95% CI)
Not estimable
9 Birth within 48 hours of
randomisation
1
84
130
Risk Ratio (MH, Random, 95% CI)
0.40 [0.05, 2.94]
28 Serious childhood disability at
approximately 2 years
0
0
Risk Ratio (MH, Random, 95% CI)
Not estimable
COMENTARIOS
45
Antibiotics for preterm rupture of membranes (Review)
Copyright 2010, La Colaboracin Cochrane. Published by
John Wiley & Sons, Ltd.
Pgina 48
Shapiro, March 2003
Resumen
The ORACLE study accounts for the vast majority of women included
in this review, 4826 out of around 6000 women. ORACLE
did not have a stopping rule, so that one cannot gauge why the study
was stopped when it was. Were repeated statistical tests done?
The impression, unfortunately, is that the study may have been
stopped when a significant result was obtained. If so, this makes the
significant conclusions untenable.
Responder
Thank you for your comments. The Medical Research Council (UK)
ORACLE Trial had both a Steering Group and a Data Monitoring
Comit. The Data Monitoring Committee agreed terms of reference
before the start of the Study. These were documented in the
trial protocol, as follows:
The independentDataMonitoringCommittee (chairman:
ProfessorAdrian Grant, Aberdeen; members:
ProfessorForresterCockburn,
Glasgow; Mr Richard Gray, Oxford; Professor Charles Rodeck, London)
will conduct interim analyses of morbidity and mortality
among all trial participants. The Trial Director and Steering Group will
be informed if at any time the randomised comparisons in this
study have provided both (i) proof beyond reasonable doubt of a
difference in a major endpoint between the study and control groups,
and (ii) evidence that would be expected to alter substantially the
choice of treatment for patients whose doctors are, in the light of the
evidence from the other randomised trials, substantially uncertain
whether to recommend antibiotics. Exact criteria of proof beyond
reasonable doubt are not specified, but members of the committee
have expressed sympathy with the view that it should generally
involve a difference of at least three standard deviations in a major
endpoint. Using this criterion has the practical advantage that the
.
Outcomes were divided into primary and secondary and
subgroup comparisons undertaken to look at the effect of
different antibiotics for primary outcomes only
HISTORIA
Protocol first published: Issue 2, 1998
Review first published: Issue 2, 1998
Fecha
Evento
Descripcin
29 January 2009
Modificado
Author contact details edited.
20 February 2008 Amended
Corrected error in dose of amoxycillin given in 'Characteristics of included studies' table for Almeida 1996a
Converted to new review format.
20 February 2008 Feedback has been incorporated
Feedback from William Stones added along with reply
from the author
24 January 2003
New citation required and conclusions have changed Substantive
amendment
47
Antibiotics for preterm rupture of membranes (Review)
Copyright 2010, La Colaboracin Cochrane. Published by
John Wiley & Sons, Ltd.
Pgina 50
CONTRIBUTIONSOFAUTHOR S
Sara Kenyon assessed the relevant trials, abstracted the data and
wrote the text of the review. Michel Boulvain and Jim Neilson checked
the extracted data and helped write the review.
DECLARATIONSOFINTERES T
Sara Kenyon was the Co-ordinator of the ORACLE Trial and led the
ORACLE Children Study both of which are included in this
revisar.
SOURCESOFSUPPORT
Internal sources
University of Liverpool, UK.
University of Geneva, Switzerland.
Leicester Royal Infirmary, UK.
University of Birmingham, UK.
External sources
No sources of support supplied
INDEXTERMS
Medical Subject Headings (MeSH)
Amoxicillin-Potassium Clavulanate Combination [adverse effects];
Anti-Bacterial Agents [adverse effects;
*
therapeutic use]; Chorioamnionitis [prevention & control]; Developmental Disabilities [prevention
& control]; Fetal Membranes, Premature Rupture [
*
drug therapy]; Infant, Newborn; Infant, Premature; Length of Stay; Macrolides
[therapeutic use]; Perinatal Mortality; Pregnancy Complications,
Infectious [mortality;
*
prevention & control]; Premature Birth [prevention & control];
Randomized Controlled Trials as Topic
MeSH check words
Nio; Female; Humans; Embarazo
48