THE NEW ENGLAND JOURNAL OF MEDICINE April 18, 1996
oxytocin if necessary. The study was also designed to
compare the two methods of inducing labor.
METHODS
The study was approved by the research-ethics committees at all
the participating centers, and the women gave informed consent before
being enrolled in the study.
Randomization was centrally controlled at the Perinatal Clinical
Epidemiology Unit at Women’s College Hospital in Toronto with the
use of a computerized randomization program, accessible by means
of a touch-tone telephone. To ensure that the four groups were comparable,
randomization was done in blocks of four and eight and stratified
according to center and parity.
Eligibility Criteria
Women were eligible for entry into the study if they had ruptured
membranes, were at 37 weeks’ gestation, and had a single fetus in a
cephalic presentation. Rupture of the membranes was determined
clinically and confirmed by positive litmus (Nitrazine) or ferning tests.
If necessary, a vaginal examination was performed with a speculum
to determine whether the membranes had ruptured. Digital vaginal
examinations were avoided.
Women were excluded from the study if they were in active labor,
if there had been a previous, failed attempt to induce labor, or if there
was a contraindication to either induction of labor (such as placenta
previa) or expectant management (such as meconium staining of the
amniotic fluid or chorioamnionitis). Before entering the study, women
were given a nonstress test and introital or vaginal swabs were taken
for the culture of group B streptococcus.
Treatment Protocol
Women were randomly assigned to one of four groups. In two of
the groups, labor was induced immediately, either with oxytocin (in
the induction-with-oxytocin group) or prostaglandin E2 gel (Prostin
E2 Vaginal Gel; in the induction-with-prostaglandin group). In the
other two groups, women waited for labor to begin spontaneously unless
there was evidence of fetal or maternal compromise, or until four
days had elapsed, in which case labor was induced with either oxytocin
or prostaglandin E2 gel in the expectant-management (oxytocin)
and the expectant-management (prostaglandin) groups, respectively.
For women assigned to the induction-with-oxytocin group, an infusion
of oxytocin was initiated and the infusion rate was titrated to contractions,
according to local hospital practice. For women assigned to
the induction-with-prostaglandin group, 1 or 2 mg of prostaglandin
E2 gel was inserted into the posterior vaginal fornix. This application
was repeated six hours later if labor had not started and was followed
by an infusion of oxytocin four or more hours later if labor still had
not started.
Women assigned to the expectant-management (oxytocin) group
were either admitted to the hospital or cared for as outpatients. Women
checked their temperatures twice daily and reported any fever,
changes in the color or odor of the amniotic fluid, or other complications.
Some women underwent additional monitoring tests. If complications
developed or if labor had not started after four days, labor was
induced with oxytocin as for women in the induction-with-oxytocin
group. For women assigned to the expectant-management (prostaglandin)
group, the approach was the same except that if labor was
induced, the method used was the same as that used for women in the
induction-with-prostaglandin group.
Decisions about other aspects of fetal and maternal care, including
the use and timing of antibiotics and the mode of delivery, were made
by the nurse, midwife, or attending physician. At delivery, cord-blood
gases were measured and Apgar scores were determined. Babies of
mothers in the study had blood samples taken for culture and whitecell
counts performed within 24 hours of birth and before treatment
with antibiotics. Other tests and treatments
administered to the babies were determined
by the attending physicians. After delivery,
women evaluated their experiences by completing
structured questionnaires to indicate
what they liked and disliked about their care.
Outcomes
The primary outcome was definite or probable
neonatal infection. Definite neonatal infection
was defined as the presence of clinical
signs of infection and one or more of the following:
a positive culture of blood, cerebrospinal
fluid, urine, tracheal aspirate, or lung
tissue; a positive Gram’s stain of cerebrospinal
fluid; a positive antigen-detection test
with blood, cerebrospinal fluid, or urine; a
chest radiograph compatible with pneumonia;
or a histologic diagnosis of pneumonia.
Probable neonatal infection was defined as
the presence of clinical signs of infection and
one or more of the following: a high or low
blood neutrophil count, a high immatureto-total
neutrophil ratio, a high actual immature
neutrophil count,10 or abnormal cerebrospinal
fluid findings showing an elevated
white-cell count, a high level of protein, or a
low level of glucose.
An adjudication committee